1,237 research outputs found
Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.
Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma.1166Ysciescopu
Membrane-Associated Transporter Protein (MATP) Regulates Melanosomal pH and Influences Tyrosinase Activity
The SLC45A2 gene encodes a Membrane-Associated Transporter Protein (MATP). Mutations of this gene cause oculocutaneous albinism type 4 (OCA4). However, the molecular mechanism of its action in melanogenesis has not been elucidated. Here, we discuss the role of MATP in melanin production. The SLC45A2 gene is highly enriched in human melanocytes and melanoma cell lines, and its protein, MATP, is located in melanosomes. The knockdown of MATP using siRNAs reduced melanin content and tyrosinase activity without any morphological change in melanosomes or the expression of melanogenesis-related proteins. Interestingly, the knockdown of MATP significantly lowered the melanosomal pH, as verified through DAMP analysis, suggesting that MATP regulates melanosomal pH and therefore affects tyrosinase activity. Finally, we found that the reduction of tyrosinase activity associated with the knockdown of MATP was readily recovered by copper treatment in the in vitro L-DOPA oxidase activity assay of tyrosinase. Considering that copper is an important element for tyrosinase activity and that its binding to tyrosinase depends on melanosomal pH, MATP may play an important role in regulating tyrosinase activity via controlling melanosomal pH.112820Ysciescopu
Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis
Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials
Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice
<p>Abstract</p> <p>Background</p> <p>Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the <it>in vivo </it>imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield.</p> <p>Methods</p> <p>CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye. <it>In vivo </it>fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured.</p> <p>Results</p> <p>QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces.</p> <p>Conclusion</p> <p>Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was demonstrated. This work was done using very low doses of injected QDs and the detection was done using a minimally invasive method.</p
Reengineering the clinical research enterprise to involve more community clinicians
<p>Abstract</p> <p>Background</p> <p>The National Institutes of Health has called for expansion of practice-based research to improve the clinical research enterprise.</p> <p>Methods</p> <p>This paper presents a model for the reorganization of clinical research to foster long-term participation by community clinicians.</p> <p>Based on the literature and interviews with clinicians and other stakeholders, we posited a model, conducted further interviews to test the viability of the model, and further adapted it.</p> <p>Results</p> <p>We propose a three-dimensional system of checks and balances to support community clinicians using research support organizations, community outreach, a web-based registry of clinicians and studies, web-based training services, quality audits, and a feedback mechanism for clinicians engaged in research.</p> <p>Conclusions</p> <p>The proposed model is designed to offer a systemic mechanism to address current barriers that prevent clinicians from participation in research. Transparent mechanisms to guarantee the safety of patients and the integrity of the research enterprise paired with efficiencies and economies of scale are maintained by centralizing some of the functions. Assigning other responsibilities to more local levels assures flexibility with respect to the size of the clinician networks and the changing needs of researchers.</p
Broadband luminescence in defect-engineered electrochemically produced porous Si/ZnO nanostructures
The fabrication, by an all electrochemical process, of porous Si/ZnO nanostructures with engineered structural defects, leading to strong and broadband deep level emission from ZnO, is presented. Such nanostructures are fabricated by a combination of metal-assisted chemical etching of Si and direct current electrodeposition of ZnO. It makes the whole fabrication process low-cost, compatible with Complementary Metal-Oxide Semiconductor technology, scalable and easily industrialised. The photoluminescence spectra of the porous Si/ZnO nanostructures reveal a correlation between the lineshape, as well as the strength of the emission, with the morphology of the underlying porous Si, that control the induced defects in the ZnO. Appropriate fabrication conditions of the porous Si lead to exceptionally bright Gaussian-type emission that covers almost the entire visible spectrum, indicating that porous Si/ZnO nanostructures could be a cornerstone material towards white-light-emitting devices
AntEpiSeeker: detecting epistatic interactions for case-control studies using a two-stage ant colony optimization algorithm
<p>Abstract</p> <p>Background</p> <p>Epistatic interactions of multiple single nucleotide polymorphisms (SNPs) are now believed to affect individual susceptibility to common diseases. The detection of such interactions, however, is a challenging task in large scale association studies. Ant colony optimization (ACO) algorithms have been shown to be useful in detecting epistatic interactions.</p> <p>Findings</p> <p>AntEpiSeeker, a new two-stage ant colony optimization algorithm, has been developed for detecting epistasis in a case-control design. Based on some practical epistatic models, AntEpiSeeker has performed very well.</p> <p>Conclusions</p> <p>AntEpiSeeker is a powerful and efficient tool for large-scale association studies and can be downloaded from <url>http://nce.ads.uga.edu/~romdhane/AntEpiSeeker/index.html</url>.</p
Properties of Graphene: A Theoretical Perspective
In this review, we provide an in-depth description of the physics of
monolayer and bilayer graphene from a theorist's perspective. We discuss the
physical properties of graphene in an external magnetic field, reflecting the
chiral nature of the quasiparticles near the Dirac point with a Landau level at
zero energy. We address the unique integer quantum Hall effects, the role of
electron correlations, and the recent observation of the fractional quantum
Hall effect in the monolayer graphene. The quantum Hall effect in bilayer
graphene is fundamentally different from that of a monolayer, reflecting the
unique band structure of this system. The theory of transport in the absence of
an external magnetic field is discussed in detail, along with the role of
disorder studied in various theoretical models. We highlight the differences
and similarities between monolayer and bilayer graphene, and focus on
thermodynamic properties such as the compressibility, the plasmon spectra, the
weak localization correction, quantum Hall effect, and optical properties.
Confinement of electrons in graphene is nontrivial due to Klein tunneling. We
review various theoretical and experimental studies of quantum confined
structures made from graphene. The band structure of graphene nanoribbons and
the role of the sublattice symmetry, edge geometry and the size of the
nanoribbon on the electronic and magnetic properties are very active areas of
research, and a detailed review of these topics is presented. Also, the effects
of substrate interactions, adsorbed atoms, lattice defects and doping on the
band structure of finite-sized graphene systems are discussed. We also include
a brief description of graphane -- gapped material obtained from graphene by
attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic
Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics
We present a quasi-model-independent search for the physics responsible for
electroweak symmetry breaking. We define final states to be studied, and
construct a rule that identifies a set of relevant variables for any particular
final state. A new algorithm ("Sleuth") searches for regions of excess in those
variables and quantifies the significance of any detected excess. After
demonstrating the sensitivity of the method, we apply it to the semi-inclusive
channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV
at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no
evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review
Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV
The inclusive cross section for production of isolated photons has been
measured in \pbarp collisions at GeV with the \D0 detector at
the Fermilab Tevatron Collider. The photons span a transverse energy ()
range from 7-49 GeV and have pseudorapidity . This measurement is
combined with to previous \D0 result at GeV to form a ratio
of the cross sections. Comparison of next-to-leading order QCD with the
measured cross section at 630 GeV and ratio of cross sections show satisfactory
agreement in most of the range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001
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