Induction of tumors in mice by genomic hypomethylation

Genome-wide DNA hypomethylation occurs in many human cancers, but whether this epigenetic change is a cause or consequence of tumorigenesis has been unclear. To explore this phenomenon, we generated mice carrying a hypomorphic DNA methyltransferase 1 (Dnmt1) allele, which reduces Dnmt1 expression to 10% of wild-type levels and results in substantial genome-wide hypomethylation in all tissues. The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.     

Ameloblastic odontoma in a dog

An ameloblastic odontoma in the right maxilla of a 10-week-old, female Springer Spaniel was treated by extensive curettage. Twelve months after surgery there was no recurrence of the neoplasm.     

Cryptococcosis in Gilbert's and long-nosed potoroo

Two cases of fatal cryptococcosis are described, one of Cryptococcus neoformans infection in a Gilbert's potoroo (Potorous gilbertii) and one of Cryptococcus gattii infection in a long-nosed potoroo (Potorous tridactylus). The diagnoses were confirmed by culture and specific immunohistochemistry, respectively. The long-nosed potoroo tested positive using the latex cryptococcal antigen test (LCAT), whereas the Gilbert's potoroo had a negative LCAT result despite having advanced disease of some duration. In both cases, the clinical presentation was a progressive neurologic disease associated with a central nervous system infection. Pulmonary infection was also observed in the long-nosed potoroo. Specific treatment with antifungal agents was unsuccessful in the long-nosed potoroo.     

Pharmacokinetics after intravenous and oral administration of enrofloxacin in sheep

OBJECTIVE: To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes. ANIMALS: 5 mature Katahdin ewes weighing 42 to 50 kg. PROCEDURE: Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg; mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg; mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 4789, 98.07, and 94.60%, respectively, and median maximum concentration (Cmax) was 1.61, 2.69, and 2.26 microg/ml, respectively. Median Cmax of the multiple-dose regimen was 2.99 microg/ml. CONCLUSIONS AND CLINICAL RELEVANCE: Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC < or = 0.29 microg/ml.     

Impacts of Accessibility on TOD: Measurement of Accessibility Around Transit Stations of Addis Ababa,Ethiopia

Today Transit-Oriented Development (TOD) is used as a tool to create a livable urban environment by improving the integration between land-use and transportation systems.The capital city of Ethiopia,Addis Ababa,aims to promote a sustainable transportation system by launching its first Light Rail Transit (LRT) network.Mitigate the need for mass transport,congestion,make transit a better choice,and encourage local economic development.Hence,a method was introduced to analyze the spatial and statistical conditions of accessibility on the existing transit stations of Addis Ababa.The methodology proposed measured the impact of accessibility around the existing TOD by defining a criterion that establishes the accessibility level[5-6].These criteria included proximity,urban densities,land-use diversity,and design of the urban spaces.The urban form of a place depends on accessibility.Mobility changes the character of a place.If the place changes,accessibility is likely to change.Therefore,TOD features that directly correlated with accessibility along the rail-based train stations will be explored.     

Compaction and rotovation effects on soil pore characteristics of a loamy sand soil with contrasting organic matter content

The high input of mechanical energy in common agricultural practice can negatively affect soil structure. The impact of compaction (P) and rotovation (R) on soil pore characteristics was compared with those in soil from untreated reference (U) plots of a loamy sand soil receiving for 14 yr, either only mineral fertilizer (MF) or, in addition, animal manure (OF). Undisturbed soil cores were taken from two separate fields in consecutive years at an identical stage in the crop rotation. We measured soil organic carbon (OC), soil microbial biomass carbon (BC), and hot‐water extractable carbon (C_hot). Water retention, air permeability and gas diffusivity were determined at ?100 hPa in both years and for a range of water potentials in one of the years. The continued addition of animal manure had increased OC, BC, and C_hot compared with the soil receiving only mineral fertilizer. Soil under treatment OF had larger porosity than that from treatment MF. Treatment P eliminated this difference and significantly reduced the volume of macropores. This interaction between soil organic matter content and mechanical impact was also reflected in the gas diffusion data. Specific air permeability was mainly influenced by mechanical treatment. Modelling the diffusion data normalized to the inter‐aggregate pore space showed no significant treatment effects on pore‐connectivity, although there was a tendency of more water blockage in soil under treatment MF. More studies are needed to confirm this interpretation. Our studies indicate that organic manure increases soil porosity, but compaction reduces the related gas exchange effects to the level of compacted soils receiving mineral fertilizer.     

Study design synopsis: Designing and performing pharmacokinetic studies for systemically administered drugs in horses

The goal of this editorial is to discuss best practice design, execution and reporting of a pharmacokinetic (PK) study in horses. Our target readers are clinicians who plan to perform this type of research, in a field, clinic or research setting but we also hope that this article might help readers of such work to appraise the articles and understand the quality of the studies. Our emphasis will be on appropriate study design and analytical method, drug and drug formulation choice and route of administration, animal choice, sample collection, storage and shipping, and reporting, rather than the PK data analysis itself.     

Proteome half-life dynamics in living human cells

Cells remove proteins by two processes: degradation and dilution due to cell growth. The balance between these basic processes is poorly understood. We addressed this by developing an accurate and noninvasive method for measuring protein half-lives, called "bleach-chase," that is applicable to fluorescently tagged proteins. Assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours. A variety of stresses that stop cell division showed the same general effect: Long-lived proteins became longer-lived, whereas short-lived proteins remained largely unaffected. This effect is due to the relative strengths of degradation and dilution and suggests a mechanism for differential killing of rapidly growing cells by growth-arresting drugs. This approach opens a way to understand proteome half-life dynamics in living cells.     

Improved procedure for implanting radiotransmitters in the coelomic cavity of snakes

Objective To investigate the expulsion of radiotransmitters in snakes and modify the surgical technique for coelomic implantation to prevent its occurrence. Design To enable monitoring of snakes for an ecological study, radiotransmitters were implanted in 23 south-west carpet pythons (Morelia spilota imbricata) using the standard surgical technique. In a further 23 pythons we used a refinement of the technique, which anchored the tracking device, using non-dissolvable sutures, to the snake's rib-cage. We also investigated the potential mechanisms for expelling the radiotransmitters in one snake that underwent an exploratory coeliotomy. Results Of the initial group of snakes, 12 (52%) expelled the radiotransmitter between 4 days and 3 years post implantation. In the later group, which underwent the refined technique of implantation, none of the radiotransmitters was expelled and no adverse responses were observed. Conclusion An appropriately sized radiotransmitter anchored to the rib-cage of the snake will prevent expulsion of the device and appears to be well tolerated. Non-attachment of the tracking device enables it to migrate along the length of the body, particularly during feeding and reproduction. Caudal positioning of the transmitter's antenna provides a possible pathogenesis for expulsion into the cloaca.