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Santos T.,University of Coimbra | Santos T.,University of Southern California | Maia J.,Matera | Agasse F.,University of Coimbra | And 6 more authors.
Integrative Biology (United Kingdom) | Year: 2012

The subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ) comprise two main germinal niches in the adult mammalian brain. Within these regions there are self-renewing and multipotent neural stem cells (NSCs) which can ultimately give rise to new neurons, astrocytes and oligodendrocytes. Understanding how to efficiently trigger NSCs differentiation is crucial to devise new cellular therapies aimed to repair the damaged brain. A large amount of data ranging from epigenetic alterations, chromatin remodelling and signalling pathways involved in NSCs differentiation are now within reach. Furthermore, a vast array of proteins and molecules have been described to modulate NSCs fate and tested in innovative therapeutic applications, however with little success so far. Nowadays, the main focus is on how to manipulate these factors to our full advantage. Unfortunately, concerns related to solubility, stability, concentration or spatial and temporal positioning can hinder their desirable effects. Biomaterials emerge as the ideal support to overcome these limitations and consequently boost NSCs differentiation towards desired phenotypes. However, the balance between biomaterials and differentiating factors must be well established, since the bioaccumulation and concomitant toxicity can be an undesired side-effect. Currently, innovative materials and formulations including more degradable carriers allow a controlled and efficient release of bioactive factors with minimal side-effects. Recently, micro- and nanoparticles have been successfully used to deliver molecules able to induce neurogenesis. This review presents recent research that highlights the role of both extracellular environmental factors as well as molecular remodelling mechanisms in the control of NSCs differentiation processes. Appropriate biomaterials that may trigger an efficient delivery of therapeutic molecules will be also discussed. Therefore, the interface between NSCs biology and tissue engineering may offer great potential in future therapeutics for treatment or amelioration of neurodegenerative diseases or brain injury. © 2012 The Royal Society of Chemistry.

Santos T.,University of Coimbra | Ferreira R.,University of Coimbra | Maia J.,Matera | Agasse F.,University of Coimbra | And 7 more authors.
ACS Nano | Year: 2012

Herein, we report the use of retinoic acid-loaded polymeric nanoparticles as a potent tool to induce the neuronal differentiation of subventricular zone neural stem cells. The intracellular delivery of retinoic acid by the nanoparticles activated nuclear retinoic acid receptors, decreased stemness, and increased proneurogenic gene expression. Importantly, this work reports for the first time a nanoparticle formulation able to modulate in vivo the subventricular zone neurogenic niche. The work further compares the dynamics of initial stages of differentiation between SVZ cells treated with retinoic acid-loaded polymeric nanoparticles and solubilized retinoic acid. The nanoparticle formulation developed here may ultimately offer new perspectives to treat neurodegenerative diseases. © 2012 American Chemical Society.

Botequim D.,Matera | Maia J.,Matera | Lino M.M.F.,Matera | Lopes L.M.F.,University of Lisbon | And 3 more authors.
Langmuir | Year: 2012

Here, we present new antimicrobial nanoparticles based on silica nanoparticles (SNPs) coated with a quaternary ammonium cationic surfactant, didodecyldimethylammonium bromide (DDAB). Depending on the initial concentration of DDAB, SNPs immobilize between 45 and 275 μg of DDAB per milligram of nanoparticle. For high concentrations of DDAB adsorbed to SNP, a bilayer is formed as confirmed by zeta potential measurements, thermogravimetry, and diffuse reflectance infrared Fourier transform (DRIFT) analyses. Interestingly, these nanoparticles have lower minimal inhibitory concentrations (MIC) against bacteria and fungi than soluble surfactant. The electrostatic interaction of the DDAB with the SNP is strong, since no measurable loss of antimicrobial activity was observed after suspension in aqueous solution for 60 days. We further show that the antimicrobial activity of the nanoparticle does not require the leaching of the surfactant from the surface of the NPs. The SNPs may be immobilized onto surfaces with different chemistry while maintaining their antimicrobial activity, in this case extended to a virucidal activity. The versatility, relative facility in preparation, low cost, and large antimicrobial activity of our platform makes it attractive as a coating for large surfaces. © 2012 American Chemical Society.

News Article
Site: www.nature.com

Why the Universe is filled with matter, rather than antimatter, is one of physics’ greatest mysteries. An experiment in Japan has now glimpsed a possible explanation: subatomic particles called neutrinos might behave differently in their matter and antimatter forms. The disparity, announced at the International Conference on High Energy Physics (ICHEP) in Chicago, Illinois, on 6 August, may turn out not to be real: more data will need to be gathered to be sure. “You would probably bet that this difference exists in neutrinos, but it would be premature to state that we can see it,” says André de Gouvêa, a theoretical physicist at Northwestern University in Evanston, Illinois. Even so, the announcement is likely to increase excitement over studies of neutrinos, the abundant but elusive particles that seem increasingly key to solving all kinds of puzzles in physics. In the 1990s, neutrinos were found1, 2 to defy the predictions of physics' standard model — a successful, but incomplete, description of nature — by virtue of possessing mass, rather than being entirely massless. Since then, neutrino experiments have sprouted up around the world, and researchers are realizing that they should look to these particles for new explanations in physics, says Keith Matera, a physicist on a US-based neutrino experiment called NOvA at the Fermi National Accelerator Laboratory (Fermilab) in Batavia, Illinois. “They are the crack in the standard model,” he says. The excess of matter over antimatter in our Universe is extraordinary, because if the mirror-image particles were produced in equal quantities after the Big Bang, they would have annihilated each other on contact, leaving nothing but radiation. Physicists have observed differences in the behaviour of some matter particles and antimatter particles, such as kaons and B mesons — but not enough to explain the dominance of matter in the Universe. One answer might be that super-heavy particles decayed in the early Universe in an asymmetric fashion and produced more matter than antimatter. Some physicists think that a heavyweight relative of the neutrino could be the culprit. Under this theory, if neutrinos and antineutrinos behave differently today, then a similar imbalance in their ancient counterparts could explain the overabundance of matter. To test this, researchers on the Tokai to Kamioka (T2K) experiment in Japan looked for differences in the way that matter and antimatter neutrinos oscillate between three types, or ‘flavours’, as they travel (see 'Changing flavours'). They shot beams of neutrinos of one flavour — muon neutrinos — from the Japan Proton Accelerator Research Complex in the seaside village of Tokaimura to the Super-Kamiokande detector, an underground steel tank more than 295 kilometres away and filled with 50,000 tons of water. The team counted how many electron neutrinos appeared — a sign that the muon neutrinos had morphed into a different flavour along the journey. They then repeated the experiment with a beam of muon antineutrinos. The two beams behaved slightly differently, said Konosuke Iwamoto, a physicist at the University of Rochester, New York, during his presentation at ICHEP. The team expected that if there were no difference between matter and antimatter, their detector would have, after almost 6 years of experiments, seen 24 electron neutrinos and — because antimatter is harder to produce and detect — 7 electron antineutrinos. Instead, they saw 32 neutrinos and 4 antineutrinos arrive in their detector. “Without getting into complicated mathematics, this suggests that matter and antimatter do not oscillate in the same way,” says Chang Kee Jung, a physicist at Stony Brook University in New York and a member of the T2K experiment. Preliminary findings from the T2K and NOvA experiments had hinted at the same idea. But the observations so far could be a chance fluctuation; there is a 1 in 20 chance (or in statistical terms, about 2 sigma) of seeing these results if neutrinos and antineutrinos behave identically, points out Jung. It will take much more data to confirm the signal. By the end of its current run in 2021, the T2K experiment should have five times more data than it has today. But the team will need 13 times more data to push statistical confidence in the finding to 3 sigma, a statistical threshold beyond which most physicists would accept the data as reasonable — but not completely convincing — evidence of the asymmetry. The T2K team has proposed extending its experiment to 2025 in order to gather the necessary data. But it is trying to speed up data-gathering by combining results with those from NOvA, which sends a neutrino beam 810 kilometres from Fermilab to a mine in northern Minnesota. NOvA has been shooting neutrino beams; it will switch to antineutrino beams in 2017. The two groups have agreed to produce a joint analysis and could together reach 3 sigma by around 2020, says Jung. Reaching the statistical certainty needed to announce a formal discovery — 5 sigma — could require a new generation of neutrino experiments already being planned around the world. Researchers from the NOvA experiment presented another exciting but preliminary finding at the ICHEP, also deduced from the study of the rate at which muon neutrinos switch to electron neutrinos: a hint at a resolution for which of neutrinos’ three different mass states is the heaviest.They found their results slightly favour a normal mass order, rather than an inverted one. Knowing which it is would help scientists to decide between rival theories about how the four forces of nature unite as a single force at high energies, such as during the Big Bang. Physicists are racking up discoveries about neutrinos on an almost annual basis, says de Gouvêa: “For the timescales of particle physics, this is changing really, really quickly.”

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