Functional interlocked systems van Dongen, Stijn F. M; Cantekin, Seda; Elemans, Johannes A. A. W ...
Chemical Society reviews,
01/2014, Volume:
43, Issue:
1
Journal Article
Peer reviewed
Open access
With the advent of supramolecular chemistry and later nanotechnology a great deal of research has been focused on new types of molecular structures, which are not held together by covalent bonds but ...by non-covalent mechanical interactions. Examples include the catenane, rotaxane, and knot interlocked structures. The design and synthesis of these architectures is an art by itself and as such is worth being reviewed. In this tutorial review we will focus, however, on the functional aspects of interlocked molecules and discuss how these can find applications,
e.g.
as artificial muscles, as molecular valves, as components of electronic devices, and as catalysts.
With the advent of supramolecular chemistry and later nanotechnology a great deal of research has been focused on new types of molecular structures, which are not held together by covalent bonds but by non-covalent mechanical interactions.
Processive Catalysis van Dongen, Stijn F. M.; Elemans, Johannes A. A. W.; Rowan, Alan E. ...
Angewandte Chemie (International ed.),
October 20, 2014, Volume:
53, Issue:
43
Journal Article
Peer reviewed
Open access
Nature’s enzymes are an ongoing source of inspiration for scientists. The complex processes behind their selectivity and efficiency is slowly being unraveled, and these findings have spawned many ...biomimetic catalysts. However, nearly all focus on the conversion of small molecular substrates. Nature itself is replete with inventive catalytic systems which modify, replicate, or decompose entire polymers, often in a processive fashion. Such processivity can, for example, enhance the rate of catalysis by clamping to the polymer substrate, which imparts a large effective molarity. Reviewed herein are the various strategies for processivity in nature’s arsenal and their properties. An overview of what has been achieved by chemists aiming to mimic one of nature’s greatest tricks is also included.
Hold the line: In processive catalysis, a catalyst binds to its substrate and performs multiple rounds of catalysis before dissociation. Nature leverages this phenomenon in its synthesis or processing of biopolymers. Processivity allows the achievement of rates of catalysis which cannot be matched by distributive systems. This Minireview describes processive catalysis and the advances that have been made in emulating it through supramolecular chemistry.
Biohybrid Polymer Capsules van Dongen, Stijn F. M; de Hoog, Hans-Peter M; Peters, Ruud J. R. W ...
Chemical reviews,
11/2009, Volume:
109, Issue:
11
Journal Article
Peer reviewed
Biohybrid polymer capsules synthesized from dendrimers are discussed. There is still tremendous potential in further research on these compounds.
Cells with implants: Porous enzyme‐loaded polymersomes were constructed that display the cell‐penetrating peptide tat on their surfaces. These nanoreactors are taken up by mammalian cells through ...macropinocytosis. Inside the cells, the polymersomes are only partially routed to acidic compartments. Polymersomes with horseradish peroxidase as a model cargo enzyme displayed sustained intracellular activity.
Porous polymersomes based on block copolymers of isocyanopeptides and styrene have been used to anchor enzymes at three different locations, namely, in their lumen (glucose oxidase, GOx), in their ...bilayer membrane (Candida antarctica lipase B, CalB) and on their surface (horseradish peroxidase, HRP). The surface coupling was achieved by click chemistry between acetylene‐functionalised anchors on the surface of the polymersomes and azido functions of HRP, which were introduced by using a direct diazo transfer reaction to lysine residues of the enzyme. To determine the encapsulation and conjugation efficiency of the enzymes, they were decorated with metal‐ion labels and analysed by mass spectrometry. This revealed an almost quantitative immobilisation efficiency of HRP on the surface of the polymersomes and a more than statistical incorporation efficiency for CalB in the membrane and for GOx in the aqueous compartment. The enzyme‐decorated polymersomes were studied as nanoreactors in which glucose acetate was converted by CalB to glucose, which was oxidised by GOx to gluconolactone in a second step. The hydrogen peroxide produced was used by HRP to oxidise 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) to ABTS.+. Kinetic analysis revealed that the reaction step catalysed by HRP is the fastest in the cascade reaction.
An enzyme triad: A porous polymersome was equipped with three different enzymes at three spatially separate locations: Candida antarctica lipase B (CalB) in its lumen, glucose oxidase (GOx) in its bilayer membrane and horseradish peroxidase (HRP) conjugated to its surface (see figure; ABTS=2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid)). The encapsulation efficiency of the enzymes was determined, and their activity as part of a three‐enzyme cascade reaction was investigated.
Abstract
As the cost of single-cell RNA-seq experiments has decreased, an increasing number of datasets are now available. Combining newly generated and publicly accessible datasets is challenging ...due to non-biological signals, commonly known as batch effects. Although there are several computational methods available that can remove batch effects, evaluating which method performs best is not straightforward. Here, we present BatchBench (https://github.com/cellgeni/batchbench), a modular and flexible pipeline for comparing batch correction methods for single-cell RNA-seq data. We apply BatchBench to eight methods, highlighting their methodological differences and assess their performance and computational requirements through a compendium of well-studied datasets. This systematic comparison guides users in the choice of batch correction tool, and the pipeline makes it easy to evaluate other datasets.
There's an APP for that: cell‐repellent APP (azido‐polylysine‐g‐PEG) is used to create substrates for spatially controlled dynamic cell adhesion. The simple addition of a functional peptide to the ...culture medium rapidly triggers cell adhesion. This highly accessible yet powerful technique allows diverse applications, demonstrated through tissue motility assays, patterned coculturing and triggered cell shape change.
Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries
. Historically, limited tissue accessibility, a lack of ...reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal-mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15
and TREM2
fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.
A discrete uncoupling process for finite spaces is introduced, called the Markov Cluster Process or the MCL process. The process is the engine for the graph clustering algorithm called the MCL ...algorithm. The MCL process takes a stochastic matrix as input, and then alternates expansion and inflation, each step defining a stochastic matrix in terms of the previous one. Expansion corresponds with taking the $k$th power of a stochastic matrix, where $k\in\N$. Inflation corresponds with a parametrized operator $\Gamma_r$, $r\geq 0$, that maps the set of (column) stochastic matrices onto itself. The image $\Gamma_r M$ is obtained by raising each entry in $M$ to the $r$th power and rescaling each column to have sum 1 again. In practice the process converges very fast towards a limit that is invariant under both matrix multiplication and inflation, with quadratic convergence around the limit points. The heuristic behind the process is its expected behavior for (Markov) graphs possessing cluster structure. The process is typically applied to the matrix of random walks on a given graph $G$, and the connected components of (the graph associated with) the process limit generically allow a clustering interpretation of $G$. The limit is in general extremely sparse and iterands are sparse in a weighted sense, implying that the MCL algorithm is very fast and highly scalable. Several mathematical properties of the MCL process are established. Most notably, the process (and algorithm) iterands posses structural properties generalizing the mapping from process limits onto clusterings. The inflation operator $\Gamma_r$ maps the class of matrices that are diagonally similar to a symmetric matrix onto itself. The phrase diagonally positive semi-definite (dpsd) is used for matrices that are diagonally similar to a positive semi-definite matrix. For $r\in\N$ and for $M$ a stochastic dpsd matrix, the image $\Gamma_r M$ is again dpsd. Determinantal inequalities satisfied by a dpsd matrix $M$ imply a natural ordering among the diagonal elements of $M$, generalizing the mapping of process limits onto clusterings. The spectrum of $\Gamma_{\infty} M$ is of the form $\{0^{n-k}, 1^k\}$, where $k$ is the number of endclasses of the ordering associated with $M$, and $n$ is the dimension of $M$. This attests to the uncoupling effect of the inflation operator.
MicroRNAs are important genetic regulators in both animals and plants. They have a range of functions spanning development, differentiation, growth, metabolism and disease. The advent of ...next-generation sequencing technologies has made it a relatively straightforward task to detect these molecules and their relative expression via sequencing. There are a large number of published studies with deposited datasets. However, there are currently few resources that capitalize on these data to better understand the features, distribution and biogenesis of miRNAs. Herein, we focus on Human and Mouse for which the majority of data are available. We reanalyse sequencing data from 461 samples into a coordinated catalog of microRNA expression. We use this to perform large-scale analyses of miRNA function and biogenesis. These analyses include global expression comparison, co-expression of miRNA clusters and the prediction of miRNA strand-specificity and underlying constraints. Additionally, we report for the first time a global analysis of miRNA epi-transcriptomic modifications and assess their prevalence across tissues, samples and families. Finally, we report a list of potentially mis-annotated miRNAs in miRBase based on their aggregated modification profiles. The results have been collated into a comprehensive online repository of miRNA expression and features such as modifications and RNA editing events, which is available at: http://wwwdev.ebi.ac.uk/enright-dev/miratlas. We believe these findings will further contribute to our understanding of miRNA function in animals and benefit the miRNA community in general.
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