Strain-engineering Mott-insulating La2CuO4.

The transition temperature Tc of unconventional superconductivity is often tunable. For a monolayer of FeSe, for example, the sweet spot is uniquely bound to titanium-oxide substrates. By contrast for La2-xSrxCuO4 thin films, such substrates are sub-optimal and the highest Tc is instead obtained using LaSrAlO4. An outstanding challenge is thus to understand the optimal conditions for superconductivity in thin films: which microscopic parameters drive the change in Tc and how can we tune them? Here we demonstrate, by a combination of x-ray absorption and resonant inelastic x-ray scattering spectroscopy, how the Coulomb and magnetic-exchange interaction of La2CuO4 thin films can be enhanced by compressive strain. Our experiments and theoretical calculations establish that the substrate producing the largest Tc under doping also generates the largest nearest neighbour hopping integral, Coulomb and magnetic-exchange interaction. We hence suggest optimising the parent Mott state as a strategy for enhancing the superconducting transition temperature in cuprates.

Electrostatic coupling and local structural distortions at interfaces in ferroelectric/paraelectric superlattices.

The performance of ferroelectric devices is intimately entwined with the structure and dynamics of ferroelectric domains. In ultrathin ferroelectrics, ordered nanodomains arise naturally in response to the presence of a depolarizing field and give rise to highly inhomogeneous polarization and structural profiles. Ferroelectric superlattices offer a unique way of engineering the desired nanodomain structure by modifying the strength of the electrostatic interactions between different ferroelectric layers. Through a combination of X-ray diffraction, transmission electron microscopy, and first-principles calculations, the electrostatic coupling between ferroelectric layers is studied, revealing the existence of interfacial layers of reduced tetragonality attributed to inhomogeneous strain and polarization profiles associated with the domain structure.

X-ray diffraction studies of 180 degrees ferroelectric domains in PbTiO3/SrTiO3 superlattices under an applied electric field.

The dielectric response of PbTiO(3)/SrTiO(3) superlattices is studied using electrical and structural measurements. While the dielectric response of paraelectric superlattices is well accounted for by the lattice contribution, superlattices with ferroelectric compositions exhibit an enhanced permittivity. X-ray diffraction allowed the presence of ordered nanodomains in ferroelectric superlattices to be established and their displacement under an applied bias to be directly probed, demonstrating that the enhanced permittivity in these artificial materials is due to domain wall motion.

New phenomena at the interfaces of very thin ferroelectric oxides.

We present a brief review of the role of interfacial physics in ferroelectric oxides, with an emphasis on the importance of boundary conditions that determine the properties of very thin ferroelectric films and superlattices. As well as discussing the screening problem, and the role of strain and electrostatics in ferroelectrics, we highlight some of the possibilities in fine period superlattices where the high density of interfaces can lead to new and potentially useful phenomena.

Outbreak of herpesviral conjunctivitis and respiratory disease in gouldian finches.

An outbreak of tracheitis, sinusitis, and conjunctivitis, originating in recently imported birds, caused high morbidity and mortality in a flock of finches in Central Illinois. Although several species were present, Gouldian finches (Erythrura [Chloebia] gouldiae) were most commonly and severely affected. Birds submitted for necropsy displayed microscopic lesions characteristic of herpesviral infection, including epithelial cytomegaly and karyomegaly with basophilic, intranuclear inclusion bodies in the nasopharynx, sinuses, trachea, parabronchi, conjunctiva, and occasionally the lacrimal gland or proximal proventricular glands. Viral particles consistent with herpesvirus were visualized within affected epithelial cells with electron microscopy. Based on a partial sequence of the viral DNA polymerase gene, this virus was found to be identical to a herpesvirus previously implicated in a similar outbreak in Canada and is most likely an alphaherpesvirus.

Unusual behavior of the ferroelectric polarization in PbTiO3/SrTiO3 superlattices.

Artificial PbTiO3/SrTiO3 superlattices were constructed using off-axis rf magnetron sputtering. X-ray diffraction and piezoelectric atomic force microscopy were used to study the evolution of the ferroelectric polarization as the ratio of PbTiO3 to SrTiO3 was changed. For PbTiO3 layer thicknesses larger than the 3-unit cell SrTiO3 thickness used in the structure, the polarization is found to be reduced as the thickness is decreased. This observation confirms the primary role of the depolarization field in the polarization reduction in thin films. For the samples with ratios of PbTiO3 to SrTiO3 of less than one, a surprising recovery of ferroelectricity that cannot be explained by electrostatic considerations was observed.

Redirection of sialic acid metabolism in genetically engineered Escherichia coli.

Most microorganisms do not produce sialic acid (sialate), and those that do appear to use a biosynthetic mechanism distinct from mammals. Genetic hybrids of nonpathogenic, sialate-negative laboratory Escherichia coli K-12 strains designed for the de novo synthesis of the polysialic acid capsule from E. coli K1 proved useful in elucidating the genetics and biochemistry of capsule biosynthesis. In this article we propose a dynamic model of sialometabolism to investigate the effects of biosynthetic neu (N-acetylneuraminic acid) and catabolic nan (N-acylneuraminate) mutations on the flux of intermediates through the sialate synthetic pathway. Intracellular sialate concentrations were determined by high pH anion exchange chromatography with pulsed amperometric detection. The results indicated that a strain carrying a null defect in the gene encoding polysialyltransferase (neuS) accumulated > 50 times more CMP-sialic acid than the wild type when strains were grown in a minimal medium supplemented with glucose and casamino acids. Metabolic accumulation of CMP-sialic acid depended on a functional sialic acid synthase (neuB), as shown by the inability of a strain lacking this enzyme to accumulate a detectable endogenous sialate pool. The neuB mutant concentrated trace sialate from the medium, indicating its potential value for quantitative analysis of free sialic acids in complex biological samples. The function of the sialate aldolase (encoded by nanA) in limiting intermediate flux through the synthetic pathway was determined by analyzing free sialate accumulation in neuA (CMP-sialic acid synthetase) nanA double mutants. The combined results demonstrate how E. coli avoids a futile cycle in which biosynthetic sialate induces the system for its own degradation and indicate the feasibility of generating sialooligosaccharide precursors through targeted manipulation of sialate metabolism.

Adaptation of signature-tagged mutagenesis to Escherichia coli K1 and the infant-rat model of invasive disease.

With the exception of the polysialic acid capsule (K1 antigen), little is known about other virulence factors needed for systemic infection by Escherichia coli K1, the leading cause of Gram-negative neonatal meningitis in humans. In this work, the functional genomics method of signature-tagged mutagenesis (STM) was adapted to E. coli K1 and the infant-rat model to identify non-capsule virulence genes. Validation of the method was demonstrated by the failure to recover a reconstructed acapsular mutant from bacterial pools used to systemically infect 5-day-old rats. Three new genes required for systemic disease were identified from a total of 192 mutants screened by STM (1.56% hit rate). Gut colonization, Southern blot hybridization, mixed-challenge infection, and DNA sequence analyses showed that the attenuating defects in the mutants were associated with transposon insertions in rfaL (O antigen ligase), dsbA (thiol:disulfide oxidoreductase), and a new gene, puvA (previously unidentified virulence gene A), with no known homologues. The results indicate the ability of STM to identify novel systemic virulence factors in E. coli K1.

Comparison of serologic testing and slaughter evaluation for assessing the effects of subclinical infection on growth in pigs.

OBJECTIVE: To compare serologic testing with slaughter evaluation in assessing effects of subclinical infection on average daily weight gain (ADG) in pigs. DESIGN: Cohort study. ANIMALS: 18 cohorts (30 to 35 pigs/cohort) of pigs on/farms. PROCEDURE: Blood samples were collected, and pigs were weighed at 8, 16, and 24 weeks of age. Sera were tested for antibodies to porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), transmissible gastroenteritis virus (TGEV), pseudorabies virus, Mycoplasma hyopneumoniae, and Actinobacillus pleuropneumoniae. At slaughter, skin, nasal turbinates, lungs, and liver were examined. Associations between ADG and results of serologic testing and slaughter evaluation were examined by use of multiple linear regression. RESULTS: Pathogens that had a significant effect on any given farm during any given year and the magnitude of that effect varied. However, at 16 and 24 weeks of age, a higher antibody titer was consistently associated with a lower ADG. Mean differences in ADG between seropositive and seronegative pigs were 18 g/d (0.04 lb/d) for SIV, 40 g/d (0.09 lb/d) for PRRSV, 38 g/d (0.08 lb/d) for M hyopneumoniae, and 116 g/d (0.26 lb/d) for TGEV. Of the evaluations performed at slaughter, only detection of lung lesions was consistently associated with a decrease in ADG. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that subclinical infection with any of a variety of pathogens commonly found in swine herds was associated with a decrease in ADG. Serologic testing was more effective than slaughter evaluation in assessing the impact of subclinical infection on ADG in these pigs.

Disseminated blastomycosis in two California sea lions (Zalophus californianus).

Two captive California sea lions (Zalophus californianus) from different facilities were diagnosed with disseminated blastomycosis. The first, a 12-yr-old male, died after a 3-wk history of progressive anorexia and lethargy. Gross examination revealed acute jejunitis with focal perforation and associated peritonitis, along with severe purulent bronchopneumonia. The second, a 15-yr-old female, was euthanized after a 2-wk history of severe cutaneous ulceration and declining clinical condition. Gross examination revealed severe pyogranulomatous bronchopneumonia and ulcerative dermatitis. Histopathologic examination in both individuals revealed severe multifocal subacute to chronic pyogranulomatous pneumonia associated with massive numbers of fungal organisms morphologically compatible with Blastomyces sp. Fungal organisms were 8-20-microm-diameter broad-based budding yeasts with thick, refractile, double-contoured walls. The male sea lion had multifocal transmural Blastomyces-induced enteritis with subsequent rupture and peritonitis. The organism was also present in the liver, with minimal associated inflammation. The female had severe multifocal pyogranulomatous ulcerative dermatitis associated with large numbers of intralesional fungal organisms. Dissemination to the spleen had occurred in both animals. A serologic immunodiffusion test for Blastomyces dermatitidis was positive in the male. The presumptive primary pathogen in both cases was Blastomyces dermatitidis.

Sialic acid metabolism's dual function in Haemophilus influenzae.

Many bacterial commensals and pathogens use the sialic acids as carbon and nitrogen sources. In Escherichia coli, the breakdown of these sugars is catalysed by gene products of the nan (Nacylneuraminate) operon; other microorganisms may use a similar catabolic strategy. Despite the known ligand and antirecognition functions of the sialic acids, the contribution of their catabolism to infection or host colonization has never been directly investigated. We addressed these questions with Haemophilus influenzae type b, which metabolizes relatively few carbohydrates, using the infant-rat infection model. The predicted H. influenzae homologue (HI0142) of the E. coli sialic acid aldolase structural gene, nanA, was subcloned and mutagenized by insertion of a kanamycin resistance cassette. Phenotypic investigation of the resulting H. influenzae aldolase mutants showed that: (i) HI0142 is essential for sialic acid degradation; (ii) the products of the open reading frames (ORFs) flanking HI0142 (HI0140, 41, 44 and 45) are likely to have the same functions as those of their counterparts in E. coli; (iii) sialylation of the lipooligosaccharide (LOS) epitope recognized by monoclonal antibody 3F11 is dependent on an environmental source of sialic acid; (iv) a nanA mutant hypersialylates its LOS sialyl acceptor, corresponding to an apparent increased fitness of the mutant in the infant-rat model; and (v) expression of the LOS sialyl acceptor is altered in cells grown without exogenous sialic acid, indicating the direct or indirect effect of sialic acid metabolism on LOS antigenicity. Taken together the data show the dual role of sialic acid catabolism in nutrition and cell surface modulation.

Peliosis hepatis in a dog infected with Bartonella henselae.

A 6-year-old spayed female Golden Retriever was examined because of generalized weakness and abdominal distention. Abdominal ultrasonography revealed a large quantity of peritoneal fluid. In addition, the liver appeared larger than normal and contained multiple, small, nodular masses and cyst-like structures. Abdominal exploratory surgery was performed, and 5 L of serosanguineous peritoneal fluid was removed. Gross lesions were not found in the stomach, kidneys, intestines, adrenal glands, or urinary bladder. There were diffuse cystic nodules in all liver lobes. The dog did not recover from anesthesia. A diagnosis of peliosis hepatis was made on the basis of gross and histologic appearance of the liver. A polymerase chain reaction assay revealed Bartonella henselae DNA in liver specimens. To our knowledge, this is the first report of molecular evidence of B henselae infection in a dog with peliosis hepatis.

Persistent activity of doramectin and ivermectin against Ascaris suum in experimentally infected pigs.

A study was conducted to investigate the persistent nematocidal activity of two avermectins against experimentally-induced infections of Ascaris suum in swine. Seventy-two nematode-free cross-bred pigs of similar bodyweight were randomly allotted to nine treatment groups of eight pigs each. Eight of the groups were treated with injectable solutions containing 300 microg of doramectin/kg (IM) or 300 microg of ivermectin/kg (SC) either 0 (same day), 7, 14, or 21 days prior to an oral challenge of 50000 embryonated A. suum eggs. The ninth group (control) was challenged in parallel without any avermectin treatment. At 41 or 42 days after challenge, pigs were euthanatized and adult and larval stages of A. suum were collected from the gastrointestinal tract of each pig and counted. Both avermectins significantly (P < 0.0002) reduced nematode counts when given on the day of challenge (0 days prior), and the efficacy was 100% and 97.5% for doramectin and ivermectin, respectively. Doramectin given 7 days prior to challenge significantly (P < 0.0001) reduced nematode counts, and the efficacy was 98.4%. For all other avermectin-treatment groups, nematode counts were not significantly reduced compared to those in control pigs. These data indicated that anthelmintic activity of ivermectin against A. suum persisted for less than 7 days and the activity of doramectin persisted for more than 7, but less than 14 days.

The effect of genotype on sensitivity to inflammatory nociception: characterization of resistant (A/J) and sensitive (C57BL/6J) inbred mouse strains.

The important role of genetic factors in the mediation of sensitivity to pain and pain inhibition is being increasingly appreciated. In an attempt to systematically study the genotypic influences on inflammatory nociception, we conducted a survey of the nociceptive responsivity of three common outbred mouse strains and 11 inbred mouse strains on the formalin test. The formalin test is known to display a biphasic temporal pattern of behavioral and electrophysiological activity, defined by an acute/early phase and a tonic/late phase. Nociceptive sensitivity (licking/biting of the affected area) to a subcutaneous injection of 5% formalin (25 microl volume) into the plantar surface of the right hindpaw displayed moderate heritability in both phases (0.38 and 0.46, respectively). One strain, A/J, was identified as extremely resistant to formalin nociception, displaying total licking in the acute and tonic phases that was 60% and 87% lower, respectively, than the grand mean of all strains. A subsequent series of experiments were performed to characterize the difference between A/J and C57BL/6J mice. The findings establish this inbred strain comparison as a useful genetic model of nociceptive sensitivity.

Rhamnus cathartica (buckthorn) hepatocellular toxicity in mice.

The toxicity of the plant Rhamnus cathartica was assessed in mice after the plant was identified as a potential cause of an idiopathic neurologic disease in horses. Another member of the Rhamnaceae family, Karwinskia humboldtiana, is neurotoxic to mammals and birds and can induce hepatic degeneration and necrosis. To investigate the toxicity of R. cathartica, a 34-day feeding trial in mice was conducted using a complete rodent diet with 0, 5, or 25% added R. cathartica. No clinical signs or gross lesions were seen, and all major tissues were histologically normal except the liver. The livers of mice fed R. cathartica had marked hepatocellular swelling. Results from periodic acid-Schiff reaction staining and from electron microscopy confirmed that the swelling was due to deposits of monoparticulate glycogen (beta particles) in the cytoplasm. Glycogen deposition is an uncommon toxic change in cells. Apparently, compound(s) in R. cathartica directly or indirectly interfered with glycogen metabolism (either glycogenesis or glycogenolysis). Mechanistic and chronicity studies with R. cathartica are needed to investigate the pathophysiology of the glycogen disturbance and to determine if hepatic injury progresses and if other organs will be injured.

Neuraminidase (sialidase) activity of Haemophilus parasuis.

Neuraminidase (sialidase), a potential virulence factor in bacteria, was demonstrated in Haemophilus parasuis, an invasive swine pathogen, but not in four other pathogens of the Pasteurellaceae family: H. influenzae, H. somnus, H. paragallinarum, or Actinobacillus pleuropneumoniae. H. parasuis neuraminidase had an acidic pH optimum and a specificity for several substrates also cleaved by other bacterial neuraminidases. Similar to the neuraminidase of Pasteurella multocida, H. parasuis neuraminidase was cell associated and did not require divalent cations for activity. Exogenous sialic acid added to growth medium of H. parasuis was cleared after a lag of about 10 h and these cultures grew to a greater final density than cultures without added sialic acid, indicating that exogenous sialic acid is metabolized. The role of sialidase in providing nutrients to H. parasuis may be an important factor in its obligate parasitism.

An enteral formula containing fish oil, indigestible oligosaccharides, gum arabic and antioxidants affects plasma and colonic phospholipid fatty acid and prostaglandin profiles in pigs.

Evidence supports a pathogenic role of arachidonic acid-derived inflammatory mediators within the gastrointestinal tract of patients with inflammatory bowel disease. The purpose of this study was to assess the effects of an ulcerative colitis nutritional formula (UCNF) containing oligosaccharides, fish oil, gum arabic and antioxidants on plasma and colonic phospholipid fatty acid and prostaglandin profiles in pigs. Twenty-four growing barrows in two replications were equally randomized among four killing times (d 0, 7, 14 and 21), and one of two diets, a control and the UCNF. Diets contained comparable levels of protein, fat, and nonstructural carbohydrate and met 100% of the energy requirements of the pig. Intake and body weight were recorded daily while blood, urine and tissue samples were collected at time of kill. Within 1 wk of ingestion of the UCNF, the composition of plasma phospholipid fatty acids showed an increase in 20:5(n-3) and 22:6(n-3) (P < 0.0001) and a decrease in 20:4(n-6) and 18:2(n-6) (P < 0.0001). Similar effects were observed for the phospholipids in the colonic and cecal mucosa. Plasma prostaglandin E was unaffected by treatment, whereas thromboxane B2 and 6-keto-prostaglandin F1 alpha levels were significantly decreased after 7 d of UCNF ingestion. Ingestion of the UCNF resulted in a suppression in the synthesis of proinflammatory prostaglandins by cecal and colonic mucosal cells. Levels of colonic and cecal prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were significantly decreased after 7 d of UCNF ingestion. These changes may have been mediated by rapid increases of (n-3) fatty acids into cellular phospholipids. Dietary supplementation with the UCNF may prove beneficial for patients with ulcerative colitis by modulating colonic prostaglandin synthesis.

Direct PCR analysis for toxigenic Pasteurella multocida.

A more rapid, accurate method to detect toxigenic Pasteurella multocida is needed for improved clinical diagnosis, farm biosecurity, and epidemiological studies. Toxigenic and nontoxigenic P. multocida isolates cannot be differentiated by morphology or standard biochemical reactions. The feasibility of using PCR for accurate, rapid detection of toxigenic P. multocida from swabs was investigated. A PCR protocol which results in amplification of an 846-nucleotide segment of the toxA gene was developed. The PCR amplification protocol is specific for toxigenic P. multocida and can detect fewer than 100 bacteria. There was concordance of PCR results with (i) detection of toxA gene with colony blot hybridization, (ii) detection of ToxA protein with colony immunoblot analysis, and (iii) lethal toxicity of sonicate in mice in a test set of 40 swine diagnostic isolates. Results of an enzyme-linked immunosorbent assay for ToxA agreed with the other assays except for a negative reaction in one of the 19 isolates that the other assays identified as toxigenic. In addition to accuracy, as required for a rapid direct specimen assay, toxigenic P. multocida was recovered efficiently from inoculated swabs without inhibition of the PCR. The results show that PCR detection of toxigenic P. multocida directly from clinical swab specimens should be feasible.

Efficacy of moxidectin 0.5% pour-on against naturally acquired nematode infections in cattle.

The efficacy of 0.5% moxidectin pour-on at two dosages was evaluated in 30 cattle with naturally acquired gastrointestinal nematode infections. The cattle were ranked according to pretreatment fecal egg counts and body weights, and were randomly assigned from replicates to three treatment groups. The mean number of trichostrongyle eggs in pretreatment fecal samples did not differ among the groups. Groups I and II received 0.5% moxidectin pour-on at dosages of 0.25 mg moxidectin per kg body weight and 0.5 mg moxidectin per kg body weight, respectively, and Group III cattle received moxidectin-free vehicle (control cattle). The cattle were euthanized by complete replicate 14 or 15 days posttreatment for recovery of nematodes and examination of the pour-on sites. Treatment with moxidectin was associated with a significant reduction in fecal trichostrongyle egg counts compared with the control cattle; efficacy was 99.7% and > 99.9% for cattle in Groups I and II, respectively. Eleven species of adult nematodes (Haemonchus contortus, Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis, Bunostomum phlebotomum, Cooperia oncophora, Cooperia punctata, Nematodirus helvetianus, Oesophagostomum radiatum and Trichuris ovis) and 4th stage larvae of Ostertagia spp. and Trichostrongylus spp. were present in sufficient numbers in control cattle to evaluate the efficacy of moxidectin 0.5% pour-on. In all cases, treatment was associated with a significant reduction in the number of nematodes recovered at necropsy, with the efficacy of both dosages exceeding 99.9%. There were no significant differences in mean worm burdens or fecal egg counts between the two treated groups, and no adverse reactions were observed.