11,304 research outputs found
Deducing topology of protein-protein interaction networks from experimentally measured sub-networks.
BackgroundProtein-protein interaction networks are commonly sampled using yeast two hybrid approaches. However, whether topological information reaped from these experimentally-measured sub-networks can be extrapolated to complete protein-protein interaction networks is unclear.ResultsBy analyzing various experimental protein-protein interaction datasets, we found that they are not random samples of the parent networks. Based on the experimental bait-prey behaviors, our computer simulations show that these non-random sampling features may affect the topological information. We tested the hypothesis that a core sub-network exists within the experimentally sampled network that better maintains the topological characteristics of the parent protein-protein interaction network. We developed a method to filter the experimentally sampled network to result in a core sub-network that more accurately reflects the topology of the parent network. These findings have fundamental implications for large-scale protein interaction studies and for our understanding of the behavior of cellular networks.ConclusionThe topological information from experimental measured networks network as is may not be the correct source for topological information about the parent protein-protein interaction network. We define a core sub-network that more accurately reflects the topology of the parent network
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The Ca2+ transient as a feedback sensor controlling cardiomyocyte ionic conductances in mouse populations.
Conductances of ion channels and transporters controlling cardiac excitation may vary in a population of subjects with different cardiac gene expression patterns. However, the amount of variability and its origin are not quantitatively known. We propose a new conceptual approach to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca2+ transient without any constraint on the action potential. Furthermore, we validate experimentally its predictions using the Hybrid Mouse Diversity Panel, a model system of genetically diverse mouse strains that allows us to quantify inter-subject versus intra-subject variability. The method predicts that conductances of inward Ca2+ and outward K+ currents compensate each other to generate a normal Ca2+ transient in good quantitative agreement with current measurements in ventricular myocytes from hearts of different isogenic strains. Our results suggest that a feedback mechanism sensing the aggregate Ca2+ transient of the heart suffices to regulate ionic conductances
Emerging Roles of Glycogen Synthase Kinase 3 in the Treatment of Brain Tumors
The constitutively active protein glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, acts paradoxically as a tumor suppressor in some cancers while potentiates growth in others. Deciphering what governs its actions is vital for understanding many pathological conditions, including brain cancer. What are seemingly disparate roles of GSK3 stems from the complex regulation of many cellular functions by GSK3. This review focuses on the regulation of GSK3, its role in survival, apoptosis and DNA damage, and finally its potential therapeutic impact in brain cancer. A thorough understanding of this versatile protein is critical for improving the outcome of various diseases, especially cancer
In-situ strain tuning of the Dirac surface states in Bi2Se3 films
Elastic strain has the potential for a controlled manipulation of the band
gap and spin-polarized Dirac states of topological materials, which can lead to
pseudo-magnetic-field effects, helical flat bands and topological phase
transitions. However, practical realization of these exotic phenomena is
challenging and yet to be achieved. Here, we show that the Dirac surface states
of the topological insulator Bi2Se3 can be reversibly tuned by an externally
applied elastic strain. Performing in-situ x-ray diffraction and in-situ
angle-resolved photoemission spectroscopy measurements during tensile testing
of epitaxial Bi2Se3 films bonded onto a flexible substrate, we demonstrate
elastic strains of up to 2.1% and quantify the resulting reversible changes in
the topological surface state. Our study establishes the functional
relationship between the lattice and electronic structures of Bi2Se3 and, more
generally, demonstrates a new route toward momentum-resolved mapping of
strain-induced band structure changes
The H alpha Galaxy Survey VI. Star-forming companions of nearby field galaxies
We present a search for star-forming satellite galaxies that are close enough
to their parent galaxies to be considered analogues of the Magellanic Clouds.
Our search technique relied on the detection of the satellites in
continuum-subtracted narrow-band H alpha imaging of the central galaxies, which
removes most of the background and foreground line-of-sight companions, thus
giving a high probability that we are detecting true satellites. The search was
performed for 119 central galaxies at distances between 20 and 40 Mpc, although
spatial incompleteness means that we have effectively searched 53 full
satellite-containing volumes. We find only 9 probable star-forming satellites,
around 9 different central galaxies, and 2 possible satellites. After
incompleteness correction, this is equivalent to 0.17/0.21 satellites per
central galaxy. The Small Magellanic Cloud is just below the median values of
both star formation rate and R-band luminosity of the 9 probable satellites.
The Large Magellanic Cloud, however, has a higher R-band luminosity than any of
the 9 and is only exceeded in star formation rate by the one satellite that
appears to be undergoing a tidally-induced starburst. Thus the Milky Way
appears to be quite unusual, both in having two star-forming satellite galaxies
and in the high luminosity of the Large Magellanic Cloud.Comment: 13 pages, accepted for publication in A&
Period-doubling Bifurcation in an Array of Coupled Stochastically-excitable Elements Subjected to Global Periodic Forcing
The collective behaviors of coupled, stochastically-excitable elements subjected to global periodic forcing are investigated numerically and analytically. We show that the whole system undergoes a period-doubling bifurcation as the driving period decreases, while the individual elements still exhibit random excitations. Using a mean-field representation, we show that this macroscopic bifurcation behavior is caused by interactions between the random excitation, the refractory period, and recruitment (spatial cooperativity) of the excitable elements
A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study
<p>Abstract</p> <p>Background</p> <p>Glomerular filtration rate (GFR) and urinary albumin excretion (UAE) are markers of kidney function that are known to be heritable. Many endocrine conditions have strong familial components. We tested for association between the Affymetrix GeneChip Human Mapping 100K single nucleotide polymorphism (SNP) set and measures of kidney function and endocrine traits.</p> <p>Methods</p> <p>Genotype information on the Affymetrix GeneChip Human Mapping 100K SNP set was available on 1345 participants. Serum creatinine and cystatin-C (cysC; n = 981) were measured at the seventh examination cycle (1998–2001); GFR (n = 1010) was estimated via the Modification of Diet in Renal Disease (MDRD) equation; UAE was measured on spot urine samples during the sixth examination cycle (1995–1998) and was indexed to urinary creatinine (n = 822). Thyroid stimulating hormone (TSH) was measured at the third and fourth examination cycles (1981–1984; 1984–1987) and mean value of the measurements were used (n = 810). Age-sex-adjusted and multivariable-adjusted residuals for these measurements were used in association with genotype data using generalized estimating equations (GEE) and family-based association tests (FBAT) models. We presented the results for association tests using additive allele model. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg Equilibrium p-value ≥ 0.001, and call rates of at least 80%.</p> <p>Results</p> <p>The top SNPs associated with these traits using the GEE method were rs2839235 with GFR (p-value 1.6*10<sup>-05</sup>), rs1158167 with cysC (p-value 8.5*10<sup>-09</sup>), rs1712790 with UAE (p-value 1.9*10<sup>-06</sup>), and rs6977660 with TSH (p-value 3.7*10<sup>-06</sup>), respectively. The top SNPs associated with these traits using the FBAT method were rs6434804 with GFR(p-value 2.4*10<sup>-5</sup>), rs563754 with cysC (p-value 4.7*10<sup>-5</sup>), rs1243400 with UAE (p-value 4.8*10<sup>-6</sup>), and rs4128956 with TSH (p-value 3.6*10<sup>-5</sup>), respectively. Detailed association test results can be found at <url>http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007</url>. Four SNPs in or near the <it>CST</it>3 gene were highly associated with cysC levels (p-value 8.5*10<sup>-09 </sup>to 0.007).</p> <p>Conclusion</p> <p>Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified.</p
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