The Trilobite Subfamily Monorakinae (Pterygometopidae)

The Monorakinae is a subfamily of the Pterygometopidae characterised by the fusion of L2 and L3 in the glabella. The resulting bicomposite lobe is expanded backwards to reach the occipital furrow, displacing L1 from contact with the axial furrow and causing the realignment of S1 to a markedly oblique orientation. The bicomposite lobe is commonly bounded adaxially by a longitudinal furrow containing three pairs of apodemal pits. The Monorakinae was probably derived from the Pterygometopinae, and includes the genera and subgenera Monorakos , Carinopyge , Ceratevenkaspis , Elasmaspis , Evenkaspis ( Evenkaspis ) and E . ( Parevenkaspis ), of which Carinopyge , Elasmaspis and Evenkaspis ( Parevenkaspis ) are known only from limited parts of the exoskeleton. Monorakines have a stratigraphical range of Caradoc–Ashgill. Their known geographical distribution in the Siberian Platform, Taimyr, the Russian Far East, and the Seward Peninsula of Alaska is restricted to areas that in the Ordovician were part of the palaeocontinents of Siberia and Arctida, which must have been connected or situated close together at that time. The occurrence of monorakines in the Taimyr Peninsula but their absence from Baltica does not support the suggestion of some workers that Taimyr was part of Baltica in the Ordovician.     

Thermal biology,torpor and behaviour in sugar gliders: a laboratory-field comparison

Most studies on animal physiology and behaviour are conducted in captivity without verification that data are representative of free-ranging animals. We provide the first quantitative comparison of daily torpor, thermal biology and activity patterns, conducted on two groups of sugar gliders (Petaurus breviceps, Marsupialia) exposed to similar thermal conditions, one in captivity and the other in the field. Our study shows that activity in captive gliders in an outdoor aviary is restricted to the night and largely unaffected by weather, whereas free-ranging gliders omit foraging on cold/wet nights and may also forage in the afternoon. Torpor occurrence in gliders was significantly lower in captivity (8.4% after food deprivation; 1.1% for all observations) than in the field (25.9%), mean torpor bout duration was shorter in captivity (6.9 h) than in the field (13.1 h), and mean body temperatures during torpor were higher in captivity (25.3°C) than in the field (19.6°C). Moreover, normothermic body temperature as a function of air temperature differed between captive and free-ranging gliders, with a >3°C difference at low air temperatures. Our comparison shows that activity patterns, thermal physiology, use of torpor and patterns of torpor may differ substantially between the laboratory and field, and provides further evidence that functional and behavioural data on captive individuals may not necessarily be representative of those living in the wild.     

Skeletal muscle mitochondrial FAT/CD36 content and palmitate oxidation are not decreased in obese women

A reduction in fatty acid oxidation has been associated with lipid accumulation and insulin resistance in the skeletal muscle of obese individuals. We examined whether this decrease in fatty acid oxidation was attributable to a reduction in muscle mitochondrial content and/or a dysfunction in fatty acid oxidation within mitochondria obtained from skeletal muscle of age-matched, lean [body mass index (BMI) = 23.3 +/- 0.7 kg/m2] and obese women (BMI = 37.6 +/- 2.2 kg/m2). The mitochondrial marker enzymes citrate synthase (-34%), beta-hydroxyacyl-CoA dehydrogenase (-17%), and cytochrome c oxidase (-32%) were reduced (P < 0.05) in obese participants, indicating that mitochondrial content was diminished. Obesity did not alter the ability of isolated mitochondria to oxidize palmitate; however, fatty acid oxidation was reduced at the whole muscle level by 28% (P < 0.05) in the obese. Mitochondrial fatty acid translocase (FAT/CD36) did not differ in lean and obese individuals, but mitochondrial FAT/CD36 was correlated with mitochondrial fatty acid oxidation (r = 0.67, P < 0.05). We conclude that the reduction in fatty acid oxidation in obese individuals is attributable to a decrease in mitochondrial content, not to an intrinsic defect in the mitochondria obtained from skeletal muscle of obese individuals. In addition, it appears that mitochondrial FAT/CD36 may be involved in regulating fatty acid oxidation in human skeletal muscle.     

Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation

A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.     

Evaluating scoring functions for docking and designing beta-secretase inhibitors

Several simple scoring methods were examined for 2 series of beta-secretase (BACE-1) inhibitors to identify a docking/scoring protocol which could be used to design BACE-1 inhibitors in a drug discovery program. Both the PLP1 score and MMFFs interaction energy (E(inter)) performed as well or better than more computationally intensive methods for a set of substrate-based inhibitors, while the latter performed well for both sets of inhibitors.     

A comparison of background correction methods for two-colour microarrays

MOTIVATION: Microarray data must be background corrected to remove the effects of non-specific binding or spatial heterogeneity across the array, but this practice typically causes other problems such as negative corrected intensities and high variability of low intensity log-ratios. Different estimators of background, and various model-based processing methods, are compared in this study in search of the best option for differential expression analyses of small microarray experiments. RESULTS: Using data where some independent truth in gene expression is known, eight different background correction alternatives are compared, in terms of precision and bias of the resulting gene expression measures, and in terms of their ability to detect differentially expressed genes as judged by two popular algorithms, SAM and limma eBayes. A new background processing method (normexp) is introduced which is based on a convolution model. The model-based correction methods are shown to be markedly superior to the usual practice of subtracting local background estimates. Methods which stabilize the variances of the log-ratios along the intensity range perform the best. The normexp+offset method is found to give the lowest false discovery rate overall, followed by morph and vsn. Like vsn, normexp is applicable to most types of two-colour microarray data. AVAILABILITY: The background correction methods compared in this article are available in the R package limma (Smyth, 2005) from http://www.bioconductor.org. SUPPLEMENTARY INFORMATION: Supplementary data are available from http://bioinf.wehi.edu.au/resources/webReferences.html.     

Asymmetric boundary shifts of tropical montane Lepidoptera over four decades of climate warming

Aim To estimate whether species have shifted at equal rates at their leading edges (cool boundaries) and trailing edges (warm boundaries) in response to climate change. We provide the first such evidence for tropical insects, here examining elevation shifts for the upper and lower boundaries shifts of montane moths. Threats to species on tropical mountains are considered. Location Mount Kinabalu, Sabah, Malaysia. Methods We surveyed Lepidoptera (Geometridae) on Mount Kinabalu in 2007, 42 years after the previous surveys in 1965. Changes in species upper and lower boundaries, elevational extents and range areas were assessed. We randomly subsampled the data to ensure comparable datasets between years. Estimated shifts were compared for endemic versus more widespread species, and for species that reached their range limits at different elevations. Results Species that reached their upper limits at 2500–2700 m (n= 28 species, 20% of those considered) retreated at both their lower and upper boundaries, and hence showed substantial average range contractions (?300 m in elevational extent and ?45 km² in estimated range area). These declines may be associated with changes in cloud cover and the presence of ecological barriers (geological and vegetation transitions) which impede uphill movement. Other than this group, most species (n= 109, 80% of the species considered) expanded their upper boundaries upwards (by an average of 152 m) more than they retreated at their lower boundaries (77 m). Main conclusions Without constraints, leading margins shifted uphill faster than trailing margins retreated, such that many species increased their elevational extents. However, this did not result in increases in range area because the area of land available declines with increasing elevation. Species close to a major ecological/geological transition zone on the mountain flank declined in their range areas. Extinction risk may increase long before species reach the summit, even when undisturbed habitats are available.     

High sero-prevalence of caseous lymphadenitis identified in slaughterhouse samples as a consequence of deficiencies in sheep farm management in the state of Minas Gerais, Brazil

Background

Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (PMEL17, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another horse breed, the Icelandic horse, which is historically quite divergent from Rocky Mountain horses.

Results

We examined 24 Icelandic horses and established that the MCOA syndrome is present in this breed. Four of these horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the PMEL17 mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen horses were heterozygous for the PMEL17 mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional horses were genotyped as PMEL17 heterozygotes, but in these horses we were unable to detect cysts or other forms of anomalies. One eye of a severely vision-impaired 18 month-old stallion, homozygous for the PMEL17 mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen.

Conclusions

The MCOA syndrome is segregating with the PMEL17 mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.