A study into the regulation of root development under osmotic stress

The mechanisms behind the regulation of root development under a lack of water (osmotic stress) is a critical subject for plant biology and global agriculture. Previously osmotic stress has been shown to inhibit root growth via an abscisic acid (ABA)-mediated reduction in auxin transport, independent of ethylene signalling. This thesis examines the impact of osmotic stress on critical developmental signals: auxin, ABA, and reactive oxygen species (ROS) minutes after encountering osmotic stress and following a longer stress period of 24 hours. The roles of these signals in the root were analysed via loss-of-function mutants, gene expression analysis, and bioimaging in concert with exogenous chemical treatment. Auxin, ABA, and ROS (represented by level of oxidation) levels were all found to rapidly increase within 10 minutes of osmotic stress leading to downstream responses. ROS and ABA appear to have a strong positive feedback relationship that can develop with minutes. Under the longer stress period of 24 hours, auxin responses were found to decrease while both ROS and ABA responses were shown to increase. PIN-mediated auxin transport was shown to play a key role in the reduction of auxin in the root tip following 24-hour osmotic stress treatment. PIN3 and PIN7 gene expression and protein distribution were altered under osmotic stress, associated with a reduction of the auxin maximum at the root tip. ROP2 was found to play a central role in root development under osmotic stress root, along with the decrease of auxin and increase in ABA signalling after 24 hours. It was also shown that several respiratory burst oxidase homologs (RBOHs) play a role in root development under standard conditions as well as under osmotic stress. PERK4 and RBOHC likely play a key role in ROS production under ABA-mediated osmotic stress response, with the loss-of-function of PERK4 significantly improving root growth under osmotic stress

A predictive model for ethylene-mediated auxin and cytokinin patterning in the Arabidopsis root

The interaction between auxin and cytokinin is important in many aspects of plant development. Experimental measurements of both auxin and cytokinin concentration and reporter gene expression clearly show the coexistence of auxin and cytokinin concentration patterning in Arabidopsis root development. However, in the context of crosstalk between auxin, cytokinin and ethylene, little is known about how auxin and cytokinin concentration patterns simultaneously emerge and how they regulate each other in the Arabidopsis root. This work utilizes a wide range of experimental observations to propose a mechanism for simultaneous patterning of auxin and cytokinin concentration. In addition to the regulatory relationships between auxin and cytokinin, the mechanism reveals that ethylene signalling is an important factor in achieving simultaneous auxin and cytokinin patterning, while also predicting other experimental observations. Combining the mechanism with a realistic in silico root model reproduces experimental observations of both auxin and cytokinin patterning. Predictions made by the mechanism can be compared with a variety of experimental observations, including those conducted by our group and other independent experiments reported by other groups. Examples of these predictions include patterning of auxin biosynthesis rate, PIN1 and PIN2 pattern changes in pin3, 4, 7 mutants, cytokinin patterning change in the pls mutant, PLS patterning, as well as various trends in different mutants. This research unravels a plausible mechanism for simultaneous patterning of auxin and cytokinin concentrations in Arabidopsis root development and suggests a key role for ethylene pattern integration. [Abstract copyright: Copyright © 2024. Published by Elsevier Inc.

Causation, complexity, and the concert: the pragmatics of causal explanation in international relations

A causal explanation provides information about the causal history of whatever is being explained. However, most causal histories extend back almost infinitely and can be described in almost infinite detail. Causal explanations therefore involve choices about which elements of causal histories to pick out. These choices are pragmatic: they reflect our explanatory interests. When adjudicating between competing causal explanations, we must therefore consider not only questions of epistemic adequacy (whether we have good grounds for identifying certain factors as causes) but also questions of pragmatic adequacy (whether the aspects of the causal history picked out are salient to our explanatory interests). Recognizing that causal explanations differ pragmatically as well as epistemically is crucial for identifying what is at stake in competing explanations of the relative peacefulness of the nineteenth-century Concert system. It is also crucial for understanding how explanations of past events can inform policy prescription

STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs

STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the endoplasmic reticulum (ER) and regulate store-operated Ca2+ entry (SOCE). The function of STIMs in the brain is only beginning to be explored, and the relevance of SOCE in nerve cells is being debated. Here we identify STIM2 as a central organizer of excitatory synapses. STIM2, but not its paralogue STIM1, influences the formation of dendritic spines and shapes basal synaptic transmission in excitatory neurons. We further demonstrate that STIM2 is essential for cAMP/PKA-dependent phosphorylation of the AMPA receptor (AMPAR) subunit GluA1. cAMP triggers rapid migration of STIM2 to ER–plasma membrane (PM) contact sites, enhances recruitment of GluA1 to these ER-PM junctions, and promotes localization of STIM2 in dendritic spines. Both biochemical and imaging data suggest that STIM2 regulates GluA1 phosphorylation by coupling PKA to the AMPAR in a SOCE-independent manner. Consistent with a central role of STIM2 in regulating AMPAR phosphorylation, STIM2 promotes cAMP-dependent surface delivery of GluA1 through combined effects on exocytosis and endocytosis. Collectively our results point to a unique mechanism of synaptic plasticity driven by dynamic assembly of a STIM2 signaling complex at ER-PM contact sites

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Bush the transnationalist: a reappraisal of the unilateralist impulse in US foreign policy, 2001-2009

This article challenges the common characterisation of George W. Bush’s foreign policy as “unilateral.” It argues that the Bush administration developed a new post-9/11 understanding of terrorism as a transnational, networked phenomenon shaped by the forces of globalisation. This led to a new strategic emphasis on bi- and multilateral security co-operation and counterterrorism operations, especially outside of Afghanistan and Iraq, driven by the perceived need to counter a transnational security challenge present in multiple locations. This (flawed) attempt to engage with transnational security challenges supplemented the existing internationalist pillar of the Bush administration’s foreign policy. Highlighting the transnational realm of international relations and the ways in which the Bush administration was able to co-opt other states to tackle perceived transnational challenges also shows the high importance the administration attached to concerted action even as it frequented eschewed institutional multilateralism

Making Research Data Accessible

This chapter argues that these benefits will accrue more quickly, and will be more significant and more enduring, if researchers make their data “meaningfully accessible.” Data are meaningfully accessible when they can be interpreted and analyzed by scholars far beyond those who generated them. Making data meaningfully accessible requires that scholars take the appropriate steps to prepare their data for sharing, and avail themselves of the increasingly sophisticated infrastructure for publishing and preserving research data. The better other researchers can understand shared data and the more researchers who can access them, the more those data will be re-used for secondary analysis, producing knowledge. Likewise, the richer an understanding an instructor and her students can gain of the shared data being used to teach and learn a particular research method, the more useful those data are for that pedagogical purpose. And the more a scholar who is evaluating the work of another can learn about the evidence that underpins its claims and conclusions, the better their ability to identify problems and biases in data generation and analysis, and the better informed and thus stronger an endorsement of the work they can offer