Neuronal Adaptations to Changes in the Social Dominance Status of Crayfish

The effect of superfused serotonin (5-HT; 50 mM) on the synaptic responses of the lateral giant (LG) interneuron in crayfish was found to depend on the social status of the animal. In socially isolated animals, 5-HT persistently increased the response of LG to sensory nerve shock. After social isolates were paired in a small cage, they fought and determined their dominant and subordinate status. After 12 d of pairing, 5-HT reversibly inhibited the response of LG in the social subordinate and reversibly increased the response of LG in the social dominant crayfish. The effect of 5-HT changed approximately linearly from response enhancement to inhibition in the new subordinate over the 12 d of pairing. If, after 12 d pairing, the subordinate was reisolated for 8 d, the response enhancement was restored. If the subordinate, instead, was paired with another subordinate and became dominant in this new pair, the inhibitory effect of 5-HT changed to an enhancing effect over the next 12 d of pairing. If, however, two dominant crayfish were paired and one became subordinate, the enhancing effect of 5-HT persisted in the new subordinate even after 38 d pairing. These different effects of serotonin result from the action of two or more molecular receptors for serotonin. A vertebrate 5-HT1 agonist had no effect on social isolates but reversibly inhibited the response of LG in both dominant and subordinate crayfish. The inhibitory effects of the agonist developed approximately linearly over the first 12 d of pairing. A vertebrate 5-HT2 agonist persistently increased the response of LG in isolate crayfish and reversibly increased the response of the cell in dominant and subordinate crayfish. Finally, although neurons that might mediate these effects of superfused 5-HT are unknown, one pair of 5-HT-immunoreactive neurons appears to contact the LG axon and initial axon segment in each abdominal ganglion in its projection caudally from the thorax

Reimagining Global Operating Models: Steps Multi-Country Organizations Are Taking to Advance Equity and Shift Power Locally

Global organizations are increasingly engaging in difficult conversations about shifting power and resourcing from capital-rich places like New York or London to local organizations and people, who hold a wealth of lived experience and cultural knowledge, along with deep relationships in communities. Some call this shift "localization." Others view it as "decolonizing" development. At the core, this is about yielding power to communities. And most agree that change, whatever it is called, has a long way to go.Those who recognize the need for change have more questions than answers. A growing number have come to The Bridgespan Group in search of practical advice about re-examining their cross-country operating models. From our interviews, we distilled five trends in practice that attempt to address these issues around power, resources, and equity. We describe each by drawing on the experiences of more than a dozen nonprofits and funders:Redefine the role of the "center" to shift power to local teamsMove central roles closer to the workElevate local voices in decision makingInvest in global and local equity capabilitiesBuild equitable employee experience

Bridging the Gap on Funding the True Costs of NGOs in India

There's a gap between funders' perspectives on how much they support indirect costs ("overhead") and organisational development, and NGOs' perspectives on just how much funders are willing to support it. Improved communication between funders and NGOs would help to build trust and shift entrenched attitudes and practices. This research along with our assessment guide and tips can support NGOs and funders in this important work

Dual and Opposing Modulatory Effects of Serotonin on Crayfish Lateral Giant Escape Command Neurons

Serotonin modulates afferent synaptic transmission to the lateral giant neurons of crayfish, which are command neurons for escape behavior. Low concentrations, or high concentrations reached gradually, are facilitatory, whereas high concentrations reached rapidly are inhibitory. The modulatory effects rapidly reverse after brief periods of application, whereas longer periods of application are followed by facilitation that persists for hours. These effects of serotonin can be reproduced by models that involve multiple interacting intracellular signaling systems that are each stimulated by serotonin. The dependence of the neuromodulatory effect on dose, rate, and duration of modulator application may be relevant to understanding the effects of natural neuromodulation on behavior and cognition and to the design of drug therapies

Applying Genomic and Bioinformatic Resources to Human Adenovirus Genomes for Use in Vaccine Development and for Applications in Vector Development for Gene Delivery

Technological advances and increasingly cost-effect methodologies in DNA sequencing and computational analysis are providing genome and proteome data for human adenovirus research. Applying these tools, data and derived knowledge to the development of vaccines against these pathogens will provide effective prophylactics. The same data and approaches can be applied to vector development for gene delivery in gene therapy and vaccine delivery protocols. Examination of several field strain genomes and their analyses provide examples of data that are available using these approaches. An example of the development of HAdV-B3 both as a vaccine and also as a vector is presented

Methotrexate Inhibits T Cell Proliferation but Not Inflammatory Cytokine Expression to Modulate Immunity in People Living With HIV

Inflammation associated with increased risk of comorbidities persists in people living with HIV (PWH) on combination antiretroviral therapy (ART). A recent placebo-controlled trial of low-dose methotrexate (MTX) in PWH found that numbers of total CD4 and CD8 T cells decreased in the low-dose MTX arm. In this report we analyzed T cell phenotypes and additional plasma inflammatory indices in samples from the trial. We found that cycling (Ki67+) T cells lacking Bcl-2 were reduced by MTX but plasma inflammatory cytokines were largely unaffected. In a series of in vitro experiments to further investigate the mechanisms of MTX activity, we found that MTX did not inhibit effector cytokine production but inhibited T cell proliferation downstream of mTOR activation, mitochondrial function, and cell cycle entry. This inhibitory effect was reversible with folinic acid, suggesting low-dose MTX exerts anti-inflammatory effects in vivo in PWH largely by blocking T cell proliferation via dihydrofolate reductase inhibition, yet daily administration of folic acid did not rescue this effect in trial participants. Our findings identify the main mechanism of action of this widely used anti-inflammatory medicine in PWH and may provide insight into how MTX works in the setting of other inflammatory conditions

Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials

Objective: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. Summary of Background Data: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. Methods: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. Results: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall Gcoefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. Conclusions: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials

Diversity and dynamics of a widespread bloom of the toxic dinoflagellate Alexandrium fundyense

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e22965, doi:10.1371/journal.pone.0022965.Historically, cosmopolitan phytoplankton species were presumed to represent largely unstructured populations. However, the recent development of molecular tools to examine genetic diversity have revealed differences in phytoplankton taxa across geographic scales and provided insight into the physiology and ecology of blooms. Here we describe the genetic analysis of an extensive bloom of the toxic dinoflagellate Alexandrium fundyense that occurred in the Gulf of Maine in 2005. This bloom was notable for its intensity and duration, covering hundreds of kilometers and persisting for almost two months. Genotypic analyses based on microsatellite marker data indicate that the open waters of the northeastern U.S. harbor a single regional population of A. fundyense comprising two genetically distinct sub-populations. These subpopulations were characteristic of early- and late-bloom samples and were derived from the northern and southern areas of the bloom, respectively. The temporal changes observed during this study provide clear evidence of succession during a continuous bloom and show that selection can act on the timescale of weeks to significantly alter the representation of genotypes within a population. The effects of selection on population composition and turnover would be magnified if sexual reproduction were likewise influenced by environmental conditions. We hypothesize that the combined effects of differential growth and reproduction rates serves to reduce gene flow between the sub-populations, reinforcing population structure while maintaining the diversity of the overall regional population.This work was supported by the National Institute of Environmental Health Sciences (1-P50-ES012742 to DMA and DLE), by the National Science Foundation through the Woods Hole Center for Oceans and Human Health (OCE-0430724), and by the ECOHAB program (NOAA Grant NA06NOS4780245)

Effect of Fibrin Glue on the Biomechanical Properties of Human Descemet's Membrane

10.1371/journal.pone.0037456PLoS ONE75