4,196 research outputs found
Programmable interactions with biomimetic DNA linkers at fluid membranes and interfaces
At the heart of the structured architecture and complex dynamics of
biological systems are specific and timely interactions operated by
biomolecules. In many instances, biomolecular agents are spatially confined to
flexible lipid membranes where, among other functions, they control cell
adhesion, motility and tissue formation. Besides being central to several
biological processes, \emph{multivalent interactions} mediated by reactive
linkers confined to deformable substrates underpin the design of
synthetic-biological platforms and advanced biomimetic materials. Here we
review recent advances on the experimental study and theoretical modelling of a
heterogeneous class of biomimetic systems in which synthetic linkers mediate
multivalent interactions between fluid and deformable colloidal units,
including lipid vesicles and emulsion droplets. Linkers are often prepared from
synthetic DNA nanostructures, enabling full programmability of the
thermodynamic and kinetic properties of their mutual interactions. The coupling
of the statistical effects of multivalent interactions with substrate fluidity
and deformability gives rise to a rich emerging phenomenology that, in the
context of self-assembled soft materials, has been shown to produce exotic
phase behaviour, stimuli-responsiveness, and kinetic programmability of the
self-assembly process. Applications to (synthetic) biology will also be
reviewed.Comment: 63 pages, revie
Steric interactions between mobile ligands facilitate complete wrapping in passive endocytosis
Receptor-mediated endocytosis is an ubiquitous process through which cells
internalize biological or synthetic nanoscale objects, including viruses,
unicellular parasites, and nanomedical vectors for drug or gene delivery. In
passive endocytosis the cell plasma membrane wraps around the "invader"
particle driven by ligand-receptor complexation. By means of theory and
numerical simulations, here we demonstrate how particles decorated by freely
diffusing and non-mutually-interacting (ideal) ligands are significantly more
difficult to wrap than those where ligands are either immobile or interact
sterically with each other. Our model rationalizes the relationship between
uptake mechanism and structural details of the invader, such as ligand size,
mobility and ligand/receptor affinity, providing a comprehensive picture of
pathogen endocytosis and helping the rational design of efficient drug delivery
vectors.Comment: Updated version of the manuscript. Accepted for publication in PR
Computational identification of transcription factor binding sites by functional analysis of sets of genes sharing overrepresented upstream motifs
BACKGROUND: Transcriptional regulation is a key mechanism in the functioning
of the cell, and is mostly effected through transcription factors binding to
specific recognition motifs located upstream of the coding region of the
regulated gene. The computational identification of such motifs is made easier
by the fact that they often appear several times in the upstream region of the
regulated genes, so that the number of occurrences of relevant motifs is often
significantly larger than expected by pure chance. RESULTS: To exploit this
fact, we construct sets of genes characterized by the statistical
overrepresentation of a certain motif in their upstream regions. Then we study
the functional characterization of these sets by analyzing their annotation to
Gene Ontology terms. For the sets showing a statistically significant specific
functional characterization, we conjecture that the upstream motif
characterizing the set is a binding site for a transcription factor involved in
the regulation of the genes in the set. CONCLUSIONS: The method we propose is
able to identify many known binding sites in S. cerevisiae and new candidate
targets of regulation by known transcription factors. Its application to less
well studied organisms is likely to be valuable in the exploration of their
regulatory interaction network.Comment: 19 pages, 1 figure. Published version with several improvements.
Supplementary material available from the author
Stable cuspidal curves and the integral Chow ring of
In this paper we introduce the moduli stack
of -marked stable at most cuspidal curves of genus and we use it to
determine the integral Chow ring of . Along the
way, we also determine the integral Chow ring of
.Comment: 47 pages, comments welcome! V2: some mistakes corrected, some new
figures added. To appear on Geometry & Topolog
A Hybrid High-Order method for multiple-network poroelasticity
We develop Hybrid High-Order methods for multiple-network poroelasticity, modelling seepage through deformable fissured porous media. The proposed methods are designed to support general polygonal and polyhedral elements. This is a crucial feature in geological modelling, where the need for general elements arises, e.g., due to the presence of fracture and faults, to the onset of degenerate elements to account for compaction or erosion, or when nonconforming mesh adaptation is performed. We use as a starting point a mixed weak formulation where an additional total pressure variable is added, that ensures the fulfilment of a discrete inf-sup condition. A complete theoretical analysis is performed, and the theoretical results are demonstrated on a complete panel of numerical tests
Early Bronze Age IV Food Trasformation and Storage Installations at Khirbet al-Batrawy, Jordan
Rapporto sui risultati degli scavi a Khirbet al-BatrawyReport on the results of the excavations at Khirbet al-Batraw
Cation-Responsive and Photocleavable Hydrogels from Noncanonical Amphiphilic DNA Nanostructures.
Funder: Imperial College LondonThanks to its biocompatibility, versatility, and programmable interactions, DNA has been proposed as a building block for functional, stimuli-responsive frameworks with applications in biosensing, tissue engineering, and drug delivery. Of particular importance for in vivo applications is the possibility of making such nanomaterials responsive to physiological stimuli. Here, we demonstrate how combining noncanonical DNA G-quadruplex (G4) structures with amphiphilic DNA constructs yields nanostructures, which we termed "Quad-Stars", capable of assembling into responsive hydrogel particles via a straightforward, enzyme-free, one-pot reaction. The embedded G4 structures allow one to trigger and control the assembly/disassembly in a reversible fashion by adding or removing K+ ions. Furthermore, the hydrogel aggregates can be photo-disassembled upon near-UV irradiation in the presence of a porphyrin photosensitizer. The combined reversibility of assembly, responsiveness, and cargo-loading capabilities of the hydrophobic moieties make Quad-Stars a promising candidate for biosensors and responsive drug delivery carriers
The decline in muscle strength and muscle quality in relation to metabolic derangements in adult women with obesity
Background & aims: The metabolic and functional characteristics related to sarcopenic obesity have not been thoroughly explored in the earlier stages of the aging process. The aim of the present study was to examine the phenotype of sarcopenic obesity, in terms of lean body mass, muscle strength and quality, in adult women with and without the Metabolic Syndrome (MetS), and its relationship with the features of myosteatosis. Methods: Study participants were enrolled at the Sapienza University, Rome, Italy. Body composition was assessed by DXA. The Handgrip strength test (HGST) was performed. HGST was normalized to arm lean mass to indicate muscle quality; intermuscular adipose tissue (IMAT) and intramyocellular lipid content (IMCL) were measured by magnetic resonance imaging and spectroscopy, as indicators of myosteatosis. Different indices of sarcopenia were calculated, based on appendicular lean mass (ALM, kg) divided by height squared, or weight. The NCEP-ATPIII criteria were used to diagnose the MetS. HOMA-IR was calculated. The physical activity level (PAL) was assessed through the IPAQ questionnaire. Results: 54 women (age: 48 ± 14 years, BMI: 37.9 ± 5.4 kg/m 2 ) were included. 54% had the MetS (metabolically unhealthy, MUO). HGST/arm lean mass was lower in MUO women than women without the MetS (6.3 ± 1.8 vs. 7.8 ± 1.6, p = 0.03). No differences emerged in terms of absolute ALM (kg) or other indices of sarcopenia (ALM/h 2 or ALM/weight) between metabolically healthy (MHO) vs. MUO women (p > 0.05). Muscle quality was negatively associated with HOMA-IR (p = 0.02), after adjustment for age, body fat, hs-CRP levels, and PAL. IMAT, but not IMCL, was significantly higher in obese women with the MetS compared to women without the MetS (p > 0.05). No association emerged between HGST/arm lean mass and IMAT or IMCL when HOMA-IR was included in the models. Conclusion: Insulin resistance, and not sarcopenia or myosteatosis per se, was associated with muscle weakness, resulting in the phenotype of “dynapenic obesity” in middle-aged women with the metabolic syndrome
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