Alginate: properties and biomedical applications

EVOLUTION: Of Mice . . .

In this review an overview about biological applications of magnetic colloidal nanoparticles will be given, which comprises their synthesis, characterization, and in vitro and in vivo applications. The potential future role of magnetic nanoparticles compared to other functional nanoparticles will be discussed by highlighting the possibility of integration with other nanostructures and with existing biotechnology as well as by pointing out the specific properties of magnetic colloids. Current limitations in the fabrication process and issues related with the outcome of the particles in the body will be also pointed out in order to address the remaining challenges for an extended application of magnetic nanoparticles in medicine.

Biological applications of magnetic nanoparticles

Intellectual curiosity has always been one of the major driving forces leading to new advances in chemistry. At the onset of the 20th century, the fact that biaryls could be optically active even if lacking asymmetrically substituted carbon atoms arose interest, hinting at a novel type of stereomerism. It took quite a while (and some bizarre explanations)1 until in 1922 Christie and Kenner2 first correctly recognized that the phenomenon was the consequence of a hindered rotation about the aryl-aryl single bondshence termed atropisomerism by Kuhn. Still, no particular attention was initially paid to this class of stereoisomers until enantiomerically pure biaryls, such as BINAP (1),3 were found to be excellent ligands in asymmetric catalysis and until the chiral biaryl unit was recognized as the decisive structural element of many natural products (Figure 1).4,5 With the modern screening techniques and the bioassayguided search for novel compounds, the number of isolated axially chiral natural biaryls is steadily increasing.4 This class of secondary metabolites is characterized by a broad structural diversity, reaching from relatively simple molecules like the C2-symmetric biphenyl 2, which solely contains the element of axial chirality,6 to more complex compounds, like, e.g., the dimeric naphthylisoquinoline alkaloids michellamine A [(P,P)-3] and its axial epimer (i.e., its atropodiastereomer), michellamine B [(P,M)-3],7,8 which possess even three biaryl axes, of which the two outer ones are stereogenic, while * To whom correspondence should be addressed. E-mail: bringmann@ chemie.uni-wuerzburg.de; breuning@chemie.uni-wuerzburg.de. † These authors contributed equally to this work. ‡ Present address: Institute of Organic Chemistry, RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany. § Present address: Kekulé Institute of Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk Str. 1, 53121 Bonn, Germany. Gerhard Bringmann was born in 1951 and studied chemistry in Gie en and Münster, Germany. After his Ph.D. with Prof. B. Franck in 1978 and postdoctoral studies with Prof. Sir D. H. R. Barton in Gif-sur-Yvette (France), he passed his habilitation at the University of Münster in 1984. In 1986, he received offers for full professorships of Organic Chemistry at the Universities of Vienna and Würzburg, of which he accepted the latter in 1987. In 1998, he was offered the position of director at the Leibniz Institute of Plant Biochemistry in Halle, which he declined. His research interests focus on the field of analytical, synthetic, and computational natural product chemistry, i.e., on axially chiral biaryls. He received several prizes and awards, among them the Otto-Klung Award in chemistry (1988), the Prize for Good Teaching of the Free State of Bavaria (1999), the Adolf-Windaus Medal (2006), the Honorary Doctorate of the University of Kinshasa (2006), the Paul-J.-Scheuer Award (2007), and the Honorary Guest Professorship of Peking University (2008). Chem. Rev. 2011, 111, 563–639 563

Atroposelective total synthesis of axially chiral biaryl natural products.

This review concerns the applications of some polysaccharides in the domain of biomaterials and bioactive polymers. Natural polysaccharides from different sources have been studied for a long time, and their main properties are summarized in this paper; some of their derivatives obtained by chemical modification are also described. The main polysaccharides currently used in the biomedical and pharmaceutical domains are chitin and its derivative chitosan, hyaluronan and alginates. Alginates are well known for their property of forming a physical gel in the presence of divalent counterions (Ca, Ba, Sr) whereas carrageenans form a thermoreversible gel; these seaweed polysaccharides are mainly used to encapsulate different materials (cells, bacteria, fungi). Other promising systems are the electrostatic complexes formed when an anionic polysaccharide is mixed with a cationic polysaccharide (e.g. alginate/chitosan or hyaluronan/chitosan). An important development of the applications of polysaccharides can be predicted for the next few years in relation to their intrinsic properties such as biocompatibility and biodegradability in the human body for some of them; they are also renewable and have interesting physical properties (film-forming, gelling and thickening properties). In addition, they are easily processed in different forms such as beads, films, capsules and fibres. Copyright © 2007 Society of Chemical Industry

Main properties and current applications of some polysaccharides as biomaterials

The BAF (BRG1/BRM-associated factor) chromatin remodelling complex is essential for the regulation of DNA accessibility and gene expression during neuronal differentiation. Mutations of its core subunit SMARCB1 result in a broad spectrum of pathologies, including aggressive rhabdoid tumours or neurodevelopmental disorders. Other mouse models have addressed the influence of a homo- or heterozygous loss of Smarcb1, yet the impact of specific non-truncating mutations remains poorly understood. Here, we have established a new mouse model for the carboxy-terminal Smarcb1 c.1148del point mutation, which leads to the synthesis of elongated SMARCB1 proteins. We have investigated its impact on brain development in mice using magnetic resonance imaging, histology, and single-cell RNA sequencing. During adolescence, Smarcb11148del/1148del mice demonstrated rather slow weight gain and frequently developed hydrocephalus including enlarged lateral ventricles. In embryonic and neonatal stages, mutant brains did not differ anatomically and histologically from wild-type controls. Single-cell RNA sequencing of brains from newborn mutant mice revealed that a complete brain including all cell types of a physiologic mouse brain is formed despite the SMARCB1 mutation. However, neuronal signalling appeared disturbed in newborn mice, since genes of the AP-1 transcription factor family and neurite outgrowth-related transcripts were downregulated. These findings support the important role of SMARCB1 in neurodevelopment and extend the knowledge of different Smarcb1 mutations and their associated phenotypes. 

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A Carboxy-terminal Smarcb1 Point Mutation Induces Hydrocephalus Formation and Affects AP-1 and Neuronal Signalling Pathways in Mice.

PURPOSE
Temporal resolution of time-lapse MRI to track individual iron-labeled cells is limited by the required data-acquisition time to fill k-space and to reach sufficient SNR. Although motion of slowly patrolling monocytes can be resolved, detection of fast-moving immune cells requires improved acquisition and reconstruction strategies.


THEORY AND METHODS
For accelerated MRI cell tracking, a Cartesian sampling scheme was designed, in which the fully sampled and undersampled k-space data for different acceleration factors were acquired simultaneously, and multiple undersampling ratios could be chosen retrospectively. Compressed-sensing reconstruction was applied using dictionary learning and low-rank constraints. Detection of iron-labeled monocytes was evaluated with simulations, rotating phantom experiments and in vivo mouse brain measurements at 9.4 T.


RESULTS
Fully sampled and 2.4-times and 4.8-times accelerated images were reconstructed and had sufficient contrast-to-noise ratio (CNR) for single cells to be resolved and followed dynamically. The phantom experiments showed an improvement in CNR of 6.1% per μm/s in the 4.8-times undersampled images. Geometric distortion of cells caused by motion was visibly reduced in the accelerated images, which enabled detection of moving cells with velocities of up to 7.0 μm/s. In vivo, additional cells were resolved in the accelerated images due to the improved temporal resolution.


CONCLUSION
The easy-to-implement flexible Cartesian sampling scheme with compressed-sensing reconstruction permits simultaneous acquisition of both fully sampled and high temporal resolution images. The CNR of moving cells is effectively improved, enabling the recovery of high velocity cells with sufficient contrast at virtually no cost.

Cornelius Faber

Papers

A Carboxy-terminal Smarcb1 Point Mutation Induces Hydrocephalus Formation and Affects AP-1 and Neuronal Signalling Pathways in Mice.

Dynamic cell tracking using time-lapse MRI with variable temporal resolution Cartesian sampling.