Dopaminergic and noradrenergic circuit development in zebrafish

Dopaminergic and noradrenergic neurons constitute some of the major far projecting systems in the vertebrate brain and spinal cord that modulate the activity of circuits controlling a broad range of behaviors. Degeneration or dysfunction of dopaminergic neurons has also been linked to a number of neurological and psychiatric disorders, including Parkinson's disease.Zebrafish (Danio rerio) have emerged over the past two decades into a major genetic vertebrate model system,and thus contributed to a better understanding of developmental mechanisms controlling dopaminergic neuron specification and axonogenesis. In this review, we want to focus on conserved and dynamic aspects of the different catecholaminergic systems, which may help to evaluate the zebrafish as a model for dopaminergic and noradrenergic cellular specification and circuit function as well as biomedical aspects of catecholamine systems.     

Multi-species predator eradication within a predator-proof fence at Ka‘ena Point, Hawai‘i

Ka‘ena Point Natural Area Reserve on O‘ahu hosts one of the largest seabird colonies in the main Hawaiian Islands and supports three species of endangered plants. In order to stop chronic predation by invasive alien mammals on native species, a peninsula-style predator-proof fence was constructed around a 20-ha portion of the reserve in 2011. Multi-species predator removal efforts began upon fence completion; diphacinone poison in bait boxes spaced 25 m apart was used to remove black rats, house mice, and small Indian mongooses. House mice also were removed with multiple-catch live traps spaced 12.5 m apart. Feral cats were removed with padded leg-hold traps. Feral cats and mongooses were eradicated in 1 month, black rats were eradicated in 2.5 months, and house mice were eradicated in about 9 months. Since eradication, incursions of cats and mongoose have been rare (1/7.2 months), but incursion frequency has been higher for black rats (1/56 days) and house mice (1/36–47 days). Buffer predator control was conducted to limit predator access and prevent reinvasion around the fence ends along the shoreline. Even with the high initial fence cost and ongoing predator incursion management, this method is expected to become more cost effective than previous predator control efforts after 16 years. Record numbers of Wedge-tailed shearwaters and Laysan albatrosses have fledged from the reserve after predator eradication, and regeneration of native plants and invertebrates is being observed. With careful planning and persistence, predator fences can be a cost-effective method of protecting natural resources, and multiple species of predators can be eradicated with traps and first-generation anti-coagulents.     

Hatching asynchrony and brood reduction influence immune response in Common Kestrel Falco tinnunculus nestlings

The onset of incubation before the end of laying imposes asynchrony at hatching and, therefore, a size hierarchy in the brood. It has been argued that hatching asynchrony might be a strategy to improve reproductive output in terms of quality or quantity of offspring. However, little is known about the mediating effect of hatching asynchrony on offspring quality when brood reduction occurs. Here, we investigate the relationship between phenotypic quality and hatching asynchrony in Common Kestrel Falco tinnunculus nestlings in Spain. Hatching asynchrony did not increase breeding success or nestling quality. Furthermore, hatching asynchrony and brood reduction had different effects on nestlings’ phytohaematogglutinin (PHA)‐mediated immune response and nestling growth. In asynchronous and reduced broods (in which at least one nestling died), nestlings showed a stronger PHA‐mediated immune response and tended to have a smaller body size compared with nestlings raised in synchronous and reduced broods. When brood reduction occurred in broods hatched synchronously, there was no effect on nestling size, but nestlings had a relatively poor PHA‐mediated immune response compared with nestlings raised in asynchronous and reduced broods. We suggest that resources for growth can be directed to immune function only in asynchronously hatched broods, resulting in improved nestling quality, as suggested by their immune response. We also found that males produced a greater PHA‐mediated immune response than females only in brood‐reduced nests without any effect on nestling size or condition, suggesting that females may trade off immune activities and body condition, size or weight. Overall, our results suggest that hatching pattern and brood reduction may mediate resource allocation to different fitness traits. They also highlight that the resolution of immune‐related trade‐offs when brood reduction occurs may differ between male and female nestlings.     

Antiglioma activity of GoPI-sugar,a novel gold(I)–phosphole inhibitor: Chemical synthesis,mechanistic studies,and effectiveness in vivo

Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-β-d-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC₅₀ of 430 μM, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC₅₀ 4.3 nM) and human glutathione reductase (IC₅₀ 88.5 nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes.     

Risk Factors for Death in 632 Patients with Sickle Cell Disease in the United States and United Kingdom

Background

The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.

Methods and Results

We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67–75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV<3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1–30.1; p<0.0001) for TRV≥3.0 m/sec, 4.6 (1.8–11.3; p = 0.001) for NT-proBNP≥160 pg/mL, and 14.9 (5.5–39.9; p<0.0001) for both TRV≥3.0 m/sec and NT-proBNP≥160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III–IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.

Conclusions

A TRV≥3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.

The study is registered in ClinicalTrials.gov with identifier

{"type":"clinical-trial","attrs":{"text":"NCT00492531","term_id":"NCT00492531"}}NCT00492531     

Remotely Monitoring Change in Vegetation Cover on the Montebello Islands,Western Australia,in Response to Introduced Rodent Eradication

The Montebello archipelago consists of 218 islands; 80 km from the north-west coast of Western Australia. Before 1912 the islands had a diverse terrestrial fauna. By 1952 several species were locally extinct. Between 1996 and 2011 rodents and cats were eradicated, and 5 mammal and 2 bird species were translocated to the islands. Monitoring of the broader terrestrial ecosystem over time has been limited. We used 20 dry-season Landsat images from 1988 to 2013 and estimation of green fraction cover in nadir photographs taken at 27 sites within the Montebello islands and six sites on Thevenard Island to assess change in vegetation density over time. Analysis of data averaged across the 26-year period suggests that 719 ha out of 2169 ha have increased in vegetation cover by up to 32%, 955 ha have remained stable and 0.6 ha have declined in vegetation cover. Over 492 ha (22%) had no vegetation cover at any time during the period analysed. Chronological clustering analysis identified two breakpoints in the average vegetation cover data occurring in 1997 and 2003, near the beginning and end of the rodent eradication activities. On many islands vegetation cover was declining prior to 1996 but increased after rodents were eradicated from the islands. Data for North West and Trimouille islands were analysed independently because of the potential confounding effect of native fauna being introduced to these islands. Mala (Lagorchestes hirsutus) and Shark Bay mice (Pseudomys fieldi) both appear to suppress native plant recruitment but not to the same degree as introduced rodents. Future research should assess whether the increase in vegetation cover on the Montebello islands is due to an increase in native or introduced plants.