Drebrin Regulates Neuroblast Migration in the Postnatal Mammalian Brain

After birth, stem cells in the subventricular zone (SVZ) generate neuroblasts that migrate along the rostral migratory stream (RMS) to become interneurons in the olfactory bulb (OB). This migration is crucial for the proper integration of newborn neurons in a pre-existing synaptic network and is believed to play a key role in infant human brain development. Many regulators of neuroblast migration have been identified; however, still very little is known about the intracellular molecular mechanisms controlling this process. Here, we have investigated the function of drebrin, an actin-binding protein highly expressed in the RMS of the postnatal mammalian brain. Neuroblast migration was monitored both in culture and in brain slices obtained from electroporated mice by time-lapse spinning disk confocal microscopy. Depletion of drebrin using distinct RNAi approaches in early postnatal mice affects neuroblast morphology and impairs neuroblast migration and orientation in vitro and in vivo. Overexpression of drebrin also impairs migration along the RMS and affects the distribution of neuroblasts at their final destination, the OB. Drebrin phosphorylation on Ser142 by Cyclin-dependent kinase 5 (Cdk5) has been recently shown to regulate F-actin-microtubule coupling in neuronal growth cones. We also investigated the functional significance of this phosphorylation in RMS neuroblasts using in vivo postnatal electroporation of phosphomimetic (S142D) or non-phosphorylatable (S142A) drebrin in the SVZ of mouse pups. Preventing or mimicking phosphorylation of S142 in vivo caused similar effects on neuroblast dynamics, leading to aberrant neuroblast branching. We conclude that drebrin is necessary for efficient migration of SVZ-derived neuroblasts and propose that regulated phosphorylation of drebrin on S142 maintains leading process stability for polarized migration along the RMS, thus ensuring proper neurogenesis.     

A Long-Term Experimental Case Study of the Ecological Effectiveness and Cost Effectiveness of Invasive Plant Management in Achieving Conservation Goals: Bitou Bush Control in Booderee National Park in Eastern Australia

Invasive plant management is often justified in terms of conservation goals, yet progress is rarely assessed against these broader goals, instead focussing on short-term reductions of the invader as a measure of success. Key questions commonly remain unanswered including whether invader removal reverses invader impacts and whether management itself has negative ecosystem impacts. We addressed these knowledge gaps using a seven year experimental investigation of Bitou Bush, Chrysanthemoides monilifera subsp. rotundata. Our case study took advantage of the realities of applied management interventions for Bitou Bush to assess whether it is a driver or passenger of environmental change, and quantified conservation benefits relative to management costs of different treatment regimes. Among treatments examined, spraying with herbicide followed by burning and subsequent re-spraying (spray-fire-spray) proved the most effective for reducing the number of individuals and cover of Bitou Bush. Other treatment regimes (e.g. fire followed by spraying, or two fires in succession) were less effective or even exacerbated Bitou Bush invasion. The spray-fire-spray regime did not increase susceptibility of treated areas to re-invasion by Bitou Bush or other exotic species. This regime significantly reduced plant species richness and cover, but these effects were short-lived. The spray-fire-spray regime was the most cost-effective approach to controlling a highly invasive species and facilitating restoration of native plant species richness to levels characteristic of uninvaded sites. We provide a decision tree to guide management, where recommended actions depend on the outcome of post-treatment monitoring and performance against objectives. Critical to success is avoiding partial treatments and treatment sequences that may exacerbate invasive species impacts. We also show the value of taking advantage of unplanned events, such as wildfires, to achieve management objectives at reduced cost.     

Tumor T1 Relaxation Time for Assessing Response to Bevacizumab Anti-Angiogenic Therapy in a Mouse Ovarian Cancer Model

Purpose

To assess whether T₁ relaxation time of tumors may be used to assess response to bevacizumab anti-angiogenic therapy. Procedures: 12 female nude mice bearing subcutaneous SKOV3ip1-LC ovarian tumors were administered bevacizumab (6.25ug/g, n=6) or PBS (control, n=6) therapy twice a week for two weeks. T₁ maps of tumors were generated before, two days, and 2 weeks after initiating therapy. Tumor weight was assessed by MR and at necropsy. Histology for microvessel density, proliferation, and apoptosis was performed.

Results

Bevacizumab treatment resulted in tumor growth inhibition (p<0.04, n=6), confirming therapeutic efficacy. Tumor T₁ relaxation times increased in bevacizumab treated mice 2 days and 2 weeks after initiating therapy (p<.05, n=6). Microvessel density decreased 59% and cell proliferation (Ki67+) decreased 50% in the bevacizumab treatment group (p<.001, n=6), but not apoptosis.

Conclusions

Findings suggest that increased tumor T₁ relaxation time is associated with response to bevacizumab therapy in ovarian cancer model and might serve as an early indicator of response.     

HIV-1 Populations in Semen Arise through Multiple Mechanisms

HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus.     

Large herbivores in sagebrush steppe ecosystems: livestock and wild ungulates influence structure and function

Improving understanding of the connections between vegetation, herbivory, and ecosystem function offers a fundamental challenge in contemporary terrestrial ecology. Using exclosures constructed during the late 1950s, we examined effects of grazing by wild and domestic herbivores on plant community structure, aboveground herbaceous primary production, and nutrient cycling at six sites in semi-arid, sagebrush rangelands during 2001-2002 in Colorado, USA. Enclosures provided three treatments: no grazing, grazing by wild ungulates only, and grazing by wild and domestic ungulates. Excluding all grazing caused an increase in shrub cover (F = 4.97, P = 0.033) and decrease in bare ground (F = 4.74, P = 0.037), but also a decrease in plant species richness (F = 6.19, P = 0.018) and plant diversity (F = 7.93, P = 0.008). Effects of wild ungulate grazing on plant cover and diversity were intermediate to the effects of combined domestic and wild grazing. Aboveground net primary production was higher in both grazed treatments than in the ungrazed one (F(wild + domestic) = 2.98, P = 0.0936 and F(wild only) = 3.55, P = 0.0684). We were unable to detect significant effects of grazing on other ecosystem states and processes including C:N ratios of standing crops, N mineralization potential, or nitrification potential. Best approximating models revealed positive correlation between N availability and herbaceous cover and a negative correlation between herbaceous primary production and the ratio of shrub-herb cover and plant diversity. We conclude that ungulate herbivory, including both wild and domestic ungulates, had significant effects on plant community structure and ecosystem function during this 42-year span. Responses to the wild ungulate treatment were consistently intermediate to responses to the no grazing and wild + domestic grazing treatments. However, we were unable to detect statistical difference between effects of wild ungulates alone and wild ungulates in combination with livestock.     

The need for pluralism in landscape models: a reply to Dunn and Majer

Dunn and Majer discuss limitations of the continuum model proposed by Fischer and Lindenmayer and describe a new patch‐based model. We argue that a range of landscape models are required to solve different problems and meet particular objectives of land management or conservation. The key issue is not whether one type of model is superior to another, but rather: what are the particular strengths and limitations of a particular model? And, given these, under what circumstances will a particular model be most appropriate? The primary value of the continuum model is that it provides a strong theoretical foundation for the management of landscape heterogeneity in addition to the protection of large patches of native vegetation.