Synthesis and Surface Characterization of Silica-Polypeptide Composite Particles

The synthesis and sequential surface characterization of silica-polypeptide composite particles is described. Nearly monodisperse colloidal silica cores were obtained by the alkaline hydrolysis of tetraethyl orthosilicate (TEOS). The hydrodynamic radius can be easily controlled in the range of ƒî 20-140 nm by the water/TEOS ratio in the starting reaction mixture. The surface of the synthesized silica cores was further passivated/functionalized (P/F) by a mixture of (3-aminopropyl) trimethoxysilane (APS) and methyl-trimethoxysilane (MTMS). The amino groups were quantified using UV-Vis spectrometry after reaction with ninhydrin. The use of zeta potential measurements of the P/F silica particles at low pH is presented as a potential alternative for the quantification of surface amino groups. The amino groups on the P/F silica cores were used as initiators for the polymerization of N-carboxyanhydrides (NCAs) yielding silica-polypeptide composite particles. The polypeptide content of silica-PBLG (silica-poly(ƒ×-benzyl-L-glutamate)) was controlled when the synthesis was performed by sequential addition of N-carboxyanhydride (monomer). The polypeptide shell in a ¡§wet¡¨ state was visualized by using positive staining with osmium tetroxide (OsO4) vapors when the particles were dispersed in pyridine. The stained composite particles were observed using transmission electron microscopy (TEM). They appear as spheres with a light corona around them. The use of an internal negative control that can be easily observed in the same field presents a compelling argument for the hypothesis that the observed corona is the polypeptide shell. The benzyl groups of PBLG on silica-PBLG composite particles were removed by reaction with hydrogen bromide yielding silica-PLGA (poly(L-glutamic acid)) particles. The hydrodynamic radii and zeta potential were studied as function of pH. The silica-PLGA composite particles appear extended and negatively charged at high pH and compact and neutral at low pH. This can be attributed to the changes on the PLGA shell. Silica-PCBL (poly(carbobenzyloxy-L-lysine)) composite particles were synthesized by the reaction of P/F silica cores with the respective NCA. The PCBL shell apparently undergoes a temperature-induced conformation transition as suggested by nuclear magnetic resonance and dynamic light scattering measurements

Organophilic, Superparamagnetic, and Reversibly Thermoresponsive Silica-Polypeptide Core-Shell Particles

Particles with a superparamagnetic cobalt inner core, silica outer core, and covalently bound homopolypeptide shell were investigated under thermal and magnetic stimuli. The homopolypeptide was poly(ϵ-carbobenzyloxy-l-lysine), PCBL, which is known to exhibit a thermoreversible coil → helix transition when dissolved as a pure polymer in m-cresol. Tethering to a core particle did not prevent PCBL from undergoing this conformational transition, as confirmed by dynamic light scattering and optical rotation, but the transition was broadened compared to that of the untethered polymer. The Co@SiO2-PCBL hybrid particles retained the superparamagnetic properties of the cobalt inner nougat. Indeed, some response remains even after aging for \u3e5 years. The aged PCBL shell also preserved its responsiveness to temperature, although differences in the shape of the size vs temperature transition curve were observed compared to the freshly made particles. A reversible coil → helix transition for a particle-bound polypeptide in a pure organic solvent is rare. In addition to providing a convenient tool for characterizing coil → helix transitions for surface-bound polypeptides without interference from pH or the strong ionic forces that dominate behavior in aqueous systems, the Co@SiO2-PCBL/m-cresol system may prove useful in studies of the effect of shell polymer conformation on colloid interactions. The stability of the magnetic core and polypeptide shell suggest a long shelf life for Co@SiO2-PCBL, which can, in principle, be deprotected to yield positively charged Co@SiO2-poly(l-lysine) particles for possible transfection or antimicrobial applications or chained magnetically to produce responsive poly(colloids)

Anti-invasive and anti-adhesive activities of a recombinant disintegrin, r-viridistatin 2, derived from the Prairie rattlesnake (Crotalus viridis viridis)

Snake venom disintegrins inhibit platelet aggregation and have anti-cancer activities. In this study, we report the cloning, expression, and functional activities of a recombinant disintegrin, r-viridistatin 2 (GenBank ID: JQ071899), from the Prairie rattlesnake. r-Viridistatin 2 was tested for anti-invasive and anti-adhesive activities against six different cancer cell lines (human urinary bladder carcinoma (T24), human fibrosarcoma (HT-1080), human skin melanoma (SK-Mel-28), human colorectal adenocarcinoma (CaCo-2), human breast adenocarcinoma (MDA-MB-231) and murine skin melanoma (B16F10)). r-Viridistatin 2 shares 96% and 64% amino acid identity with two other Prairie rattlesnake medium-sized disintegrins, viridin and viridistatin, respectively. r-Viridistatin 2 was able to inhibit adhesion of T24, SK-MEL-28, HT-1080, CaCo-2 and MDA-MB-231 to various extracellular matrix proteins with different affinities. r-Viridistatin 2 decreased the ability of T24 and SK-MEL-28 cells to migrate by 62 and 96% respectively, after 24 h of incubation and the invasion of T24, SK-MEL-28, HT-1080 and MDA-MB-231 cells were inhibited by 80, 85, 65 and 64% respectively, through a reconstituted basement membrane using a modified Boyden chamber. Finally, r-viridistatin 2 effectively inhibited lung colonization of murine melanoma cells in BALB/c mice by 71%, suggesting that r-viridistatin 2 could be a potent anti-cancer agent in vivo

Status, sources and contamination levels of organochlorine pesticide residues in urban and agricultural areas: a preliminary review in central–southern Italian soils

Organochlorine pesticides (OCPs) are synthetic chemicals commonly used in agricultural activities to kill pests and are persistent organic pollutants (POPs). They can be detected in different environmental media, but soil is considered an important reservoir due to its retention capacity. Many different types of OCPs exist, which can have different origins and pathways in the environment. It is therefore important to study their distribution and behaviour in the environment, starting to build a picture of the potential human health risk in different contexts. This study aimed at investigating the regional distribution, possible sources and contamination levels of 24 OCP compounds in urban and rural soils from central and southern Italy. One hundred and forty-eight topsoil samples (0–20 cm top layer) from 78 urban and 70 rural areas in 11 administrative regions were collected and analysed by gas chromatography–electron capture detector (GC–ECD). Total OCP residues in soils ranged from nd (no detected) to 1043 ng/g with a mean of 29.91 ng/g and from nd to 1914 ng/g with a mean of 60.16 ng/g in urban and rural area, respectively. Endosulfan was the prevailing OCP in urban areas, followed by DDTs, Drins, Methoxychlor, HCHs, Chlordane-related compounds and HCB. In rural areas, the order of concentrations was Drins > DDTs > Methoxychlor > Endosulfans > HCHs > Chlordanes > HCB. Diagnostic ratios and robust multivariate analyses revealed that DDT in soils could be related to historical application, whilst (illegal) use of technical DDT or dicofol may still occur in some urban areas. HCH residues could be related to both historical use and recent application, whilst there was evidence that modest (yet significant) application of commercial technical HCH may still be happening in urban areas. Drins and Chlordane compounds appeared to be mostly related to historical application, whilst Endosulfan presented a complex mix of results, indicating mainly historical origin in rural areas as well as potential recent applications on urban areas. Contamination levels were quantified by Soil Quality Index (SoQI), identifying high levels in rural areas of Campania and Apulia, possibly due to the intensive nature of some agricultural practices in those regions (e.g., vineyards and olive plantations). The results from this study (which is in progress in the remaining regions of Italy) will provide an invaluable baseline for OCP distribution in Italy and a powerful argument for follow-up studies in contaminated areas. It is also hoped that similar studies will eventually constitute enough evidence to push towards an institutional response for more adequate regulation as well as a full ratification of the Stockholm Convention

Diverse values of nature for sustainability

Twenty-five years since foundational publications on valuing ecosystem services for human well-being(1,2), addressing the global biodiversity crisis(3) still implies confronting barriers to incorporating nature's diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever(4). Notwithstanding agreements to incorporate nature's values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)(5) and the UN Sustainable Development Goals(6), predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature(7). Arguably, a 'values crisis' underpins the intertwined crises of biodiversity loss and climate change(8), pandemic emergence(9) and socio-environmental injustices(10). On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature's diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions(7,11). Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures

Multimessenger NuEM Alerts with AMON

The Astrophysical Multimessenger Observatory Network (AMON), has developed a real-time multi-messenger alert system. The system performs coincidence analyses of datasets from gamma-ray and neutrino detectors, making the Neutrino-Electromagnetic (NuEM) alert channel. For these analyses, AMON takes advantage of sub-threshold events, i.e., events that by themselves are not significant in the individual detectors. The main purpose of this channel is to search for gamma-ray counterparts of neutrino events. We will describe the different analyses that make-up this channel and present a selection of recent results

Pseudoacromegaly

© 2018 Elsevier Inc. Individuals with acromegaloid physical appearance or tall stature may be referred to endocrinologists to exclude growth hormone (GH) excess. While some of these subjects could be healthy individuals with normal variants of growth or physical traits, others will have acromegaly or pituitary gigantism, which are, in general, straightforward diagnoses upon assessment of the GH/IGF-1 axis. However, some patients with physical features resembling acromegaly – usually affecting the face and extremities –, or gigantism – accelerated growth/tall stature – will have no abnormalities in the GH axis. This scenario is termed pseudoacromegaly, and its correct diagnosis can be challenging due to the rarity and variability of these conditions, as well as due to significant overlap in their characteristics. In this review we aim to provide a comprehensive overview of pseudoacromegaly conditions, highlighting their similarities and differences with acromegaly and pituitary gigantism, to aid physicians with the diagnosis of patients with pseudoacromegaly.PM is supported by a clinical fellowship by Barts and the London Charity. Our studies on pituitary adenomas and related conditions received support from the Medical Research Council, Rosetrees Trust and the Wellcome Trust

Synthesis and rapid characterization of amine-functionalized silica

Amine-functionalized colloidal silica finds use in a variety of applications and fundamental investigations. To explore convenient methods of synthesis and characterization of research-grade materials in relatively large quantities, nearly monodisperse colloidal silica particles were prepared by base-catalyzed hydrolysis of reagent-grade tetraethyl orthosilicate (TEOS) without the traditional time- and energy-consuming distillation step. Radius was varied reliably from 30 to 125 nm by changing the water/TEOS ratio. Asymmetric flow field flow fractionation (AF4) methods with online light scattering detection proved effective in assessing the uniformity of the various preparations. Even highly uniform commercial standards were resolved by AF4. The surface of the colloidal silica was decorated with amino groups using (3-aminopropyl) trimethoxysilane and spacer methyl groups from methyl-trimethoxysilane. The surface density of amino groups was quantified spectrophotometrically after reaction with ninhydrin; the nature of this analysis avoids interference from sample turbidity. As an alternative to the ninhydrin test, an empirical relationship between surface density of amino groups and zeta potential at low pH was found. The size of the colloidal silica was predictably decreased by etching with HF; this method will be effective for some preparations, despite a modest reduction in size uniformity

Function Based Brain Modeling and Simulation of an Ischemic Region in Post-Stroke Patients using the Bidomain

Background. Several studies have shown that post-stroke patients develop divergent activity in the sensorimotor areas of the affected hemisphere of the brain compared to healthy people during motor tasks. Proper mathematical models will help us understand this activity and clarify the associated underlying mechanisms. New Method. This research describes an anatomically based brain computer model in post-stroke patients. We simulate an ischemic region for arm motion using the bidomain approach. Two scenarios are considered: a healthy subject and a post-stroke patient with motion impairment. Next, we limit the volume of propagation considering only the sensorimotor area of the brain. Comparison with existing methods. In comparison to existing methods, we combine the use of the bidomain for modeling the propagation of the electrical activity across the brain volume with functional information to limit the volume of propagation and the position of the expected stimuli, given a specific task. Whereas just using the bidomain without limiting the functional volume, propagates the electrical activity into non-expected areas. Results. To validate the simulation, we compare the activity with patient measurements using functional near-infrared spectroscopy during arm motion (n=5) against controls (n=3). The results are consistent with empirical measurements and previous research and show that there is a disparity between position and number of spikes in post-stroke patients in contrast to healthy subjects. Conclusions. These results hold promise in improving the understanding of brain deterioration in stroke patients and the re-arrangement of brain networks. Furthermore, shows the use of functionality based brain modeling