Fate of inflammatory neutrophils within the joint

OBJECTIVE: Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. METHODS AND RESULTS: DSS was calculated using (mean diastolic velocity x 8 x blood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, -2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; P

Fate and transport of volatile organic compounds in glacial till and groundwater at an industrial site in Northern Ireland

Volatile organic compound (VOC) contamination of subsurface geological material and groundwater was discovered on the Nortel Monkstown industrial site, Belfast, Northern Ireland. The objectives of this study were to (1) investigate the characteristics of the geological material and its influences on contaminated groundwater flow across the site using borehole logs and hydrological evaluations, and (2) identify the contaminants and examine their distribution in the subsurface geological material and groundwater using chemical analysis. This report focuses on the eastern car park (ECP) which was a former storage area associated with trichloroethene (TCE) degreasing operations. This is where the greatest amount of volatile organic compounds (VOCs), particularly TCE, were detected. The study site is on a complex deposit of clayey glacial till with discontinuous coarser grained lenses, mainly silts, sands and gravel, which occur at 0.45–7.82 m below ground level (bgl). The lenses overall form an elongated formation that acts as a small unconfined shallow aquifer. There is a continuous low permeable stiff clayey till layer beneath the lenses that performs as an aquitard to the groundwater. Highest concentrations of VOCs, mainly TCE, in the geological material and groundwater are in these coarser lenses at ~4.5–7 m bgl. Highest TCE measurements at 390,000 µg L-1 for groundwater and at 39,000 µg kg-1 at 5.7 m for geological material were in borehole GA19 in the coarse lens zone. It is assumed that TCE gained entrance to the subsurface near this borehole where the clayey till was thin to absent above coarse lenses which provided little retardation to the vertical migration of this dense non-aqueous phase liquid (DNAPL) into the groundwater. However, TCE is present in low concentrations in the geological material overlying the coarse lens zone. Additionally, VOCs appear to be associated with poorly drained layers and in peat

A comparison of nitogen fate and transport in catchments underlain by high and low permeability aquifers using chemical and isotopic tools.

Variability in nitrogen fate and transport in different catchments types is often not considered. This research considers the importance of such nitrogen processes within groundwater pathways in two agricultural catchments in Ireland; a well drained catchment, underlain by karstified Carboniferous limestone, and a poorly drained catchment, underlain by Silurian greywacke.
Depth specific low-flow groundwater sampling was used to evaluate the hydrochemical stratification in groundwater. Groundwater samples, as well as surface water samples, along river courses were analysed for nitrogen species (NO3, NH4 and NO2) and nitrate isotopes (d15N and d18O) as well as field parameters and major ions
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The dominant nitrate (NO3) groundwater pathway in the poorly drained greywacke catchment is through the shallow weathered bedrock, as indicated by transmissivity values and the ionic and isotopic signatures, and a clear reduction in NO3 concentration is observed with depth. A similar chloride trend would suggest dilution is a major factor, however d15N and d18O isotopic values producing an enrichment ratio of 1.8 indicate that denitrification is also an important process involved in the fate of the NO3 within the groundwater flow system. This consistent trend with depth is in contrast to the stratification pattern observed in the karstified catchment. NO3 was not detected in the shallow groundwater pathway; the dominant groundwater pathway is in the deeper groundwater where there is little change in the nitrate isotope values with depth (d15N values range between 4.1 and 4.6 ‰). This deeper groundwater contributes the dominant proportion of the river flow through a number of springs. As a result, the deeper groundwater, springs and river have a similar ionic signature and NO3 concentration range (23 ± 3 mg/l). Despite this pattern, the NO3 isotopes show a distinct difference in isotopic values between the deeper groundwater in the diffuse karst and the springs indicating some denitrification is occurring during groundwater discharge into the river. Furthermore the isotopes give an indication of the variability of the spatial extent of the springs and the complexities of the fissures through which they are fed. The results of this study clearly show the importance of the geology in the fate and transport of NO3 in agricultural catchments.

Investigation of organic xenobiotic transfers, partitioning and processing in air-soil-plant systems using a microcosm apparatus. Part II:comparing the fate of chlorobenzenes in grass planted soil

A microcosm system was used to investigate and compare transfers of 14C labeled-1,2-dichlorobenzene (DCB), 1,2,4-trichlorobenzene (TCB) and hexachlorobenzene (HCB) in an air-soil-plant system using single grass tillers planted into spiked soil. This study was the second phase of a development investigation for eventual study of a range of xenobiotic pollutants. Recoveries from the system were excellent at >90%. The predominant loss pathway for 14C labeled-1,2-DCB and 1,2,4-TCB was volatilisation with 85% and 76% volatilisation of parent compound and volatile metabolites over 5 weeks respectively. Most of the added label in the hexachlorobenzene spiked system remained in soil. Mineralisation was

Tracking the Fate of Microbially Sequestered Carbon Dioxide in Soil Organic Matter

The microbial contribution to soil organic matter (SOM) has recently been shown to be much larger than previously thought and thus its role in carbon sequestration may also be underestimated. In this study we employ C-13 ((CO2)-C-13) to assess the potential CO2 sequestration capacity of soil chemoautotrophic bacteria and combine nuclear magnetic resonance (NMR) with stable isotope probing (SIP), techniques that independently make use of the isotopic enrichment of soil microbial biomass. In this way molecular information generated from NMR is linked with identification of microbes responsible for carbon capture. A mathematical model is developed to determine real-time CO2 flux so that net sequestration can be calculated. Twenty-eight groups of bacteria showing close homologies with existing species were identified. Surprisingly, Ralstonia eutropha was the dominant group. Through NMR we observed the formation of lipids, carbohydrates, and proteins produced directly from CO2 utilized by microbial biomass. The component of SOM directly associated with CO2 capture was calculated at 2.86 mg C (89.21 mg kg(-1)) after 48 h. This approach can,differentiate between SOM derived through microbial uptake of CO2 and other SOM constituents and represents a first step in tracking the fate and dynamics of microbial biomass in soil.

Air-Sea Exchange of Legacy POPs in the North Sea Based on Results of Fate and Transport, and Shelf-Sea Hydrodynamic Ocean Models

The air-sea exchange of two legacy persistent organic pollutants (POPs), γ-HCH and PCB 153, in the North Sea, is presented and discussed using results of regional fate and transport and shelf-sea hydrodynamic ocean models for the period 1996–2005. Air-sea exchange occurs through gas exchange (deposition and volatilization), wet deposition and dry deposition. Atmospheric concentrations are interpolated into the model domain from results of the EMEP MSC-East multi-compartmental model (Gusev et al, 2009). The North Sea is net depositional for γ-HCH, and is dominated by gas deposition with notable seasonal variability and a downward trend over the 10 year period. Volatilization rates of γ-HCH are generally a factor of 2–3 less than gas deposition in winter, spring and summer but greater in autumn when the North Sea is net volatilizational. A downward trend in fugacity ratios is found, since gas deposition is decreasing faster than volatilization. The North Sea is net volatilizational for PCB 153, with highest rates of volatilization to deposition found in the areas surrounding polluted British and continental river sources. Large quantities of PCB 153 entering through rivers lead to very high local rates of volatilization.

Modelling the fate of persistent organic pollutants (POPs) in the North Sea system

The environmental fate of selected persistent organic pollutants (POPs) in the North Sea system is modelled with a high resolution Fate and Transport Ocean Model (FANTOM) that uses hydrodynamic model output from the Hamburg Shelf Ocean Model (HAMSOM). Large amounts of POPs enter the North Sea from the surrounding highly populated, industrialised and agricultural countries. Major pathways to the North Sea are atmospheric deposition and river inputs, with additional contributions coming from bottom sediments and adjacent seas. The model domain covers the entire North Sea region, extending northward as far as the Shetland Islands, and includes adjacent basins such as the Skagerrak, Kattegat, and the westernmost part of the Baltic Sea. Model resolution (for both models) is 1.5’ latitude x 2.5’ longitude (approximately 3 km horizontal resolution) with 30 vertical levels. The POP model also has 20 sediment layers. Important model processes controlling the fate of POPs in the North Sea system are discussed. Results focus on Lindane gamma- HCH or gamma-hexachlorocyclohexane) and PCB 153.

MicroRNA-199b modulates vascular cell fate during iPS cell differentiation by targeting the notch ligand jagged1 and enhancing VEGF signaling

Aims: Recent ability to derive endothelial cells (ECs) from induced pluripotent stem (iPS) cells holds a great therapeutic potential for personalised medicine and stem cell therapy. We aimed that better understanding of the complex molecular signals that are evoked during iPS cell differentiation towards ECs may allow specific targeting of their activities to enhance cell differentiation and promote tissue regeneration.

Methods and Results: In this study we have generated mouse iPS cells from fibroblasts using established protocol. When iPS cells were cultivated on type IV mouse collagen-coated dishes in differentiation medium, cell differentiation toward vascular lineages were observed. To study the molecular mechanisms of iPS cell differentiation, we found that miR-199b is involved in EC differentiation. A step-wise increase in expression of miR-199 was detected during EC differentiation. Notably, miR-199b targeted the Notch ligand JAG1, resulting in VEGF transcriptional activation and secretion through the transcription factor STAT3. Upon shRNA-mediated knockdown of the Notch ligand JAG1, the regulatory effect of miR-199b was ablated and there was robust induction of STAT3 and VEGF during EC differentiation. Knockdown of JAG1 also inhibited miR-199b-mediated inhibition of iPS cell differentiation towards SMCs. Using the in vitro tube formation assay and implanted Matrigel plugs, in vivo, miR-199b also regulated VEGF expression and angiogenesis.

Conclusions: This study indicates a novel role for miR-199b as a regulator of the phenotypic switch during vascular cell differentiation derived from iPS cells by regulating critical signaling angiogenic responses.

Assessing the environmental fate of selected polybrominated diphenyl ethers in the region surrounding the Zhuoshui River of Taiwan based on an Equilibrium Constant fugacity model

Polybrominated diphenyl ethers (PBDEs) are a group of flame retardants that have been in use since the 1970s. They are included in the list of hazardous substances known as persistent organic pollutants (POPs) because they are extremely hazardous to the environment and human health. PBDEs have been extensively used in industry and manufacturing in Taiwan, thus its citizens are at high risk of exposure to these chemicals.
An assessment of the environmental fate of these compounds in the Zhuoshui river and Changhua County regions of western Taiwan, and also including the adjacent area of the Taiwan Strait, was conducted for three high risk congeners, BDE-47, -99 and -209, to obtain information regarding the partitioning, advection, transfer and long range transport potential of the PBDEs in order to identify the level of risk posed by the pollutants in this region.
The results indicate that large amounts of PBDEs presently reside in all model compartments – air, soil, water, and sediment – with particularly high levels found in air and especially in sediment. The high levels found in sediment, particularly for BDE-209, are significant, since there is the threat of these pollutants entering the food chain, either directly through benthic feeding, or through resuspension and subsequent feeding in the pelagic region of the water column which is a distinct possibility in the strong currents found within the Taiwan Strait. Another important result is that a substantial portion of emissions leave the model domain directly through advection, particularly for BDE-47 (58%) and BDE-209 (75%), thus posing a risk to adjacent communities.
Model results were generally in reasonable agreement with available measured concentrations. In air, model concentrations are in reasonably good agreement with available measured values. For both BDE-47 and -99, model concentrations are a factor of 2-3 higher and BDE-209 within the range of measured values. In soil, model results are somewhat less than measured values. In sediment, model results are at the high end of measured values.

The fate of chemoresistance in triple negative breast cancer (TNBC)

Background: Treatment options for women presenting with triple negative breast cancer (TNBC) are limited due to the lack of a therapeutic target and as a result, are managed with standard chemotherapy such as paclitaxel (Taxol®). Following chemotherapy, the ideal tumour response is apoptotic cell death. Post-chemotherapy, cells can maintain viability by undergoing viable cellular responses such as cellular senescence, generating secretomes which can directly enhance the malignant phenotype. 
Scope of Review: How tumour cells retain viability in response to chemotherapeutic engagement is discussed. In addition we discuss the implications of this retained tumour cell viability in the context of the development of recurrent and metastatic TNBC disease. Current adjuvant and neo-adjuvant treatments available and the novel potential therapies that are being researched are also reviewed. 
Major conclusions: Cellular senescence and cytoprotective autophagy are potential mechanisms of chemoresistance in TNBC. These two non-apoptotic outcomes in response to chemotherapy are inextricably linked and are neglected outcomes of investigation in the chemotherapeutic arena. Cellular fate assessments may therefore have the potential to predict TNBC patient outcome. 
General Significance: Focusing on the fact that cancer cells can bypass the desired cellular apoptotic response to chemotherapy through cellular senescence and cytoprotective autophagy will highlight the importance of targeting non-apoptotic survival pathways to enhance chemotherapeutic efficacy