405 research outputs found
Identification of domains in apoA-I susceptible to proteolysis by mast cell chymase. Implications for HDL function.
When stimulated, rat serosal mast cells degranulate and secrete a cytoplasmic neutral protease, chymase. We studied the fragmentation of apolipoprotein (apo) A-I during proteolysis of HDL(3) by chymase, and examined how chymase-dependent proteolysis interfered with the binding of eight murine monoclonal antibodies (Mabs) against functional domains of apoA-I. Size exclusion chromatography of HDL(3) revealed that proteolysis for up to 24 h did not alter the integrity of the alpha-migrating HDL, whereas a minor peak containing particles of smaller size with prebeta mobility disappeared after as little as 15 min of incubation. At the same time, generation of a large (26 kDa) polypeptide containing the N-terminus of apoA-I was detected. This large fragment and other medium-sized fragments of apoA-I produced after prolonged treatment with chymase were found to be associated with the alphaHDL; meanwhile, small lipid-free peptides were rapidly produced. Incubation of HDL(3) with chymase inhibited binding of Mab A-I-9 (specific for prebeta(1)HDL) most rapidly (within 15 min) of the eight studied Mabs. This rapid loss of binding was paralleled by a similar reduction in the ability of HDL(3) to induce high-affinity efflux of cholesterol from macrophage foam cells, indicating that proteolysis had destroyed an epitope that is critical for this function. In sharp contrast, prolonged degradation of HDL(3) by chymase failed to reduce the ability of HDL(3) to activate LCAT, even though it led to modification of three epitopes in the central region of apoA-I that are involved in lecithin cholesterol acyltransferase (LCAT) activation. This differential sensitivity of the two key functions of HDL(3) to the proteolytic action of mast cell chymase is compatible with the notion that, in reverse cholesterol transport, intactness of apoA-I is essential for prebeta(1)HDL to promote the high-affinity efflux of cellular cholesterol, but not for the alpha-migrating HDL particles to activate LCAT
Correlated dynamics in egocentric communication networks
We investigate the communication sequences of millions of people through two
different channels and analyze the fine grained temporal structure of
correlated event trains induced by single individuals. By focusing on
correlations between the heterogeneous dynamics and the topology of egocentric
networks we find that the bursty trains usually evolve for pairs of individuals
rather than for the ego and his/her several neighbors thus burstiness is a
property of the links rather than of the nodes. We compare the directional
balance of calls and short messages within bursty trains to the average on the
actual link and show that for the trains of voice calls the imbalance is
significantly enhanced, while for short messages the balance within the trains
increases. These effects can be partly traced back to the technological
constrains (for short messages) and partly to the human behavioral features
(voice calls). We define a model that is able to reproduce the empirical
results and may help us to understand better the mechanisms driving technology
mediated human communication dynamics.Comment: 7 pages, 6 figure
Circadian pattern and burstiness in mobile phone communication
The temporal communication patterns of human individuals are known to be
inhomogeneous or bursty, which is reflected as the heavy tail behavior in the
inter-event time distribution. As the cause of such bursty behavior two main
mechanisms have been suggested: a) Inhomogeneities due to the circadian and
weekly activity patterns and b) inhomogeneities rooted in human task execution
behavior. Here we investigate the roles of these mechanisms by developing and
then applying systematic de-seasoning methods to remove the circadian and
weekly patterns from the time-series of mobile phone communication events of
individuals. We find that the heavy tails in the inter-event time distributions
remain robustly with respect to this procedure, which clearly indicates that
the human task execution based mechanism is a possible cause for the remaining
burstiness in temporal mobile phone communication patterns.Comment: 17 pages, 12 figure
Discovering and Predicting Temporal Patterns of WiFi-interactive Social Populations
Extensive efforts have been devoted to characterizing the rich connectivity
patterns among the nodes (components) of such complex networks (systems), and
in the course of development of research in this area, people have been
prompted to address on a fundamental question: How does the fascinating yet
complex topological features of a network affect or determine the collective
behavior and performance of the networked system? While elegant attempts to
address this core issue have been made, for example, from the viewpoints of
synchronization, epidemics, evolutionary cooperation, and the control of
complex networks, theoretically or empirically, this widely concerned key
question still remains open in the newly emergent field of network science.
Such fruitful advances also push the desire to understand (mobile) social
networks and characterize human social populations with the interdependent
collective dynamics as well as the behavioral patterns. Nowadays, a great deal
of digital technologies are unobtrusively embedded into the physical world of
human daily activities, which offer unparalleled opportunities to explosively
digitize human physical interactions, who is contacting with whom at what time.
Such powerful technologies include the Bluetooth, the active Radio Frequency
Identification (RFID) technology, wireless sensors and, more close to our
interest in this paper, the WiFi technology. As a snapshot of the modern
society, a university is in the coverage of WiFi signals, where the WiFi system
records the digital access logs of the authorized WiFi users when they access
the campus wireless services. Such WiFi access records, as the indirect proxy
data, work as the effective proxy of a large-scale population's social
interactions.Comment: 11 pages, 10 page
Lysophosphatidylcholine in phospholipase A(2)-modified LDL triggers secretion of angiopoietin 2
Background and aims: Secretory phospholipase A(2) (PLA(2)) hydrolyzes LDL phospholipids generating modified LDL particles (PLA(2)-LDL) with increased atherogenic properties. Exocytosis of Weibel-Palade bodies (WPB) releases angiopoietin 2 (Ang2) and externalizes P-selectin, which both play important roles in vascular inflammation. Here, we investigated the effects of PLA(2)-LDL on exocytosis of WPBs. Methods: Human coronary artery endothelial cells (HCAECs) were stimulated with PLA(2)-LDL, and its uptake and effect on Ang2 release, leukocyte adhesion, and intracellular calcium levels were measured. The effects of PLA(2)-LDL on Ang2 release and WPB exocytosis were measured in and ex vivo in mice. Results: Exposure of HCAECs to PLA(2)-LDL triggered Ang2 secretion and promoted leukocyte-HCAEC interaction. Lysophosphatidylcholine was identified as a critical component of PLA(2)-LDL regulating the WPB exocytosis, which was mediated by cell-surface proteoglycans, phospholipase C, intracellular calcium, and cytoskeletal remodeling. PLA(2)-LDL also induced murine endothelial WPB exocytosis in blood vessels in and ex vivo, as evidenced by secretion of Ang2 in vivo, P-selectin translocation to plasma membrane in intact endothelial cells in thoracic artery and tracheal vessels, and reduced Ang2 staining in tracheal endothelial cells. Finally, in contrast to normal human coronary arteries, in which Ang2 was present only in the endothelial layer, at sites of advanced atherosclerotic lesions, Ang2 was detected also in the intima, media, and adventitia. Conclusions: Our studies reveal PLA(2)-LDL as a potent agonist of endothelial WPB exocytosis, resulting in increased secretion of Ang2 and translocation of P-selectin. The results provide mechanistic insight into PLA(2)-LDL-dependent promotion of vascular inflammation and atherosclerosis.Peer reviewe
Bursty egocentric network evolution in Skype
In this study we analyze the dynamics of the contact list evolution of
millions of users of the Skype communication network. We find that egocentric
networks evolve heterogeneously in time as events of edge additions and
deletions of individuals are grouped in long bursty clusters, which are
separated by long inactive periods. We classify users by their link creation
dynamics and show that bursty peaks of contact additions are likely to appear
shortly after user account creation. We also study possible relations between
bursty contact addition activity and other user-initiated actions like free and
paid service adoption events. We show that bursts of contact additions are
associated with increases in activity and adoption - an observation that can
inform the design of targeted marketing tactics.Comment: 7 pages, 6 figures. Social Network Analysis and Mining (2013
Weighted temporal event graphs
The times of temporal-network events and their correlations contain
information on the function of the network and they influence dynamical
processes taking place on it. To extract information out of correlated event
times, techniques such as the analysis of temporal motifs have been developed.
We discuss a recently-introduced, more general framework that maps
temporal-network structure into static graphs while retaining information on
time-respecting paths and the time differences between their consequent events.
This framework builds on weighted temporal event graphs: directed, acyclic
graphs (DAGs) that contain a superposition of all temporal paths. We introduce
the reader to the temporal event-graph mapping and associated computational
methods and illustrate its use by applying the framework to temporal-network
percolation
APAC treatment limits collar-induced carotid atherosclerotic plaque development in apoE-/- mice
Biopharmaceutic
Spatiotemporal correlations of handset-based service usages
We study spatiotemporal correlations and temporal diversities of
handset-based service usages by analyzing a dataset that includes detailed
information about locations and service usages of 124 users over 16 months. By
constructing the spatiotemporal trajectories of the users we detect several
meaningful places or contexts for each one of them and show how the context
affects the service usage patterns. We find that temporal patterns of service
usages are bound to the typical weekly cycles of humans, yet they show maximal
activities at different times. We first discuss their temporal correlations and
then investigate the time-ordering behavior of communication services like
calls being followed by the non-communication services like applications. We
also find that the behavioral overlap network based on the clustering of
temporal patterns is comparable to the communication network of users. Our
approach provides a useful framework for handset-based data analysis and helps
us to understand the complexities of information and communications technology
enabled human behavior.Comment: 11 pages, 15 figure
Hormone replacement therapy enhances IGF-1 signaling in skeletal muscle by diminishing miR-182 and miR-223 expressions: a study on postmenopausal monozygotic twin pairs
MiRNAs are fine-tuning modifiers of skeletal muscle regulation, but knowledge of
their hormonal control is lacking. We used a co-twin case-control study design,
that is, monozygotic postmenopausal twin pairs discordant for estrogen-based
hormone replacement therapy (HRT) to explore estrogen-dependent skeletal muscle
regulation via miRNAs. MiRNA profiles were determined from vastus lateralis
muscle of nine healthy 54-62-years-old monozygotic female twin pairs discordant
for HRT (median 7 years). MCF-7 cells, human myoblast cultures and mouse muscle
experiments were used to confirm estrogen's causal role on the expression of
specific miRNAs, their target mRNAs and proteins and finally the activation of
related signaling pathway. Of the 230 miRNAs expressed at detectable levels in
muscle samples, qPCR confirmed significantly lower miR-182, miR-223 and
miR-142-3p expressions in HRT using than in their nonusing co-twins.
Insulin/IGF-1 signaling emerged one common pathway targeted by these miRNAs.
IGF-1R and FOXO3A mRNA and protein were more abundantly expressed in muscle
samples of HRT users than nonusers. In vitro assays confirmed effective targeting
of miR-182 and miR-223 on IGF-1R and FOXO3A mRNA as well as a dose-dependent
miR-182 and miR-223 down-regulations concomitantly with up-regulation of FOXO3A
and IGF-1R expression. Novel finding is the postmenopausal HRT-reduced miRs-182,
miR-223 and miR-142-3p expression in female skeletal muscle. The observed
miRNA-mediated enhancement of the target genes' IGF-1R and FOXO3A expression as
well as the activation of insulin/IGF-1 pathway signaling via phosphorylation of
AKT and mTOR is an important mechanism for positive estrogen impact on skeletal
muscle of postmenopausal women
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