Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta

We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization.     

Analyzing the effect of stepping stones on target patch colonisation in structured landscapes for Eurasian lynx

With habitat loss and fragmentation having become two of the major threats to the viability of species, the question of how to manage landscapes for species conservation has attracted much attention. In this context, the planning of stepping stones has been proposed to increase connectivity in fragmented landscapes. We present a simulation study with a neutral landscape approach to assess the effects of stepping stones on colonization success. To that end, we used a spatially explicit, calibrated population model of the European lynx (Lynx lynx) coupled with structured landscapes, in which we could control the landscape parameters of dispersal habitat coverage and contagion, as well as the number and size of stepping stones available for breeding. In general, we found that colonization success increased with increasing habitat coverage but decreased with increasing habitat contagion, while the introduction of stepping stones had significant effects in critical situations. Especially at low to medium dispersal habitat coverage and high disperser mortality, stepping stones had a positive effect on colonization success when they were large enough to produce new dispersers, but negative effects when they were small and located in a way that dispersers would be distracted from more suitable breeding habitat patches. The latter clearly constituted a shading effect and argues for a thorough consideration of the trade-offs related to stepping stone size and location when implementing stepping stones as a conservation measure, especially when the number of individuals of conservation concern is low.     

Wind dispersal of oribatid mites as a mode of migration

Oribatid mites are important colonizers of young soils, but little is known about their immigration pathways. In this study, one often-stated hypothesis was tested quantitatively: that wind is an important dispersal pathway. The aim was (1) to detect wind dispersal in oribatid mites (using sticky traps at different heights above ground level) and to determine factors influencing wind dispersal, (2) to investigate whether oribatids can survive wind dispersal and immigrate by wind into young soils (using mini-pitfall traps in test plots with oribatid-free substrate, active immigration being prohibited) and (3) to find out whether those oribatids are able to colonize young soils (using soil cores from the test plots). The results demonstrate (1) that mainly arboreal oribatid species were dispersed by wind - even at 160 m height - and can therefore be spread over large distances. Nevertheless, about 10% of the wind-dispersed oribatid mites belonged to species able to live in the soil and may therefore be potential colonizers of young soils. The number of specimen and species transported by wind was the highest close to the soil surface and the number of dispersed individuals was mainly influenced by seasonality and humidity. The results also suggest that the probability of a soil oribatid being dispersed by wind depends on its original microhabitat (tree habitats > soil surface > deeper soil layers) and its body weight. It was also shown that soil-dwelling oribatid mites survived wind dispersal and immigrated by wind into the test plots and that colonization of the test plots took at least 2 months longer than immigration. However, colonization success was low during the first 2 years of investigation and only Trichoribates incisellus was found several times in the nutrient-poor substrate. Therefore, wind dispersal is an important migration pathway, especially for arboreal oribatids. We suggest that immigration into young soils most likely occurs by repeated short-distance dispersal. Only some species are able to survive the hostile conditions of wind dispersal as well as of pioneer soils, but those that do are potentially the founders of new populations.     

Preliminary investigation of concurrent administration of phenylbutazone and romifidine in healthy horses

ObjectiveTo characterize the cardiorespiratory and electrocardiographic effects of the combined administration of phenylbutazone and romifidine.Study designProspective four-period, four-treatment, blinded, randomized, crossover trial.AnimalsFive, healthy, mixed breed horses.MethodsPrior to treatment administration, a catheter was introduced into the intra-thoracic cranial vena cava via the jugular vein and a subcutaneously located carotid artery was catheterised. All treatments were administered intravenously (IV) and consisted of saline placebo (PLC), phenylbutazone (PBZ, 4.4 mg kg^?1) romifidine (ROM, 80 μg kg^?1) and a combination of phenylbutazone (4.4 mg kg^?1) and romifidine (80 μg kg^?1). There was at least a 1 week washout period between treatments. Heart rate (HR), respiratory rate (f_R), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures and central venous pressure (CVP) were recorded for baseline (prior to drug administration) and at 5 minute intervals thereafter for 30 minutes. Electrocardiographic abnormalities were recorded. Data were analyzed by anova.ResultsFor the cardiovascular variables there were no statistically significant (p > 0.05) differences between horses treated with ROM and PBZ_ROM. Statistically significant (p < 0.05) differences only occurred between treatments with romifidine (ROM and PBZ_ROM) and without romifidine (PLC and PBZ). Within treatments, for ROM, changes over time were statistically significant (p < 0.05) for HR, SAP, DAP, MAP and CVP. For PBZ_ROM, changes over time were statistically significant (p < 0.05) for CVP. Sino-atrial and atrio-ventricular blocks occurred in horses treated with ROM and PBZ_ROM.Conclusions and clinical relevanceThe combined IV administration of phenylbutazone and romifidine had no statistically significant effect on cardiorespiratory variables. These limited data suggest no evidence why both agents should not be included in a preoperative medication protocol for healthy horses but do not exclude the possibility of interactions occurring in a larger population.     

A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds

Background

Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers.

Findings

Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers.

Conclusions

A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as “hereditary ataxia” in Fox Terriers and “spinocerebellar ataxia with myokymia, seizures or both” in the Russell group of terriers.     

Metabolism of the lignan macromolecule into enterolignans in the gastrointestinal lumen as determined in the simulator of the human intestinal microbial ecosystem

Estrogenic plant compounds from the human diet such as the lignan secoisolariciresinol diglucoside (SDG, 1) can exert biological activity in the human body upon ingestion and bioactivation to enterodiol (END, 5) and enterolactone (ENL, 6). Bioavailability of lignans is influenced by the food matrix and gut microbial action, of which the latter is subject to a large interindividual variation. In this study, the fate of the lignan precursor SDG, present in the lignan macromolecule of flax seed ( Linum usitatissimum), was determined during an artificial stomach and small intestinal digestion and during metabolism by two different enterolignan phenotypes in a TWINSHIME environment (TWIN Simulator of the Human Intestinal Microbial Ecosystem). The lignan macromolecule acted as a delivery system of SDG in the large intestine. SDG was only hydrolyzed into secoisolariciresinol (SECO, 2) through microbial action in the ascending colon, after which it was bioactivated into enterolignans from the transverse colon onward. Single demethylation was a first step in the bioactivation, followed by dehydroxylation. Enterolignan phenotypes remained stable throughout the experimental period. The establishment of END and ENL production equilibria reflected the subdominance of ENL-producing bacteria in the gastrointestinal tract.     

Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing

Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD). These variants are thought to be defective in activation of nuclear factor kappaB (NF-kappaB) and antibacterial defenses, but CD clinical specimens display elevated NF-kappaB activity. To illuminate the pathophysiological function of NOD2, we introduced such a variant to the mouse Nod2 locus. Mutant mice exhibited elevated NF-kappaB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1beta (IL-1beta). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion.     

Reconstruction of the lower eyelid by third eyelid lateral advancement and local transposition cutaneous flap after "en bloc" resection of squamous cell carcinoma in 5 cats

OBJECTIVE: To describe a novel technique for blepharoplasty to cover a tissue defect involving >/=50% of the lower eyelid. STUDY DESIGN: Prospective clinical study. ANIMALS: Five cats with lower eyelid squamous cell carcinoma (SCC). METHODS: En bloc resection of SCC by removing >/=50% of the lower lid with either the medial or lateral canthus was performed without other adjunctive treatment for SCC. The lid defect was reconstructed with a transposition skin flap derived from the frontal (medial defect) or temporal (lateral defect) region. The third eyelid was advanced laterally without dissection from its insertion; its outer conjunctival layer was removed, and the skin flap was sutured with single interrupted sutures dorsally over the nictitating membrane, ventrally to the cutaneous edge of the surgical wound and medially or laterally (depending on the canthus removed) to the skin of the remaining lower lid. RESULTS: Satisfactory cosmetic and functional results were achieved and the Schirmer tear tests were normal. In 2 cats, the skin flap needed monthly hair trimming to avoid corneal lesions. CONCLUSIONS: After en bloc resection of SCC involving >/=50% of the lower eyelid, reconstruction can be achieved by relocation of the third eyelid and use of a cutaneous transposition flap sutured to the scarified external surface of the third eyelid. Eyelid apposition and lacrimal function were preserved. CLINICAL RELEVANCE: Blepharoplasty using a cutaneous transposition flap sutured to the scarified surface of a relocated third eyelid should be considered for reconstruction of lower eyelid defects with >/=50% tissue loss of the lid margin.     

Pathogenicity determinants in smut fungi revealed by genome comparison

Biotrophic pathogens, such as the related maize pathogenic fungi Ustilago maydis and Sporisorium reilianum, establish an intimate relationship with their hosts by secreting protein effectors. Because secreted effectors interacting with plant proteins should rapidly evolve, we identified variable genomic regions by sequencing the genome of S. reilianum and comparing it with the U. maydis genome. We detected 43 regions of low sequence conservation in otherwise well-conserved syntenic genomes. These regions primarily encode secreted effectors and include previously identified virulence clusters. By deletion analysis in U. maydis, we demonstrate a role in virulence for four previously unknown diversity regions. This highlights the power of comparative genomics of closely related species for identification of virulence determinants.