Temporal and Taxonomic Variability in Response of Fauna to Riparian Restoration

Evaluating the success of restoration projects requires well‐designed studies. Among the decisions that need to be made are what taxonomic groups to study and when to conduct the monitoring. To explore how these decisions can influence assessments of restoration success, we examined species richness and composition data collected over several years on different terrestrial fauna (landbirds, rodents, bees, and beetles) at Sacramento River restoration and remnant riparian sites. Our selection of study organisms enabled us to ask whether variability in species richness among restoration sites is less for vagile taxa than for sedentary taxa, and if invertebrates display greater variability among sites than vertebrates. Our results demonstrate that responses to restoration can vary depending upon the season when it is assessed, and the taxa that are studied. For all taxa except bees, there was considerable variability in the relative performance of taxa at restoration sites from one sampling date to the next, such that the relative ranking of the sites often changed dramatically. Comparisons of β ‐diversity (variability in species richness across sites) revealed that certain taxonomic groups were more spatially variable in their response to restoration than others. Among vertebrates, sedentary taxa (rodents) had significantly higher variability in species richness across sites than highly vagile taxa (birds); however, no such pattern was observed for invertebrates. Overall, vertebrates had lower variability than invertebrates, suggesting that evaluations of restoration success based on a few better‐known taxonomic groups (e.g., birds, rodents) may be inadequate to represent the biodiversity response of other groups (e.g., insects).     

Residual beta cell function in newly diagnosed type 1 diabetes after treatment with atorvastatin: the Randomized DIATOR Trial

Background

Recent evidence suggests that the lipid-lowering agent atorvastatin is also a potent immunomodulator. The aim of this study was to investigate the possible effect of atorvastatin on the decline of residual beta cell function in recent-onset type 1 diabetes.

Methods and Findings

The randomised placebo-controlled Diabetes and Atorvastatin (DIATOR) Trial included 89 patients with newly diagnosed type 1 diabetes and islet autoantibodies (mean age 30 years, 40% females), in 12 centres in Germany. Patients received placebo or 80 mg/d atorvastatin for 18 months. As primary outcome stimulated serum C-peptide levels were determined 90 min after a standardized liquid mixed meal. An intent-to-treat analysis was performed. Fasting and stimulated C-peptide levels were not significantly different between groups at 18 months. However, median fasting serum C-peptide levels dropped from baseline to 12 and 18 months in the placebo group (from 0. 34 to 0.23 and 0.20 nmol/l, p<0.001) versus a nonsignificant decline in the atorvastatin group (from 0.34 to 0.27 and 0.30 nmol/l, ns). Median stimulated C-peptide concentrations declined between baseline and 12 months (placebo from 0.89 to 0.71 nmol/l, atorvastatin from 0.88 to 0.73 nmol/l, p<0.01 each) followed by a major loss by month 18 in the placebo group (to 0.48 nmol/l, p = 0.047) but not in the atorvastatin group (to 0.71 nmol/l, ns). Median levels of total cholesterol and C-reactive protein decreased in the atorvastatin group only (p<0.001 and p = 0.04). Metabolic control was similar between groups.

Conclusions

Atorvastatin treatment did not significantly preserve beta cell function although there may have been a slower decline of beta-cell function which merits further study.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00974740","term_id":"NCT00974740"}}NCT00974740     

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.     

Aberrant expression of caspase-14 in epithelial tumors

Cysteine-dependent aspartate-specific proteases (caspases) are the cellular executors of apoptosis. Caspase-14 is the most divergent member of the family of mammalian caspases and displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. During induction of apoptosis, it is not processed, whereas terminal differentiation in skin leads to cleavage of caspase-14. Here we show that 40% of lung squamous cell carcinomas, 22% of breast cancers, and about 80% of cervical carcinomas express caspase-14. Immunohistochemistry reveals that caspase-14 is localized in areas of ongoing differentiation close to necrotic sites but is not strictly associated with the differentiation markers keratin-1/-10. Caspase-14 is neither mutated nor alternatively spliced in the tumors analyzed. Furthermore, caspase-14 is not processed into a small and large subunit, a process critical for the proteolytic activation of known effector caspases. We conclude that conditions exist in tumors leading to re-expression of this normally silent gene.     

An RNA-binding domain in the thyroid hormone receptor enhances transcriptional activation

Thyroid hormone plays important roles in development, differentiation, and metabolic homeostasis by binding to nuclear thyroid hormone receptors, which regulate target gene expression by interacting with DNA response elements and coregulatory proteins. We show that thyroid hormone receptors also are single-stranded RNA binding proteins and that this binding is functionally significant. By using a series of deletion mutants, a novel RNA-binding domain was localized to a 41-amino acid segment of thyroid hormone receptor alpha1 between the second zinc finger and the ligand-binding domain. This RNA-binding domain was necessary and sufficient for thyroid hormone receptor binding to the steroid receptor RNA activator (SRA). Although SRA does not bind directly to steroid receptors, it has been identified as a steroid receptor coactivator, and was thought not to be a coactivator for thyroid hormone receptors. However, transfection studies revealed that SRA enhances thyroid hormone induction of appropriate reporter genes and that the thyroid hormone receptor RNA-binding domain is important for this enhancement. We conclude that thyroid hormone receptors bind RNA through a novel domain and that the interaction of this domain with SRA, and perhaps other RNAs, enhances thyroid hormone receptor function.     

Synthesis and biological evaluation of 5-substituted and 4,5-disubstituted-2-arylamino oxazole TRPV1 antagonists

The synthesis and structure–activity relationships of a series of 5-monosubstituted and 4,5-disubstituted 2-arylaminooxazoles as novel antagonists of the transient receptor potential vanilloid 1 (TRPV1) receptor are described. The 7-hydroxy group of the tetrahydronaphthyl moiety on the 2-amino substituent of the oxazole ring was important for obtaining excellent in vitro potency at the human TRPV1 receptor, while a variety of alkyl and phenyl substituents at the 4- and 5-positions of the oxazole ring were well tolerated and yielded potent TRPV1 antagonists. Despite excellent in vitro potency, the 5-monosubstituted compounds suffered from poor pharmacokinetics. It was found that 4,5-disubstitution on the oxazole ring was critical to the improvement of the overall pharmacokinetic profile of these analogues, which led to the discovery of compound (R)-27, a novel TRPV1 antagonist with good oral activity in preclinical animal models of pain.     

Zonal hierarchy of differentiation markers and nestin expression during oval cell mediated rat liver regeneration

Oval cells constitute a heterogeneous population of proliferating progenitors found in rat livers following carcinogenic treatment (2-acetylaminofluorene and 70% hepatectomy). The aim of this study was to investigate the cellular pattern of various differentiation and cell type markers in this model of liver regeneration. Immunophenotypic characterisation revealed at least two subtypes emerging from the portal field. First, a population of oval cells formed duct-like structures and expressed bile duct (CD49f) as well as hepatocytic markers (α-foetoprotein, CD26). Second, a population of non-ductular oval cells was detected between and distally from the ductules expressing the neural marker nestin and the haematopoietic marker Thy1. Following oval cell isolation, a subset of the nestin-positive cells was shown to co-express hepatocytic and epithelial markers (albumin, CD26, pancytokeratin) and could be clearly distinguished from anti-desmin reactive hepatic stellate cells. The gene expression profiles (RT-PCR) of isolated oval cells and oval cell liver tissue were found to be similar to foetal liver (ED14). The present results suggest that the two oval cell populations are organised in a zonal hierarchy with a marker gradient from the inner (displaying hepatocytic and biliary markers) to the outer zone (showing hepatocytic and extrahepatic progenitor markers) of the proliferating progeny clusters.