648 research outputs found
Mechanobiological Principles Influence the Immune Response in Regeneration: Implications for Bone Healing
A misdirected or imbalanced local immune composition is often one of the reasons for unsuccessful regeneration resulting in scarring or fibrosis. Successful healing requires a balanced initiation and a timely down-regulation of the inflammation for the re-establishment of a biologically and mechanically homeostasis. While biomaterial-based approaches to control local immune responses are emerging as potential new treatment options, the extent to which biophysical material properties themselves play a role in modulating a local immune niche response has so far been considered only occasionally. The communication loop between extracellular matrix, non-hematopoietic cells, and immune cells seems to be specifically sensitive to mechanical cues and appears to play a role in the initiation and promotion of a local inflammatory setting. In this review, we focus on the crosstalk between ECM and its mechanical triggers and how they impact immune cells and non-hematopoietic cells and their crosstalk during tissue regeneration. We realized that especially mechanosensitive receptors such as TRPV4 and PIEZO1 and the mechanosensitive transcription factor YAP/TAZ are essential to regeneration in various organ settings. This indicates novel opportunities for therapeutic approaches to improve tissue regeneration, based on the immune-mechanical principles found in bone but also lung, heart, and skin
Molecular modeling of an antigenic complex between a viral peptide and a class I major histocompatibility glycoprotein
Computer simulation of the
conformations of short antigenic peptides (&lo
residues) either free or bound to their receptor,
the major histocompatibility complex (MHC)-
encoded glycoprotein H-2 Ld, was employed to
explain experimentally determined differences
in the antigenic activities within a set of related
peptides. Starting for each sequence from the
most probable conformations disclosed by a
pattern-recognition technique, several energyminimized
structures were subjected to molecular
dynamics simulations (MD) either in vacuo
or solvated by water molecules. Notably, antigenic
potencies were found to correlate to the
peptides propensity to form and maintain an
overall a-helical conformation through regular
i,i + 4 hydrogen bonds. Accordingly, less active
or inactive peptides showed a strong tendency
to form i,i+3 hydrogen bonds at their Nterminal
end. Experimental data documented
that the C-terminal residue is critical for interaction
of the peptide with H-2 Ld. This finding
could be satisfactorily explained by a 3-D
Q.S.A.R. analysis postulating interactions between
ligand and receptor by hydrophobic
forces. A 3-D model is proposed for the complex
between a high-affinity nonapeptide and the H-
2 Ld receptor. First, the H-2 Ld molecule was
built from X-ray coordinates of two homologous
proteins: HLA-A2 and HLA-Aw68, energyminimized
and studied by MD simulations. With
HLA-A2 as template, the only realistic simulation
was achieved for a solvated model with minor
deviations of the MD mean structure from
the X-ray conformation. Water simulation of the
H-2 Ld protein in complex with the antigenic
nonapeptide was then achieved with the template-
derived optimal parameters. The bound
peptide retains mainly its a-helical conformation
and binds to hydrophobic residues of H-2
Ld that correspond to highly polymorphic positions
of MHC proteins. The orientation of the
nonapeptide in the binding cleft is in accordance
with the experimentally determined distribution
of its MHC receptor-binding residues
(agretope residues). Thus, computer simulation was successfully employed to explain functional
data and predicts a-helical conformation
for the bound peptid
The role of public policy in stimulating radical environmental impact reduction in the automotive sector: The need to focus on product-service system innovation
This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 InderscienceProduct-service system (PSS) innovation is a promising approach to address sustainability challenges in the automotive industry. Starting form this assumption, this paper presents and discusses the potential contribution that policy measures can have in fostering the automotive sector in innovating on a PSS level. A set of policy instruments (general instruments and specific PSS-targeted ones) are presented and classified, underlining the effects they could produce at the company and environmental levels. In order to effectively support sustainable PSS diffusion in the automotive industry, the paper suggests the integration of general policy measures (such as internalisation of external costs, extended producer responsibility programmes and informative policies), with the PSS-targeted ones (such as Green Public Procurement focused on sustainable PSS, support of companies in acquiring information related to PSS, support of demonstrative pilot projects). In addition, the paper suggests the necessity to involve actively universities and research centres
Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein
Processing of endogenously synthesized proteins generates short peptides that are presented by MHC class I molecules to CD8 T lymphocytes. Here it is documented that not only the sequence of the presented peptide but also the residues by which it is flanked in the protein determine the efficiency of processing and presentation. This became evident when a viral sequence of proven antigenicity was inserted at different positions into an unrelated carrier protein. Not different peptides, but different amounts of the antigenic insert itself were retrieved by isolation of naturally processed peptides from cells expressing the different chimeric proteins. Low yield of antigenic peptide from an unfavorable integration site could be overcome by flanking the insert with oligo-alanine to space it from disruptive neighboring sequences. Notably, the degree of protection against lethal virus disease related directly to the amount of naturally processed antigenic peptide
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