Repeated cocaine enhances ventral hippocampal‐stimulated dopamine efflux in the nucleus accumbens and alters ventral hippocampal NMDA receptor subunit expression

Dopaminergic neurotransmission in the nucleus accumbens is important for various reward‐related cognitive processes including reinforcement learning. Repeated cocaine enhances hippocampal synaptic plasticity, and phasic elevations of accumbal dopamine evoked by unconditioned stimuli are dependent on impulse flow from the ventral hippocampus. Therefore, sensitized hippocampal activity may be one mechanism by which drugs of abuse enhance limbic dopaminergic activity. In this study, in vivo microdialysis in freely moving adult male Sprague–Dawley rats was used to investigate the effect of repeated cocaine on ventral hippocampus‐mediated dopaminergic transmission within the medial shell of the nucleus accumbens. Following seven daily injections of saline or cocaine (20 mg/kg, ip), unilateral infusion of N‐methyl‐d ‐aspartate (NMDA, 0.5 μg) into the ventral hippocampus transiently increased both motoric activity and ipsilateral dopamine efflux in the medial shell of the nucleus accumbens, and this effect was greater in rats that received repeated cocaine compared to controls that received repeated saline. In addition, repeated cocaine altered NMDA receptor subunit expression in the ventral hippocampus, reducing the NR2A : NR2B subunit ratio. Together, these results suggest that repeated exposure to cocaine produces maladaptive ventral hippocampal‐nucleus accumbens communication, in part through changes in glutamate receptor composition.

     

Mobilization of Circulating Endothelial Progenitor Cells Correlates with the Clinical Course of Hantavirus Disease

Infections with hemorrhagic fever viruses are characterized by increased permeability leading to capillary leakage. Hantavirus infection is associated with endothelial dysfunction, and the clinical course is related to the degree of vascular injury. Circulating endothelial progenitor cells (cEPCs) play a pivotal role in the repair of the damaged endothelium. Therefore, we analyzed the number of cEPCs and their mobilizing growth factors in patients suffering from hantavirus disease induced by infection with Puumala virus. The numbers of EPCs of 36 hantavirus-infected patients and age- and gender-matched healthy controls were analyzed by flow cytometry. Concentrations of cEPC-mobilizing growth factors in plasma were determined by enzyme-linked immunosorbent assay. Laboratory parameters were correlated with the number of cEPCs. In patients infected with hantavirus, the number of cEPCs was significantly higher than that in healthy controls. Levels of mobilizing cytokines were upregulated in patients, and the mobilization of cEPCs is paralleled with the normalization of clinical parameters. Moreover, higher levels of cEPCs correlated with higher serum albumin levels and platelet concentrations. Our data indicate that cEPCs may play a role in the repair of hantavirus-induced endothelial damage, thereby influencing the clinical course and the severity of symptoms.     

Comparison of predator–prey interactions with and without intraguild predation by manipulation of the nitrogen source

Theory predicts that intraguild predation leads to different community dynamics than the trophic cascades of a linear food chain. However, experimental comparisons of these two food‐web modules are rare. Mixotrophic plankton species combine photoautotrophic and heterotrophic nutrition by grazing upon other phytoplankton species. We found that the mixotrophic chrysophyte Ochromonas can grow autotrophically on ammonium, but not on nitrate. This offered a unique opportunity to compare predator–prey interactions in the presence and absence of intraguild predation, without changing the species composition of the community. With ammonium as nitrogen source, Ochromonas can compete with its autotrophic prey for nitrogen and therefore acts as intraguild predator. With nitrate, Ochromonas acts solely as predator, and is not in competition with its prey for nitrogen. We parameterized a simple intraguild predation model based on chemostat experiments with monocultures of Ochromonas and the toxic cyanobacterium Microcystis. Subsequently, we tested the model predictions by inoculating Ochromonas into the Microcystis monocultures, and vice versa. The results showed that Microcystis was a better competitor for ammonium than Ochromonas. In agreement with theoretical predictions, Microcystis was much more strongly suppressed by intraguild predation on ammonium than by top–down predation on nitrate. Yet, Microcystis persisted at very low population densities, because the type III functional response of Ochromonas implied that the grazing pressure upon Microcystis became low when Microcystis was rare. Our results provide experimental support for intraguild predation theory, and indicate that intraguild predation may enable biological control of microbial pest species.     

Early Detection of Motor Dysfunction in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis (ALS) Using Home Cage Running Wheels

The SOD1^G93A mouse has been used since 1994 for preclinical testing in amyotrophic lateral sclerosis (ALS). Despite recent genetic advances in our understanding of ALS, transgenic mice expressing mutant SOD1 remain the best available, and most widely used, vertebrate model of the disease. We previously described an optimised and rapid approach for preclinical studies in the SOD1^G93A mouse. Here we describe improvements to this approach using home cage running wheels to obtain daily measurements of motor function, with minimal intervention. We show that home cage running wheels detect reductions in motor function at a similar time to the rotarod test, and that the data obtained are less variable allowing the use of smaller groups of animals to obtain satisfactory results. This approach refines use of the SOD1^G93A model, and reduces the number of animals undergoing procedures of substantial severity, two central principles of the 3Rs (replacement, reduction and refinement of animal use in research). The small group sizes and rapid timescales enable affordable large-scale therapeutic pre-screening in the SOD1^G93A mouse, as well as rapid validation of published positive effects in a second laboratory, one of the major stumbling blocks in ALS preclinical therapy development.     

NCI Workshop Report: Clinical and Computational Requirements for Correlating Imaging Phenotypes with Genomics Signatures

The National Cancer Institute (NCI) Cancer Imaging Program organized two related workshops on June 26–27, 2013, entitled “Correlating Imaging Phenotypes with Genomics Signatures Research” and “Scalable Computational Resources as Required for Imaging-Genomics Decision Support Systems.” The first workshop focused on clinical and scientific requirements, exploring our knowledge of phenotypic characteristics of cancer biological properties to determine whether the field is sufficiently advanced to correlate with imaging phenotypes that underpin genomics and clinical outcomes, and exploring new scientific methods to extract phenotypic features from medical images and relate them to genomics analyses. The second workshop focused on computational methods that explore informatics and computational requirements to extract phenotypic features from medical images and relate them to genomics analyses and improve the accessibility and speed of dissemination of existing NIH resources. These workshops linked clinical and scientific requirements of currently known phenotypic and genotypic cancer biology characteristics with imaging phenotypes that underpin genomics and clinical outcomes. The group generated a set of recommendations to NCI leadership and the research community that encourage and support development of the emerging radiogenomics research field to address short-and longer-term goals in cancer research.     

Survivin is essential for fertile egg production and female fertility in mice

Survivin is the smallest member of the inhibitor of apoptosis protein (IAP) family and acts as a bifunctional protein involved in mitosis regulation and apoptosis inhibition. To identify the physiological role of Survivin in female reproduction, we selectively disrupted Survivin expression in oocytes and granulosa cells (GCs), two major cell types in the ovary, by two different Cre-Loxp conditional knockout systems, and found that both led to defective female fertility. Survivin deletion in oocytes did not affect oocyte growth, viability and ovulation, but caused tetraploid egg production and thus female infertility. Further exploration revealed that Survivin was essential for regulating proper meiotic spindle organization, spindle assembly checkpoint activity, timely metaphase-to-anaphase transition and cytokinesis. Mutant mice with Survivin depleted in GCs showed reduced ovulation and subfertility, caused by defective follicular growth, increased follicular atresia and impaired luteinization. These findings suggest that Survivin has an important role in regulating folliculogenesis and oogenesis in the adult mouse ovary.     

Plant tolerance and resistance in food webs: community-level predictions and evolutionary implications

While evolutionary ecologists emphasize different ways in which plants can evolutionarily respond to herbivory, such as resistance or tolerance, community ecology has lagged in its understanding of how these different plant traits can influence interactions, abundance, composition, and diversity within more complex food webs. In this paper, we present a series of models comparing community level outcomes when plants either resist or tolerate herbivory. We show that resistance and tolerance can lead to very different outcomes. A particularly important result is that resistant species should often coexist locally with other, less resistant competitors, whereas tolerant species should not be able to coexist locally with less tolerant competitors, although priority effects allow them to coexist regionally. We also use these models to suggest some insights into the evolution of these traits within more complex communities. We emphasize how understanding the differential effects of plant tolerance and resistance in food webs provides greater appreciation of a variety of empirical patterns that heretofore have appeared enigmatic. This revised version was published online in July 2006 with corrections to the Cover Date.     

The Contribution of Paraserianthes (Albizia) falcataria to Sustainable Swidden Management Practices among The Baduy of West Java

There is a prohibition on the use of modern external inputs, such as chemical fertilizers, in Baduy swidden farming. Ordinarily, the consequence of this in a situation of acute forest pressure would be a decrease in fallow times, and an inevitable depletion of soil fertility. The Baduy (particularly Outer Baduy) have several ways of alleviating this problem, one of which is the introduction of Paraserianthes (Albizia) falcataria. By alternating this commercially valuable perennial leguminous tree with rice, soil fertility is maintained and the socio-economic position of the Baduy improved. As a result, swidden farming, which is considered by the Baduy to be central to their cultural identity, continues to be viable, despite increasing population density and the continuing depletion of mature forest.