Differential evolutionary conservation of motif modes in the yeast protein interaction network

BACKGROUND: The importance of a network motif (a recurring interconnected pattern of special topology which is over-represented in a biological network) lies in its position in the hierarchy between the protein molecule and the module in a protein-protein interaction network. Until now, however, the methods available have greatly restricted the scope of research. While they have focused on the analysis in the resolution of a motif topology, they have not been able to distinguish particular motifs of the same topology in a protein-protein interaction network. RESULTS: We have been able to assign the molecular function annotations of Gene Ontology to each protein in the protein-protein interactions of Saccharomyces cerevisiae. For various motif topologies, we have developed an algorithm, enabling us to unveil one million "motif modes", each of which features a unique topological combination of molecular functions. To our surprise, the conservation ratio, i.e., the extent of the evolutionary constraints upon the motif modes of the same motif topology, varies significantly, clearly indicative of distinct differences in the evolutionary constraints upon motifs of the same motif topology. Equally important, for all motif modes, we have found a power-law distribution of the motif counts on each motif mode. We postulate that motif modes may very well represent the evolutionary-conserved topological units of a protein interaction network. CONCLUSION: For the first time, the motifs of a protein interaction network have been investigated beyond the scope of motif topology. The motif modes determined in this study have not only enabled us to differentiate among different evolutionary constraints on motifs of the same topology but have also opened up new avenues through which protein interaction networks can be analyzed

Ixora parviflora Protects against UVB-Induced Photoaging by Inhibiting the Expression of MMPs, MAP Kinases, and COX-2 and by Promoting Type I Procollagen Synthesis

Ixora parviflora with high polyphenol content exhibited antioxidant activity and reducing UVB-induced intracellular reactive oxygen species production. In this study, results of the photoaging screening experiments revealed that IPE at 1000 μg/mL reduced the activity of bacterial collagenase by 92.7 ± 4.2% and reduced the activity of elastase by 32.6 ± 1.4%. Therefore, we investigated the mechanisms by which IPE exerts its anti-photoaging activity. IPE at 1 μg/mL led to an increase in type I procollagen expression and increased total collagen synthesis in fibroblasts at 5 μg/mL. We found that IPE inhibited MMP-1, MMP-3, and MMP-9 expression at doses of 1, 5, and 10 μg/mL, respectively, in fibroblasts exposed to UV irradiation (40 mJ/cm2). Gelatin zymography assay showed that IPE at 50 μg/mL inhibited MMP-9 secretion/activity in cultured fibroblasts after UVB exposure. In addition, IPE inhibited the phosphorylation of p38, ERK, and JNK induced by UVB. Furthermore, IPE inhibited the UVB-induced expression of Smad7. In addition, IPE at 1 μg/mL inhibited NO production and COX-2 expression in UV-exposed fibroblasts. These findings show that IPE exhibits anti-inflammatory and anti-photoaging activities, indicating that IPE could be a potential anti-aging agent

Comparison of domiciliary oxygen using liquid oxygen and concentrator in northern Taiwan

Background/PurposeLong-term oxygen therapy has become standard treatment for patients with chronic respiratory insufficiency. However, patterns of long-term home oxygen therapy have not been well studied in Taiwan. Oxygen concentrator systems are commonly used in Taiwan, but liquid oxygen delivery systems are portable and may provide advantages over the concentrator system. This study compared oxygen usage between patients from a liquid oxygen group (LOG) and an oxygen concentrator group (OCG). The authors also assessed the physiologic responses of patients with chronic obstructive pulmonary disease (COPD) to ambulatory oxygen use at home.MethodsThe study used a retrospective, cross-sectional, observational survey design. The LOG comprised 42 patients, and the OCG comprised 102 patients. We recruited participants in northern Taiwan from July 2009 to April 2010. The questionnaire instruments that were used to collect data consisted of three parts: demographic characteristics, devices used in respiratory care, and activity status with portable oxygen. Two-minute walking tests were performed on COPD patients in their homes.ResultsCOPD was the most common diagnosis in our study, with more than 50% of patients who received oxygen long term in both groups having received this diagnosis. The LOG used oxygen for an average of 21.7 hours per day, whereas OCG averaged 15.2 hours per day (p<0.001). In the OCG, 92.2% of patients used a concentrator alone, whereas 23.8% of the LOG used liquid oxygen alone (p<0.001). The LOG patients were involved in significantly more outdoors activities (p=0.002) and reported traveling with oxygen more often (p<0.001) than the OCG patients. For patients with the same dyspnea level of COPD severity, those using liquid oxygen had a lower increase in pulse rate after the walking test, in comparison with the concentrator users.ConclusionPatients in the LOG used oxygen for longer hours, went on more outings, and were more likely to travel with oxygen than patients in the OCG. Being ambulatory with liquid oxygen might enable patients with COPD to walk more effectively

Drosophila eyes absent is a Novel mRNA Target of the Tristetraprolin (TTP) Protein DTIS11

The Tristetraprolin (TTP) protein family includes four mammalian members (TTP, TIS11b, TIS11d, and ZFP36L3), but only one in Drosophila melanogaster (DTIS11). These proteins bind target mRNAs with AU-rich elements (AREs) via two C3H zinc finger domains and destabilize the mRNAs. We found that overexpression of mouse TIS11b or DTIS11 in the Drosophila retina dramatically reduced eye size, similar to the phenotype of eyes absent (eya) mutants. The eya transcript is one of many ARE-containing mRNAs in Drosophila. We showed that TIS11b reduced levels of eya mRNA in vivo. In addition, overexpression of Eya rescued the TIS11b overexpression phenotype. RNA pull-down and luciferase reporter analyses demonstrated that the DTIS11 RNA-binding domain is required for DTIS11 to bind the eya 3′ UTR and reduce levels of eya mRNA. Moreover, ectopic expression of DTIS11 in Drosophila S2 cells decreased levels of eya mRNA and reduced cell viability. Consistent with these results, TTP proteins overexpressed in MCF7 human breast cancer cells were associated with eya homologue 2 (EYA2) mRNA, and caused a decrease in EYA2 mRNA stability and cell viability. Our results suggest that eya mRNA is a target of TTP proteins, and that downregulation of EYA by TTP may lead to reduced cell viability in Drosophila and human cells

Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment

<p>Abstract</p> <p>Background</p> <p>Methotrexate (MTX) is the most commonly prescribed disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis. ATP-binding cassette transporter-A1 (ABCA1) and 27-Hydroxylase (HY27) are known antiatherogenic proteins that promote cellular cholesterol efflux. In THP-1 macrophages, MTX can promote the reversal of cholesterol transport, limit foam cell formation and also reverse COX-2 inhibitor-mediated downregulation of ABCA1. Despite its antiatherogenic potential <it>in vitro</it>, the impact of clinical use of low-dose MTX on cholesterol metabolism in humans is unknown. Objective of the study was to examine whether clinical MTX use is associated with altered blood lipids and/or <it>ABCA1/HY27 </it>expressions.</p> <p>Methods</p> <p>In all, 100 rheumatoid arthritis subjects were recruited from a medical center in central Taiwan. Plasma lipid profiles and peripheral blood mononuclear cell <it>HY27 </it>and <it>ABCA1 </it>expressions were compared between subjects taking MTX (MTX+) and other disease-modifying antirheumatic drugs (DMARDs) (MTX-). Dietary intake was assessed by a registered dietician.</p> <p>Results</p> <p>Though no difference observed in the blood lipids between MTX+ and MTX- subjects, the expressions of <it>ABCA1 </it>and <it>HY27 </it>were significantly elevated in MTX+ subjects (n = 67) compared to MTX- subjects (n = 32, p < 0.05). ABCA expression correlated with MTX doses (r = 0.205, p = 0.042), and MTX+ subjects are more likely to have increased <it>HY27 </it>compared to MTX- subjects (OR = 2.5, p = 0.038). Prevalence of dyslipidemia and overweight, and dietary fat/cholesterol intake were lower than that of the age-matched population. Although no differences were observed in the blood lipids, the potential impacts of MTX on cholesterol metabolism should not be overlooked and the atheroprotective effects from MTX induced <it>HY27 </it>and <it>ABCA1 </it>expressions may still be present in those persons with pre-existing dyslipidemia.</p> <p>Conclusions</p> <p>We demonstrated novel findings on the increased gene expressions of atheroprotective protein <it>HY27 </it>and <it>ABCA1 </it>in human peripheral blood mononuclear cells (PBMCs) with clinical use of low-dose MTX. Whether MTX induced <it>HY27 </it>and <it>ABCA1 </it>expressions can protect against cardiovascular disease in patients with chronic inflammation through the facilitation of cholesterol export remains to be established. Further studies on the impacts of low-dose MTX on hypercholesterolemic patients are underway.</p

Prokaryotic assemblages and metagenomes in pelagic zones of the South China Sea

Background: Prokaryotic microbes, the most abundant organisms in the ocean, are remarkably diverse. Despite numerous studies of marine prokaryotes, the zonation of their communities in pelagic zones has been poorly delineated. By exploiting the persistent stratification of the South China Sea (SCS), we performed a 2-year, large spatial scale (10, 100, 1000, and 3000 m) survey, which included a pilot study in 2006 and comprehensive sampling in 2007, to investigate the biological zonation of bacteria and archaea using 16S rRNA tag and shotgun metagenome sequencing. Results: Alphaproteobacteria dominated the bacterial community in the surface SCS, where the abundance of Betaproteobacteria was seemingly associated with climatic activity. Gammaproteobacteria thrived in the deep SCS, where a noticeable amount of Cyanobacteria were also detected. Marine Groups II and III Euryarchaeota were predominant in the archaeal communities in the surface and deep SCS, respectively. Bacterial diversity was higher than archaeal diversity at all sampling depths in the SCS, and peaked at mid-depths, agreeing with the diversity pattern found in global water columns. Metagenomic analysis not only showed differential %GC values and genome sizes between the surface and deep SCS, but also demonstrated depth-dependent metabolic potentials, such as cobalamin biosynthesis at 10 m, osmoregulation at 100 m, signal transduction at 1000 m, and plasmid and phage replication at 3000 m. When compared with other oceans, urease at 10 m and both exonuclease and permease at 3000 m were more abundant in the SCS. Finally, enriched genes associated with nutrient assimilation in the sea surface and transposase in the deep-sea metagenomes exemplified the functional zonation in global oceans. Conclusions: Prokaryotic communities in the SCS stratified with depth, with maximal bacterial diversity at mid-depth, in accordance with global water columns. The SCS had functional zonation among depths and endemically enriched metabolic potentials at the study site, in contrast to other oceans

Genetic population structure of the alpine species Rhododendron pseudochrysanthum sensu lato (Ericaceae) inferred from chloroplast and nuclear DNA

<p>Abstract</p> <p>Background</p> <p>A complex of incipient species with different degrees of morphological or ecological differentiation provides an ideal model for studying species divergence. We examined the phylogeography and the evolutionary history of the <it>Rhododendron pseudochrysanthum </it>s. l.</p> <p>Results</p> <p>Systematic inconsistency was detected between gene genealogies of the cpDNA and nrDNA. Rooted at <it>R. hyperythrum </it>and <it>R. formosana</it>, both trees lacked reciprocal monophyly for all members of the complex. For <it>R. pseudochrysanthum </it>s.l., the spatial distribution of the cpDNA had a noteworthy pattern showing high genetic differentiation (F_ST= 0.56-0.72) between populations in the Yushan Mountain Range and populations of the other mountain ranges.</p> <p>Conclusion</p> <p>Both incomplete lineage sorting and interspecific hybridization/introgression may have contributed to the lack of monophyly among <it>R. hyperythrum</it>, <it>R. formosana </it>and <it>R. pseudochrysanthum </it>s.l. Independent colonizations, plus low capabilities of seed dispersal in current environments, may have resulted in the genetic differentiation between populations of different mountain ranges. At the population level, the populations of Central, and Sheishan Mountains may have undergone postglacial demographic expansion, while populations of the Yushan Mountain Range are likely to have remained stable ever since the colonization. In contrast, the single population of the Alishan Mountain Range with a fixed cpDNA haplotype may have experienced bottleneck/founder's events.</p

Relationship Between Foveal Cone Specialization and Pit Morphology in Albinism

Purpose.Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism. Methods. We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured. Results. We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism. Conclusions. Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue