How stress affects rice: a characterization of the rice transcriptome during single and simultaneous abiotic and biotic stresses

2019 Spring.Includes bibliographical references.Environmental stresses, both abiotic and biotic, are large contributors to pre-harvest crop loss. Abiotic stresses, such as drought, salinity, non-optimal temperature and others, are non-living factors in the environment that have a negative effect on plants. Biotic stresses are biological factors that can harm plants, including pathogens, pests and competition from other plants. With climate change increasing the incidence of abiotic stresses and the constant pressures of pests and pathogens, it is critical to world agriculture that varieties of plants broadly tolerant to stresses are developed. For this, it is necessary to understand how plants respond to multiple simultaneous stresses. The goal of this work is to characterize the stress response of the global staple food plant rice. Here, I present the results of two comprehensive transcriptome studies. In the first, I characterize how the rice transcriptome changes in response to simultaneous heat stress and infection by the bacterial pathogen Xanthomonas oryzae (Xo). Xo includes the causal agent for the economically important bacterial blight disease of rice, Xo pathovar oryzae (Xoo). Bacterial blight is more severe during abiotic stresses such as high temperature and drought. Most rice resistance (R) genes that target Xoo lose function at high temperature; however, function of the R-gene Xa7 is enhanced when the host is subjected to abiotic stresses. Understanding why Xa7 is more effective during heat stress gives insight into host processes that are important during combined abiotic and biotic stresses. The major finding of this study was that the abscisic acid (ABA) pathway is a node of cross-talk in the interactions between heat stress and pathogen attack, during both susceptible and resistant interactions. In the second comprehensive study, I characterize how the rice transcriptome is universally regulated by all stresses. Understanding universalities in rice stress response transcriptomes provides insight into how plants endure a wide variety of stresses in the field. To explore the universal rice transcriptome response, I developed a custom workflow to analyze publicly available RNA-Seq data from rice stress response studies, including the abiotic stresses drought, salinity, heat and cold, and the biotic stresses bacterial leaf streak, bacterial blight, rice blast, and two viral diseases. From this study, I concluded that the rice stress response is a robust system with many overlapping features. This core response includes down-regulation of photosynthetic processes and up-regulation of downstream signaling of the hormones ABA, salicylic acid and jasmonic acid. Within this dissertation, I present networks of gene regulation in four major rice responses: (1) response to a susceptible interaction with Xo during high temperature, (2) response to a resistant interaction with Xo during high temperature, (3) core response to abiotic stresses and (4) core response to biotic stresses. Common among all of these pathways are the pathways upstream and downstream of the plant hormone ABA. ABA-related processes are universally up-regulated by abiotic and biotic stresses, and are only repressed during the enhanced Xa7 response at high temperature. Because ABA signaling is critical for stress response, we need a thorough understanding of how genes in the ABA response network interact to most efficiently improve rice to be tolerant to multiple and simultaneous stresses. The gene networks I have characterized can be integrated with genome and transcriptome data from stress-tolerant rice varieties. By having a complete understanding of the rice stress response, we can develop an informed approach for developing new varieties of rice that are resistant to stress

Prevention and partial reversion of the lupus phenotype in ABIN1[D485N] mice by an IRAK4 inhibitor

OBJECTIVE: We have reported previously that the IRAK4 inhibitor PF06426779 given to ubiquitin-binding-defective ABIN1[D485N] mice at 6 weeks of age prevents the major facets of lupus that develop 10 weeks later. The present study was undertaken to investigate whether PF06426779 could reverse the lupus phenotype when administered to 13-week-old ABIN1[D485N] mice that had already developed symptoms of lupus. METHODS: Splenomegaly, the number of splenic neutrophils, T(FH) and Germinal Centre B (GCB) cells, serum levels of immunoglobulins, the extent of kidney, liver and lung pathology, and glomerular IgA and IgM were measured after feeding 13-week-old ABIN1[D485N] and wild-type mice for another 10 weeks with R&M3 diet with and without PF06426779 (4 g/kg). RESULTS: Following drug treatment, spleen size and weight, splenic neutrophil numbers, and serum IgA and glomerular IgA levels of ABIN1[D485N] mice returned to those seen in wild-type mice. The rise in splenic T(FH) and GCB numbers, the increase in kidney and liver pathology, and the concentrations of serum IgG1, IgG2A and IgE between 13 and 23 weeks were suppressed. There was no reduction in the level of anti-self double-stranded DNA, anti-self nuclear antigens or IgM during the drug treatment. CONCLUSIONS: The results demonstrate the therapeutic potential of IRAK4 inhibitors for the treatment of lupus and raise the possibility of monitoring efficacy by measuring decreases in the serum levels of IgA. Our results support the view that there may be a closer connection between lupus and IgA nephropathy than realised previously

Understanding Schools and Schooling. (Book Review)

A review of a book written by Clive Chitty (2002 with a useful focus on issues of equity and social justice, including prejudice, discrimination and bullying in secondary schools. Education policy makers need to explore the extent to which it is important to produce interested, motivated and socially balanced young adults. It is well researched and documented

Parental Age and Cognitive Disability among Children in the United States

Abstract: Some risks of having children at older ages are widely documented, and the "biological clock" is a popular media concern, but the association between cognitive disability generally and both mothers' and fathers' age is not well known. This article assesses descriptively the relationship between children's cognitive disability and parents' age at birth, using a sample of 353,119 children aged five to eleven living with two married parents from the 2009-2011 American Community Survey. Cognitive disability varied by parental age categories from 1.8 percent to 5.4 percent, with overall rates of 2.2 percent. Odds of disability were much more strongly associated with mothers' age at birth than with fathers' age at birth, with the highest odds for children whose mothers were age 45 or higher at the time of their birth (adjusted odds ratio 2.7 relative to age 30 to 34) and the lowest for those born to mothers in their early 30s. These results demonstrate that the risk is strongly associated with the mother's age at birth-but not the father's. This is consistent with previous research showing that it is the mother's health, rather than age per se, that is most important for the health of their children

Moral panic and social theory: Beyond the heuristic

Copyright @ 2011 by International Sociological Association.Critcher has recently conceptualized moral panic as a heuristic device, or 'ideal type'. While he argues that one still has to look beyond the heuristic, despite a few exceptional studies there has been little utilization of recent developments in social theory in order to look 'beyond moral panic'. Explicating two current critical contributions - the first, drawing from the sociologies of governance and risk; the second, from the process/figurational sociology of Norbert Elias - this article highlights the necessity for the continuous theoretical development of the moral panic concept and illustrates how such development is essential to overcome some of the substantial problems with moral panic research: normativity, temporality and (un) intentionality

Distinct signals and immune cells drive liver pathology and glomerulonephritis in ABIN1[D485N] mice

We report that TLR7, IL-6, and the adaptive immune system are essential for autoimmunity and glomerulonephritis but not for liver pathology in mice expressing the ubiquitin-binding-defective ABIN1[D485N] mutant. The blood and organs of ABIN1[D485N] mice have exceptionally high numbers of patrolling monocytes (pMo), which develop independently of IL-6 and the adaptive immune system. They are detectable in the blood months before autoimmunity and organ pathology are seen and may have diagnostic potential. The splenic pMo, inflammatory monocytes (iMo), and neutrophils of ABIN1[D485N] mice expressed high levels of mRNAs encoding proteins released during NETosis, which together with the high numbers of monocyte-derived dendritic cells (MoDCs) may drive the liver pathology in ABIN1[D485N] mice, and contribute to the pathology of other organs. The splenic iMo of ABIN1[D485N] mice displayed high expression of mRNAs encoding proteins controlling cell division and were actively dividing; this may underlie the increased pMo and MoDC numbers, which are derived from iMo. An orally active IRAK4 inhibitor suppressed all facets of the disease phenotype and prevented the increase in pMo numbers

HOIL-1 ubiquitin ligase activity targets unbranched glucosaccharides and is required to prevent polyglucosan accumulation

HOIL‐1, a component of the linear ubiquitin chain assembly complex (LUBAC), ubiquitylates serine and threonine residues in proteins by esterification. Here, we report that mice expressing an E3 ligase‐inactive HOIL‐1[C458S] mutant accumulate polyglucosan in brain, heart and other organs, indicating that HOIL‐1’s E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL‐1 monoubiquitylates glycogen and α1:4‐linked maltoheptaose in vitro and identify the C6 hydroxyl moiety of glucose as the site of ester‐linked ubiquitylation. The monoubiquitylation of maltoheptaose was accelerated > 100‐fold by the interaction of Met1‐linked or Lys63‐linked ubiquitin oligomers with the RBR domain of HOIL‐1. HOIL‐1 also transferred pre‐formed ubiquitin oligomers to maltoheptaose en bloc, producing polyubiquitylated maltoheptaose in one catalytic step. The Sharpin and HOIP components of LUBAC, but not HOIL‐1, bound to unbranched and infrequently branched glucose polymers in vitro, but not to highly branched mammalian glycogen, suggesting a potential function in targeting HOIL‐1 to unbranched glucosaccharides in cells. We suggest that monoubiquitylation of unbranched glucosaccharides may initiate their removal from cells, preventing precipitation as polyglucosan

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

Prion-like Aggregation of Mitochondrial Antiviral Signaling Protein in Lupus Patients Is Associated With Increased Levels of Type I Interferon: MAVS AGGREGATION AND TYPE I IFN IN LUPUS

Increased levels of Type I interferon (IFN-I) and IFN-I-regulated genes are found in patients with systemic lupus erythematosus (SLE) and may be central to its pathogenesis. The mitochondrial adaptor protein MAVS is a key regulator of IFN-I that undergoes a dramatic prion-like aggregation and self-propagates the activation signal from viral RNA to amplify downstream IFN production. We wondered if such MAVS aggregates might play a role in the sustained increased production of IFN-I in SLE

Prospects for Advancing Tuberculosis Control Efforts through Novel Therapies

BACKGROUND: Development of new, effective, and affordable tuberculosis (TB) therapies has been identified as a critical priority for global TB control. As new candidates emerge from the global TB drug pipeline, the potential impacts of novel, shorter regimens on TB incidence and mortality have not yet been examined. METHODS AND FINDINGS: We used a mathematical model of TB to evaluate the expected benefits of shortening the duration of effective chemotherapy for active pulmonary TB. First, we considered general relationships between treatment duration and TB dynamics. Next, as a specific example, we calibrated the model to reflect the current situation in the South-East Asia region. We found that even with continued and rapid progress in scaling up the World Health Organization's DOTS strategy of directly observed, short-course chemotherapy, the benefits of reducing treatment duration would be substantial. Compared to a baseline of continuing DOTS coverage at current levels, and with currently available tools, a 2-mo regimen introduced by 2012 could prevent around 20% (range 13%–28%) of new cases and 25% (range 19%–29%) of TB deaths in South-East Asia between 2012 and 2030. If effective treatment with existing drugs expands rapidly, overall incremental benefits of shorter regimens would be lower, but would remain considerable (13% [range 8%–19%] and 19% [range 15%–23%] reductions in incidence and mortality, respectively, between 2012 and 2030). A ten-year delay in the introduction of new drugs would erase nearly three-fourths of the total expected benefits in this region through 2030. CONCLUSIONS: The introduction of new, shorter treatment regimens could dramatically accelerate the reductions in TB incidence and mortality that are expected under current regimens—with up to 2- or 3-fold increases in rates of decline if shorter regimens are accompanied by enhanced case detection. Continued progress in reducing the global TB burden will require a balanced approach to pursuing new technologies while promoting wider implementation of proven strategies