Responsive Nucleic Acid-Based Organosilica Nanoparticles

The development of smart nanoparticles (NPs) that encode responsive features in the structural framework promises to extend the applications of NP-based drugs, vaccines, and diagnostic tools. New nanocarriers would ideally consist of a minimal number of biocompatible components and exhibit multiresponsive behavior to specific biomolecules, but progress is limited by the difficulty of synthesizing suitable building blocks. Through a nature-inspired approach that combines the programmability of nucleic acid interactions and sol-gel chemistry, we report the incorporation of synthetic nucleic acids and analogs, as constitutive components, into organosilica NPs. We prepared different nanomaterials containing single-stranded nucleic acids that are covalently embedded in the silica network. Through the incorporation of functional nucleic acids into the organosilica framework, the particles respond to various biological, physical, and chemical inputs, resulting in detectable physicochemical changes. The one-step bottom-up approach used to prepare organosilica NPs provides multifunctional systems that combine the tunability of oligonucleotides with the stiffness, low cost, and biocompatibility of silica for different applications ranging from drug delivery to sensing

Supramolecular Nucleic Acid-Based Organosilica Nanoparticles Responsive to Physical and Biological Inputs

Organosilica nanoparticles that contain responsive organic building blocks as constitutive components of the silica network offer promising opportunities for the development of innovative drug formulations, biomolecule delivery, and diagnostic tools. However, the synthetic challenges required to introduce dynamic and multifunctional building blocks have hindered the realization of biomimicking nanoparticles. In this study, capitalizing on our previous research on responsive nucleic acid-based organosilica nanoparticles, we combine the supramolecular programmability of nucleic acid (NA) interactions with sol-gel chemistry. This approach allows us to create dynamic supramolecular bridging units of nucleic acids in a silica-based scaffold. Two peptide nucleic acid-based monoalkoxysilane derivatives, which self-assemble into a supramolecular bis-alkoxysilane through direct base pairing, were chosen as the noncovalent units inserted into the silica network. In addition, a bridging functional NA aptamer leads to the specific recognition of ATP molecules. In a one-step bottom-up approach, the resulting supramolecular building blocks can be used to prepare responsive organosilica nanoparticles. The supramolecular Watson-Crick-Franklin interactions of the organosilica nanoparticles result in a programmable response to external physical (i.e., temperature) and biological (i.e., DNA and ATP) inputs and thus pave the way for the rational design of multifunctional silica materials with application from drug delivery to theranostics

Has Selection for Improved Agronomic Traits Made Reed Canarygrass Invasive?

Plant breeders have played an essential role in improving agricultural crops, and their efforts will be critical to meet the increasing demand for cellulosic bioenergy feedstocks. However, a major concern is the potential development of novel invasive species that result from breeders' efforts to improve agronomic traits in a crop. We use reed canarygrass as a case study to evaluate the potential of plant breeding to give rise to invasive species. Reed canarygrass has been improved by breeders for use as a forage crop, but it is unclear whether breeding efforts have given rise to more vigorous populations of the species. We evaluated cultivars, European wild, and North American invader populations in upland and wetland environments to identify differences in vigor between the groups of populations. While cultivars were among the most vigorous populations in an agricultural environment (upland soils with nitrogen addition), there were no differences in above- or below-ground production between any populations in wetland environments. These results suggest that breeding has only marginally increased vigor in upland environments and that these gains are not maintained in wetland environments. Breeding focuses on selection for improvements of a specific target population of environments, and stability across a wide range of environments has proved elusive for even the most intensively bred crops. We conclude that breeding efforts are not responsible for wetland invasion by reed canarygrass and offer guidelines that will help reduce the possibility of breeding programs releasing cultivars that will become invasive

Changes in bone marrow lesions in response to weight-loss in obese knee osteoarthritis patients: a prospective cohort study

BACKGROUND: Patients are susceptible for knee osteoarthritis (KOA) with increasing age and obesity and KOA is expected to become a major disabling disease in the future. An important feature of KOA on magnetic resonance imaging (MRI) is changes in the subchondral bone, bone marrow lesions (BMLs), which are related to the future degeneration of the knee joint as well as prevalent clinical symptoms. The aim of this study was to investigate the changes in BMLs after a 16-week weight-loss period in obese subjects with KOA and relate changes in BMLs to the effects of weight-loss on clinical symptoms. METHODS: This prospective cohort study included patients with a body mass index ≥ 30 kg/m(2), an age ≥ 50 years and primary KOA. Patients underwent a 16 weeks supervised diet program which included formula products and dietetic counselling (ClinicalTrials.gov: NCT00655941). BMLs in tibia and femur were assessed on MRI before and after the weight-loss using the Boston-Leeds Osteoarthritis Knee Score. Response to weight-loss in BML scores was dichotomised to patients experiencing a decrease in BML scores (responders) and patients who did not (non-responders). The association of BMLs to weight-loss was assessed by logistic regressions and correlation analyses. RESULTS: 39 patients (23%) were classified as responders in the sum of all BML size scores whereas 130 patients (77%) deteriorated or remained stable and were categorized as non-responders. Logistic regression analyses revealed no association between weight-loss < or ≥ 10% and response in BMLs in the most affected compartment (OR 1.86 [CI 0.66 to 5.26, p=0.24]). There was no association between weight-loss and response in maximum BML score (OR 1.13 [CI 0.39 to 3.28, p=0.81]). The relationship between changes in BMLs and clinical symptoms revealed that an equal proportion of patients classified as BML responders and non-responders experienced an OMERACT-OARSI response (69 vs. 71%, p=0.86). CONCLUSIONS: Weight-loss did not improve the sum of tibiofemoral BML size scores or the maximum tibiofemoral BML score, suggesting that BMLs do not respond to a rapidly decreased body weight. The missing relationship between clinical symptoms and BMLs calls for further investigation

A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis

Introduction: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. Methods: A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. Results: In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Conclusion: Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. Systematic review: PROSPERO registration number: CRD 4201300500

Will ocean acidification affect marine microbes?

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 5 (2011): 1-7, doi:10.1038/ismej.2010.79.The pH of the surface ocean is changing as a result of increases in atmospheric carbon dioxide (CO2) and there are concerns about potential impacts of lower pH and associated alterations in seawater carbonate chemistry on the biogeochemical processes in the ocean. However, it is important to place these changes within the context of pH in the present day ocean, which is not constant; it varies systematically with season, depth and along productivity gradients. Yet this natural variability in pH has rarely been considered in assessments of the effect of ocean acidification on marine microbes. Surface pH can change as a consequence of microbial utilisation and production of carbon dioxide, and to a lesser extent other microbiallymediated processes such as nitrification. Useful comparisons can be made with microbes in other aquatic environments that readily accommodate very large and rapid pH change. For example, in many freshwater lakes, pH changes that are orders of magnitude greater than those projected for the 22nd century oceans can occur over periods of hours. Marine and freshwater assemblages have always experienced variable pH conditions. Therefore, an appropriate null hypothesis may be, until evidence is obtained to the contrary, that major biogeochemical processes in the oceans other than calcification will not be fundamentally different under future higher CO2 / lower pH conditions.Funding from the Gordon and Betty Moore Foundation, and logistical support from the Plymouth Marine Laboratory and the Center for Microbial Oceanography: Research and Education (National Science Foundation grant EF-0424599) are gratefully acknowledged

Guanosine stimulates neurite outgrowth in PC12 cells via activation of heme oxygenase and cyclic GMP

Undifferentiated rat pheochromocytoma (PC12) cells extend neurites when cultured in the presence of nerve growth factor (NGF). Extracellular guanosine synergistically enhances NGF-dependent neurite outgrowth. We investigated the mechanism by which guanosine enhances NGF-dependent neurite outgrowth. Guanosine administration to PC12 cells significantly increased guanosine 3-5-cyclic monophosphate (cGMP) within the first 24 h whereas addition of soluble guanylate cyclase (sGC) inhibitors abolished guanosine-induced enhancement of NGF-dependent neurite outgrowth. sGC may be activated either by nitric oxide (NO) or by carbon monoxide (CO). \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$N^{\omega }$$ \end{document}-Nitro-l-arginine methyl ester (l-NAME), a non-isozyme selective inhibitor of nitric oxide synthase (NOS), had no effect on neurite outgrowth induced by guanosine. Neither nNOS (the constitutive isoform), nor iNOS (the inducible isoform) were expressed in undifferentiated PC12 cells, or under these treatment conditions. These data imply that NO does not mediate the neuritogenic effect of guanosine. Zinc protoporphyrin-IX, an inhibitor of heme oxygenase (HO), reduced guanosine-dependent neurite outgrowth but did not attenuate the effect of NGF. The addition of guanosine plus NGF significantly increased the expression of HO-1, the inducible isozyme of HO, after 12 h. These data demonstrate that guanosine enhances NGF-dependent neurite outgrowth by first activating the constitutive isozyme HO-2, and then by inducing the expression of HO-1, the enzymes responsible for CO synthesis, thus stimulating sGC and increasing intracellular cGMP

Antioxidant and cytotoxic activities of sulfated polysaccharides from five different edible seaweeds

In recent times, there has been a growing interest in the exploration of antioxidants and global trend toward the usage of seaweeds in the food industries. The low molecular weight up to 14 kDa sulfated polysaccharides of seaweeds (Portieria hornemannii, Spyridia hypnoides, Asparagopsis taxiformis, Centroceras clavulatum and Padina pavonica) were evaluated for in vitro antioxidant activities and cytotoxic assay using HeLa cell line and also characterized by FTIR. The high yield (7.74% alga dry wt.) of sulfated polysaccharide was observed in P. hornemannii followed by S. hypnoides (0.69%), C. clavulaum (0.55%) and A. taxiformis (0.17%). In the brown seaweed P. pavonica, the sulfated polysaccharide yield was 2.07%. High amount of sulfate was recorded in the polysaccharide of A. taxiformis followed by C. clavulaum, P. pavonica, S. hypnoides and P. hornemannii as indicative for bioactivity. The FTIR spectroscopic analysis supports the sulfated polysaccharides of S. hypnoides, C. clavulatum and A. taxiformis are similar to agar polymer whereas the spectral characteristics of P. hornemannii have similarities to carrageenan. The higher DPPH activity and reducing power were recorded in the polysaccharide of brown seaweed P. pavonica than the red seaweeds as follows: DPPH activities: S. hypnoides > A. taxiformis > C. clavulatum > P. hornimanii; Reducing power: A. taxiformis > P. hornimanii > S. hypnoides > C. clavulatum. The polysaccharide fractions contain up to 14 kDa from red seaweeds P. hornemannii and S. hypnoides followed by brown seaweed P. pavonica exhibit cytotoxic activity in HeLa cancer cell line (and are similar to structural properties of carrageenan extracted from P. hornemannii). The low molecular weight agar like polymer of S. hypnoides and alginate like brown seaweed P. pavonica showing better in vitro antioxidant activities that are capable of exhibiting cytotoxicity against HeLa cell line can be taken up further in-depth investigation for nutraceutical study.University of Algarve: DL 57/2016info:eu-repo/semantics/publishedVersio