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Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Ccomplex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

The two main ultraviolet‐signatures resulting from the Io‐magnetosphere interaction are the local auroras on Io's atmosphere, and the Io footprints on Jupiter. We study here how Io's daily eclipses affect the footprint. Previous observations showed that its atmosphere collapses in eclipse. While remote observers can observe Io's local auroras briefly when Io disappears behind Jupiter, Juno is able to follow the Io footprint in the unlit hemisphere. Theoretical models of the variability of the energy flux fed into the Alfvén wings, ultimately powering the footprints, are not sufficiently constrained by observations. For the first time, we use observations of Io's footprint from the Ultraviolet Spectrograph (UVS) on Juno recorded as Io went into eclipse. We benchmark the trend of the footprint brightness using observations by UVS taken over Io's complete orbit and find that the footprint emitted power variation with Jupiter's rotation shows fairly consistent trends with previous observations. Two exploitable data sets provided measurements when Io was simultaneously in eclipse. No statistically significant changes were recorded as Io left and moved into eclipse, respectively, suggesting either that (i) Io's atmospheric densities within and outside eclipse are large enough to produce a saturated plasma interaction, that is, in the saturated state, changes in Io's atmospheric properties to first order do not control the total Alfvénic energy flux, (ii) the atmospheric collapse during the Juno observations was less than previously observed, or (iii) additional processes of the Alfvén wings in addition to the Poynting flux generated at Io control the footprint luminosity. Juno‐UVS observed for the first time the Io footprints while Io went into eclipseThe effect of Io's atmospheric collapse on the footprint emitted power is investigatedNo significant variation of the footprint emitted power is observed during eclipse

A large set of observations of Jupiter's ultraviolet aurora was collected with the Hubble Space Telescope concurrently with the NASA‐Juno mission, during an eight‐month period, from 30 November 2016 to 18 July 2017. These Hubble observations cover Juno orbits 3 to 7 during which Juno in situ and remote sensing instruments, as well as other observatories, obtained a wealth of unprecedented information on Jupiter's magnetosphere and the connection with its auroral ionosphere. Jupiter's ultraviolet aurora is known to vary rapidly, with timescales ranging from seconds to one Jovian rotation. The main objective of the present study is to provide a simplified description of the global ultraviolet auroral morphology that can be used for comparison with other quantities, such as those obtained with Juno. This represents an entirely new approach from which logical connections between different morphologies may be inferred. For that purpose, we define three auroral subregions in which we evaluate the auroral emitted power as a function of time. In parallel, we define six auroral morphology families that allow us to quantify the variations of the spatial distribution of the auroral emission. These variations are associated with changes in the state of the Jovian magnetosphere, possibly influenced by Io and the Io plasma torus and by the conditions prevailing in the upstream interplanetary medium. This study shows that the auroral morphology evolved differently during the five ~2 week periods bracketing the times of Juno perijove (PJ03 to PJ07), suggesting that during these periods, the Jovian magnetosphere adopted various states. The study presents the results of a large HST campaign observing Jupiter's UV aurora, concurrently with the in situ exploration of its magnetosphere with JunoThe study provides an original analysis method based on the definition of six morphological families tentatively associated with Jupiter's magnetospheric stateThis HST data set provides crucial synergistic measurements and additional opportunities to augment the Juno mission science return

We present an analysis of Europa's far‐UV spectral albedo using observations during the 1999–2015 time period made by the Space Telescope Imaging Spectrograph on the Hubble Space Telescope. Disk‐integrated observations show that the far‐UV spectrum in the ~130 to 170‐nm range is relatively flat or slightly blue (increasing albedo with decreasing wavelength) for the studied hemispheres: the leading, trailing, and anti‐Jovian hemispheres. At Lyman‐α (121.6 nm), the albedo of the trailing hemisphere continues the blue trend, but it reddens for the leading hemisphere. Also at this wavelength, the albedo of the leading hemisphere, which is higher than the trailing hemisphere at near‐UV and visible wavelengths, is lower than the trailing hemisphere, exhibiting spectral inversion. We find no evidence of a sharp water‐ice absorption edge at 165 nm on any hemisphere of Europa, which is intriguing since such an absorption feature has been observed on the icy Saturnian satellites. We used observations spanning from 1999 to 2015 obtained by the Space Telescope Imaging Spectrograph on the Hubble Space Telescope to study the surface reflectance of Europa at far‐ultraviolet (UV) wavelengths. We find that Europa has a low reflectance in the UV and that there is little variation in the surface brightness at most of the UV wavelengths. When observed at visible wavelengths, one of Europa's hemispheres is brighter than the other, but at the UV wavelength of 121.6 nm, the hemisphere brightness is reversed. We also find that Europa looks different from the icy moons of Saturn at far‐UV wavelengths. HST observations show that the spectrum of Europa in the far‐UV is very flat or slightly blueAt Lyman‐alpha, Europa is brighter on the leading hemisphere than the trailing, opposite of what is observed in the visible and near‐UVEuropa's spectrum lacks the sharp absorption feature at 165 nm observed on the icy Saturnian satellites

CD40–CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti‐CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti‐CD40 antibody can still promote graft survival. The parent anti‐CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC‐mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc‐silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98–100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well‐tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc‐silent anti‐CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection. The authors evaluate the novel, blocking, nondepleting CD40‐specific antibody CFZ533 as a monotherapy in a cynomolgus model of kidney transplantation, showing that it facilitates allograft survival, function, and morphology, and suppresses a gene signature associated with acute rejection, suggesting utility in clinical transplantation.

CD40–CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98–100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.

We analyze Hubble Space Telescope observations of Ganymede made with the Space Telescope Imaging Spectrograph between 1998 and 2017 to generate a brightness map of Ganymede's oxygen emission at 1,356 Å. Our Mercator projected map demonstrates that the brightness along Ganymede's northern and southern auroral ovals strongly varies with longitude. To quantify this variation around Ganymede, we investigate the brightness averaged over 36°‐wide longitude corridors centered around the sub‐Jovian (0° W), leading (90° W), anti‐Jovian (180° W), and trailing (270° W) central longitudes. In the northern hemisphere, the brightness of the auroral oval is 3.7 ± 0.4 times lower in the sub‐Jovian and anti‐Jovian corridors compared to the trailing and leading corridors. The southern oval is overall brighter than the northern oval, and only 2.5 ± 0.2 times fainter on the sub‐ and anti‐Jovian corridors compared to the trailing and leading corridors. This demonstrates that Ganymede's auroral ovals are strongly structured in auroral crescents on the leading side (plasma downstream side) and on the trailing side (plasma upstream side). We also find that the brightness is not symmetric with respect to the 270° meridian, but shifted by ∼20° towards the Jovian‐facing hemisphere. Our map will be useful for subsequent studies to understand the processes that generate the aurora in Ganymede's non‐rotationally driven, sub‐Alfvénic magnetosphere. Northern lights often illuminate the night sky in a shimmering green or red tone at high geographic latitudes. This emission, scientifically referred to as aurora, is a result of electrically charged particles that move along Earth's magnetic field lines and interact with its atmosphere to produce auroral emission. Apart from the Earth, multiple other planets in our solar system also exhibit auroral emission. By characterizing the brightness and structure of these lights, we are therefore able to deduce insights about a planet's atmosphere, magnetic field and the physical processes occurring along the field lines from afar. In this work, we used observations from the Hubble Space Telescope to analyze the auroral emission of Jupiter's largest moon Ganymede. We combined multiple images of Ganymede to create the first complete map that displays the auroral brightness. Our map revealed that the emission on Ganymede's auroral ovals varies strongly in brightness with divisions into two distinct bright and faint regions. They resemble two auroral crescents in the north and south respectively, and demonstrate the uniqueness of Ganymede's aurora in comparison with the auroral ovals of other planets in the solar system. Brightness map of Ganymede's ultraviolet auroral emission has been constructed based on Hubble Space Telescope observations from 1998 to 2017Auroral ovals are structured in upstream and downstream “crescents”Brightness on sub‐Jovian and anti‐Jovian side is strongly reduced by a factor of 3–4 compared to upstream and downstream side Brightness map of Ganymede's ultraviolet auroral emission has been constructed based on Hubble Space Telescope observations from 1998 to 2017 Auroral ovals are structured in upstream and downstream “crescents” Brightness on sub‐Jovian and anti‐Jovian side is strongly reduced by a factor of 3–4 compared to upstream and downstream side

Chemokine receptors have gained attention as potential targets for novel therapeutic strategies. We investigated the mechanisms of allograft rejection in chemokine receptor Cxcr3-deficient mice using a model of acute heart allograft rejection in the strain combination BALBc to C57BL6. Allograft survival was minimally prolonged in Cxcr3-deficient mice compared to wild-type (wt) animals (8 vs. 7 days) and treatment with a subtherapeutic dose of cyclosporine A (CsA) led to similar survival in Cxcr3-deficient and wt recipients (13 vs. 12 days). At rejection grafts were histologically indistinguishable. Microarray analysis revealed that besides Cxcr3 only few genes were differentially expressed in grafts or in spleens from transplanted or untransplanted animals. Transcript analysis by quantitative RT-PCR of selected cytokines, chemokines, or chemokine receptors or serum levels of selected cytokines and chemokines showed similar levels between the two groups. Furthermore, in a rat heart allograft transplantation model treatment with a small molecule CXCR3 antagonist did not prolong survival despite full blockade of Cxcr3 in vivo. In summary, Cxcr3 deficiency or pharmacologic blockade does not diminish graft infiltration, tempo and severity of rejection. Thus, Cxcr3 does not appear to play a pivotal role in the allograft rejection models described here.

Chemokine receptors have gained attention as potential targets for novel therapeutic strategies. We investigated the mechanisms of allograft rejection in chemokine receptor Cxcr3-deficient mice using a model of acute heart allograft rejection in the strain combination BALB/c to C57BL/6. Allograft survival was minimally prolonged in Cxcr3-deficient mice compared to wild-type (wt) animals (8 vs. 7 days) and treatment with a subtherapeutic dose of cyclosporine A (CsA) led to similar survival in Cxcr3-deficient and wt recipients (13 vs. 12 days). At rejection grafts were histologically indistinguishable. Microarray analysis revealed that besides Cxcr3 only few genes were differentially expressed in grafts or in spleens from transplanted or untransplanted animals. Transcript analysis by quantitative RT-PCR of selected cytokines, chemokines, or chemokine receptors or serum levels of selected cytokines and chemokines showed similar levels between the two groups. Furthermore, in a rat heart allograft transplantation model treatment with a small molecule CXCR3 antagonist did not prolong survival despite full blockade of Cxcr3 in vivo. In summary, Cxcr3 deficiency or pharmacologic blockade does not diminish graft infiltration, tempo and severity of rejection. Thus, Cxcr3 does not appear to play a pivotal role in the allograft rejection models described here.

Lightning discharge generated in the protoplanetary nebula is viewed as a temporally isolated surge in the flow of electrically charged particles, similar to that of terrestrial lightning. If the current is intense enough, a powerful circular impulse magnetic field is generated around the instantaneous virtual electric conductor. Such magnetic field is capable of magnetizing dust grains containing ferromagnetic components present in its vicinity to their saturation levels. As a result, dust grains attract one another, forming the aggregates. This magnetically driven attraction suggests an important process possibly operational at an early stage of the planetary accretion. Based on both a classical model for electric conductor, and the theory of Lienard–Wiechert electromagnetic potentials, our calculations show that the magnetic impulse due to a discharge channel of a few cm in diameter transferring a charge of about 104electrons reaches as high as 10 T. At these magnetic fields, the ferromagnetic dust grains, and possibly the already-formed larger aggregates as well, are easily magnetized to the saturation levels, producing compact clusters exhibiting permanent magnetic moments.

Rhombomeres are segmental units of the developing vertebrate hindbrain that underlie the reiterated organisation of cranial neural crest migration and neuronal differentiation. valentino (val), a zebrafish homologue of the mouse bzip transcription factor-encoding gene, kreisler, is required for segment boundary formation caudal to rhombomere 4 (r4). val is normally expressed in r5/6 and is required for cells to contribute to this region. In val(-) mutants, rX, a region one rhombomere in length and of mixed identity, lies between r4 and r7. While a number of genes involved in establishing rhombomeric identity are known, it is still largely unclear how segmental integrity is established and boundaries are formed. Members of the Eph family of receptor tyrosine kinases and their ligands, the ephrins, are candidates for functioning in rhombomere boundary formation. Indeed, expression of the receptor ephB4a coincides with val in r5/6, whilst ephrin-B2a, which encodes a ligand for EphB4a, is expressed in r4 and r7, complementary to the domain of val expression. Here we show that in val(-) embryos, ephB4a expression is downregulated and ephrin-B2a expression is upregulated between r4 and r7, indicating that Val is normally required to establish the mutually exclusive expression domains of these two genes. We show that juxtaposition of ephB4a-expressing cells and ephrin-B2a-expressing cells in the hindbrain leads to boundary formation. Loss of the normal spatial regulation of eph/ephrin expression in val mutants correlates not only with absence of boundaries but also with the inability of mutant cells to contribute to wild-type r5/6. Using a genetic mosaic approach, we show that spatially inappropriate Eph signalling underlies the repulsion of val(-) cells from r5/6. We propose that Val controls eph expression and that interactions between EphB4a and Ephrin-B2a mediate cell sorting and boundary formation in the segmenting caudal hindbrain.

beta-Thymosins are polypeptides that bind monomeric actin and thereby function as actin buffers in many cells. We show that during zebrafish development, β-thymosin expression is tightly correlated with neuronal growth and differentiation. It is transiently expressed in a subset of axon-extending neurons, essentially primary neurons that extend long axons, glia and muscle. Non-neuronal expression in the brain is restricted to a subset of glia surrounding newly forming axonal tracts. Skeletal muscle cells in somites, jaw and fin express beta-thymosin during differentiation, coinciding with the time of innervation. Injection of beta-thymosin antisense RNA into zebrafish embryos results in brain defects and impairment of the development of beta-thymosin-associated axon tracts. Furthermore, irregularities in somite formation can be seen in a subset of embryos. Compared to wild-type, antisense-injected embryos show slightly weaker and more diffuse engrailed staining at the midbrain-hindbrain boundary and a strong reduction of Isl-1 labeling in Rohon Beard and trigeminal neurons. The decreased expression is not based on a loss of neurons indicating that beta-thymosin may be involved in the maintenance of the expression of molecules necessary for neuronal differentiation. Taken together, our results strongly indicate that beta-thymosin is an important regulator of development.

The behavior ofMyiopharus doryphoraeandM. aberrans, North American tachinid parasitoids of the Colorado potato beetle, was recorded under field and laboratory conditions throughout three growing seasons in western Massachusetts. Eight common behaviors associated with resting, searching, feeding, and larviposition were distinguished, which together accounted for nearly all daytime activity of the females of both tachinids. Several of these behaviors, and in particular larviposition, were closely related to temperature but differed between species. A sequence of five defensive behaviors by the different larval stages of the Colorado potato beetle prevented larviposition in 49% of resisted attempts and perhaps one-fourth of total larviposition attempts byMyiopharusspecies, yet both parasitoids were highly successful in allocating their progeny during most of the summer. Second- and third-instar beetle larvae were least effective in resisting larviposition. Females of bothMyiopharusspecies actively guarded recently parasitized hosts from otherMyiopharusfemales for a period of several minutes after larviposition during the last month of the growing season when second- and third-instar Colorado potato beetle larvae were most scarce. Laboratory studies based on the field observation that femaleM. aberransdoggedly pursued circum-diapausing adult beetles led to the first recorded account ofM. aberranslarvipositing in adult hosts. Flies gained access to a beetle’s vulnerable abdominal dorsum at the instant it lifted its elytra to initiate flight. The late-season switch ofM. aberransto adult Colorado potato beetles contributed to a seasonal sequence of larviposition-related behaviors concordant with prevailing host densities, which should lend complementarity toM. doryphoraeandM. aberransas biological controls of pest populations.

Twelve of 102 woodchucks submitted for necropsy to the New York State College of Veterinary Medicine had clinical histories of central nervous system disorder. All had multifocal eosinophilic encephalitis with formation of granulomas. Nematode larvae, identified as Baylisascaris sp. were found in six of the 12 and were assumed to be the etiologic agent in all affected woodchucks. Both wild and captive (wild-trapped) woodchucks were affected, and all occurrences were between mid-June and early September.

The Apollo 17 ALSE VHF radar provided imagery and continuous profiling data around the Moon during two revolutions. The imagery data are used to derive depth and diameter measurements of small craters (diameter <30 km). The profiling data are used to study the topography of a few large craters: the bulged floors in Hevelius, Neper, and Aitken; central peaks in Neper and Buisson; and the depressed floor of Maraldi. The same data provided accurate (better than 25 m) profiles of Mare Crisium and Mare Serenitatis.

Lunar position differences between thirteen lunar craters in Mare Serenitatis were computed from VHF radar-imagery obtained by the Lunar Sounder instrument flown on the Apollo 17 Command Module. The radar-derived position differences agree with those obtained by conventional photogrammetric reductions of Apollo metric photography. This demonstrates the feasibility of using the Apollo Lunar Sounder data to determine the positions of lunar features along the Apollo 17 orbital tracks. This will be particularly useful for western limb and farside areas, where no Apollo metric camera pictures are available.

Generic characters are given for distinguishing the genus Parasymploce. Descriptions are given for 41 species, of which 19 are new. The taxa are grouped according to geographical areas, and regional keys to the males are provided. Based on male characters, the taxa are placed in two species-groups. Distribution checklists are given, arranged by species, and geographical location.

The Apollo 17 ALSE VHF radar provided imagery and continuous profiling data around the Moon during two revolutions. The imagery data are used to derive depth and diameter measurements of small craters (diameter <30 km). The profiling data are used to study the topography of a few large craters: the bulged floors in Hevelius, Neper, and Aitken; central peaks in Neper and Buisson; and the depressed floor of Maraldi. The same data provided accurate (better than 25 m) profiles of Mare Crisium and Mare Serenitatis.

Lunar position differences between thirteen lunar craters in Mare Serenitatis were computed from VHF radar-imagery obtained by the Lunar Sounder instrument flown on the Apollo 17 Command Module. The radar-derived position differences agree with those obtained by conventional photogrammetric reductions of Apollo metric photography. This demonstrates the feasibility of using the Apollo Lunar Sounder data to determine the positions of lunar features along the Apollo 17 orbital tracks. This will be particularly useful for western limb and farside areas, where no Apollo metric camera pictures are available.

As in other animals, the renal clearance of salicylate in the rat is greater when the urine is alkaline than when it is acid. In none of the present experiments was the rate of salicylate excretion greater than the rate of its glomerular filtration. Nevertheless, net secretion of salicylate was observed in the proximal tubules of alkalotic, nonalkalotic diuretic, and normal hydropenic animals when the plasma concentration of salicylate was below 150 microgram/ml. Alkalosis enhanced the salicylate content of proximal tubular fluid (approximately 30%). The enhancement is less than would be expected from published reports of proximal tubular fluid pH, if non-ionized salicylate were the only permeant form of the drug. In the absence of alkalosis and at high plasma concentrations, net reabsorption in the proximal tubule was observed. In some circumstances there is net reabsorption of salicylate between the end of the accessible portion of the proximal tubule and the beginning of the distal. Salicylate is reabsorbed from the distal tubule. There was only a small difference in distal reabsorptive rate between normal and alkalotic animals.

The renal excretion and certain pharmacokinetic properties of cimetidine were studied in anesthetized rats undergoing moderate osmotic diuresis. When cimetidine concentrations in plasma (Pcim) were low, ca. 2 micrograms/ml, the clearance of cimetidine (Ccim) was 2.64-fold greater than the glomerular filtration rate (GFR). Ccim was lower at higher concentrations, e.g., at ca. 200 micrograms/ml, Ccim/GFR was 1.24. When animals with low Pcim were alkalotic (bicarbonate infusion), Ccim/GFR was 1.82 (different from control, P less than 0.01). In nonalkalotic animals, Ccim/GFR was not influenced by changes in urine flow rate. High levels of Pcim completely blocked net secretion of the cation, tetraethylammonium ion, but did not inhibit the secretion of the anion p-aminohippurate. The half-time of cimetidine in plasma was 43 to 49 min. The apparent volume of distribution was 3.6-fold greater than estimated total body water. We conclude that cimetidine is secreted by the renal organic cation transport mechanism and that it probably undergoes passive reabsorption (nonionic diffusion) to a modest extent when the urine is alkaline. The relatively long half-life of the drug in the body, despite its very high renal clearance, is attributable to the large volume of distribution.

The effects of four levels of continuous stocking rate on herbage allowance level (HAL, units of herbage DM/unit of grazer BW and growth, morphology and dietary attributes of Coastal bermudagrass (Cynodon dactylonL. pers) were evaluated. Single pastures were stocked to achieve mean herbage allowances of 8.9, 34.5, 80.7 and 148.3 kg DM/100 kg BW of cattle from June 1 through September 17. Daily net herbage growth rate decreased linearly (P< .01) with advancing date and was not affected by HAL. Quadratic interactions existed (P< .05) between HAL and date for the proportion of leaf in herbage and diet. The proportion of dietary leaf declined quadratically (P< .01) at each HAL with advancing date. Linear and quadratic interactions between HAL and date existed (P< .01) for the NDF content of herbage and dietary leaf. Dietary leaf NDF increased linearly (P< .01) with increased HAL at all dates. Within date and HAL, the NDF content of herbage leaf was similar to that of stem. Grazing selectivity for diet leaf of lower NDF content (diet leaf NDF/herbage leaf NDF) increased as HAL was reduced. Decreasing HAL via increasing grazing pressure reduced the mean age of the herbage mass by responses in the morphology and growth of the herbage and reduced the fraction of herbage mass prehensible by the animal.

The livers of 16 woodchucks with naturally acquired chronic infection with woodchuck hepatitis virus were examined both grossly and histologically in 14 biopsy specimens and seven necropsy specimens. Fifteen woodchucks had lesions characteristic of chronic hepatitis; ten of these had chronic active hepatitis, four had chronic persistent hepatitis, and one had cirrhosis with nodular regeneration. In one woodchuck there was massive hepatic necrosis attributed to infection with an unclassified protozoan. Thirteen woodchucks had primary hepatocellular carcinoma. Metastasis to the lung was observed in only one woodchuck. These results were compared to liver lesions in 149 woodchuck hepatitis virus-negative woodchucks. Chronic hepatitis comparable to that associated with woodchuck hepatitis virus infection was not observed in woodchuck hepatitis virus-negative woodchucks although in one, a single, small hepatocellular adenoma was found.

Abstract: Properties of specific gravity, viscosity and flow rate were measured for cottonseed and soybean oil mixed with selected blank pesticide formulations without the active ingredient, i.e., blank-formulations. Fluid temperature ranged from 5 to 70 C for the measurements. Specific gravity of soybean oil mixtures was found to vary approximately 5% inversely with temperature over the temperature range. Above 65 C the mixtures exhibited approximately the same viscosity. Cottonseed oil viscosity remained less than the soybean oil viscosity over the entire range of temperatures studied. Addition of blank-formulation materials resulted in more reduction in viscosity at lower temperatures. Flow rates were measured over the temperature range for selected mixtures through different sizes and types of hydraulic spray nozzles. Fitted equations were derived to predict the necessary pressure correction for temperature for each nozzle and mixtures tested.

The behavior of small cracks growing out of the roots of blunt notches in compact type specimens of an austenitic steel was characterized under fatigue loading in wet H2 plus air environment. The growth rates of cracks in the size range of 0.125 mm to 0.75 mm were up to two orders of magnitude higher than the rates expected for conventional cracks at equal stress intensity range, ?K. It was also observed that the small cracks grew at these fast rates only in corrosive environments when the loading frequency was 0.02 Hz or less. At a frequency of 10 Hz, the behavior was in agreement with the trend predicted for conventional size cracks.

Hopanoids and other lipids were extracted from Zymomonas mobilis and quantitatively analyzed by highperformance liquid chromatography. Previous methods for hopanoid analysis required derivatization of the hopanoids via periodate oxidation or acetylation. The current method employs a normal-phase silica gel column, a ternary gradient of hexane-isopropanol-water-triethylamine, and detection with a flame ionization detector. Three major hopanoid classes were separated and quantified by this new method, and together they comprised 30 to 40% of the total lipid in these cells. Mass spectrometry confirmed that chemical structures of these hopanoids were consistent with those previously proposed. In addition, several other common lipid classes (free fatty acids and six classes of common phospholipids), comprising the remaining 60 to 70% of the total lipids, were also separated and quantified. This new chromatographic method represents the first technique for the analysis and purification of intact hopanoids. This method should be useful for the analysis and purification of hopanoids from other bacterial species.Copyright 1995, 1999 Academic Press, Inc.

During investigations of the evolution of experimental laboratory infections of woodchucks (Marmota monax) with the woodchuck hepatitis virus (WHV), eight hepatocellular carcinomas (HCC) were observed, six in newborns and two in young adult animals, all within 17-36 months after infection. The absence of an external cocarcinogenic effect in the well-monitored woodchucks indicates the carcinogenicity of WHV and suggests the same for the genetically and biologically similar human hepatitis B virus (HBV). Laboratory infections of woodchucks with two strains of WHV, not reported here in detail, resembled human and chimpanzee HBV infections histologically and serologically. In these studies, eight woodchucks became carriers of surface antigen of WHV for greater than 1 year. All eight woodchucks developed HCC, indicating a 100% risk of HCC in experimentally infected chronic WHV antigen carriers, which is analogous to the high risk of HCC in human hepatitis B surface antigen carriers. Histologically, the absence of cirrhosis in the examined pericarcinomatous tissue permits recognition of gradual transition from normal parenchyma to neoplastic nodules to HCC of rising anaplasia, indicating a continuum of increasingly more malignant neoplastic stages, as known for chemical carcinogenesis. The HCC developed in carrier woodchucks infected as newborns with only minor, if any, hepatitic changes but is associated with antigen-carrying hepatocytes and sometimes with hyperplastic nodules. This stage was preceded in infected adults by an early, acute, weeks-long hepatitis coinciding with the appearance of surface antigen. These findings are also analogous to typical HBV infection in human newborns and young adults, respectively. At the time of HCC development in all animals with adequate histologic material, an acute recent necroinflammation appeared around the tumor, associated with abnormal hematopoietic cells around and within the tumor. A promoting role in carcinogenesis of this necroinflammation of yet unestablished pathogenesis is being postulated, to be confirmed by determination of the status of the WHV DNA in the HCC and by prospective histologic study of the inflammatory reaction.

1. Laminar profiles of the average evoked potentials and current-source-density analysis were used to study the input provided by the medial perforant path (PP) to the hippocampus in the urethan-anesthetized rat. 2. Stimulation of the PP activated an early latency sink in the middle molecular layer of the dentate gyrus (DG) and in the stratum lacunosum-moleculare in CA1. The DG current sink was generated by excitatory synaptic currents activated by the PP on dentate granule cells. In the normal rat, the peak current sink in the DG was typically five times greater than that of CA1. However, the CA1 sink could be distinguished from the DG sink in several ways: 1) it peaked when the DG sink was subsiding; 2) it showed paired-pulse facilitation, whereas the DG sink did not; and 3) in rats in which the DG was lesioned by local colchicine injection, the DG sink was reduced much more than the CA1 sink. 3. The PP afferents to CA1 required a slightly higher stimulus threshold (> 100 microA) for activation than those projecting to the DG granule cells (< 30 microA). The onset latency of the early CA1 sink (2.5 +/- 0.2 ms, mean +/- SE) was also slightly longer than that of the DG sink (1.7 +/- 0.1 ms), suggesting that the axons of entorhinal layer III cells that project to CA1 have a slightly lower conduction velocity than the axons of the layer II cells that project to the DG. 4. The short-latency current sink activated by the PP in the distal dendritic layers of CA1 was likely provided by excitatory currents at the distal apical dendrites of CA1 pyramidal cells. The accompanying current source was mainly confined to stratum radiatum and appeared not to involve the cell body layer. Thus the electrotonic current spread may not be effective enough to depolarize the cell body or axon hillock. Contribution of interneurons to the above source-sink profile is possible, with the provision that these interneurons must have dendritic processes that span strata radiatum and lacunosum moleculare. 5. Extracellular field recordings provided no evidence that PP evoked a short-latency (< 9 ms) CA1-generated population spike, even with the use of micropipettes filled with mM bicuculline. Similarly, unit recordings in CA1 revealed only long-latency (9-17 ms) unit firing after PP stimulation, corresponding to a late, di/trisynaptic excitation of CA1 via the Schaffer collaterals.(ABSTRACT TRUNCATED AT 400 WORDS)

Objective:To assess the efficacy and safety of oral sulindac in preventing the recurrence of preterm labor.

Monospecific, polyclonal antibodies to the nodC and nodA gene products of Rhizobium meliloti were used in combination with immunogold labeling and transmission electron microscopy to localize the NodC and NodA proteins in cultures of R. meliloti. Both NodC and NodA were detected in the cytoplasm and cell envelope in thin sections of free-living rhizobia treated with luteolin, a known inducer of nod gene expression; however, only NodC was detected on cell surfaces when immunolabeling was performed with intact induced cells. In view of biochemical data characterizing NodC as an outer membrane protein with a large extracellular domain, the pattern of immunolabeling on thin sections suggests that NodC is produced on free cytoplasmic ribosomes prior to assembly in the membrane. The pattern of NodA labeling on thin sections is consistent with biochemical data detecting NodA in both soluble and membrane fractions of NodA-overexpressing strains of R. meliloti.

Properties of specific gravity, viscosity and flow rate were measured for cottonseed and soybean oil mixed with selected blank pesticide formulations without the active ingredient, i.e., blank-formulations. Fluid temperature ranged from 5 to 70 C for the measurements. Specific gravity of soybean oil mixtures was found to vary approximately 5% inversely with temperature over the temperature range. Above 65 C the mixtures exhibited approximately the same viscosity. Cottonseed oil viscosity remained less than the soybean oil viscosity over the entire range of temperatures studied. Addition of blank-formulation materials resulted in more reduction in viscosity at lower temperatures. Flow rates were measured over the temperature range for selected mixtures through different sizes and types of hydraulic spray nozzles. Fitted equations were derived to predict the necessary pressure correction for temperature for each nozzle and mixtures tested.

INTRODUCTION Electron miscroscopic studies of the central nervous system have emphasized the virtual absence of detectable extracellular spaces.1-4 These observations have provoked dissatisfaction with the chloride ion as an indicator of the extracellular space of brain. Calculations based on the assumption that chloride is entirely extracellular would indicate a compartment amounting to approximately 30% of brain weight.5 Although an extracellular space of this order of magnitude is clearly untenable, it seems to us that it is equally unreasonable to interpret the electron photomicrographs too literally and thus conclude that there is essentially no fluid outside of cellular membranes. Resolution of these widely different findings is important to the understanding of the transfer of substances into brain as well as such neuropathologic phenomena as cerebral edema. A more satisfactory indicator of extracellular brain water is required and we have investigated the sulfate ion with this in view. S35

1. The functional unity of cirri and membranelles can result structurally only from extensions of the ciliary membrane. 2. The pellicle is composed of an outer pellicular membrane and an inner cytoplasmic membrane. 3. The ciliary rootlets are composed of numerous filaments 120 A in diameter with central areas of low density. They have no periodic structure. 4. The ciliary membrane is a double-layered structure continuous with the pellicular membrane. The cilia show the typical arrangement of nine double, peripheral and two single, central fibrils. All fibrils pass into the basal region, the peripheral ones joining with the rootlet filaments, while the central fibrils from the extreme proximal position of the basal region turn back toward the pellicle and appear to unite just beneath the cytoplasmic membrane. 5. The cilia (300 mµ diameter) taper at their tips to a diameter at least as small as 50 mµ. At a diameter of about 150 mµ, the fibrils begin to show a reduction in number. 6. The central ciliary fibrils may determine the possible directions of ciliary beat. These fibrils show an intrafibrillar structure in their basal portion, which involves regularly spaced 40 A granules. 7. These observations on Euplotes, together with the other evidence cited, are consistent with the hypothesis that ciliary motion is produced by the contraction of the peripheral fibrils, while the central fibrils perhaps determine the plane in which the cilia can bend.

Sections of mitochondria in Paramecium and Euplotes present a consistent pattern. The mitochondrion in these cells can be conceived of as a twisted mass of closely compacted tubules. Two general kinds of substances can be recognized: the electron-dense that borders the lumen of the tubule, and the less dense that forms the continuum. In sections of mitochondria in rat kidney and snail oviduct, tubular internal organization can be recognized. In the same organs, mitochondria with lamellar internal structure can be demonstrated. The thesis is developed that the mitochondrion is a structure capable of differentiation and change, and that developmental continuity among the different kinds may exist. Mitochondria that appear to be different may be quite similar basically; mitochondria that appear to be similar in structure may be different in other ways. The tubule is proposed as the most basic of the presently recognized mitochondrial structures.

Procedures have been developed for selective degradation of bovine sperm and for isolation of segments. Such degradation of sperm can be achieved by (1) pronase digestion in sodium citrate followed by carbonate-bicarbonate buffer at pH 10.5, (2) pronase in CaCl2, and (3) nitrogen pressure and cavitation. Pressure cavitation and pronase digestion cleaved sperm at the capitulum-implantation fossa junction. In addition, the plasmalemma was removed; the remaining intact unit was composed of the mitochondrial sheath and the outer dense fibers. When the digestion process was used, the capitulum was separated from the outer dense fibers. Also, the microtubules of the axoneme were degraded by pronase used for 5–6 h. Following cell cleavage, centrifugation at 23,300 g with a sucrose gradient yielded pure head and mitochondria outer dense fiber fractions. These methods can be carried out on large quantities of sperm and allow selective degradation and fractionation, structural relationship studies, and chemical analyses of the separate cell segments and components.