Distributed Control of Microscopic Robots in Biomedical Applications

Current developments in molecular electronics, motors and chemical sensors could enable constructing large numbers of devices able to sense, compute and act in micron-scale environments. Such microscopic machines, of sizes comparable to bacteria, could simultaneously monitor entire populations of cells individually in vivo. This paper reviews plausible capabilities for microscopic robots and the physical constraints due to operation in fluids at low Reynolds number, diffusion-limited sensing and thermal noise from Brownian motion. Simple distributed controls are then presented in the context of prototypical biomedical tasks, which require control decisions on millisecond time scales. The resulting behaviors illustrate trade-offs among speed, accuracy and resource use. A specific example is monitoring for patterns of chemicals in a flowing fluid released at chemically distinctive sites. Information collected from a large number of such devices allows estimating properties of cell-sized chemical sources in a macroscopic volume. The microscopic devices moving with the fluid flow in small blood vessels can detect chemicals released by tissues in response to localized injury or infection. We find the devices can readily discriminate a single cell-sized chemical source from the background chemical concentration, providing high-resolution sensing in both time and space. By contrast, such a source would be difficult to distinguish from background when diluted throughout the blood volume as obtained with a blood sample

A new landscape of host–protozoa interactions involving the extracellular vesicles world

This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. © Cambridge University Press 2018Extracellular vesicles (EVs) are released by a wide number of cells including blood cells, immune system cells, tumour cells, adult and embryonic stem cells. EVs are a heterogeneous group of vesicles (~30–1000 nm) including microvesicles and exosomes. The physiological release of EVs represents a normal state of the cell, raising a metabolic equilibrium between catabolic and anabolic processes. Moreover, when the cells are submitted to stress with different inducers or in pathological situations (malignancies, chronic diseases, infectious diseases.), they respond with an intense and dynamic release of EVs. The EVs released from stimulated cells vs those that are released constitutively may themselves differ, both physically and in their cargo. EVs contain protein, lipids, nucleic acids and biomolecules that can alter cell phenotypes or modulate neighbouring cells. In this review, we have summarized findings involving EVs in certain protozoan diseases. We have commented on strategies to study the communicative roles of EVs during host–pathogen interaction and hypothesized on the use of EVs for diagnostic, preventative and therapeutic purposes in infectious diseases. This kind of communication could modulate the innate immune system and reformulate concepts in parasitism. Moreover, the information provided within EVs could produce alternatives in translational medicine.Peer reviewedFinal Accepted Versio

Aptamers in oncology: a diagnostic perspective

Nucleic acid sequences can produce a wide variety of three-dimensional conformations. Some of these structural forms are able to interact with proteins and small molecules with high affinity and specificity. These sequences, comprising either double or single stranded oligonucleotides, are called 'aptamers' based on the Greek word aptus, which means 'to fit'. Using an efficient selection process, randomised oligonucleotide libraries can be rapidly screened for aptamers with the appropriate binding characteristics. This technology has spawned the development of a new class of oligonucleotide therapeutic products. However, while interest among pharmaceutical companies continues to grow with some candidates already in clinical trials and one in the market, there appears to be some reluctance to fully explore the diagnostic potential of this technology. This article will review aptamer developments in diagnostics, compare them with other oligonucleotide therapeutics and highlight both potentials and pitfalls of technological development in this area

Epigenetic reprogramming of muscle progenitors: inspiration for clinical therapies

In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD)