749 research outputs found
The adaptor protein PID1 regulates receptor-dependent endocytosis of postprandial triglyceride-rich lipoproteins.
ObjectiveInsulin resistance is associated with impaired receptor dependent hepatic uptake of triglyceride-rich lipoproteins (TRL), promoting hypertriglyceridemia and atherosclerosis. Next to low-density lipoprotein (LDL) receptor (LDLR) and syndecan-1, the LDLR-related protein 1 (LRP1) stimulated by insulin action contributes to the rapid clearance of TRL in the postprandial state. Here, we investigated the hypothesis that the adaptor protein phosphotyrosine interacting domain-containing protein 1 (PID1) regulates LRP1 function, thereby controlling hepatic endocytosis of postprandial lipoproteins.MethodsLocalization and interaction of PID1 and LRP1 in cultured hepatocytes was studied by confocal microscopy of fluorescent tagged proteins, by indirect immunohistochemistry of endogenous proteins, by GST-based pull down and by immunoprecipitation experiments. The in vivo relevance of PID1 was assessed using whole body as well as liver-specific Pid1-deficient mice on a wild type or Ldlr-deficient (Ldlr-/-) background. Intravital microscopy was used to study LRP1 translocation in the liver. Lipoprotein metabolism was investigated by lipoprotein profiling, gene and protein expression as well as organ-specific uptake of radiolabelled TRL.ResultsPID1 co-localized in perinuclear endosomes and was found associated with LRP1 under fasting conditions. We identified the distal NPxY motif of the intracellular C-terminal domain (ICD) of LRP1 as the site critical for the interaction with PID1. Insulin-mediated NPxY-phosphorylation caused the dissociation of PID1 from the ICD, causing LRP1 translocation to the plasma membrane. PID1 deletion resulted in higher LRP1 abundance at the cell surface, higher LDLR protein levels and, paradoxically, reduced total LRP1. The latter can be explained by higher receptor shedding, which we observed in cultured Pid1-deficient hepatocytes. Consistently, PID1 deficiency alone led to increased LDLR-dependent endocytosis of postprandial lipoproteins and lower plasma triglycerides. In contrast, hepatic PID1 deletion on an Ldlr-/- background reduced lipoprotein uptake into liver and caused plasma TRL accumulation.ConclusionsBy acting as an insulin-dependent retention adaptor, PID1 serves as a regulator of LRP1 function controlling the disposal of postprandial lipoproteins. PID1 inhibition provides a novel approach to lower plasma levels of pro-atherogenic TRL remnants by stimulating endocytic function of both LRP1 and LDLR in the liver
Exchange interaction in chirally coupled quantum dots
We present transport measurements on a system of two lateral quantum dots in a perpendicular magnetic field. Due to edge channel formation in an open conducting region, the quantum dots are chirally coupled. When both quantum dots are tuned into the Kondo regime simultaneously, we observe a change in the temperature dependence of the differential conductance. This is explained by the RKKY exchange interaction between the two dots. As a function of bias the differential conductance shows a splitting of the Kondo resonance which changes in the presence of RKKY interaction.DFG/EXC/QUESTNTH School for Contacts in Nanosystem
Differential effect of behavioural strategies on the management of conduct disorder among adolescents in correctional centres in Lagos State, Nigeria
Adolescent period is a significant phase in human development. Empirical evidences from diverse
nations revealed that the period is characterized by a number of misbehaviours of which conduct
disorder is paramount. Conduct disorder is a repetitive behaviour that violates the rights of others. It
entails rule violation, aggression, hostility, and deceitfulness. There are adolescents in correctional
centres in several nations of the world because of their engagement in conduct disorder. Several
behavioural techniques have been adopted to ensure that conduct disorder is overcome. It, however,
appears from literature that concentrated attempts have not been made to treat or determine the
efficacy of behavioural techniques. This study examined the efficacy of two behavioural strategies to
manage maladjusted behaviour in correctional centres in Lagos State, Nigeria. Participants for the
study were 90 adolescents purposively selected from two special correctional centres in Lagos State.
The research design utilized for the study was 3 x 2 factorial design. Conduct Disorder Scale by Gilliam
was used to generate data. The result of the two hypotheses showed that significant difference existed
between participants exposed to cognitive restructuring, behavioural rehearsal and control group (F (2,
87) = 46.622, p < 0.05) while there was no significant difference between participants exposed to
cognitive restructuring and behavioural rehearsal groups (t = 0.313, df = 58, p = 0.756). From the study,
the two behavioural methods could be employed to manage conduct disorder. Consequently, they are
recommended as techniques for handling adolescentsâ conduct disorde
Blockchain technology in quantum chemistry: A tutorial review for running simulations on a blockchain
Simulations of molecules have recently been performed directly on a blockchain virtual computer at atomic resolution. This tutorial review covers the current applications of blockchain technology for molecular modeling in physics, chemistry, and biology, and provides a step-by-step tutorial for computational scientists looking to use blockchain computers to simulate physical and scientific processes in general. Simulations of carbon monoxide have been carried out using molecular dynamics software on the Ethereum blockchain in order to facilitate the tutorial
The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells
International audienceMature granule cells are poorly excitable neurons that were recently shown to fire action potentials, preferentially in bursts. It is believed that the particularly pronounced short-term facilitation of mossy fiber synapses makes granule cell bursting a very effective means of properly transferring information to CA3. However, the mechanism underlying the unique bursting behavior of mature granule cells is currently unknown. Here, we show that Cav3.2 T-type channels at the axon initial segment are responsible for burst firing of mature granule cells in rats and mice. Accordingly, Cav3.2 knockout mice fire tonic spikes and exhibit impaired bursting, synaptic plasticity and dentate-to-CA3 communication. The data show that Cav3.2 channels are strong modulators of bursting and can be considered a critical molecular switch that enables effective information transfer from mature granule cells to the CA3 pyramids
Fermionic counting of RSOS-states and Virasoro character formulas for the unitary minimal series M(\nu,\nu+1). Exact results
The Hilbert space of an RSOS-model, introduced by Andrews, Baxter, and
Forrester, can be viewed as a space of sequences (paths) {a_0,a_1,...,a_L},
with a_j-integers restricted by 1<=a_j<=\nu, |a_j-a_{j+1}|=1, a_0=s, a_L=r. In
this paper we introduce different basis which, as shown here, has the same
dimension as that of an RSOS-model. Following McCoy et al, we call this basis
-- fermionic (FB). Our first theorem Dim(FB)=Dim(RSOS-basis) can be succinctly
expressed in terms of some identities for binomial coefficients. Remarkably,
these binomial identities can be q-deformed. Here, we give a simple proof of
these q-binomial identities in the spirit of Schur's proof of the
Rogers-Ramanujan identities. Notably, the proof involves only the elementary
recurrences for the q-binomial coefficients and a few creative observations.
Finally, taking the limit L --> \infty in these q-identities, we derive an
expression for the character formulas of the unitary minimal series
M(\nu,\nu+1) "Bosonic Sum = Fermionic Sum". Here, Bosonic Sum denotes
Rocha-Caridi representation (\chi_{r,s=1}^{\nu,\nu+1}(q)) and Fermionic Sum
stands for the companion representation recently conjectured by the Stony Brook
group.Comment: 33pp, LaTex, BONN-HE-94-04, spelling errors and typos corrected,
references added, to appear in Nucl. Phys. B431 (1994
Herausforderungen bei der SchÀtzung von Trends in Schulleistungsstudien. Eine Skalierung der deutschen PISA-Daten
Internationale Schulleistungsstudien wie das Programme for International Student Assessment (PISA) dienen den teilnehmenden LĂ€ndern zur Feststellung der LeistungsfĂ€higkeit ihrer Schulsysteme. In PISA wird die Zielpopulation (15-jĂ€hrige SchĂŒlerinnen und SchĂŒler) alle 3 Jahre getestet. Von besonderer Bedeutung sind dabei die Trendinformationen, die fĂŒr die Zielpopulation ausweisen, ob sich ihre Leistungen gegenĂŒber denen aus frĂŒheren Erhebungen verĂ€ndert haben. Um solche Trends valide interpretieren zu können, sollten die PISA-Erhebungen unter möglichst vergleichbaren Bedingungen durchgefĂŒhrt und die verwendeten statistischen Verfahren vergleichbar bleiben. In PISA 2015 wurde erstmalig computerbasiert getestet; zuvor mittels Papier-und-Bleistift-Tests. Es wurde das Skalierungsmodell verĂ€ndert und in den Naturwissenschaften wurden neue Aufgabenformate eingesetzt. Im vorliegenden Beitrag gehen wir anhand der nationalen PISA-Stichproben von 2000 bis 2015 der Frage nach, inwiefern der Wechsel des Testmodus und der Wechsel des Skalierungsmodells die Interpretation der TrendschĂ€tzungen beeinflussen. Die Analysen belegen, dass die VerĂ€nderung von Papier-und-Bleistift-Tests auf Computertestung die TrendschĂ€tzung fĂŒr Deutschland verzerrt haben könnte. (DIPF/Orig.)International large-scale assessments, for instance, the Programme for International Student Assessment (PISA), are conducted to provide information on the effectiveness of educational systems. In PISA, the target population of 15-year-old students is assessed every 3 years. Trends show whether competencies have changed for the target population between PISA cycles. To ensure valid trend information, it is necessary to keep the test conditions and statistical methods in all PISA cycles as constant as possible. In PISA 2015, however, several changes were established; the test model changed from paper pencil to computer tests, scaling methods were changed, and new types of tasks were used in science. In this article, we investigate the effects of these changes on trend estimation in PISA using German data from all PISA cycles (2000 - 2015). Findings suggest that the change from paper pencil to computer tests could have biased the trend estimation. (DIPF/Orig.
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