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The Truth and Reconciliation Commission
\"15 April 2016 marked 20 years since the Truth and Reconciliation Commission (TRC) hearings began. The TRC was set up to give an opportunity for perpetrators of human rights transgressions to come clean about the atrocities that happened during those evil days of apartheid. Sadly, only half of the truth came to the fore. Many families still do not know what happened to their loved ones. There are few people better placed than Mary Burton to write about the TRC, having been one of its Commissioners. Burton's pocket book provides an informed account from the inside of the process and workings of the TRC and a measured and balanced assessment of its outcomes and significance. Even at the time of its existence, the TRC came in for criticism from a variety of quarters: both the African National Congress and ex-President F.W. de Klerk took legal action to challenge or prevent the publication of the Commission's report; however, the Commission also fulfilled a vital and important role in the transition from apartheid to democracy, and it has become a model for other countries wishing to undertake similar journeys to deal with past atrocities and come to some kind of national resolution, reconciliation or closure.\"--Publisher's website.
Book
Gene expression changes governing extreme dehydration tolerance in an Antarctic insect
Among terrestrial organisms, arthropods are especially susceptible to dehydration, given their small body size and high surface area to volume ratio. This challenge is particularly acute for polar arthropods that face near-constant desiccating conditions, as water is frozen and thus unavailable for much of the year. The molecular mechanisms that govern extreme dehydration tolerance in insects remain largely undefined. In this study, we used RNA sequencing to quantify transcriptional mechanisms of extreme dehydration tolerance in the Antarctic midge, Belgica antarctica, the world’s southernmost insect and only insect endemic to Antarctica. Larvae of B. antarctica are remarkably tolerant of dehydration, surviving losses up to 70% of their body water. Gene expression changes in response to dehydration indicated up-regulation of cellular recycling pathways including the ubiquitin-mediated proteasome and autophagy, with concurrent down-regulation of genes involved in general metabolism and ATP production. Metabolomics results revealed shifts in metabolite pools that correlated closely with changes in gene expression, indicating that coordinated changes in gene expression and metabolism are a critical component of the dehydration response. Finally, using comparative genomics, we compared our gene expression results with a transcriptomic dataset for the Arctic collembolan, Megaphorura arctica. Although B. antarctica and M. arctica are adapted to similar environments, our analysis indicated very little overlap in expression profiles between these two arthropods. Whereas several orthologous genes showed similar expression patterns, transcriptional changes were largely species specific, indicating these polar arthropods have developed distinct transcriptional mechanisms to cope with similar desiccating conditions.
Journal Article
Amazons : a love story
\"When E.J. Levy arrived in northern Brazil on a fellowship from Yale at the age of 21, she was hoping to save the Amazon rain forest; she didn't realize she would soon have to save herself. Amazons: a love story recounts an idealistic young woman's coming of age against the backdrop of the magnificent rain forest and exotic city of Salvador.\"--Publisher's description.
Book
Shorter telomeres precede population extinction in wild lizards
Identifying the early warning signals of catastrophic extinctions has recently became a central focus for ecologists, but species’ functional responses to environmental changes remain an untapped source for the sharpening of such warning signals. Telomere length (TL) analysis represents a promising molecular tool with which to raise the alarm regarding early population decline, since telomere attrition is associated with aging processes and accelerates after a recurrent exposure to environmental stressors. In the southern margin of their range, populations of the common lizard (Zootoca vivipara) recently became extinct at lowest elevations due to changes in climate conditions. However, the proximal signals involved in these demographic declines are still unknown. Here, we sampled 100 yearling lizards from 10 natural populations (n = 10 per population) along an extinction risk gradient. Relative lizard abundance dramatically dropped over 12 years in low-altitude populations characterized by warmer ambient temperatures and higher body growth of lizards early in life. A non-linear relationship was found between TL and population extinction risk, with shorter telomeres in populations facing high risk of extinction when compared to non-threatened ones. Our results identify TL as an extremely promising biomarker and imply that population extinctions might be preceded by a loop of physiological aging.
Journal Article
Infiltration of inflammatory macrophages and neutrophils and widespread pyroptosis in lung drive influenza lethality in nonhuman primates
Severe influenza kills tens of thousands of individuals each year, yet the mechanisms driving lethality in humans are poorly understood. Here we used a unique translational model of lethal H5N1 influenza in cynomolgus macaques that utilizes inhalation of small-particle virus aerosols to define mechanisms driving lethal disease. RNA sequencing of lung tissue revealed an intense interferon response within two days of infection that resulted in widespread expression of interferon-stimulated genes, including inflammatory cytokines and chemokines. Macaques with lethal disease had rapid and profound loss of alveolar macrophages (AMs) and infiltration of activated CCR2 + CX3CR1 + interstitial macrophages (IMs) and neutrophils into lungs. Parallel changes of AMs and neutrophils in bronchoalveolar lavage (BAL) correlated with virus load when compared to macaques with mild influenza. Both AMs and IMs in lethal influenza were M1-type inflammatory macrophages which expressed neutrophil chemotactic factors, while neutrophils expressed genes associated with activation and generation of neutrophil extracellular traps (NETs). NETs were prominent in lung and were found in alveolar spaces as well as lung parenchyma. Genes associated with pyroptosis but not apoptosis were increased in lung, and activated inflammatory caspases, IL-1β and cleaved gasdermin D (GSDMD) were present in bronchoalveolar lavage fluid and lung homogenates. Cleaved GSDMD was expressed by lung macrophages and alveolar epithelial cells which were present in large numbers in alveolar spaces, consistent with loss of epithelial integrity. Cleaved GSDMD colocalized with viral NP-expressing cells in alveoli, reflecting pyroptosis of infected cells. These novel findings reveal that a potent interferon and inflammatory cascade in lung associated with infiltration of inflammatory macrophages and neutrophils, elaboration of NETs and cell death by pyroptosis mediates lethal H5N1 influenza in nonhuman primates, and by extension humans. These innate pathways represent promising therapeutic targets to prevent severe influenza and potentially other primary viral pneumonias in humans.
Journal Article
Distribution of SUN OVATE, LC and FAS in the tomato germplasm and the relationship to fruit shape diversity
Phenotypic diversity within cultivated tomato (Solanum lycopersicum) is particularly evident for fruit shape and size. Four genes that control tomato fruit shape have been cloned. SUN and OVATE control elongated shape whereas FASCIATED (FAS) and LOCULE NUMBER (LC) control fruit locule number and flat shape. We investigated the distribution of the fruit shape alleles in the tomato germplasm and evaluated their contribution to morphology in a diverse collection of 368 predominantly tomato and tomato var. cerasiforme accessions. Fruits were visually classified into eight shape categories that were supported by objective measurements obtained from image analysis using the Tomato Analyzer software. The allele distribution of SUN, OVATE, LC, and FAS in all accessions was strongly associated with fruit shape classification. We also genotyped 116 representative accessions with additional 25 markers distributed evenly across the genome. Through a model-based clustering we demonstrated that shape categories, germplasm classes, and the shape genes were nonrandomly distributed among five genetic clusters (P < 0.001), implying that selection for fruit shape genes was critical to subpopulation differentiation within cultivated tomato. Our data suggested that the LC, FAS, and SUN mutations arose in the same ancestral population while the OVATE mutation arose in a separate lineage. Furthermore, LC, OVATE, and FAS mutations may have arisen prior to domestication or early during the selection of cultivated tomato whereas the SUN mutation appeared to be a postdomestication event arising in Europe.
Journal Article
Cytokines and Their STATs in Cutaneous and Visceral Leishmaniasis
Cytokines play a critical role in shaping the host immune response to Leishmania infection and directing the development of protective and non-protective immunities during infection. Cytokines exert their biological activities through the activation and translocation of transcription factors into the nucleus whether they drive the expression of specific cytokine-responsive genes. Signal transducer and activator of transcription (STATs) are transcription factors which play a critical role in mediating signaling downstream of cytokine receptors and are important for shaping the host immune response during Leishmania infection. Here we discuss the signature cytokines and their associated STATs involved in the host immune response during cutaneous and visceral leishmaniasis.
Journal Article
A Kalman Filter Approach for Estimating Daily Discharge Using Space‐Based Discharge Estimates
The SWOT satellite mission is the first to conduct a global survey of the Earth's surface waters, measuring water surface height, river width, and water surface slope, based on which river discharge is estimated. At mid‐latitudes, the repeat orbit design of SWOT only allows a sampling of twice per repeat cycle, which is considered too low for most hydrological applications. To address the spatiotemporal limitations of SWOT, we develop a method that assimilates SWOT observations across continuous reaches within a single‐branch river network to obtain daily discharge estimates. Our model‐free assimilation method provides a linear dynamic system that includes a process model based on a physically based spatiotemporal discharge correlation model and observation equations utilizing SWOT products. We solve this dynamic system using a simple Kalman filter in the time domain, assimilating SWOT observations and incorporating the physically based prior to estimate daily discharge. Since SWOT discharge products were not yet available during the period of this research, we used synthetic SWOT data sets, introducing random and systematic errors through Monte Carlo simulation. The validation of the estimated discharge against true discharge over all test cases leads to a median correlation as high as 0.95, a median NSE for residuals (mean‐removed discharge) as high as 0.81, and a median relative bias as low as 5%, respectively. These promising results suggest that daily discharge for continuous reaches in a river network can be obtained through our data assimilation framework.
Journal Article
A putative de novo evolved gene required for spermatid chromatin condensation in Drosophila melanogaster
Comparative genomics has enabled the identification of genes that potentially evolved de novo from non-coding sequences. Many such genes are expressed in male reproductive tissues, but their functions remain poorly understood. To address this, we conducted a functional genetic screen of over 40 putative de novo genes with testis-enriched expression in Drosophila melanogaster and identified one gene, atlas , required for male fertility. Detailed genetic and cytological analyses showed that atlas is required for proper chromatin condensation during the final stages of spermatogenesis. Atlas protein is expressed in spermatid nuclei and facilitates the transition from histone- to protamine-based chromatin packaging. Complementary evolutionary analyses revealed the complex evolutionary history of atlas . The protein-coding portion of the gene likely arose at the base of the Drosophila genus on the X chromosome but was unlikely to be essential, as it was then lost in several independent lineages. Within the last ~15 million years, however, the gene moved to an autosome, where it fused with a conserved non-coding RNA and evolved a non-redundant role in male fertility. Altogether, this study provides insight into the integration of novel genes into biological processes, the links between genomic innovation and functional evolution, and the genetic control of a fundamental developmental process, gametogenesis.
Journal Article
The genomics of rapid climatic adaptation and parallel evolution in North American house mice
Parallel changes in genotype and phenotype in response to similar selection pressures in different populations provide compelling evidence of adaptation. House mice ( Mus musculus domesticus ) have recently colonized North America and are found in a wide range of environments. Here we measure phenotypic and genotypic differentiation among house mice from five populations sampled across 21° of latitude in western North America, and we compare our results to a parallel latitudinal cline in eastern North America. First, we show that mice are genetically differentiated between transects, indicating that they have independently colonized similar environments in eastern and western North America. Next, we find genetically-based differences in body weight and nest building behavior between mice from the ends of the western transect which mirror differences seen in the eastern transect, demonstrating parallel phenotypic change. We then conduct genome-wide scans for selection and a genome-wide association study to identify targets of selection and candidate genes for body weight. We find some genomic signatures that are unique to each transect, indicating population-specific responses to selection. However, there is significant overlap between genes under selection in eastern and western house mouse transects, providing evidence of parallel genetic evolution in response to similar selection pressures across North America.
Journal Article