In vivo imaging reveals novel aspects of retinal disease progression in Rs1h(-/Y) mice but no therapeutic effect of carbonic anhydrase inhibition

Purpose X-linked juvenile retinoschisis (XLRS) is the most common juvenile maculopathy in men and is caused by mutations in the gene encoding retinoschisin (RS1). Evidence in the literature on the therapeutic effect of carboanhydrase inhibitors (CAIs) to treat schisis formation in the retina has remained equivocal. Here, we evaluate the effect of the CAI dorzolamide on the structural and functional disease progression in the mouse model for XLRS (Rs1h(-/y) ). Methods Rs1h ( -/y ) mice were treated unilaterally with dorzolamide eye drops (Trusopt(?) 20?mg/mL) every 12?h for 2?weeks starting on postnatal day 14 (n?=?27). Changes of retinal structure were monitored by confocal scanning laser ophthalmoscopy and spectral domain optical coherence tomography 12?h, 14?days, 4?weeks, 2?months, and 6?months after completion of the treatment. Results Schisis formation (peak at 3?months) preceded photoreceptor degeneration and hyper-fluorescence (peak at 7?months). Structural pathology was most severe in the superior hemi-retina with previously unreported hyper-fluorescent lesions. Quantitative analysis showed no significant differences regarding the inner or outer retinal thickness of the treated vs. untreated eyes 12?h after the completion of treatment (IRT(12?h) =?-1.29?±?1.89?μm; ORT(12?h) =?0.61?±?2.08?μm; mean?±?95%CI) or at any later time point. Conclusion Time line analysis after short-term treatment with CAI failed to show short-, intermediate-, or long-term evidence of structural improvement in Rs1h(-/y) mice. Schisis formation in the inner retina peaked at the age of 3?months and was followed by photoreceptor degeneration predominantly in the superior hemi-retina. Previously unreported hyper-fluorescent lesions co-register with structural retinal pathologies.     

Effect of <Emphasis Type="Italic">Meloidogyne ethiopica</Emphasis> parasitism on water management and physiological stress in tomato

Root-knot nematodes (RKN) are obligate endoparasites that severely damage the host root system. Nutrient and water uptake are substantially reduced in infested plants, resulting into altered physiological processes and reduced plant growth. The effect of nematode infestation on the morphological changes of roots and subsequent physiological plant responses of infested tomatoes with the RKN Meloidogyne ethiopica was studied in a pot experiment. Plants were infested with two inoculum densities (10 or 50 eggs per cm³ substrate) and its effect was evaluated 74 and 102 days post inoculation (DPI). Morphological changes and root growth was determined by analysing scanned images of the whole root system. Nematode infestation reduced the portion of fine roots and increased that of coarse roots due to gall formation. Fine roots of non-infested control plants represented around 51% of the area of the whole root system at 74 and 102 DPI. In comparison to controls, plants inoculated with low and high nematode density had 2.1 and 3.2-times lower surface area of fine roots at 102 DPI. Root analyses revealed that plants had a very limited ability to mitigate the effects of the root-knot nematodes infestation by altering root growth. Root galls had a major influence on the hydraulic conductivity of the root system, which was significantly reduced. The low leaf water potential of infested plants coincided with decreased stomatal conductivity, transpiration and photosynthesis. The latter two were reduced by 60–70% when compared to non-infested control plants.     

Identification of the Cdc48•20S proteasome as an ancient AAA+ proteolytic machine

Proteasomes are the major energy-dependent proteolytic machines in the eukaryotic and archaeal domains of life. To execute protein degradation, the 20S core peptidase combines with the AAA+ ring of the 19S regulatory particle in eukarya or with the AAA+ proteasome-activating nucleotidase ring in some archaea. Here, we find that Cdc48 and 20S from the archaeon Thermoplasma acidophilum interact to form a functional proteasome. Cdc48 is an abundant and essential double-ring AAA+ molecular machine ubiquitously present in archaea, where its function has been uncertain, and in eukarya where Cdc48 participates by largely unknown mechanisms in diverse cellular processes, including multiple proteolytic pathways. Thus, proteolysis in collaboration with the 20S peptidase may represent an ancestral function of the Cdc48 family.     

European hemp industry: Cultivation, processing and product lines

Summary Two fibre plants are under cultivation in the European Union – flax on approximately 125,000 ha and hemp on approximately 15,500 ha in the year 2004. Seeds, hurds and especially fibres of hemp are used for further processing. The most important markets for hemp fibres produced in the EU are pulp and paper and the automotive industry. Just under 5% of the EU hemp fibres were used in the construction sector. Approximately 95% the whole production of 40,000 t of the hemp hurds are used as animal bedding and 95% of the estimated 6000 t per year hemp seeds are sold for animal feed, mainly as bird feed.     

Neglecting genotype × environment interaction results in biased predictions from selection index calculations

This study investigated effects of neglecting genotype × environment (G × E) interaction on the efficiency of index selection, genetic gain and dollar response. Two indices were established. Index P (P for practical) represents an index that would be used in practice. It assumed that no effects of G × E interactions were present. Index T (T for true) accounted for a prevailing level of G × E interactions in a real data set. Since the true underlying genetic parameters of the data set were unknown, different instances of possible G × E interaction levels for Index T were generated through a sampling procedure. The average difference between the genetic correlations used in Index P and T reduced the efficiency of Index P by between 1% and 24.8%. The total dollar response per year was on average 33% overpredicted, but this could be as high as 114%. Larger differences between the correlations resulted in higher variation in efficiency. Larger G × E interactions resulted in larger overpredictions in total dollar response. The effects of not accommodating or assuming the wrong extent of G × E interaction can be considerable in index calculations.     

Multiple meningiomas in three dogs

Three dogs with seizures were diagnosed with multiple intracranial meningiomas. Two of the three dogs were golden retrievers, and ages ranged from 9 to 11 years. Treatment consisted of surgery and radiation (n=2) or chemotherapy (n=1). In all three cases, the masses were two distinct tumors as determined by imaging, surgery, or necropsy. In two dogs, the meningiomas had the same histological pattern, while in one dog the histological subtypes were different.     

Adjusting worm egg counts for faecal moisture in sheep

The number of eggs from gastrointestinal nematodes per gram of faeces (worm egg count WEC) is commonly used to determine the need for anti-parasite treatments and the breeding value of animals when selecting for worm resistance. Diarrhoea increases faecal moisture and may dilute the number of worm eggs observed. To quantify this effect, egg counts in sheep at pasture were simulated by dosing 15 animals with chromic oxide particles. The simulated WEC diminished as faecal moisture increased. When faeces were dried, simulated WEC per unit dry matter was not influenced by the amount of faecal moisture present prior to drying. The results suggest that adjustment for faecal moisture may provide an improved estimate of FEC. Drying faeces to calculate the WEC per unit dry matter would provide such an adjustment but may not be practical for industry application. In the past, the CSIRO McMaster Laboratory has used an adjustment factor developed by Gordon based on the classification of faecal consistency derived from the morphology of faeces. To examine the utility of an adjustment factor based on faecal consistency score (FCS), the relationships between FCS and simulated WEC and dry matter were examined. Dry matter and simulated WEC exhibited an exponential decline as FCS increased. The relationship between FCS and dry matter was further examined in 368 samples collected over 12 months from sheep at pasture, where it was observed that dry matter showed a linear decline as FCS increased. Adjustment factors based on dry matter were similar to those proposed by Gordon however adjustment factors predicted from simulated WEC diverged from the remainder for FCS>4. As no samples scored FCS 5 in the study of simulated FEC, the adjustment factors based on the larger study that included samples with FCS 5 was therefore considered more robust. Adjustment factors were given by the equation: WEC(estimated)=(WEC(observed)/(34.21-5.15 FCS))x29.06. This equation estimates for samples with FCS>1 the WEC that would be expected if the samples were FCS 1, the faecal consistency score for normal faeces. The impact of adjustment of observed WEC for faecal moisture predicted by FCS on decision points for treatment and on estimated breeding values requires further examination.     

DNA vaccines encoding the envelope protein of West Nile virus lineages 1 or 2 administered intramuscularly,via electroporation and with recombinant virus protein induce partial protection in large falcons (Falco spp.)

As West Nile virus (WNV) can cause lethal diseases in raptors, a vaccination prophylaxis of free-living and captive populations is desirable. In the absence of vaccines approved for birds, equine vaccines have been used in falcons, but full protection against WNV infection was not achieved. Therefore, two DNA vaccines encoding the ectodomain of the envelope protein of WNV lineages 1 and 2, respectively, were evaluated in 28 large falcons. Four different vaccination protocols were used, including electroporation and booster-injections of recombinant WNV domain III protein, before challenge with the live WNV lineage 1 strain NY99. Drug safety, plasmid shedding and antibody production were monitored during the vaccination period. Serological, virological, histological, immunohistochemical and molecular biological investigations were performed during the challenge trials. Antibody response following vaccination was low overall and lasted for a maximum of three weeks. Plasmid shedding was not detected at any time. Viremia, mortality and levels, but not duration, of oral virus shedding were reduced in all of the groups during the challenge trial compared to the non-vaccinated control group. Likewise, clinical scoring, levels of cloacal virus shedding and viral load in organs were significantly reduced in three vaccination groups. Histopathological findings associated with WNV infections (meningo-encephalitis, myocarditis, and arteritis) were present in all groups, but immunohistochemical detection of the viral antigen was reduced. In conclusion, the vaccines can be used safely in falcons to reduce mortality and clinical signs and to lower the risk of virus transmission due to decreased levels of virus shedding and viremia, but full protection was not achieved in all groups.