511 research outputs found
Genersatztherapie bei hereditären Netzhauterkrankungen
No full textZusammenfassungCharakteristisch für erblich bedingte Netzhauterkrankungen sind Funktionsausfälle in der Reizaufnahme und Reizweiterleitung innerhalb der Netzhaut, die zur Reduktion des Sehvermögens bis zur Blindheit führen. Dabei verursachen genetisch bedingte Ausfälle photorezeptorspezifischer Gene eine große Zahl von klinisch und ursächlich abgrenzbaren Krankheitsbildern, wobei jedes für sich zu den seltenen Erkrankungen gehört. In ihrer Gesamtheit und mit einer Prävalenz von 1 : 2500 sind die erblichen Netzhauterkrankungen jedoch ein klinisch bedeutsamer Erkrankungstypus – insbesondere auch im Hinblick auf die damit einhergehenden Einschränkungen in der Erwerbsfähigkeit und dem Verlust an Lebensqualität für die Betroffenen. Bis heute konnten Mutationen in über 250 Genen identifiziert werden, die für die verschiedenen Formen erblicher Netzhautdystrophien verantwortlich sind (https://sph.uth.tmc.edu/Retnet). Die präklinische Forschung an geeigneten Tiermodellen hat in den letzten Jahren große Fortschritte im Verständnis der Mutation zugrunde liegender pathologischer und molekularbiologischer Vorgänge ermöglicht. Basierend auf diesen Erkenntnissen haben sich neue Perspektiven für die Entwicklung innovativer Therapiestrategien für erbliche Netzhauterkrankungen beim Menschen eröffnet, welche weltweit bislang noch nicht heilbar sind. Der Erfolg präklinischer Studien hat zum Beginn mehrerer humaner Translationen geführt. Die Ergebnislage der laufenden humanen Studien macht jedoch auch die Notwendigkeit sichtbar, Optimierungsstrategien des neuen therapeutischen Ansatzes zu entwickeln und zu prüfen.</jats:p
BK Channels Mediate Pathway-Specific Modulation of Visual Signals in the In Vivo Mouse Retina
No full textCRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice
No full textItem does not contain fulltextMutations in the CRB1 gene lead to retinal dystrophies ranging from Leber congenital amaurosis (LCA) to early-onset retinitis pigmentosa (RP), due to developmental defects or loss of adhesion between photoreceptors and Muller glia cells, respectively. Whereas over 150 mutations have been found, no clear genotype-phenotype correlation has been established. Mouse Crb1 knockout retinas show a mild phenotype limited to the inferior quadrant, whereas Crb2 knockout retinas display a severe degeneration throughout the retina mimicking the phenotype observed in RP patients associated with CRB1 mutations. Crb1Crb2 double mutant retinas have severe developmental defects similar to the phenotype observed in LCA patients associated with CRB1 mutations. Therefore, CRB2 is a candidate modifying gene of human CRB1-related retinal dystrophy. In this study, we studied the cellular localization of CRB1 and CRB2 in human retina and tested the influence of the Crb2 gene allele on Crb1-retinal dystrophies in mice. We found that in contrast to mice, in the human retina CRB1 protein was expressed at the subapical region in photoreceptors and Muller glia cells, and CRB2 only in Muller glia cells. Genetic ablation of one allele of Crb2 in heterozygote Crb1(+/-) retinas induced a mild retinal phenotype, but in homozygote Crb1 knockout mice lead to an early and severe phenotype limited to the entire inferior retina. Our data provide mechanistic insight for CRB1-related LCA and RP
Lack of the sodium-driven chloride bicarbonate exchanger NCBE impairs visual function in the mouse retina
No full textAuthor Correction: A detailed map of Higgs boson interactions by the ATLAS experiment ten years after the discovery
No full textSearch for non-resonant Higgs boson pair production in final states with leptons, taus, and photons in pp collisions at √s = 13 TeV with the ATLAS detector
No full textA search is presented for non-resonant Higgs boson pair production, targeting the
bbZZ, 4V (V = W or Z), V V τ τ , 4τ , γγV V and γγτ τ decay channels. Events are categorised
based on the multiplicity of light charged leptons (electrons or muons), hadronically decaying
tau leptons, and photons. The search is based on a data sample of proton-proton collisions at
√s = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider,
corresponding to an integrated luminosity of 140 fb−1
. No evidence of the signal is found and
the observed (expected) upper limit on the cross-section for non-resonant Higgs boson pair
production is determined to be 17 (11) times the Standard Model predicted cross-section
at 95% confdence level under the background-only hypothesis. The observed (expected)
constraints on the HHH coupling modifer, κλ, are determined to be −6.2 < κλ < 11.6
(−4.5 < κλ < 9.6) at 95% confdence level, assuming the Standard Model for the expected
limits and that new physics would only afect κλ
MPP3 regulates levels of PALS1 and adhesion between photoreceptors and Muller cells.
No full textItem does not contain fulltextMPP3 and CRB1 both interact directly with PALS1/MPP5 and through this scaffold protein may form a large protein complex. To investigate the role of MPP3 in the retina we have analyzed conditional mutant Mpp3 knockout mice. Ultrastructural localization studies revealed that MPP3 is predominantly localized in apical villi of Muller glia cells. Retinas lacking MPP3 developed late onset retinal degeneration, with sporadic foci of rosette formation in the central part of the retina. Retinal degeneration in Mpp3 cKO mice was accelerated by exposure to moderate levels of white light. Electroretinography recordings in aging mice under both scotopic and photopic conditions ranged from normal to mildly subnormal, while the magnitude correlated with the strength and extent of morphological alterations. Loss of MPP3 resulted in significant loss of PALS1 at the subapical region adjacent to adherens junctions, and loss of MPP3 in Pals1 conditional knockdown retinas significantly accelerated the onset of retinal degeneration. These data suggest that MPP3 is required for maintaining proper levels of PALS1 at the subapical region, and indicate that the MPP3 gene is a candidate modulator of the Crumbs complex.01 oktober 201
Study of high-transverse-momentum Higgs boson production in association with a vector boson in the qqbb final state with the ATLAS detector
No full textThis Letter presents the first study of Higgs boson production in association with a vector boson (
V
=
W
or
Z
) in the fully hadronic
q
q
b
b
final state using data recorded by the ATLAS detector at the LHC in proton-proton collisions at
√
s
=
13
TeV
and corresponding to an integrated luminosity of
137
fb
−
1
. The vector bosons and Higgs bosons are each reconstructed as large-radius jets and tagged using jet substructure techniques. Dedicated tagging algorithms exploiting
b
-tagging properties are used to identify jets consistent with Higgs bosons decaying into
b
¯
b
. Dominant backgrounds from multijet production are determined directly from the data, and a likelihood fit to the jet mass distribution of Higgs boson candidates is used to extract the number of signal events. The
V
H
production cross section is measured inclusively and differentially in several ranges of Higgs boson transverse momentum: 250–450, 450–650, and greater than 650 GeV. The inclusive signal yield relative to the standard model expectation is observed to be
μ
=
1.4
+
1.0
−
0.9
and the corresponding cross section is
3.1
±
1.3
(
stat
)
+
1.8
−
1.4
(
syst
)
pb
Search for a new heavy scalar particle decaying into a Higgs boson and a new scalar singlet in final states with one or two light leptons and a pair of τ-leptons with the ATLAS detector
No full textA search for a new heavy scalar particle X decaying into a Standard Model (SM) Higgs boson and a new singlet scalar particle S is presented. The search uses a proton-proton (pp) collision data sample with an integrated luminosity of 140 fb−1 recorded at a centre-of-mass energy of √s = 13 TeV with the ATLAS detector at the Large Hadron Collider. The most sensitive mass parameter space is explored in X mass ranging from 500 to 1500 GeV, with the corresponding S mass in the range 200–500 GeV. The search selects events with two hadronically decaying τ-lepton candidates from H → τ+τ− decays and one or two light leptons (ℓ = e, μ) from S → VV (V = W, Z) decays while the remaining V boson decays hadronically or to neutrinos. A multivariate discriminant based on event kinematics is used to separate the signal from the background. No excess is observed beyond the expected SM background and 95% confidence level upper limits between 72 fb and 542 fb are derived on the cross-section σ(pp → X → SH) assuming the same SM-Higgs boson-like decay branching ratios for the S → VV decay. Upper limits on the visible cross-sections σ(pp → X → SH → WWττ) and σ(pp → X → SH → ZZττ) are also set in the ranges 3–26 fb and 6–33 fb, respectively
Measurement of electroweak Z(v (v)over-bar)gamma jj production and limits on anomalous quartic gauge couplings in pp collisions at root s=13 TeV with the ATLAS detector
No full textThe electroweak production of Z(νν ̄) γ in association with two jets is studied in a regime with a photon of high transverse momentum above 150 GeV using proton–proton collisions at a centre-of-mass energy of 13 TeV at the Large Hadron Collider. The analysis uses a data sample with an integrated luminosity of 139 fb−1 collected by the ATLAS detector during the 2015–2018 LHC data-taking period. This process is an important probe of the electroweak symmetry breaking mechanism in the Standard Model and is sensitive to quartic gauge boson couplings via vector-boson scattering. The fiducial Z(νν ̄) γjj cross section for electroweak production is measured to be 0.77−0.30+0.34 fb and is consistent with the Standard Model prediction. Evidence of electroweak Z(νν ̄) γjj production is found with an observed significance of 3.2σ for the background-only hypothesis, compared with an expected significance of 3.7σ. The combination of this result with the previously published ATLAS observation of electroweak Z(νν ̄) γjj production yields an observed (expected) signal significance of 6.3σ (6.6σ). Limits on anomalous quartic gauge boson couplings are obtained in the framework of effective field theory with dimension-8 operators. [Figure not available: see fulltext.]
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