Anti-tumor activity of functionalized biomimetic magnetite nanoparticles produced in the presence of MamC protein of Magnetococcus marinus MC-1

Magnetite Nanoparticles (MNPs) find many applications, including biotechnology, as they can be manipulated by an external magnetic field and functionalized with different molecules. Magnetotactic bacteria bio-mineralize magnetosomes (membrane-enveloped magnetites), which are the ideal magnetic particle. However, scaling-up magnetosome production is still challenging, so bio-mimetics, i.e. in vitro magnetite synthesis mediated by magnetosome-associated proteins is being explored. Our group is working with MamC from Magnetococcus marinus MC-1 that controls the morphology and size of the crystals, producing well faceted Biomimetic Magnetic Nanoparticles (BMNPs) of ~40 nm, which are paramagnetic at room and body temperature while having a large magnetic moment per particle under an external magnetic field. These BMNPs were cytocompatible and biocompatible in vivo. BMNPs were functionalized (isothermal adsorption) with a monoclonal antibody (mAb) recognizing the ectodomain of the human Met/HGF receptor (overexpressed in many cancers) and the chemotherapeutic Doxorubicin (DOXO). The functionalized BMNPs present hyperthermia and were stable at physiological pH, while releasing the adsorbed DOXO at acidic pH. mAb functionalization of BMNPs favored their interaction with cells expressing the Met/HGFR and cellular DOXO uptake and toxicity, which was enhanced upon cell exposition to a continuous magnetic field. Real-time cytotoxicity of the BMNPs showed that DOXO-mAb-BMNPs were significantly more toxic than DOXO-BMNPs on Met/HGFR expressing cells, while no differential toxicity was observed on cells not expressing this receptor. When DOXO-BMNPs were injected intravenously in tumor bearing mice and an external magnetic field was applied there, a higher amount of BMNPs accumulated in the tumor and tumor growth was decreased in comparison to mice in which no magnetic field was applied. These BMNPs could thus represent effective nano-carriers for targeted drug delivery and might be combined with hyperthermia to increase efficiency, resulting in a targeted local treatment of tumors with a decrease in the deleterious systemic side effects

Violent Crime, Epilepsy, and Traumatic Brain Injury

Jan Volavka discusses new research by Seena Fazel and colleagues that reports increased risk for violent crime among people with traumatic brain injury and epilepsy

Using zeta-potential measurements to quantify peptide partition to lipid membranes

© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively

Synergy between magneto-rheological fluids and aluminum foams. Prospective alternative for seismic damping

This is the accepted manuscript. Access to the published article can be gained at: http://jim.sagepub.com/cgi/reprint/1045389X15596624v1.pdf?ijkey=SyFHNQwE4XMQqBF&keytype=finiteThis article presents the experimental study of a preliminary investigation of a seismic damper device aimed at improving the behavior of structures when subjected to earthquakes. The damper is the result of a binomial material formed by aluminum foam with pores 1 mm in diameter, wetted by a magnetorheological fluid (MRF). The objective of the present work is to explore the synergy between the two components in a magnetorheological test, and to evaluate the effect of the Al foam pores in the structure buildup of the fluid. The analysis is completed with a compressive test carried out on the MRF-filled foam in the presence of a magnetic field. This kind of test demonstrates that the deformation of the foam for very small loads is limited by the hardening of the fluid because of its MR response. The results of this research suggest that there is a mutual benefit between the components of the device, presumably leading to an enhanced dissipation of vibration energy.Proyectos PE2012-FQM694 (Junta de Andalucía, Spain), FIS2013-47666-C3-1-R (MINECO, Spain), SENER-CONACYT "151496" (UNAM Mexico), CONACYT National Quality Graduate Progra

Focal Cerebral Magnetic Resonance Changes Associated with Partial Status Epilepticus

We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4-month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T 2 signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with “cryptogenic” temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T 2 Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T 2 intensity, without gadolinium enhancement, but with mild mass effect over the right anteroinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long-standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65221/1/j.1528-1157.1994.tb02909.x.pd

Full-scale simulation of indoor humidity and moisture buffering properties of clay

It is important to control indoor humidity level in buildings as it influences occupant’s health and comfort. Some materials, when exposed to the indoor environment, help regulate relative humidity levels due to their capacity to absorb and desorb water vapour. The potential of earthen plasters to improve indoor comfort was investigated through experimentation and simulation. Results of clay moisture buffering capacity and computational simulation of the diurnal moisture variation in a clay plastered test room are discussed. This study compares measurement obtained in the laboratory with simulations output and identifies a discrepancy between the two methods in the quantification of the moisture buffering potential

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

Peer reviewe

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Horizontal low gradient magnetophoresis behaviour of iron oxide nanoclusters at the different steps of the synthesis route

In this work the use of Horizontal Low Gradient Magnetic Field (HLGMF) (<100T/m) for filtration, control and separation of synthesized magnetic nanoparticles (NPs) is investigated. The characteristics of the suspension, size and type of the NPs are considered and discussed. For these purposes, Fe2O3 silica coated nanoclusters of about 150 nm are synthesized by co-precipitation, monodispersion and silica coating. SQUID, TEM, XRD, and z potential techniques were used to characterize the synthesized nanoclusters. An extensive magnetophoresis study was performed at different magnetophoretical conditions. Different reversible aggregation times were observed at different HLGMF, at each step of the synthesis route. In particular, differences of several orders of magnitude were observed when comparing citric acid modified NPs with silica coated nanoclusters . Reversible aggregation times are correlated to the properties of the NPs at different steps of synthesis route.Fundação para a Ciência e a Tecnologia (FCT) - Bolsa NANO/NMed-SD/0156/2007, PTCD/CTM/69316/2006

Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micro-metastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas. We searched for a gene signature that discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events. An unbiased approach identified, amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature as predictive of PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by hindering tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the produced lipid second messenger PIP3 , with a selective decrease of C36:2 PI-3,4,5-P3 . Tumoural PI3Kα inactivation prevented the accumulation of pro-tumoural CD206-positive macrophages in the tumour-adjacent tissue. Tumour cell-intrinsic PI3Kα promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution