Bone Activity Biomarkers and Bone Mineral Density in Children with Chronic Kidney Disease

Introduction: Chronic kidney disease - mineral and bone disorder (CKD-MBD) is a spectrum of bone minerals changes that range from high turnover lesions of secondary hyperparathyroidism to the low turnover lesions of adynamic bone disease. Bone biopsy is the gold standard for the diagnosis, but it is not routinely performed because it is invasive technique. Methods: Fifteen CKD children on regular hemodialysis (group I) and 15 CKD children on conservative management (group II) were selected from the nephrology clinics of Zagazig University Hospitals along with 15 age and sex-matched healthy controls. Participants were subjected to biochemical assessment that included osteocalcin (OC), total and bone-specific alkaline phosphatase (tALP and bALP), isomerized beta form of type I collagen cross-linked telopeptide (β-Crosslaps) and intact parathyroid hormone (iPTH) levels. Patients with CKD also had their bone mineral density (BMD) measured using dual energy X-ray absorptiometry (DEXA) at lumbar spine and femoral neck. Results: Serum β-Crosslaps, OC and bALP were significantly higher in patient groups than controls and in group I compared to group II .There was a negative significant correlation between mean Z-score at lumbar spines and bALP, OC and iPTH in group I and with β-Crosslaps in both patient groups. The mean Z-score at femoral neck correlated negatively with bALP in group I, with OC in group II and with iPTH and β-Crosslaps in both groups. Conclusion: Biochemical bone markers and assessment of BMD in patients with CKD may have a role in the early detection of CDK-MBD. Keywords: chronic kidney disease; bone mineral density; bone biomarker

Characteristics of micro-propagated banana (Musa spp.) cultures stressed with NaCl and polyethylene glycol

The effect of NaCl and PEG was assessed on plant micro-propagation rate in banana (Musa spp.) cv., Basrai. Well micro-propagated plantlets were cultured on four different stresses of NaCl and PEG-4000 including control level: MS2b (MS0 + 3.0 mg l-1 BAP), MS2c (MS0 + 100 mol m-3 NaCl), MS2d (MS0 + 5% PEG) and MS2e (MS0 + 100 mol m-3 NaCl + 5 % PEG) for 6-weeks. Efficiency of plant micro-propagation was reduced significantly among the stressed cultures. Similarly, photosynthetic pigments like chl a was decreased non-significantly but chl b, chl ab were decreased significantly. Total carotenoids were increased in the saline as well as PEG stressed cultures. Cell size of epidermis and aerenchyma was increased (p < 0.05), while parenchyma decreased. Proline and glycinebetain contents were increased (p < 0.05) in each stressed culture but were high in MS2 than in MS3 and MS4 cultures. Meanwhile, proteins, sugars, phenolics and nitrates were observed to be in the reversed (p < 0.05) phenomena. In conclusion, NaCl treatment was observed to be most toxic than the PEG or PEG with NaCl on the banana micro-propagation.Key words: Musa spp., micro-propagation, NaCl (sodium chloride), PEG (polyethylene glycol), chlorophyll contents, proline, reducing sugars

Transition Metal Migration Can Facilitate Ionic Diffusion in Defect Garnet-Based Intercalation Electrodes

The importance of metal migration during multielectron redox activity has been characterized, revealing a competing demand to satisfy bonding requirements and local strains in structures upon alkali intercalation. The local structural evolution required to accommodate intercalation in Y2(MoO4)3 and Al2(MoO4)3 has been contrasted by operando characterization methods, including X-ray absorption spectroscopy and diffraction, along with nuclear magnetic resonance measurements. Computational modeling further rationalized behavioral differences. The local structure of Y2(MoO4)3 was maintained upon lithiation, while the structure of Al2(MoO4)3 underwent substantial local atomic rearrangements as the more ionic character of the bonds in Al2(MoO4)3 allowed Al to mix off its starting octahedral position to accommodate strain during cycling. However, this mixing was prevented in the more covalent Y2(MoO4)3, which accommodated strain through rotational motion of polyhedral subunits. Knowing that an increased ionic character can facilitate the diffusion of redox-inactive metals when cycling multielectron electrodes offers a powerful design principle when identifying next-generation intercalation hosts

DITrust Chain: Towards Blockchain-Based Trust Models for Sustainable Healthcare IoT Systems

© 2013 IEEE. Today, internet and device ubiquity are paramount in individual, formal and societal considerations. Next generation communication technologies, such as Blockchains (BC), Internet of Things (IoT), cloud computing, etc. offer limitless capabilities for different applications and scenarios including industries, cities, healthcare systems, etc. Sustainable integration of healthcare nodes (i.e. devices, users, providers, etc.) resulting in healthcare IoT (or simply IoHT) provides a platform for efficient service delivery for the benefit of care givers (doctors, nurses, etc.) and patients. Whereas confidentiality, accessibility and reliability of medical data are accorded high premium in IoHT, semantic gaps and lack of appropriate assets or properties remain impediments to reliable information exchange in federated trust management frameworks. Consequently, We propose a Blockchain Decentralised Interoperable Trust framework (DIT) for IoT zones where a smart contract guarantees authentication of budgets and Indirect Trust Inference System (ITIS) reduces semantic gaps and enhances trustworthy factor (TF) estimation via the network nodes and edges. Our DIT IoHT makes use of a private Blockchain ripple chain to establish trustworthy communication by validating nodes based on their inter-operable structure so that controlled communication required to solve fusion and integration issues are facilitated via different zones of the IoHT infrastructure. Further, text{C}mathrm {sharp } implementation using Ethereum and ripple Blockchain are introduced as frameworks to associate and aggregate requests over trusted zones

Robust Generation of Quiescent Porcine Valvular Interstitial Cell Cultures

Background Valvular interstitial cells (VICs) in the healthy aortic valve leaflet exhibit a quiescent phenotype, with 90% of cells. The inability to preserve a healthy VIC phenotype during in vitro studies has hampered the elucidation of mechanisms involved in calcific aortic valve disease. This study describes the generation of quiescent populations of porcine VICs in 2‐dimensional in vitro culture and their utility in studying valve pathobiology. Methods and Results Within 4 days of isolation from fresh porcine hearts, VICs cultured in standard growth conditions were predominantly myofibroblastic (activated VICs). This myofibroblastic phenotype was partially reversed within 4 days, and fully reversed within 9 days, following application of a combination of a fibroblast media formulation with culture on collagen coatings. Specifically, culture in this combination significantly reduced several markers of VIC activation, including proliferation, apoptosis, α‐smooth muscle actin expression, and matrix production, relative to standard growth conditions. Moreover, VICs raised in a fibroblast media formulation with culture on collagen coatings exhibited dramatically increased sensitivity to treatment with transforming growth factor β1, a known pathological stimulus, compared with VICs raised in either standard culture or medium with a fibroblast media formulation. Conclusions The approach using a fibroblast media formulation with culture on collagen coatings generates quiescent VICs that more accurately mimic a healthy VIC population and thus has the potential to transform the study of the mechanisms of VIC activation and dysfunction involved in the early stages of calcific aortic valve disease

Gene silencing in tick cell lines using small interfering or long double-stranded RNA

Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system

Bromocarbons in the tropical coastal and open ocean atmosphere during the 2009 Prime Expedition Scientific Cruise (PESC-09)

Abstract. Atmospheric concentrations of very short-lived species (VSLS) bromocarbons, including CHBr3, CH2Br2, CHCl2Br, CHClBr2, and CH2BrCl, were measured in the Strait of Malacca and the South China and Sulu–Sulawesi seas during a two-month research cruise in June–July 2009. The highest bromocarbon concentrations were found in the Strait of Malacca, with smaller enhancements in coastal regions of northern Borneo. CHBr3 was the most abundant bromocarbon, ranging from 5.2 pmol mol−1 in the Strait of Malacca to 0.94 pmol mol−1 over the open ocean. Other bromocarbons showed lower concentrations, in the range of 0.8–1.3 pmol mol−1 for CH2Br2, 0.1–0.5 pmol mol−1 for CHCl2Br, and 0.1–0.4 pmol mol−1 for CHClBr2. There was no significant correlation between bromocarbons and in situ chlorophyll a, but positive correlations with both MODIS and SeaWiFS satellite chlorophyll a. Together, the short-lived bromocarbons contribute an average of 8.9 pmol mol−1 (range 5.2–21.4 pmol mol−1) to tropospheric bromine loading, which is similar to that found in previous studies from global sampling networks (Montzka et al., 2011). Statistical tests showed strong Spearman correlations between brominated compounds, suggesting a common source. Log–log plots of CHBr3/CH2Br2 versus CHBr2Cl/CH2Br2 show that both chemical reactions and dilution into the background atmosphere contribute to the composition of these halocarbons at each sampling point. We have used the correlation to make a crude estimate of the regional emissions of CHBr3 and to derive a value of 32 Gg yr−1 for the Southeast (SE) Asian region (10° N–20° S, 90–150° E). Finally, we note that satellite-derived chlorophyll a (chl a) products do not always agree well with in situ measurements, particularly in coastal regions of high turbidity, meaning that satellite chl a may not always be a good proxy for marine productivity. We would like to thank MOSTI (Malaysian Ministry of Science, Technology and Innovation). for giving opportunities and financial support for the University of Malaya (UM) and Universiti Kebangsaan Malaysia to participate in this scientific cruise, and other Malaysian public universities and agencies who helped during sampling. The Malaysian Royal Navy is thanked for their help and assistance in all aspects of the cruise. We also thank the SHIVA European FP7 project (grant 226224), NERC, NERC-NCAS and the British Council, through a PMI2 grant, for their support. Neil Harris would like to thank NERC for his Research Fellowship; Emma Leedham and Matt Ashfold thank NERC for studentships, and Doreena Dominick, Lin Chin Yik, Fatimah Ahamad and Nur Ily Hamizah for their assistance and the Ministry of Higher Education Malaysia (KPT’s) ERGS grant ER025-2013A. Finally, we also would like to thank Universiti Kebangsaan Malaysia (UKM) for the ICONIC-2013-004 grant, MOSTI e-science grant 04-01-02-SF-0752 for Universiti Kebangsaan Malaysia (UKM), UKM GGPM-2013-080 and UKM DPP-2014-162 and GUP-2013-057 for financial support.This paper was originally published in Atmospheric Chemistry and Physics, 14, 8137-8148, doi:10.5194/acp-14-8137-2014, 201

The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis,independent of RANK ligand, which disrupts normal bone homeostasisleading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications