Investigating the cause of dieback in the invasive plant, Parkinsonia aculeata

Invasive plants cost Australia, directly and indirectly, around AU$4 billion pa; displacing native species, changing sensitive ecosystems and sometimes affecting human health and safety. Developing novel tools to control invasive species will benefit landholders and the environment, not just in Australia, but globally. Biocontrol of invasive plants via dieback causative agents is one such potential tool. Dieback causes a progressive reduction in plant population health, resulting in the death of plant parts and often complete plant death. It is prevalent in many invasive woody weeds in Australia and has been suggested as a potential mechanism for their biocontrol, particularly because local native plants appear unaffected. Parkinsonia aculeata L. (Fabaceae; referred to hereafter as “parkinsonia”) is an invasive tree in northern Australia, with native populations in South and Central America and southern USA. It is a perennial thorny shrub that forms dense thickets along waterways, floodplains and throughout paddocks, seriously impacting the pastoral industry, local biodiversity, and providing shelter to other invasive species such as feral pigs. Some Australian parkinsonia populations are affected by dieback, resulting in localised control. Despite previous and ongoing research, the cause of parkinsonia dieback remains elusive and dieback has not been observed in parkinsonia’s native range. This thesis investigates the potential cause(s) of dieback in parkinsonia to contribute towards research on determining its suitability as a biological control tool. My goals were to describe the microbial endophytes of parkinsonia, identify correlations of microbial community composition and dieback occurrence, and identify patterns and pathogens that might be involved in dieback. First, I analysed the community composition of archaeal, bacterial and fungal endophytes from the roots, stems and stem tips of healthy and dieback-affected parkinsonia. Samples were taken from Charters Towers in Queensland (QLD), Australia in May 2013. I used terminal restriction fragment length polymorphism (T-RFLP) analysis with taxon-specific primers for archaea, bacteria and fungi, followed by statistical analysis to determine how endophyte community composition relates to plant part and disease status. Archaeal and fungal community structures were significantly correlated with dieback occurrence and plant part. Bacterial community composition showed significant correlation to dieback occurrence but not plant part. The results showed that endophyte community composition in parkinsonia is associated with the occurrence of dieback and that endophyte communities vary across plants parts. I hypothesised that dieback occurrence may be due to the lack of potentially protective endophytes or the presence of putative pathogens. As a complimentary study to the T-RFLP analysis, I used the same samples collected in QLD to characterise the culturable fungal endophyte communities in healthy and dieback-affected parkinsonia. I identified 219 isolates via amplicon sequencing of the internal transcribed spacer (ITS) to reveal a library of 54 unique species from 25 families. Eight isolates, identified as putative pathogens, were selected for a 10-week pathogenicity trial, including water stress treatments, on parkinsonia seedlings to determine whether inoculations of parkinsonia with these isolates would result in dieback-like symptoms, and whether stress due to drought or inundation enhanced these responses. Of the eight putative pathogenic isolates tested in the pathogenicity trial, inoculation with Lasiodiplodia pseudotheobromae, Botryosphaeria dothidea and Pestalotiopsis mangiferae resulted in the largest lesions, but systemic infection or dieback-like symptoms were not observed, despite significant reductions in plant health due to water stress. As systemic infection or dieback symptoms were not observed, I determined that these pathogens are either not involved in parkinsonia dieback, that different or more extreme abiotic or biotic stress levels are required to trigger dieback-like symptoms, or that changes to the inoculation method are needed. Combining these factors will be essential in evaluating which factors are most important in initiating dieback in parkinsonia. Determining the cause of dieback in affected weeds may present land managers with a ‘silver bullet’ of biological control that could become a self-managed, perpetual instrument, reducing weed management costs and increasing biodiversity and land productivity. As such, future work in the use of dieback and host-specific phytopathogens for biological control of invasive plants should continue

Neural circuitry and immunity

Research during the last decade has significantly advanced our understanding of the molecular mechanisms at the interface between the nervous system and the immune system. Insight into bidirectional neuroimmune communication has characterized the nervous system as an important partner of the immune system in the regulation of inflammation. Neuronal pathways, including the vagus nerve-based inflammatory reflex are physiological regulators of immune function and inflammation. In parallel, neuronal function is altered in conditions characterized by immune dysregulation and inflammation. Here, we review these regulatory mechanisms and describe the neural circuitry modulating immunity. Understanding these mechanisms reveals possibilities to use targeted neuromodulation as a therapeutic approach for inflammatory and autoimmune disorders. These findings and current clinical exploration of neuromodulation in the treatment of inflammatory diseases defines the emerging field of Bioelectronic Medicine

Leveraging Epidemiology to Improve Risk Assessment.

The field of environmental public health is at an important crossroad. Our current biomonitoring efforts document widespread exposure to a host of chemicals for which toxicity information is lacking. At the same time, advances in the fields of genomics, proteomics, metabolomics, genetics and epigenetics are yielding volumes of data at a rapid pace. Our ability to detect chemicals in biological and environmental media has far outpaced our ability to interpret their health relevance, and as a result, the environmental risk paradigm, in its current state, is antiquated and ill-equipped to make the best use of these new data. In light of new scientific developments and the pressing need to characterize the public health burdens of chemicals, it is imperative to reinvigorate the use of environmental epidemiology in chemical risk assessment. Two case studies of chemical assessments from the Environmental Protection Agency Integrated Risk Information System database are presented to illustrate opportunities where epidemiologic data could have been used in place of experimental animal data in dose-response assessment, or where different approaches, techniques, or studies could have been employed to better utilize existing epidemiologic evidence. Based on the case studies and what can be learned from recent scientific advances and improved approaches to utilizing human data for dose-response estimation, recommendations are provided for the disciplines of epidemiology and risk assessment for enhancing the role of epidemiologic data in hazard identification and dose-response assessment

The pro-kk-solvable topology on a free group

We prove that, given a finitely generated subgroup $H$ of a free group $F$, the following questions are decidable: is $H$ closed (dense) in $F$ for the pro-(met)abelian topology? is the closure of $H$ in $F$ for the pro-(met)abelian topology finitely generated? We show also that if the latter question has a positive answer, then we can effectively construct a basis for the closure, and the closure has decidable membership problem in any case. Moreover, it is decidable whether $H$ is closed for the pro-${\bf V}$ topology when ${\bf V}$ is an equational pseudovariety of finite groups, such as the pseudovariety ${\bf S}_k$ of all finite solvable groups with derived length $\leq k$. We also connect the pro-abelian topology with the topologies defined by abelian groups of bounded exponent

The pro-supersolvable topology on a free group: deciding denseness

Let $F$ be a free group of arbitrary rank and let $H$ be a finitely generated subgroup of $F$. Given a pseudovariety $\mathbf{V}$ of finite groups, i.e. a class of finite groups closed under taking subgroups, quotients and finitary direct products, we endow $F$ with its pro-$\mathbf{V}$ topology. Our main result states that it is decidable whether $H$ is $\mathbf{Su}$-dense, where $\mathbf{Su}\subset \mathbf{S}$ denote respectively the pseudovarieties of all finite supersolvable groups and all finite solvable groups. Our motivation stems from the following open problem: is it decidable whether $H$ is $\mathbf{S}$-dense

On the closure of cyclic subgroups of a free group in pro-V topologies

We determine the closure of a cyclic subgroup $H$ of a free group for the pro-{\bf V} topology when {\bf V} is an extension-closed pseudovariety of finite groups. We show that $H$ is always closed for the pro-nilpotent topology and compute its closure for the pro-$\mathbf{G}_p$ and pro-$\mathbf{V}_p$ topologies, where $\mathbf{G}_p$ and $\mathbf{V}_p$ denote respectively the pseudovariety of finite $p$-groups and the pseudovariety of finite groups having a normal Sylow $p$-subgroup with quotient an abelian group of exponent dividing $p-1$. More generally, given any nonempty set $P$ of primes, we consider the pseudovariety $\mathbf{G}_P$ of all finite groups having order a product of primes in $P$

On the pseudovariety of groups U=⋁p∈PAb(p)∗Ab(p−1)\mathbf{U} = \displaystyle\bigvee_{p \in \mathbb{P}} {\bf Ab}(p) \ast {\bf Ab}(p-1)

We prove that the pseudovariety of finite groups ${\bf Ab}(p) \ast {\bf Ab}(d)$ (where $p$ is a prime and $d$ divides $p-1$) is finitely generated and compute its free objects. We consider also the pseudovariety of finite groups $\mathbf{U} = \displaystyle\bigvee_{p \in \mathbb{P}} {\bf Ab}(p) \ast {\bf Ab}(p-1)$, where $\mathbb{P}$ is the set of all primes. We show that $\mathbf{U}$ consists of all finite supersolvable groups with elementary abelian derived subgroup and abelian Sylow subgroups, being therefore decidable. We prove that it is decidable whether or not a finitely generated subgroup of a free group is closed or dense for the pro-$\mathbf{U}$ topology

Attention Felons: Evaluating Project Safe Neighborhoods in Chicago

This research uses a quasi-experimental design to evaluate the impact of Project Safe Neighborhood (PSN) initiatives on neighborhood level crime rates in Chicago. Four interventions are analyzed: (1) increased federal prosecutions for convicted felons carrying or using guns, (2) the length of sentences associated with federal prosecutions, (3) supply-side firearm policing activities, and (4) social marketing of deterrence and social norms messages through justice-style offender notification meetings. Using an individual growth curve models and propensity scores to adjust for non-random group assignment, our findings suggest that several PSN interventions are associated with greater declines of homicide in the treatment neighborhoods as compared to the control neighborhoods. The largest effect is associated with the offender notification meetings that stress individual deterrence, normative change in offender behavior, and increasing views on legitimacy and procedural justice. Possible competing hypotheses and directions for individual-level analysis are also discussed

Safety Profile of Stromal Hydration of Clear Corneal Incisions with Cefuroxime in the Mouse Model

PURPOSE: The use of sutureless clear corneal incisions (CCIs) for phacoemulsification is an established surgical technique, but the dynamic morphology of the wound and poor construction can lead to an increased risk of postoperative endophthalmitis. Stromal hydration with balanced salt solution (BSS) can improve the self-sealing status. Intracameral cefuroxime has reduced endophthalmitis rates. This study investigates the safety profile of stromal hydration with cefuroxime, as sequestering antibiotic at the wound may potentially provide added protection against infection. METHODS: MF-1 mice underwent bilateral CCI, followed by stromal hydration with 5 μL of 10 mg/mL cefuroxime, cefuroxime-texas red conjugate (for detection using confocal microscopy), or BSS. Corneas were harvested from 1 h to 12 weeks postoperatively; gross morphology, histology, and apoptotic cell death levels were investigated to determine the safety profile. Bactericidal activity of cefuroxime was assayed using homogenized whole cornea following stromal hydration at 1 h, 24 h, and day 7 against gram-negative Escherichia coli. RESULTS: Cefuroxime stromal hydration did not alter corneal morphology, with no evidence of corneal scarring or vascularization. Corneal histology and levels of apoptosis were minimal and comparable to the BSS groups up to 12 weeks. Confocal microscopy detected cefuroxime-texas red up to 1 week surrounding the corneal wound. Whole corneal tissue homogenates displayed bactericidal activity up to 24 h postoperatively. CONCLUSIONS: Stromal hydration of CCI with cefuroxime is safe in mouse corneas. A reservoir of antibiotic at the wound can potentially act as a barrier of defense against infection following cataract and associated ocular surgery

High-mobility Group Box 1 Protein Initiates Postoperative Cognitive Decline by Engaging Bone Marrow-derived Macrophages

Background: Aseptic trauma engages the innate immune response to trigger a neuroinflammatory reaction that results in postoperative cognitive decline. The authors sought to determine whether high-mobility group box 1 protein (HMGB1), an ubiquitous nucleosomal protein, initiates this process through activation and trafficking of circulating bone marrow-derived macrophages to the brain. Methods: The effects of HMGB1 on memory (using trace fear conditioning) were tested in adult C57BL/6J male mice; separate cohorts were tested after bone marrow-derived macrophages were depleted by clodrolip. The effect of anti-HMGB1 neutralizing antibody on the inflammatory and behavioral responses to tibial surgery were investigated. Results: A single injection of HMGB1 caused memory decline, as evidenced by a decrease in freezing time (52 11% vs. 39 +/- 5%; n = 16-17); memory decline was prevented when bone marrow-derived macrophages were depleted (39 +/- 5% vs. 50 +/- 9%; n = 17). Disabling HMGB1 with a blocking monoclonal antibody, before surgery, reduced postoperative memory decline (52 +/- 11% vs. 29 +/- 5%; n = 15-16); also, hippocampal expression of monocyte chemotactic protein-1 was prevented by the neutralizing antibody (n = 6). Neither the systemic nor the hippocampal inflammatory responses to surgery occurred in mice pretreated with anti-HMGB1 neutralizing antibody (n = 6). Conclusion: Postoperative neuroinflammation and cognitive decline can be prevented by abrogating the effects of HMGB1. Following the earlier characterization of the resolution of surgery-induced memory decline, the mechanisms of its initiation are now described. Together, these data may be used to preoperatively test the risk to surgical patients for the development of exaggerated and prolonged postoperative memory decline that is reflected in delirium and postoperative cognitive dysfunction, respectively