Conserved features of cohesin binding along fission yeast chromosomes

High-resolution analysis of cohesin localization on fission yeast chromosomes reveals that several determinants, previously thought to be organism-specific, come together to shape overall distribution

Engineering microrobots for targeted cancer therapies from a medical perspective

Systemic chemotherapy remains the backbone of many cancer treatments. Due to its untargeted nature and the severe side effects it can cause, numerous nanomedicine approaches have been developed to overcome these issues. However, targeted delivery of therapeutics remains challenging. Engineering microrobots is increasingly receiving attention in this regard. Their functionalities, particularly their motility, allow microrobots to penetrate tissues and reach cancers more efficiently. Here, we highlight how different microrobots, ranging from tailor-made motile bacteria and tiny bubble-propelled microengines to hybrid spermbots, can be engineered to integrate sophisticated features optimised for precision-targeting of a wide range of cancers. Towards this, we highlight the importance of integrating clinicians, the public and cancer patients early on in the development of these novel technologies

Synthesis and properties of perfluoroalkyl groups containing double four-ring spherosilicate (siloxysilsesquioxane) precursors

Organically modified cage-like double four-ring spherosilicates have received considerable interest in the construction of nanosized hybrid materials, as well as building units for structural well-defined polymers. This group is extended by perfluoroalkyl ligands containing spherosilicates, synthesized by addition reaction of the octahydridodimethlysiloxyoctasilsesquioxane [H(CH3)2Si]8Si8O20 and heptadecafluorodecyl methacrylate. The resultant liquid spherosilicate substituted with eight terminal perfluoroalkyl groups was characterized by 29 and 13C NMR spectroscopies and MALDI Time-of-Flight mass spectrometry. Partial substitution of perfluoroalkyl ligands by trimethoxysilyl containing groups provides condensable precursors for the synthesis of hydrophobic and oleophobic materials via the sol-gel process. This new spherosilicate, carrying on average four perfluoroalkyl groups and four trimethoxysilyl groups shows better hydrophobic and oleophobic properties compared with commonly used perfluoroalkyltrialkoxysilanes under identical concentration of perfluoroalkyl chains. In addition a comprehensive literature survey is given on structural well characterized, organically modified cage-like double four-ring spherosilicates

On Your MARK, Get SET(D2), Go! H3K36me3 Primes DNA Mismatch Repair

Trimethylation of histone H3 on Lys36 (H3K36me3) by SETD2 is linked to actively transcribed regions. Li et al. identify a novel role for H3K36me3 that facilitates DNA mismatch repair (MMR) in cells by targeting the MMR machinery to chromatin during the cell cycle, thereby explaining certain cases of MMR-defective cancers

Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes.

In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown. Prior studies investigating confined mitosis have mainly used 2D cell culture systems. Here, we mimic aspects of metastasizing tumor cells dividing inside blood capillaries by investigating single-cell divisions of living human cancer cells, trapped inside 3D rolled-up, transparent nanomembranes. We assess the molecular effects of tubular confinement on key mitotic features, using optical high- and super-resolution microscopy. Our experiments show that tubular confinement affects the morphology and dynamics of the mitotic spindle, chromosome arrangements, and the organization of the cell cortex. Moreover, we reveal that membrane blebbing and/or associated processes act as a potential genome-safety mechanism, limiting the extent of genomic instability caused by mitosis in confined circumstances, especially in tubular 3D microenvironments. Collectively, our study demonstrates the potential of rolled-up nanomembranes for gaining molecular insights into key cellular events occurring in tubular 3D microenvironments in vivo.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 311529 (S.S.) and the Volkswagen Foundation no. 86 362 (S.S. and W.X.), a FEBS Return-to-Europe fellowship (C.K.S.), the Wellcome Trust (092096/Z/10/Z for N.L.; 094587/Z/10/Z for R.B.), and a European Research Council (ERC) Starting Researcher Grant (R.E.C.-S.; SYSGRO). O.G.S. acknowledges financial support from the DFG Research Unit 1713 “Sensorische Mikro und Nanosysteme”. D.H.G. acknowledges funding from the Alexander von Humboldt Foundation and the U.S. National Science Foundation (Grants: CMMI 1200241 and CBET-1442014). Research in the S.P.J. laboratory is funded by Cancer Research U.K., the ERC, and the European Community Seventh Framework Programme (DDResponse), with core infrastructure provided by Cancer Research U.K. and the Wellcome Trust.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acsnano.6b0046

Biodegradable electroactive polymers for electrochemically-triggered drug delivery

We report biodegradable electroactive polymer (EAP)-based materials and their application as drug delivery devices. Copolymers composed of oligoaniline-based electroactive blocks linked to either polyethylene glycol or polycaprolactone blocks via ester bonds were synthesized in three steps from commercially available starting materials and isolated without the need for column chromatography. The physicochemical and electrochemical properties of the polymers were characterized with a variety of techniques. The ability of the polymers to deliver the anti-inflammatory drug dexamethasone phosphate on the application of electrochemical stimuli was studied spectroscopically. Films of the polymers were shown to be degradable and cell adhesive in vitro. Such EAP-based materials have prospects for integration in implantable fully biodegradable/bioerodible EAP-based drug delivery devices that are capable of controlling the chronopharmacology of drugs for future clinical application

1 H, 13 C, 15 N backbone resonance assignment for the 1–164 construct of human XRCC4

From Springer Nature via Jisc Publications RouterHistory: received 2021-03-04, accepted 2021-06-14, registration 2021-06-15, pub-electronic 2021-06-25, online 2021-06-25, pub-print 2021-10Publication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/N019997/1Abstract: DNA double-strand breaks (DSBs) represent the most cytotoxic DNA lesions, as—if mis- or unrepaired—they can cause cell death or lead to genome instability, which in turn can cause cancer. DSBs are repaired by two major pathways termed homologous recombination and non-homologous end-joining (NHEJ). NHEJ is responsible for repairing the vast majority of DSBs arising in human cells. Defects in NHEJ factors are also associated with microcephaly, primordial dwarfism and immune deficiencies. One of the key proteins important for mediating NHEJ is XRCC4. XRCC4 is a dimer, with the dimer interface mediated by an extended coiled-coil. The N-terminal head domain forms a mixed alpha–beta globular structure. Numerous factors interact with the C-terminus of the coiled-coil domain, which is also associated with significant self-association between XRCC4 dimers. A range of construct lengths of human XRCC4 were expressed and purified, and the 1–164 variant had the best NMR properties, as judged by consistent linewidths, and chemical shift dispersion. In this work we report the 1H, 15 N and 13C backbone resonance assignments of human XRCC4 in the solution form of the 1–164 construct. Assignments were obtained by heteronuclear multidimensional NMR spectroscopy. In total, 156 of 161 assignable residues of XRCC4 were assigned to resonances in the TROSY spectrum, with an additional 11 resonances assigned to His-Tag residues. Prediction of solution secondary structure from a chemical shift analysis using the TALOS + webserver is in good agreement with the published X-ray crystal structures of this protein

Conducting polymer-based multilayer films for instructive biomaterial coatings

Aim: To demonstrate the design, fabrication and testing of conformable conducting biomaterials that encourage cell alignment. Materials & methods: Thin conducting composite biomaterials based on multilayer films of poly (3,4-ethylenedioxythiophene) derivatives, chitosan and gelatin were prepared in a layer-by-layer fashion. Fibroblasts were observed with fluorescence microscopy and their alignment (relative to the dipping direction and direction of electrical current passed through the films) was determined using ImageJ. Results: Fibroblasts adhered to and proliferated on the films. Fibroblasts aligned with the dipping direction used during film preparation and this was enhanced by a DC current. Conclusion: We report the preparation of conducting polymer-based films that enhance the alignment of fibroblasts on their surface which is an important feature of a variety of tissues. Lay abstract: Cells inhabit environments known as the extracellular matrix (ECM) which consists of a mixture of different biomolecules, and the precise composition and topographical properties are different in different tissues (e.g., bone, brain, muscle, skin). Cells interact intimately with the ECM, not only constructing the biomolecules, but assist its organization in 3D space, and its degradation (which is important for tissue remodeling); reciprocally, cells respond to the ECM (e.g., by modifying their size, shape, etc). Cellular alignment is observed in organs and tissues such as bones, muscles and skin, and this alignment is important for the healthy functioning of the organ/tissue. Here, we present a novel method of aligning cells on biomaterials, simply by applying an electrical current through the biomaterial

Mechanical properties of α-tricalcium phosphate-based bone cements incorporating regenerative biomaterials for filling bone defects exposed to low mechanical loads

Calcium phosphate-based cements with enhanced regenerative potential are promising biomaterials for the healing of bone defects. With a view to the use of such cements for low load bearing applications such as sinus augmentation or filling extraction sites, we have prepared α-tricalcium phosphate (α-TCP)-based bone cements including materials that we would expect to improve their regenerative potential, and describe the mechanical properities of the resulting formulations herein. Formulations incorporated α-TCP, hydroxyapatite, biopolymer-thickened wetting agents, sutures, and platelet poor plasma. The mechanical properties of the composites were composition dependent, and optimized formulations had clinically relevant mechanical properties. Such calcium phosphate-based cements have potential as replacements for cements such as those based on polymethylmethacrylate (PMMA)