Ocean acidification alters microeukaryotic and bacterial food web interactions in a eutrophic subtropical mesocosm.

Ocean acidification (OA) is known to influence biological and ecological processes, mainly focusing on its impacts on single species, but little has been documented on how OA may alter plankton community interactions. Here, we conducted a mesocosm experiment with ambient (∼410 ppmv) and high (1000 ppmv) CO2 concentrations in a subtropical eutrophic region of the East China Sea and examined the community dynamics of microeukaryotes, bacterioplankton and microeukaryote-attached bacteria in the enclosed coastal seawater. The OA treatment with elevated CO2 affected taxa as the phytoplankton bloom stages progressed, with a 72.89% decrease in relative abundance of the protist Cercozoa on day 10 and a 322% increase in relative abundance of Stramenopile dominated by diatoms, accompanied by a 29.54% decrease in relative abundance of attached Alphaproteobacteria on day 28. Our study revealed that protozoans with different prey preferences had differing sensitivity to high CO2, and attached bacteria were more significantly affected by high CO2 compared to bacterioplankton. Our findings indicate that high CO2 changed the co-occurrence network complexity and stability of microeukaryotes more than those of bacteria. Furthermore, high CO2 was found to alter the proportions of potential interactions between phytoplankton and their predators, as well as microeukaryotes and their attached bacteria in the networks. The changes in the relative abundances and interactions of microeukaryotes between their predators in response to high CO2 revealed in our study suggest that high CO2 may have profound impacts on marine food webs.

Roles of Alkaline Phosphatase PhoA in Algal Metabolic Regulation under Phosphorus-replete Conditions.

Alkaline phosphatase (AP) in plants and algae is known to hydrolyze dissolved organophosphate (DOP) in order to obtain phosphorus when the preferred dissolved inorganic phosphorus (DIP) is present in limited supply. By conducting comparative analyses of physiologies and transcriptomes on a mutant of PhoA type AP (mPhoA) and wild type (WT) of the marine diatom Phaeodactylum tricornutum CCAP 1055/1 under P-replete and P-depleted conditions, we document other roles of this gene than DOP scavenging. PhoA mutation created by CRISPR/Cas9 diminished its DOP hydrolase activity but led to significant increases in cellular contents of pigment, carbon, and lipids, photosynthetic rate, growth rate, and the transcriptional levels of their corresponding metabolic pathways. All the results in concert indicate that besides P-nutrient scavenging under DIP deficiency, AP also functions, under the P-replete condition, to constrain pigment biosynthesis, photosynthesis, fatty acid biosynthesis, and cell division. These functions have important implications in maintaining metabolic homeostasis and preventing premature cell division.

CD44 targeting magnetic glyconanoparticles for atherosclerotic plaque imaging.

PURPOSE: The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. METHODS: Magnetic glyconanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 was evaluated in vitro by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model. RESULTS: The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments. CONCLUSIONS: Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging.

The Influence of Dexmedetomidine as an Adjuvant in Intrathecal Labor Analgesia: A Multicenter Study on Efficacy and Maternal Satisfaction.

In this study, we examined the impact of dexmedetomidine (DEX) on the effectiveness of epidural analgesia and labor outcomes. We administered different doses of DEX combined with 0.1% ropivacaine for epidural analgesia to evaluate the clinical effects and safety. To assess the effects of different concentrations of DEX in parturient women receiving epidural analgesia, we conducted a randomized double-blind trial. We selected 400 parturient women and randomly assigned them to 4 groups, with 100 parturient women in each group: S0.1 (0.1 µg/mL DEX), S0.2 (0.2 µg/mL DEX), S0.3 (0.3 µg/mL DEX), and a control group (0.3 µg/mL sufentanil). Post-analgesia, we recorded the Bromage score, duration of labor, method of delivery, bleeding, neonatal Apgar score, adverse reactions, and maternal satisfaction. The number of patients with a Bromage score of ≥2 and the incidence of bradycardia were higher in the S0.3 group compared with the other 3 groups (P < .05), whereas the high satisfaction rate was lower in the S0.3 group (P < .05). Moreover, we found that the number of times that additional patient-controlled analgesia was administered was higher in the S0.1 group compared with the remaining 3 groups (P < .05). The control group exhibited a higher incidence of pruritus than the other 3 groups (P < .05). In conclusion, when administering spinal anesthesia for the relief of labor pain, epidural analgesia with 0.1% ropivacaine combined with 0.2 µg/mL DEX provides relatively ideal analgesic effects, higher maternal satisfaction, and reduces the incidence of pruritus, compared with the combination of 0.1% ropivacaine and 0.3 µg/mL sufentanil.

[Prenatal diagnosis of a case with X-linked spondyloepiphyseal dysplasia tarda].

OBJECTIVE: To analyze TRAPPC2 gene mutation in a family with X-linked spondyloepiphyseal dysplasia tarda and to provide genetic counseling and prenatal diagnosis. METHODS: All of 4 exons of the TRAPPC2 gene and their flanking sequences in the proband and her father were analyzed with polymerase chain reaction and direct DNA sequencing. Genomic DNA of the probands' fetus was extracted from amniotic fluid sampled at 18th gestational week. Gender of the fetus was determined by the presence of SRY gene. The sequence of fetal TRAPPC2 gene was also analyzed. RESULTS: A c.209G>A mutation was identified in exon 4 of the TRAPPC2 gene in the proband and her father. The fetus of was determined to be a male and also have carried the c.209G>A mutation. CONCLUSION: A c.209G>A mutation of TRAPPC2 exon 4 probably underlies the clinical manifestations in this family. The proband is a carrier, and her fetus is a male carrying the same mutation. Prenatal diagnosis is an effective method for the prevention of the disease.

Differential responses of bloom-forming Ulva intestinalis and economically important Gracilariopsis lemaneiformis to marine heatwaves under changing nitrate conditions.

Marine heatwaves (MHWs) are affecting the survival of macroalgae. However, little is known regarding how the impacts of MHWs are regulated by nitrogen availability. In this study, we investigated the physiological and genetic responses of a green-tide macroalga Ulva intestinalis Linnaeus and a commercially cultivated macroalga Gracilariopsis lemaneiformis (Bory) E.Y. Dawson, Acleto & Foldvik under different nitrate conditions to simulated MHWs. Under nitrogen limited conditions (LN), heatwaves did not significantly affect biomass or Fv/Fm of U. intestinalis although it led to an earlier biomass decline due to more reproduction events, and meanwhile an upregulation in genes related to TCA cycle and oxidative phosphorylation was detected, supporting sporulation. Under nitrogen replete conditions (HN), heatwaves did not change biomass, Fv/Fm or photosynthetic pigments but reduced reproduction rate along with insignificant change of oxidative phosphorylation and TCA cycle related genes. Meanwhile, genes related to photosynthesis and glutathione metabolism were upregulated. Regarding G. lemaneiformis, heatwaves reduced its Fv/Fm and photosynthetic pigments content, leading to bleaching and death, and photosynthesis-related genes were also downregulated at LN. Fv/Fm was improved and photosynthesis-related genes were up-regulated by the combination of nitrogen enrichment and heatwaves, whereas G. lemaneiformis remained bleached and died by day 12. Therefore, U. intestinalis could survive heatwaves through shifting to micropropagules at LN and protecting its photosynthesis at HN. In contrast, G. lemaneiformis died of bleaching when suffering heatwaves regardless of nitrogen availability. These findings suggest that in future oceans with eutrophication and MHWs, the harmful alga U. intestinalis may have more advantages over the economic alga G. lemaneiformis.

Enhancement of diatom growth and phytoplankton productivity with reduced O2 availability is moderated by rising CO2.

Many marine organisms are exposed to decreasing O2 levels due to warming-induced expansion of hypoxic zones and ocean deoxygenation (DeO2). Nevertheless, effects of DeO2 on phytoplankton have been neglected due to technical bottlenecks on examining O2 effects on O2-producing organisms. Here we show that lowered O2 levels increased primary productivity of a coastal phytoplankton assemblage, and enhanced photosynthesis and growth in the coastal diatom Thalassiosira weissflogii. Mechanistically, reduced O2 suppressed mitochondrial respiration and photorespiration of T. weissflogii, but increased the efficiency of their CO2 concentrating mechanisms (CCMs), effective quantum yield and improved light use efficiency, which was apparent under both ambient and elevated CO2 concentrations leading to ocean acidification (OA). While the elevated CO2 treatment partially counteracted the effect of low O2 in terms of CCMs activity, reduced levels of O2 still strongly enhanced phytoplankton primary productivity. This implies that decreased availability of O2 with progressive DeO2 could boost re-oxygenation by diatom-dominated phytoplankton communities, especially in hypoxic areas, with potentially profound consequences for marine ecosystem services in coastal and pelagic oceans.

Elevated pCO2 changes community structure and function by affecting phytoplankton group-specific mortality.

The rise of atmospheric pCO2 has created a number of problems for marine ecosystem. In this study, we initially quantified the effects of elevated pCO2 on the group-specific mortality of phytoplankton in a natural community based on the results of mesocosm experiments. Diatoms dominated the phytoplankton community, and the concentration of chlorophyll a was significantly higher in the high-pCO2 treatment than the low-pCO2 treatment. Phytoplankton mortality (percentage of dead cells) decreased during the exponential growth phase. Although the mortality of dinoflagellates did not differ significantly between the two pCO2 treatments, that of diatoms was lower in the high-pCO2 treatment. Small diatoms dominated the diatom community. Although the mortality of large diatoms did not differ significantly between the two treatments, that of small diatoms was lower in the high-pCO2 treatment. These results suggested that elevated pCO2 might enhance dominance by small diatoms and thereby change the community structure of coastal ecosystems.

Application Value of Information-Based Health Education and Continuity of Care in Patients With Peptic Ulcer.

Objective: This study is to assess the application value of information-based health education and continuity of care in patients with PU (peptic ulcer). Methods: Patients (116) with PU who have been treated in the hospital between January 2019 and October 2020 were taken as research objects and equally assigned to a control group and an observation group in a random manner. In contrast to the routine care applied to the control group, the observation group received information-based health education and continuity of care intervention. The clinical efficacy, the mastery of health knowledge, self-care ability, medication compliance, quality of life, mental state, and nursing satisfaction of the two groups were compared. Results: After the intervention, the total effective rate, health knowledge adequate rate, Exercise of Self-Care Agency (ESCA) scores of all dimensions, the MOS 36-item short-form health survey (SF-36) scores of all dimensions, medication compliance rate, and total nursing satisfaction of the observation group all notably exceeded those of the control group, with a p < 0.05. Patients of the group with continuity of care intervention showed lower Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores, as compared to the group with conventional care (p < 0.05). Conclusion: Information-based health education and continuity of care elevates the medication adherence and nursing satisfaction of patients with PU, enhances disease-related knowledge of patients and their self-care ability, and eventually ameliorates the quality of life and psychological state. It is worthy of clinical application.

Responses of Intertidal Bacterial Biofilm Communities to Increasing pCO2.

The effects of ocean acidification on ecosystems remain poorly understood, because it is difficult to simulate the effects of elevated CO2 on entire marine communities. Natural systems enriched in CO2 are being used to help understand the long-term effects of ocean acidification in situ. Here, we compared biofilm bacterial communities on intertidal cobbles/boulders and bedrock along a seawater CO2 gradient off Japan. Samples sequenced for 16S rRNA showed differences in bacterial communities with different pCO2 and between habitat types. In both habitats, bacterial diversity increased in the acidified conditions. Differences in pCO2 were associated with differences in the relative abundance of the dominant phyla. However, despite the differences in community composition, there was no indication that these changes would be significant for nutrient cycling and ecosystem function. As well as direct effects of seawater chemistry on the biofilm, increased microalgal growth and decreased grazing may contribute to the shift in bacterial composition at high CO2, as documented by other studies. Thus, the effects of changes in bacterial community composition due to globally increasing pCO2 levels require further investigation to assess the implications for marine ecosystem function. However, the apparent lack of functional shifts in biofilms along the pCO2 gradient is a reassuring indicator of stability of their ecosystem functions in shallow ocean margins.

Noninvasive detection and localization of vulnerable plaque and arterial thrombosis with computed tomography angiography/positron emission tomography.

BACKGROUND: It has been shown that plaque uptake of fluorodeoxyglucose is proportional to macrophage density. We tested the hypothesis that arterial thrombosis occurs in areas with high fluorodeoxyglucose uptake and that computed tomography angiography (CTA) can detect thrombi in vessels. METHODS AND RESULTS: Twenty New Zealand White rabbits were studied before and after atherosclerosis induction through de-endothelialization and a high-cholesterol diet; 14 were then thrombus triggered. CTA/positron emission tomography scans were performed before cholesterol diet, at the middle diet feeding, at the end of diet feeding, and after triggering. Serum inflammatory markers were measured. Maximal standardized uptake value was measured over the thoracic and upper and lower abdominal aortas and correlated with thrombosis and macrophage density on sections from the same sites. Aortic diameters averaged 2.84+/-1.16 mm. The sensitivity, specificity, and accuracy of CTA for detecting thrombi were 92%, 89%, and 90%, respectively. Plasminogen activator inhibitor-1 and C-reactive protein levels increased with atherosclerosis and thrombosis triggering. Maximal standardized uptake value at baseline was 0.62+/-0.13, 0.96+/-0.33 at the middle of feeding, and 1.06+/-0.38 at the end of feeding. Segments that developed thrombosis had the highest maximal standardized uptake value of 1.32+/-0.69 (113% increase; P=0.002) and had a 129% increase in macrophage density compared with segments without thrombi (P=0.01). CONCLUSIONS: Fluorodeoxyglucose uptake was proportional to the duration of cholesterol feeding and peaked with plaque disruption and thrombosis. CTA was highly accurate in detecting thrombi. Our findings in this animal model of atherosclerotic plaques with high macrophage density showed that CTA/positron emission tomography can be used to identify and localize inflamed plaques and thrombosis. With the currently available technology and nuclear tracers, however, many challenges remain before clinical applications are possible.

Corrigendum: A Potential Role for Epigenetic Processes in the Acclimation Response to Elevated pCO2 in the Model Diatom Phaeodactylum tricornutum.

[This corrects the article DOI: 10.3389/fmicb.2018.03342.].

A Potential Role for Epigenetic Processes in the Acclimation Response to Elevated pCO2 in the Model Diatom Phaeodactylum tricornutum.

Understanding of the molecular responses underpinning diatom responses to ocean acidification is fundamental for predicting how important primary producers will be shaped by the continuous rise in atmospheric CO2. In this study, we have analyzed global transcriptomic changes of the model diatom Phaeodactylum tricornutum following growth for 15 generations in elevated pCO2 by strand-specific RNA sequencing (ssRNA-seq). Our results indicate that no significant effects of elevated pCO2 and associated carbonate chemistry changes on the physiological performance of the cells were observed after 15 generations whereas the expression of genes encoding histones and other genes involved in chromatin structure were significantly down-regulated, while the expression of transposable elements (TEs) and genes encoding histone acetylation enzymes were significantly up-regulated. Furthermore, we identified a series of long non-protein coding RNAs (lncRNAs) specifically responsive to elevated pCO2, suggesting putative regulatory roles for these largely uncharacterized genome components. Taken together, our integrative analyses reveal that epigenetic elements such as TEs, histone modifications and lncRNAs may have important roles in the acclimation of diatoms to elevated pCO2 over short time scales and thus may influence longer term adaptive processes in response to progressive ocean acidification.

Carbon assimilation and losses during an ocean acidification mesocosm experiment, with special reference to algal blooms.

A mesocosm experiment was conducted in Wuyuan Bay (Xiamen), China, to investigate the effects of elevated pCO2 on bloom formation by phytoplankton species previously studied in laboratory-based ocean acidification experiments, to determine if the indoor-grown species performed similarly in mesocosms under more realistic environmental conditions. We measured biomass, primary productivity and particulate organic carbon (POC) as well as particulate organic nitrogen (PON). Phaeodactylum tricornutum outcompeted Thalassiosira weissflogii and Emiliania huxleyi, comprising more than 99% of the final biomass. Mainly through a capacity to tolerate nutrient-limited situations, P. tricornutum showed a powerful sustained presence during the plateau phase of growth. Significant differences between high and low CO2 treatments were found in cell concentration, cumulative primary productivity and POC in the plateau phase but not during the exponential phase of growth. Compared to the low pCO2 (LC) treatment, POC increased by 45.8-101.9% in the high pCO2 (HC) treated cells during the bloom period. Furthermore, respiratory carbon losses of gross primary productivity were found to comprise 39-64% for the LC and 31-41% for the HC mesocosms (daytime C fixation) in phase II. Our results suggest that the duration and characteristics of a diatom bloom can be affected by elevated pCO2. Effects of elevated pCO2 observed in the laboratory cannot be reliably extrapolated to large scale mesocosms with multiple influencing factors, especially during intense algal blooms.

Thrombostatin, a bradykinin metabolite, reduces platelet activation in a model of arterial wall injury.

OBJECTIVE: Thrombin activates platelets and contributes to the occlusion of arteries following thrombolytic therapy or angioplasty. Thrombostatin (RPPGF), the angiotensin converting enzyme degradation product of bradykinin, inhibits alpha-thrombin induced platelet activation. We hypothesized that thrombostatin prevents platelet aggregation and adhesion after balloon angioplasty (BA). METHODS: Platelet-rich plasma (PRP) was obtained from 22 Beagle dogs before sacrifice and 10% of the PRP was labeled with 111In. Carotid arteries were then removed from each dog and mounted in a dual perfusion chamber and intimal injury was performed with BA. 111In-PRP with or without thrombostatin or aspirin alone was perfused through the arteries for 60 min. During perfusion, platelet volume was measured using a Coulter counter and a laser-light scattering technique. Platelet adhesion to arteries was measured by radioactivity count. RESULTS: Arterial injury alone compared to non-injury increased platelet volume in the circuit by 1.4 times (x) (P<0.05) using a Coulter counter or 1.8x (P<0.05) using laser-light scattering and increased platelet adhesion by 2.3x (P<0.01). When compared to BA injury alone, the addition of thrombostatin reduced platelet volume by 1.8x (P<0.03) as measured by Coulter counter or 1.9x (P<0.01) by laser-light scattering and platelet adhesion by 4.2x (P<0.05). Compared to BA injury alone, aspirin reduced platelet volume by 1.2x (P<0.01) as assessed by Coulter counter or 1.5x (P<0.03) using laser-light scattering and platelet adhesion by 1.8x (P<0.02). CONCLUSION: Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury.

Evidence that cocaine- and amphetamine-regulated transcript is a novel intraovarian regulator of follicular atresia.

We recently obtained evidence that cocaine- and amphetamine-regulated transcript (CART), a potent anorectic neuropeptide, is expressed in the bovine ovary. The objectives of this study were to characterize bovine ovarian CART and determine its localization, regulation, and regulatory role during follicular development. CART mRNA was detected in stroma of adult ovaries and in large follicles, but was undetectable in several peripheral tissues, fetal ovaries, and corpora lutea. Within the ovary, CART mRNA and peptide were localized to the granulosal layer of some, but not all, antral follicles, with low, but detectable, expression in oocytes and cumulus cells. CART mRNA was undetectable in granulosal cells of dominant ovulatory follicles collected before and after the preovulatory gonadotropin surge, but was detected in the granulosal layer of adjacent subordinate follicles. In addition, amounts of CART mRNA and follicular fluid concentrations of CART peptide were greater in subordinate follicles vs. dominant follicles of the first follicular wave. Furthermore, CART treatment inhibited basal estradiol production, but not progesterone production, by granulosal cells in a dose-dependent fashion, and the effect was dependent on stage of cell differentiation. We conclude that granulosal cell CART expression is temporally regulated and potentially associated with follicle health status, and CART can inhibit granulosal cell estradiol production. Thus, CART may be a novel local regulator of follicular atresia in the bovine ovary.

Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or ß-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal ß-cell function) were calculated in maternal and cord blood respectively. RESULTS: Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM. CONCLUSIONS: Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

Preliminary proteomic-based identification of a novel protein for Down's syndrome in maternal serum.

Prenatal screening for Down's syndrome (DS) is in need of improvement. As a powerful platform, proteomics techniques could also be used for identification of new biomarkers for DS screening. In this case-control proteome study, pregnant women were diagnosed prenatally by karyotype analysis from amniotic fluid (AF). Maternal serum samples were collected from six pregnancies with fetuses affected by DS and six pregnancies with normal fetuses. First, we used two-dimensional electrophoresis and mass spectrometry to identify the different levels of expression of proteins in maternal serum between the DS and control groups in the second trimester. Second, we used bioinformatics to analyze the proteins by DAVID. Then, the interesting candidates were further tested by enzyme-linked immunosorbent assay (ELISA). Twenty-nine proteins were successfully identified in maternal serum obtained from pregnancies with fetuses affected by DS. The top five proteins up-regulated were serotransferrin (TF), alpha-1b-glycoprotein (A1BG), desmin (DES), alpha-1-antitrypsin (SERPINA1) and ceruloplasmin (CP), while serum amyloid P-component (APCS) was the most down-regulated protein. These 29 proteins were categorized based on binding, catalytic activity and enzyme regulator activity. The biological roles were involved in biological regulation, metabolic processes, cellular processes and response to a stimulus. Based on ELISA, the median concentrations of CP and complement factor B (CFB) were 332.3 and 412.3 ng/mL, respectively. The concentrations of CP and CFB were significantly higher in the DS group than in the control group (P < 0.05). In conclusion, proteomic approaches offer the possibility of further improving the performance of DS screening and our identification of up- and down-regulated proteins may lead to new candidates for DS screening.

Bioinformatics characterization of differential proteins in serum of mothers carrying Down syndrome fetuses: combining bioinformatics and ELISA.

INTRODUCTION: Characterization of novel proteins in maternal serum derived from mothers carrying Down syndrome (DS) fetuses. MATERIAL AND METHODS: Based on last comparative proteomic analysis, five significant differences of expressed proteins in serum from four groups have been confirmed by ELISA. DAVID and GeneGo MetaCore were used to bioinformatically analyze candidate protein markers. RESULTS: The serum levels of ceruloplasmin (CP) and complement factor B (CFB) were significantly increased in mother carried DS fetuses (346.5 ng/ml and 466.8 ng/ml vs. 248.6 ng/ml and 293.5 ng/ml, p< 0.05). Twenty-nine proteins were mainly categorized into binding, catalytic activity and enzyme regulator activity proteins, and their biological roles were involved in biological regulation, metabolic processes, cellular processes, and response to stimuli. The immune response alternative complement pathway was the most significant GeneGo Pathway related to DS. CONCLUSIONS: These 29 proteins have relations with the development of Down syndrome, especially CP and CFB play more important roles.

Effect of statins on cholesterol crystallization and atherosclerotic plaque stabilization.

Pleiotropic effects of statins have not been fully elucidated. Recently we demonstrated that cholesterol expands when crystallizing and may trigger plaque rupture. The present study evaluated the potential direct effects of statins in altering cholesterol crystallization as a possible mechanism for plaque stabilization independent of cholesterol lowering. Cholesterol powder was dissolved in oil with and without pravastatin, simvastatin, or atorvastatin (10 to 90 mg) and then allowed to crystallize to measure peak volume expansion (ΔVE) in graduated cylinders. Effect of ΔVE on fibrous membrane damage was also evaluated. Human coronary, carotid, and peripheral arterial plaques (65 plaques from 55 patients) were incubated with statin or saline solution using matched plaque segments to evaluate direct effects of statins on preformed crystals. Also, the effect of in vivo use of oral statins on crystal structure was examined by scanning electron microscopy and crystal content in plaques scored from 0 to +3. For all statins, ΔVE decreased significantly in a dose-dependent fashion (0.76 ± 0.1 vs 0 ml at 60 mg, p <0.001). By scanning electron microscopy crystal structure with statins had loss of pointed tip geometries, averting fibrous membrane damage. Cholesterol crystal density was markedly decreased and appeared dissolved in human plaques incubated with statins (+2.1 ± 1.1 vs +1.3 ± 1.0, p = 0.0001). Also, plaques from patients taking oral statins compared to controls had significantly more dissolving crystals (p = 0.03). In conclusion, statins decreased ΔVE by altering cholesterol crystallization and blunting sharp-tipped crystal structure and dissolving cholesterol crystals in human arteries in vivo and in vitro, providing plaque stabilization.