11,388 research outputs found
Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases inĀ Inflammation and Fibrosis of Skeletal Muscles
In skeletal muscles, levels and activity of Matrix MetalloProteinases (MMPs) and Tissue Inhibitors of MetalloProteinases (TIMPs) have been involved in myoblast migration, fusion and various physiological and pathological remodeling situations including neuromuscular diseases. This has opened perspectives for the use of MMPs' overexpression to improve the efficiency of cell therapy in muscular dystrophies and resolve fibrosis. Alternatively, inhibition of individual MMPs in animal models of muscular dystrophies has provided evidence of beneficial, dual or adverse effects on muscle morphology or function. We review here the role played by MMPs/TIMPs in skeletal muscle inflammation and fibrosis, two major hurdles that limit the success of cell and gene therapy. We report and analyze the consequences of genetic or pharmacological modulation of MMP levels on the inflammation of skeletal muscles and their repair in light of experimental findings. We further discuss how the interplay between MMPs/TIMPs levels, cytokines/chemokines, growth factors and permanent low-grade inflammation favor cellular and molecular modifications resulting in fibrosis
Instability of supersymmetric microstate geometries
We investigate the classical stability of supersymmetric, asymptotically
flat, microstate geometries with five non-compact dimensions. Such geometries
admit an "evanescent ergosurface": a timelike hypersurface of infinite
redshift. On such a surface, there are null geodesics with zero energy relative
to infinity. These geodesics are stably trapped in the potential well near the
ergosurface. We present a heuristic argument indicating that this feature is
likely to lead to a nonlinear instability of these solutions. We argue that the
precursor of such an instability can be seen in the behaviour of linear
perturbations: nonlinear stability would require that all linear perturbations
decay sufficiently rapidly but the stable trapping implies that some linear
perturbation decay very slowly. We study this in detail for the most symmetric
microstate geometries. By constructing quasinormal modes of these geometries we
show that generic linear perturbations decay slower than any inverse power of
time.This work was supported by European Research Council grant ERC-2011-StG279363-HiDGR.This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/JHEP10(2016)03
Photoconfigurable, Cell-Remodelable Disulfide Cross-linked Hyaluronic Acid Hydrogels.
Dynamic photoresponsive synthetic hydrogels offer important advantages for biomaterials design, from the ability to cure hydrogels and encapsulate cells in situ to the light-mediated control of cell-spreading and tissue formation. We report the facile and effective photocuring and photoremodeling of disulfide-cross-linked hyaluronic acid hydrogels, based on photo-oxidation of corresponding thiol residues and their radical-mediated photodegradation. We find that the mechanical properties of disulfide hydrogels and the extent of their photoremodeling can be tuned by controlling the photo-oxidation and photodegradation reactions, respectively. This enables not only the photopatterning of the mechanical properties of hydrogels but also their self-healing and photomediated healing. Finally, we demonstrate the ability to encapsulate mesenchymal stromal cells within these materials and to regulate their protrusion and spreading in 3D matrices by controlling the mechanical properties of the disulfide networks. Therefore, synthetically accessible photoconfigurable disulfide hydrogels offer interesting opportunities for the design of soft biomaterials and the regulation of cell encapsulation and matrix remodeling for tissue engineering
Most Complex Non-Returning Regular Languages
A regular language is non-returning if in the minimal deterministic
finite automaton accepting it there are no transitions into the initial state.
Eom, Han and Jir\'askov\'a derived upper bounds on the state complexity of
boolean operations and Kleene star, and proved that these bounds are tight
using two different binary witnesses. They derived upper bounds for
concatenation and reversal using three different ternary witnesses. These five
witnesses use a total of six different transformations. We show that for each
there exists a ternary witness of state complexity that meets the
bound for reversal and that at least three letters are needed to meet this
bound. Moreover, the restrictions of this witness to binary alphabets meet the
bounds for product, star, and boolean operations. We also derive tight upper
bounds on the state complexity of binary operations that take arguments with
different alphabets. We prove that the maximal syntactic semigroup of a
non-returning language has elements and requires at least
generators. We find the maximal state complexities of atoms of
non-returning languages. Finally, we show that there exists a most complex
non-returning language that meets the bounds for all these complexity measures.Comment: 22 pages, 6 figure
Functional features of an ssi signal of plasmid pGKV21 in Escherichia coli
A single-strand initiation (ssi) signal was detected on the Lactococcus lactis plasmid pGKV21 containing the replicon of pWV01 by its ability to complement the poor growth of an M13 phage derivative (M13??lac182) lacking the complementary-strand origin in Escherichia coli. This ssi signal was situated at the 229-nucleotide (nt) DdeI-DraI fragment and located within the 109 nt upstream of the nick site of the putative plus origin. SSI activity is orientation specific with respect to the direction of replication. We constructed an ssi signal-deleted plasmid and then examined the effects of the ssi signal on the conversion of the single-stranded replication intermediate to double-stranded plasmid DNA in E. coli. The plasmid lacking an ssi signal accumulated much more plasmid single-stranded DNA than the wild-type plasmid did. Moreover, deletion of this region caused a great reduction in plasmid copy number or plasmid maintenance. These results suggest that in E. coli, this ssi signal directs its lagging-strand synthesis as a minus origin of plasmid pGKV21. Primer RNA synthesis in vitro suggests that E. coli RNA polymerase directly recognizes the 229-nt ssi signal and synthesizes primer RNA dependent on the presence of E. coli single-stranded DNA binding (SSB) protein. This region contains two stem-loop structures, stem-loop I and stem-loop II. Deletion of stem-loop I portion results in loss of priming activity by E. coli RNA polymerase, suggesting that stem-loop I portion is essential for priming by E. coli RNA polymerase on the SSB-coated single-stranded DNA template.open5
Hepaticocystic duct and a rare extra-hepatic "cruciate" arterial anastomosis: a case report
<p>Abstract</p> <p>Introduction</p> <p>The variations in the morphological characteristics of the extra-hepatic biliary system are interesting.</p> <p>Case presentation</p> <p>During the dissection of cadavers to study the morphological characteristics of the extra-hepatic biliary system, a 46-year-old male cadaver was found to have drainage of the common hepatic duct drains directly into the gall bladder neck. The right and left hepatic ducts were not seen extra-hepatically. Further drainage of the bile away from the gallbladder and into the duodenum was provided by the cystic duct. Formation of the common bile duct by the union of the common hepatic duct and cystic duct was absent. Further more the right hepatic artery was found to be communicating with the left hepatic artery by a "bridging artery" after giving rise to the cystic artery. An accessory hepatic artery originated from the "bridging artery" forming a "cruciate" hepatic arterial anastomosis.</p> <p>Conclusion</p> <p>Combination of a Hepaticocystic duct and an aberrant variation in the extra-hepatic arterial system is extremely rare.</p
Genome sequence, population history, and pelage genetics of the endangered African wild dog (Lycaon pictus)
BACKGROUND: The African wild dog (Lycaon pictus) is an endangered sub-Saharan canid threatened by severe habitat fragmentation, human-wildlife conflict, and infectious disease. A highly specialized carnivore, it is distinguished by its social structure, dental morphology, absence of dewclaws, and colorful pelage.
RESULTS: We sequenced the genomes of two individuals from populations representing two distinct ecological histories (Laikipia County, Kenya and KwaZulu-Natal Province, South Africa). We reconstructed population demographic histories for the two individuals and scanned the genomes for evidence of selection.
CONCLUSIONS: We show that the African wild dog has undergone at least two effective population size reductions in the last one million years. We found evidence of Lycaon individual-specific regions of low diversity, suggestive of inbreeding or population-specific selection. Further research is needed to clarify whether these population reductions and low diversity regions are characteristic of the species as a whole. We documented positive selection on the Lycaon mitochondrial genome. Finally, we identified several candidate genes (ASIP, MITF, MLPH, PMEL) that may play a role in the characteristic Lycaon pelage
Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films
Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B)
and phosphorous (P) ions. Different samples, prepared by varying the ion
dose in the range to 5 x and ion energy in the range
150-350 keV, were investigated by the Raman spectroscopy, photoluminescence
(PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman
results from dose dependent B implanted samples show red-shifted and
asymmetrically broadened Raman line-shape for B dose greater than
ions cm. The asymmetry and red shift in the Raman line-shape is
explained in terms of quantum confinement of phonons in silicon nanostructures
formed as a result of ion implantation. PL spectra shows size dependent visible
luminescence at 1.9 eV at room temperature, which confirms the presence
of silicon nanostructures. Raman studies on P implanted samples were also
done as a function of ion energy. The Raman results show an amorphous top SOS
surface for sample implanted with 150 keV P ions of dose 5 x ions
cm. The nanostructures are formed when the P energy is increased to
350 keV by keeping the ion dose fixed. The GAXRD results show consistency with
the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in
SILICON(SPRINGER
The formation of professional identity in medical students: considerations for educators
<b>Context</b> Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity ā ways of being and relating in professional contexts.<p></p>
<b>Objectives</b> This article conceptualises the processes underlying the formation and maintenance of medical studentsā professional identity drawing on concepts from social psychology.<p></p>
<b>Implications</b> A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.<p></p>
<b>Conclusions</b> Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education
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