Predatory impact of the freshwater invader Dikerogammarus villosus (Crustacea : Amphipoda)

To assess the increasing threats to aquatic ecosystems from invasive species, we need to elucidate the mechanisms of impacts of current and predicted future invaders. Dikerogammarus villosus, a Ponto-Caspian amphipod crustacean, is invading throughout Europe and predicted to invade the North American Great Lakes. European field studies show that populations of macroinvertebrates decline after D. villosus invasion. The mechanism of such impacts has not been addressed empirically; however, D. villosus is known to prey upon and replace other amphipods. Therefore, in this study, we used microcosm and mesocosm laboratory experiments, with both single and mixed prey species scenarios, to assess any predatory impact of D. villosus on a range of macro invertebrate taxa, trophic groups, and body sizes. Dikerogammarus villosus predatory behaviour included shredding of prey and infliction of

Post-Translational Inhibition of IP-10 Secretion in IEC by Probiotic Bacteria: Impact on Chronic Inflammation

Background: Clinical and experimental studies suggest that the probiotic mixture VSL#3 has protective activities in the context of inflammatory bowel disease (IBD). The aim of the study was to reveal bacterial strain-specific molecular mechanisms underlying the anti-inflammatory potential of VSL#3 in intestinal epithelial cells (IEC).

Methodology/Principal Findings: VSL#3 inhibited TNF-induced secretion of the T-cell chemokine interferon-inducible protein (IP-10) in Mode-K cells. Lactobacillus casei (L. casei) cell surface proteins were identified as active anti-inflammatory components of VSL#3. Interestingly, L. casei failed to block TNF-induced IP-10 promoter activity or IP-10 gene transcription at the mRNA expression level but completely inhibited IP-10 protein secretion as well as IP-10-mediated T-cell transmigration. Kinetic studies, pulse-chase experiments and the use of a pharmacological inhibitor for the export machinery (brefeldin A) showed that L. casei did not impair initial IP-10 production but decreased intracellular IP-10 protein stability as a result of blocked IP-10 secretion. Although L. casei induced IP-10 ubiquitination, the inhibition of proteasomal or lysosomal degradation did not prevent the loss of intracellular IP-10. Most important for the mechanistic understanding, the inhibition of vesicular trafficking by 3-methyladenine (3-MA) inhibited IP-10 but not IL-6 expression, mimicking the inhibitory effects of L. casei. These findings suggest that L. casei impairs vesicular pathways important for the secretion of IP-10, followed by subsequent degradation of the proinflammatory chemokine. Feeding studies in TNF Delta ARE and IL-10(-/-) mice revealed a compartimentalized protection of VSL#3 on the development of cecal but not on ileal or colonic inflammation. Consistent with reduced tissue pathology in IL-10(-/-) mice, IP-10 protein expression was reduced in primary epithelial cells.

Conclusions/Significance: We demonstrate segment specific effects of probiotic intervention that correlate with reduced IP-10 protein expression in the native epithelium. Furthermore, we revealed post-translational degradation of IP-10 protein in IEC to be the molecular mechanism underlying the anti-inflammatory effect.

Taking as Giving, Appropriation as Access: Transfers of Land Development Rights and China’s Recent Experiments

Economic development at both the domestic and global levels is associated with increasing tensions which are inextricably linked to the meaning and allocation of property rights, which has a great impact on appropriation of resources and may lead to different paths of development. “Taking”-- the appropriation of private land for public needs -- is a typical example that exhibits those tensions, posing a challenge to the conventional conception of property as individualistic and exclusive rights of possession, use, and disposition and to the associated neoliberal model of development. Should the individual landowner be left to bear the cost of a regulatory intervention which endures to the wider benefit of the whole community? How to mitigate the tensions between private ownership and public regulation? If we take the liberal concept of property, then private property seems to be in constant conflict with public interests and wider social concerns. Meanwhile, community, situating between the state and the individuals, and community’s relationship to development rights, have not provoked enough discussion. The paper explores the different ways land development rights might be seen both in Western, essentially common law systems, and in China, especially now and in view of two case studies. An empirical example in Wugang, China reveals the importance of integrating the “community lens” proposed by Roger Cotterrell into studies of the transfer of land development rights. Reading through the community lens, taking could be giving and appropriation could also be access. This approach provides a new perspective to re-evaluate the relationship between legal appropriation and development.

Deep impact: in situ functional responses reveal context-dependent interactions between vertically migrating invasive and native mesopredators and shared prey

The ecological effects of invasive species depend on myriad environmental contexts, rendering understanding problematic. Functional responses provide a means to quantify resource use by consumers over short timescales and could therefore provide insight into how the effects of invasive species vary over space and time. Here, we use novel in situ microcosm experiments to track changes in the functional responses of two aquatic mesopredators, one native and the other an invader, as they undergo diel vertical migrations through a lake water column.
The Ponto–Caspian mysid, Hemimysis anomala, a known ecologically damaging invader, generally had higher a functional response towards cladoceran prey than did a native trophic analogue, Mysis salemaai. However, this differential was spatiotemporally dependent, being minimal during the day on the lake bottom, and increasing at night, particularly inshore.
Because the functional response of the native predator was spatiotemporally consistent, the above pattern was driven by changes in the invader functional response over the diel cycle. In particular, the functional response of H. anomala was significantly reduced on the lake bottom during the daytime relative to night, and predation was especially pronounced in shallow surface waters.
We demonstrate the context dependency of the effects of an invasive predator on prey populations and emphasise the utility of functional responses as tools to inform our understanding of predator–prey interactions. In situ manipulations integrate experimental rigour with field relevance and have the potential to reveal how impacts manifest over a range of spatiotemporal scales.

Mitotic Arrest Deficiency Protein 2 (MAD2) and Histone Deacetylase 6 (HDAC6) Present a Complex Relationship in Their Regulation and Expression and Subsequent Impact on Chemoresponsiveness

Introduction:
Ovarian cancer patients presenting with advanced stage (III/IV)
canceraretreatedwithcarboplatinumincombinationwithpaclitaxel.Despitea
significant initial response rate, fewer than 20% of patients become long-term
survivors. We have published that low MAD2 expression levels associate with
reduced progression free survival (PFS) in patients with high-grade serous
epithelial ovarian cancer (EOC). Moreover, we have demonstrated that MAD2
expressionisdown-regulatedbythemicroRNAmiR-433(
Furlong et al., 2011
).
Interestingly, miR-433 also down-regulates HDAC6 (
Simon et al., 2010
), which
uniquely deacetylates
a
-tubulin prior to HDAC6s binding to
b
-tubulin.
In vitro
studies have shown that HDAC6 inhibition in combination with paclitaxel
treatment enhances chemoresistant cancer cell death. To date, an interaction
between MAD2 and HDAC6 has not been reported.
Experimental design:
MAD2 and HDAC6 immunohistochemistry (IHC) and
Western blot analyses were performed to investigate the role of HDAC6 and
MAD2 in chemoresistance to paclitaxel in high-grade serous EOC.
Results and Discussion:
In vitro
experiments demonstrated that overex-
pression of pre-miR-433, which targets MAD2, resulted in down-regulation
of HDAC6 in EOC cell lines. High levels of HDAC6 are co-expressed with
MAD2 in the paclitaxel resistant UPN251 and OVCAR7 cell lines. While, all
4 paclitaxel resistant EOC cell lines express higher levels of miR-433 than
the paclitaxel sensitive A2780 cells, only ovca432 and ovca433 demonstrated
down-regulation of both HDAC6 and MAD2. Paclitaxel binds to
b
-tubulin and
causesmicrotubulepolymerizationinpaclitaxelsensitivecellsasdemonstrated
by tubulin acetylation in A2780 cells. However, paclitaxel failed to cause a
significant acetylation of
a
-tubulin and microtubule stabilisation in the resistant
UPN251 cells. Therefore resistance in this cell line may be mediated by
aberrantly high HDAC6 activity. We have previously shown that MAD2 knock-
down cells are resistant to paclitaxel (
Furlong F., et al., 2011; Prencipe M.,
et al., 2009
). We measured HDAC6 protein expression in MAD2 knockdown
cells and showed that MAD2 knockdown is associated with concomitant
up-regulation of HDAC6. We hypothesise that the up-regulation of HDAC6
by MAD2 knockdown renders cancer cells more resistant to paclitaxel and
increases the invasive potential of these cells. On-going experiments will test
this hypothesis. Lastly we have observed differential MAD2 and HDAC6 IHC
staining intensity in formalin fixed paraffin embedded EOC samples.
In conclusion
, we have reported on a novel interaction between MAD2 and
HDAC6 which may have important consequences for paclitaxel resistant EOC.
Moreover, understanding chemo-responsiveness in ovarian tumours will lead
to improved patient management and treatment options for women diagnosed
with this disease

Optimisation of a two-liquid component pre-filled acrylic bone cement system: A design of experiments approach to optimise cement final properties

The initial composition of acrylic bone cement along with the mixing and delivery technique used can influence its final properties and therefore its clinical success in vivo. The polymerisation of acrylic bone cement is complex with a number of processes happening simultaneously. Acrylic bone cement mixing and delivery systems have undergone several design changes in their advancement, although the cement constituents themselves have remained unchanged since they were first used. This study was conducted to determine the factors that had the greatest effect on the final properties of acrylic bone cement using a pre-filled bone cement mixing and delivery system. A design of experiments (DoE) approach was used to determine the impact of the factors associated with this mixing and delivery method on the final properties of the cement produced. The DoE illustrated that all factors present within this study had a significant impact on the final properties of the cement. An optimum cement composition was hypothesised and tested. This optimum recipe produced cement with final mechanical and thermal properties within the clinical guidelines and stated by ISO 5833 (International Standard Organisation (ISO), International standard 5833: implants for surgery—acrylic resin cements, 2002), however the low setting times observed would not be clinically viable and could result in complications during the surgical technique. As a result further development would be required to improve the setting time of the cement in order for it to be deemed suitable for use in total joint replacement surgery.

A spatio-temporal contrast of the predatory impact of an invasive freshwater crustacean

Aim: Impacts of invasive species may vary across invasion gradients, owing to trait-based sorting of individuals through dispersal: those aggregating at invasion fronts may be more aggressive and voracious. We examine, in the field and laboratory, variation in the predatory impacts of an invasive Ponto-Caspian crustacean Hemimysis anomala G.O. Sars, 1907 at two sites along a spatio-temporal gradient of invasion.

Location: Republic of Ireland.

Methods: We used reciprocal transplant field-deployed mesocosms to compare predation rates of invasion front and well-established H. anomala on natural zooplankton assemblages. In the laboratory, we measured the functional response (relationship between predation rate and prey supply) of H. anomala from both sites, for a per capita mechanistic comparison of predation efficiency. We also assessed prey selectivity of H. anomala in the mesocosm experiments to further compare feeding behaviour. Finally, we used a correlative approach to assess the community impact of H. anomala across sites, including a nearby uninvaded site, by comparing zooplankton diversities and densities.

Results: Invasion front H. anomala had higher predation rates than well-established H. anomala at high in situ zooplankton densities. Invasion front H. anomala also had higher functional responses - in particular showing higher 'attack rates' - indicating a heightened ability to locate and capture prey. Prey selectivity was consistent across the spatio-temporal contrast, with positive selection for cladocerans. Zooplankton diversity and density declined with time since H. anomala invasion, both being maximal at the uninvaded site.

Main conclusions: Our study, for the first time, (1) reveals differences in predatory per capita effects and associated behavioural traits between two sites along a spatio-temporal invasion gradient and (2) shows a negative community-level impact of the invasive H. anomala in natural water bodies. Further spatio-temporal comparisons of predatory per capita effects of invaders are needed to assess the generality of these results.

Electron-impact ionization of the boron atom

Accurate knowledge of the electron-impact ionization of the B atom is urgently needed in current fusion plasma experiments to help design ITER wall components. Since no atomic measurements exist, nonperturba- tive time-dependent close-coupling (TDCC) calculations are carried out to accurately determine the direct ionization cross sections of the outer two subshells of B. Perturbative distorted-wave and semiempirical binary encounter calculations are found to yield cross sections from 26% lower to an order of magnitude higher than the current TDCC results. Unlike almost all neutral atoms, large excitation-autoionization contributions are found for the B atom. Nonperturbative R matrix with pseudostates (RMPS) calculations are also carried out to accurately determine the total ionization cross section of B. Previous 60 LS-term RMPS calculations are found to yield cross sections up to 40% higher than the current more extensive 476 LS-term RMPS results

Electron-impact ionization of B+

Electron-impact ionization cross sections are calculated for the ground and metastable states of B+. Com- parisons between perturbative distorted-wave and nonperturbative close-coupling calculations find reductions in the direct ionization cross sections due to long-range electron correlation effects of approximately 10% for the ground state and approximately 15% for the metastable state. Previous crossed-beams experiments, with a metastable to ground ratio of between 50% and 90%, are found to be in reasonable agreement with metastable state close-coupling results. New crossed-beams experiments, with a metastable to ground ratio of only 9%, are found to be in reasonable agreement with ground state close-coupling results. Combined with previous work on neutral B and B2+, the nonperturbative close-coupling calculations provide accurate ionization cross sections for the study of edge plasmas in controlled fusion research.

Grazing impact of microzooplankton upon phytoplankton

Alterations of freshwater flow regimes and increasing eutrophication can lead to alterations in phytoplankton biomass, composition, and growth in estuaries and adjacent coastal waters. Since phytoplankton is the first trophic level of most aquatic foodwebs, these changes can be propagated to other biological compartments, eventually impacting water quality and ecosystem services. However, phytoplankton responses to environmental changes in abiotic variables (e.g., light, nutrients) are additionally controlled by mortality or removal processes (e.g., grazing, horizontal advection and viral lysis). Grazing exerted by microzooplankton, usually dominated by phagotrophic protists, is considered the most relevant phytoplankton mortality factor in most aquatic systems (see Calbet, Landry 2004). In fact, grazing impact of microzooplankton can prevent phytoplankton accumulation in marine systems despite an overall increase in phytoplankton replication rate. By consequence, microzooplankton grazing may minimize problems associated to increased eutrophication and, ultimately, prevent the occurrence of harmful phytoplankton blooms. Thus, microzooplankton grazing on phytoplankton constitutes a key biological process required to understand and predict relationships between hydrological and biological processes in aquatic ecosystems and to use ecosystem properties to improve water quality and enhance ecosystem services, general principles of the Ecohydrology Concept (Zalewski 2000).

The Impact of R10-Hydroxywarfarin on CYP2C9-Mediated S-Warfarin Metabolism

Thesis (Master's)--University of Washington, 2014

Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder

Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets

Prescribed burning impact on forest soil properties – a fuzzy boolean nets approach

The Portuguese northern forests are often and severely affected by wildfires during the Summer season. These occurrences significantly affect and negatively impact all ecosystems, namely soil, fauna and flora. In order to reduce the occurrences of natural wildfires, some measures to control the availability of fuel mass are regularly implemented. Those preventive actions concern mainly prescribed burnings and vegetation pruning. This work reports on the impact of a prescribed burning on several forest soil properties, namely pH, soil moisture, organic matter content and iron content, by monitoring the soil self-recovery capabilities during a one year span. The experiments were carried out in soil cover over a natural site of Andaluzitic schist, in Gramelas, Caminha, Portugal, which was kept intact from prescribed burnings during a period of four years. Soil samples were collected from five plots at three different layers (0–3, 3–6 and 6–18) 1 day before prescribed fire and at regular intervals after the prescribed fire. This paper presents an approach where Fuzzy Boolean Nets (FBN) and Fuzzy reasoning are used to extract qualitative knowledge regarding the effect of prescribed fire burning on soil properties. FBN were chosen due to the scarcity on available quantitative data. The results showed that soil properties were affected by prescribed burning practice and were unable to recover their initial values after one year.

The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to penicillinase-negative isolates but failed against penicillinase-producing organisms. This suggested that penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.