Clinical field study to evaluate the efficacy and safety of the amino-acetonitrile derivative, monepantel, compared with registered anthelmintics against gastrointestinal nematodes of sheep in Australia

Objective   To determine the efficacy of monepantel, a developmental compound from the amino-acetonitrile derivative class of anthelmintics, against field infections of gastrointestinal nematodes in sheep.
Procedures   Comparisons of efficacy (using standard faecal worm egg count reduction tests) and safety (on the basis of visual observations) were made in a large-scale field study in Australia, between groups of sheep treated with either an oral solution of monepantel or a registered anthelmintic. The sheep were naturally infected with the major gastrointestinal nematode genera present in Australia.
Results   The post-treatment efficacy results for monepantel were: at 7 days (±1 day) efficacy was >98%; at 14 days (±1 day) it was generally close to or >99%; and at 21 days (±1 day) efficacy was consistently >99%. A high proportion of the targeted nematode populations were confirmed as being resistant to one or more of the currently available anthelmintic classes.
Conclusions   Monepantel when used under field conditions at a minimum dose rate of 2.5 mg/kg was highly effective against mixed-genus natural field infections of the major gastrointestinal nematode genera including Haemonchus , Teladorsagia ( Ostertagia ), Trichostrongylus , Nematodirus , Chabertia and Oesophagostomum . This result included efficacy against some populations resistant to the currently available broad-spectrum anthelmintics. Few Cooperia spp. were present to allow confirmation of efficacy against this genus. On no occasion after treatment did any commercial anthelmintic-treated groups have significantly lower faecal egg counts than the monepantel-treated groups. Monepantel was safe for the target animals and human operators when used in a field situation.     

Analysis of a backcross population from a multi-copy transgenic Brassica napus line

Brassica napus is one of the crops at the forefront of biotechnological development. The procedures used to produce transgenic varieties are all prone to generating plants with multiple transgene copies. There has been considereable interest in the behaviour of such multi-copy lines because gene dosage rarely appears to correlate simply with gene expression. Here we report the analysis of a population of 107 progeny from a B. napus transformant containing multiple copies of a GUS marker gene construct. A total of 12 GUS sequence copies were identified including one that was non-functional. The expression of GUS increased with increasing copy number but this increase only made up a small proportion of the total variation between lines. There was no evidence of interaction between the various GUS copies and they appeared to segregate independently. The variation between progeny lines indicated that the number of gene copies was not a good guide to the expression of the gene product and hence that the expression of the gene in progeny from a multiple-copy parent could not be predicted. The importance of these findings in relation to plant breeding and the risk assessment process is discussed. This revised version was published online in August 2006 with corrections to the Cover Date.     

Identification and characterization of T-DNA inserts by T-DNA fingerprinting

A T-DNA fingerprinting method is presented based on amplified fragmentlength polymorphism with an anchored polymerase chain reaction step. Thismethod allows discrimination between different T-DNA inserts in stablytransformed plants. The technique was evaluated by analyzing 51 transgenicArabidopsis lines that had been characterized in detail by genomicblotting. Comparison of the obtained fingerprints with the availableintegration information demonstrated that fingerprints were correlated tothe predicted patterns, except for the inverted repeat junctions and forthose inserts with large deletions at the left or right border. Ourexperiments show that by using T-DNA fingerprinting multi-copy transgeniclines can be eliminated efficiently so that the technique can be used toenrich a population of transgenic plants for putative single-copytransformants.     

Diagnosis of bromethalin toxicosis in the dog

Dogs given a single oral dose of bromethalin at 6.25 mg/kg developed a toxic syndrome characterized by hyperexcitability, tremors, seizures, depression, and death within 15-63 hours after bromethalin administration. Gross lesions included mild cerebral edema (2/5) and mild pulmonary congestion (2/5). Histologic lesions included diffuse white matter spongiosis (5/5), mild microgliosis (3/5), optic nerve vacuolization (3/5), mild thickening of Bowman's capsule (2/5), and occasional splenic megakaryocytes (2/5). Ultramicroscopic examination of midbrain stem revealed occasional swollen axons, intramyelinic vacuolization, and myelin splitting at the intraperiod line. Bromethalin was detected in kidney, liver, fat, and brain tissues, using gas chromatography with electron capture detection. Photodegradation of extracted bromethalin may limit accurate quantification of tissue residues.     

Acute aflatoxicosis in feeder pigs, resulting from improper storage of corn

Aflatoxicosis was diagnosed in 600 feeder pigs, of which 400 died, 150 were destroyed, and 50 were marketed. The pigs were exposed to 2,500 to 3,500 micrograms of aflatoxins/kg of feed. Drought-stressed damaged corn infected with Aspergillus flavus was stored under ambient conditions in a glass-lined silo, and this storage environment provided conditions that favored rapid fungal growth and mycotoxin production.     

Stratospheric Mean Ages and Transport Rates from Observations of Carbon Dioxide and Nitrous Oxide

Measurements of stratospheric carbon dioxide (CO2) and nitrous oxide (N2O) concentrations were analyzed to investigate stratospheric transport rates. Temporal variations in tropospheric CO2 were observed to propagate into the stratosphere, showing that tropospheric air enters the lower tropical stratosphere continuously, ascends, and is transported rapidly (in less than 1 month) to both hemispheres. The mean age A of stratospheric air determined from CO2 data is approximately 5 years in the mid-stratosphere. The mean age is mathematically equivalent to a conserved tracer analogous to exhaust from stratospheric aircraft. Comparison of values for A from models and observations indicates that current model simulations likely underestimate pollutant concentrations from proposed stratospheric aircraft by 25 to 100 percent.     

Intestinal infection following aerosol challenge of calves with Mycobacterium avium subspecies paratuberculosis

ABSTRACT: A challenge experiment was performed to investigate whether administration of Mycobacterium avium subsp. paratuberculosis (MAP) via the respiratory route leads to MAP infection in calves. Eighteen calves from test negative dams were randomly allocated to four groups. Six calves were challenged with MAP nasally and six calves were challenged by transtracheal injection; three orally challenged calves served as positive controls, and three non challenged calves as negative controls. The challenge was performed as a nine-fold trickle dose, 107 CFU in total. Blood and faecal samples were collected frequently. Calves were euthanized three months post-challenge and extensively sampled. Blood samples were tested for the presence of antibodies and interferon gamma producing cells by ELISA. Faecal and tissue samples were cultured in a liquid culture system and the presence of MAP was confirmed by IS900 realtime PCR. Fourteen out of fifteen calves had no MAP antibody response. The negative controls remained negative; all positive controls became infected. Two nasally challenged calves showed a Purified Protein Derivative Avian (PPDA) specific interferon gamma response. In all nasally challenged calves, MAP positive intestinal samples were detected. In three calves of the nasal group MAP positive retropharyngeal lymph nodes or tonsils were detected. In all calves of the transtracheal group MAP positive intestinal tissues were detected as well and three had a MAP positive tracheobronchial lymph node. These findings indicate that inhalation of MAP aerosols can result in infection. These experimental results may be relevant for transmission under field conditions since viable MAP has been detected in dust on commercial dairy farms.     

QTL mapping of powdery mildew susceptibility in hop (Humulus lupulus L.)

Hop powdery mildew [Podosphaera macularis (Wallr.) U. Braun & S. Takam.] is best controlled via the production of resistant varieties. Recent evidence supports selection against plant susceptibility genes to fungal pathogens as a more durable resistance mechanism than selection for resistance genes. The objective of this study was to identify molecular-based QTLs, their genetic effects and epistasis among QTLs associated with susceptibility to powdery mildew. Parents and offspring from the cross, ‘Perle’ × ‘USDA 19058M’, were clonally replicated and inoculated in a greenhouse using a CRD experimental design in Corvallis, OR. DNA was extracted, purified and analyzed via three different marker systems. Analysis of the resulting markers was based upon the “two-way pseudo-testcross” procedure. QTL mapping using multiple interval mapping and Bayesian interval mapping analyses were performed using WinQTL Cartographer 2.5_003. Comparison amongst mapping analyses identified three persistent QTLs on three linkage groups without significant epistatic effect upon expression. The persistent QTL on linkage group C7 had both additive and dominant effects controlling phenotype expression. The presence or absence of the two AFLP markers bordering the QTL on C7 defined susceptibility in offspring. This is the first report in hop identifying molecular markers linked to QTLs associated with disease susceptibility.     

Resolution of a signal transfer region from a general binding domain in gbeta for stimulation of phospholipase C-beta2

Signaling by guanine nucleotide-binding proteins (G proteins) involves sequential protein-protein interactions. G protein-betagamma subunit (Gbetagamma) interactions with phospholipase C-beta2 (PLC-beta2) were studied to determine if all Gbeta contacts are required for signaling. A peptide encoding Gbeta amino acid residues 86 to 105 stimulated PLC-beta2. Six residues (96 to 101) within this sequence could transfer signals and thus constitute a core signal transfer region. Another peptide, encoding Gbeta amino acid residues 115 to 135, did not substantially stimulate PLC-beta2 by itself but inhibited Gbetagamma stimulation, indicating that residues 115 to 135 constitute a general binding domain. Resolution of signal transfer regions from general binding domains indicates that all protein-protein contacts are not required for signal transfer and that it may be feasible to synthesize agonists and antagonists that regulate intracellular signal flow.     

An examination of "transfer of learning" by nucleic Acid

Nucleic acid extracted from brains of trained animals and injected intraperitoneally into naive animals produced no "transfer of learning" effect on several tasks under many conditions. P(325)-Labeled RNA was not found in the brain after intraperitoneal administration. Even intraventricular injections of nucleic acid produced no "transfer" effect.