Rights-based approaches and beyond : challenges of linking rights and participation

As more and more development and human rights organisations critically assess their impact and strategies, there is growing convergence in the questions they raise about how to be most effective in addressing structural, systemic causes of poverty and exclusion and thus, make a positive difference in the lives of poor and marginalised people. This paper explores the growing trend of “rights-based approaches” (RBA) to development, drawing from interviews with a range of primarily US-based international human rights and development organisations as well as from insights through the authors’ years of experience working with development and rights groups in the global south. While the theory of RBA has been broadly embraced as key to getting at the root causes of poverty, many organisations are struggling to make sense of the significance of RBA in practice. We begin to unravel some key concerns with a brief discussion on critical considerations for groups as they advance rights-based work. Next, we focus on clarifying meanings, offering our own definitions of what seem to be critical components of RBA, namely participation, rights, and power. Next we summarise some of the current thinking and practice among international human rights and development organisations that are deepening their work in RBA. This includes some of the key tensions, challenges and opportunities they are encountering. Finally, in building on forgotten experiences and innovations we look at a handful of practical experiences from the past that offer valuable insights and lessons as groups seek to maximise the full practical potential of RBA. Keywords: rights, democracy, governance, participation

Sexual and social stimuli elicit rapid and contrasting genomic responses

Sensory physiology has been shown to influence female mate choice, yet little is known about the mechanisms within the brain that regulate this critical behaviour. Here we examine preference behaviour of 58 female swordtails, Xiphophorus nigrensis, in four different social environments (attractive and unattractive males, females only, non-attractive males only and asocial conditions) followed by neural gene expression profiling. We used a brain-specific cDNA microarray to identify patterns of genomic response and candidate genes, followed by quantitative PCR (qPCR) examination of gene expression with variation in behaviour. Our microarray results revealed patterns of genomic response differing more between classes of social stimuli than between presence versus absence of stimuli. We identified suites of genes showing diametrically opposed patterns of expression: genes that are turned ‘on’ while females interact with attractive males are turned ‘off’ when interacting with other females, and vice versa. Our qPCR results identified significant predictive relationships between five candidate genes and specific mate choice behaviours (preference and receptivity) across females exposed to males, with no significant patterns identified in female or asocial conditions or with overall locomotor activity. The identification of stimulus- and behaviour-specific responses opens an exciting window into the molecular pathways associated with social behaviour and mechanisms that underlie sexual selection

Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles

We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Neuronal specification by homeodomain transcription factors in Caenorhabditis elegans

The goal of this project was to elucidate the role of the homeodomain transcription factor family in terminal fate specification of an entire nervous system. In pursuit of this, I systematically identified the expression patterns of all 102 homeobox genes in the L4/adult stage C. elegans nervous system at a single-neuron resolution. This involved acquiring and/or generating high-quality fluorescent reporter reagents to tag all 102 homeodomain transcription factor proteins. Then, analyzing the expression of those reagents using a novel tool for whole nervous system identification in C. elegans, called NeuroPAL. The resulting expression atlas is the first complete picture of the homeobox family in any nervous system. It allowed the identification of new terminal selector proteins, including ceh-8, ceh-32, and ceh-31, in various neuron types and will continue to serve as a guide for future terminal selector identification across the nervous system. We discovered that every neuron type, and many subtypes, of the C. elegans nervous system express a completely unique set of homeodomain transcription factors. This unique expression code, along with the scores of homeodomain terminal selectors, suggests the possibility that every C. elegans neuron type is specified by a homeodomain terminal selector. We further probed the importance of the homeobox family in neuron specification by comparing its expression pattern with other transcription factor families. This necessitated high-quality data for the other major transcription factor families, bHLH, ZF, AtHook, bZip, and NHR, in every C. elegans neuron type. In collaboration with the labs of David Miller III at Vanderbilt and Marc Hammarlund at Yale, we used single cell RNA sequencing (scRNA-Seq) to molecularly profile all neuron types of the L4 stage C. elegans nervous system. We found that our homeodomain protein atlas was recapitulated fairly well in the scRNA-Seq data when thresholded and determined that the homeodomain transcription factor family is not alone in generating unique expression profiles for every neuron type. Two larger transcription factor families, ZF and NHR, are also uniquely expressed in each neuron identity. Instead, we found that the homeodomain transcription factor family is set apart from other families by their distinctly sparse expression across the nervous system at comparatively high levels. These expression patterns along with the numerous examples of functional homeodomain terminal selectors suggest that the family is an underlying theme in neuronal specification. We further extended this analysis to available scRNA-Seq datasets in the mouse nervous system and noted select commonalities in homeobox family expression across organisms. In all, this study shows yet again that analyzing homeodomain transcription factors leads to fruitful insights on organismal development. We found that the complexity of the C. elegans nervous system can be categorized and largely specified by a single family of transcription factors, building on previous studies of their importance in neuronal function