661 research outputs found
Isolation and characterization of a spontaneously immortalized bovine retinal pigmented epithelial cell line
<p>Abstract</p> <p>Background</p> <p>The Retinal Pigmented Epithelium (RPE) is juxtaposed with the photoreceptor outer segments of the eye. The proximity of the photoreceptor cells is a prerequisite for their survival, as they depend on the RPE to remove the outer segments and are also influenced by RPE cell paracrine factors. RPE cell death can cause a progressive loss of photoreceptor function, which can diminish vision and, over time, blindness ensues. Degeneration of the retina has been shown to induce a variety of retinopathies, such as Stargardt's disease, Cone-Rod Dystrophy (CRD), Retinitis Pigmentosa (RP), Fundus Flavimaculatus (FFM), Best's disease and Age-related Macular Degeneration (AMD). We have cultured primary bovine RPE cells to gain a further understanding of the mechanisms of RPE cell death. One of the cultures, named tRPE, surpassed senescence and was further characterized to determine its viability as a model for retinal diseases.</p> <p>Results</p> <p>The tRPE cell line has been passaged up to 150 population doublings and was shown to be morphologically similar to primary cells. They have been characterized to be of RPE origin by reverse transcriptase PCR and immunocytochemistry using the RPE-specific genes <it>RPE65 </it>and <it>CRALBP </it>and RPE-specific proteins RPE65 and Bestrophin. The tRPE cells are also immunoreactive to vimentin, cytokeratin and zonula occludens-1 antibodies. Chromosome analysis indicates a normal diploid number. The tRPE cells do not grow in suspension or in soft agar. After <sup>3</sup>H thymidine incorporation, the cells do not appear to divide appreciably after confluency.</p> <p>Conclusion</p> <p>The tRPE cells are immortal, but still exhibit contact inhibition, serum dependence, monolayer growth and secrete an extra-cellular matrix. They retain the <it>in-vivo </it>morphology, gene expression and cell polarity. Additionally, the cells endocytose exogenous melanin, A2E and purified lipofuscin granules. This cell line may be a useful <it>in-vitro </it>research model for retinal maculopathies.</p
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The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.
Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies
The Two Faces of Anomaly Mediation
Anomaly mediation is a ubiquitous source of supersymmetry (SUSY) breaking
which appears in almost every theory of supergravity. In this paper, we show
that anomaly mediation really consists of two physically distinct phenomena,
which we dub "gravitino mediation" and "Kahler mediation". Gravitino mediation
arises from minimally uplifting SUSY anti-de Sitter (AdS) space to Minkowski
space, generating soft masses proportional to the gravitino mass. Kahler
mediation arises when visible sector fields have linear couplings to SUSY
breaking in the Kahler potential, generating soft masses proportional to beta
function coefficients. In the literature, these two phenomena are lumped
together under the name "anomaly mediation", but here we demonstrate that they
can be physically disentangled by measuring associated couplings to the
goldstino. In particular, we use the example of gaugino soft masses to show
that gravitino mediation generates soft masses without corresponding goldstino
couplings. This result naively violates the goldstino equivalence theorem but
is in fact necessary for supercurrent conservation in AdS space. Since
gravitino mediation persists even when the visible sector is sequestered from
SUSY breaking, we can use the absence of goldstino couplings as an unambiguous
definition of sequestering.Comment: 21 pages, 1 table; v2, references added, extended discussion in
introduction and appendix; v3, JHEP versio
A new measurement of the properties of the rare decay K -> pi+ e+ e-
A large low-background sample of events (10300) has been collected for the
rare decay of kaons in flight K+ -> pi+ e+ e- by experiment E865 at the
Brookhaven AGS. The decay products were accepted by a broad band
high-resolution charged particle spectrometer with particle identification. The
branching ratio (2.94 +- 0.05(stat.) +- 0.13(syst.) +- 0.05(model))*10**{-7}
was determined normalizing to events from the decay chain K+ -> pi+ pi0; pi0 ->
e+ e- gamma. From the analysis of the decay distributions the vector nature of
this decay is firmly established now, and limits on scalar and tensor
contributions are deduced. From the (e+ e-) invariant mass distribution the
decay form factor f(z)=f0(1+ delta*z) (z=M(ee)**2/m(K)**2) is determined with
delta=2.14 +- 0.13 +- 0.15. Chiral QCD perturbation theory predictions for the
form factor are also tested, and terms beyond leading order O(p**4) are found
to be important.Comment: 4 pages, 5 figure
Identified baryon and meson distributions at large transverse momenta from Au+Au collisions at GeV
Transverse momentum spectra of , and up to 12 GeV/c
at mid-rapidity in centrality selected Au+Au collisions at GeV are presented. In central Au+Au collisions, both and
show significant suppression with respect to binary scaling at
4 GeV/c. Protons and anti-protons are less suppressed than
, in the range 1.5 6 GeV/c. The and
ratios show at most a weak dependence and no significant
centrality dependence. The ratios in central Au+Au collisions approach
the values in p+p and d+Au collisions at 5 GeV/c. The results at high
indicate that the partonic sources of , and have
similar energy loss when traversing the nuclear medium.Comment: 6 pages, 4 figure
Longitudinal double-spin asymmetry and cross section for inclusive jet production in polarized proton collisions at sqrt(s) = 200 GeV
We report a measurement of the longitudinal double-spin asymmetry A_LL and
the differential cross section for inclusive midrapidity jet production in
polarized proton collisions at sqrt(s)=200 GeV. The cross section data cover
transverse momenta 5 < pT < 50 GeV/c and agree with next-to-leading order
perturbative QCD evaluations. The A_LL data cover 5 < pT < 17 GeV/c and
disfavor at 98% C.L. maximal positive gluon polarization in the polarized
nucleon.Comment: 6 pages, 3 figures. Minor changes from review process in Phys. Rev.
Lett. Plain text tables of data in STAR publications may be found at
http://www.star.bnl.gov/central/publications
Longitudinal double-spin asymmetry for inclusive jet production in p+p collisions at sqrt(s)=200 GeV
We report a new STAR measurement of the longitudinal double-spin asymmetry
A_LL for inclusive jet production at mid-rapidity in polarized p+p collisions
at a center-of-mass energy of sqrt(s) = 200 GeV. The data, which cover jet
transverse momenta 5 < p_T < 30 GeV/c, are substantially more precise than
previous measurements. They provide significant new constraints on the gluon
spin contribution to the nucleon spin through the comparison to predictions
derived from one global fit of polarized deep-inelastic scattering
measurements.Comment: 7 pages, 4 figures + 1 tabl
Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study
Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015
Neutral Kaon Interferometry in Au+Au collisions at sqrt(s_NN) = 200 GeV
We present the first statistically meaningful results from two-K0s
interferometry in heavy-ion collisions. A model that takes the effect of the
strong interaction into account has been used to fit the measured correlation
function. The effects of single and coupled channel were explored. At the mean
transverse mass m_T = 1.07 GeV, we obtain the values R = 4.09 +/- 0.46 (stat.)
+/- 0.31 (sys) fm and lambda = 0.92 +/- 0.23 (stat) +/- 0.13 (sys), where R and
lambda are the invariant radius and chaoticity parameters respectively. The
results are qualitatively consistent with m_T systematics established with
pions in a scenario characterized by a strong collective flow.Comment: 11 pages, 10 figure
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