bluuebunny/crossref_metadata_2025 huggingface dataset:
The Structure-Based Expert Model of the Mental Disorders – A Validation Study
Authors: Egli Samy , Streule Roland , Läge Damian
Published: July 2008

Background: In an earlier study, our research group presented an alternative approach to measuring knowledge about mental disorders by constructing a structure-based expert model of the ICD-10 mental disorders. This article presents a validation of this expert model by measuring the emergence of such knowledge structures in psychotherapy students. Sampling and Methods: The participants of a continuing education program in cognitive behavioral psychotherapy rated a selection of mental disorders based on their phenomenological similarity. The similarity judgments of each student were translated by nonmetric multidimensional scaling (NMDS) into a cognitive map. In a quasi-longitudinal section design, the maps of the students of the first to the fourth year of training were compared with each other and with an expert map (the expert model) of experienced therapists. Results: The discrepancies of the trainee maps compared with each other and with the expert map significantly decreased with increasing training level. Conclusions: The convergence of the students’ maps towards the expert model indicates that the structural knowledge about mental disorders of experienced therapists can also be found to be emerging in psychotherapy students. This finding supports the validity of the expert model and may reflect a general knowledge-structuring principle of the mental disorders. In spite of the statistical significance found, in view of the small number of participants in the third and fourth years of training, the results should be treated with caution and should be regarded as first indicators which need further confirmation.
A Comparison of Life Events in Adolescents with Major Depression, Borderline Personality Disorder and Matched Controls: A Pilot Study
Authors: Horesh Netta , Ratner Sharon , Laor Nathaniel , Toren Paz
Published: July 2008

Background: The study assessed the prevalence of life events (LE) in adolescents with major depressive disorder (MDD, n = 19), borderline personality disorder (BPD, n = 20) and matched controls (n = 20). Methods: Assessment measures included: the Child Suicide Potential Scale, the Beck Depression Inventory, the Life Events Checklist, the Childhood Sexual Abuse Questionnaire and the Childhood Trauma Questionnaire. Results: The percentage of negative lifetime LE was significantly higher in both MDD and BPD groups than in the control group, while the opposite was true for the percentage of positive LE. No difference was detected between the groups in the number of negative LE in the year preceding their admission. The MDD group reported more death-related LE than the control group, while the BPD group reported more sexual abuse LE than the control and MDD groups. Conclusions: The present study is a cross-sectional study, and therefore, we cannot draw definite conclusions regarding causality. Yet, the significance of negative LE as contributors to and of positive LE as protective factors against the development of nonsuicidal psychopathology is suggested. Further, the possible association between death of a first-degree relative and MDD and between sexual abuse occurring in early childhood and BPD is raised.
Cellular and Humoral Mechanisms of Immune Tolerance in Immediate-Type Allergy Induced by Specific Immunotherapy
Authors: Möbs Christian , Slotosch Caroline , Löffler Harald , Pfützner Wolfgang , Hertl Michael
Published: July 2008

The management of immediate-type allergy (ITA) is based on allergen avoidance, symptomatic pharmacological therapy and specific immunotherapy (SIT). Among these, SIT presents the only curative treatment. The efficacy of SIT in the treatment of IgE-mediated ITA has been proven in numerous clinical studies and is well established. This review discusses the relevance of immunoregulative humoral and cellular mechanisms leading to immune tolerance in ITA. Special focus is placed on the role of antibodies potentially interfering with the IgE-mediated immune reaction and regulatory T (Treg) cells including their immunosuppressive cytokines, which play a critical role in shifting the T helper 2 cell-driven allergic immune response towards allergen tolerance. Distinct subsets of constitutive and inducible Treg cells have been identified inhibiting the activation of allergen-specific effector T cells via cell contact- or cytokine-dependent suppression. Current research suggests that both inducible interleukin-10-producing CD4+ Treg cells and naturally occurring CD4+CD25+ Treg cells actively control allergic responses and that the disturbance of their function or number may contribute to the development or progression of allergy. Thus, the fine balance between allergen-specific T helper 2 and Treg cells constitutes a critical factor for the successful treatment of ITA by SIT.
Suppression of Allergic Inflammatory Response in the Skin of Alloxan-Diabetic Rats: Relationship with Reduced Local Mast Cell Numbers
Authors: de F. Carvalho Vinicius , Campos Leandro V. , Farias-Filho Francisco A. , Florim Luisa T. , Barreto Emiliano O. , Pirmez Claude , Savino Wilson , Martins Marco A. , e Silva Patrícia M.R.
Published: July 2008

Background: Diabetic patients are refractory to allergic inflammatory diseases. In this study, the influence of alloxan-induced diabetes on allergic skin inflammation was investigated. Methods: Diabetes was induced by intravenous injection of alloxan into male Wistar rats, and the analyses were performed 21 days later. Animals were actively sensitized with a mixture of aluminium hydroxide plus ovalbumin and challenged intradermally with ovalbumin on day 14. Results: Diabetic sensitized rats exhibited a less pronounced antigen-induced protein extravasation in the dorsal skin when compared with normal animals. Also, fragments of the dorsal subcutaneous tissue from diabetic sensitized rats showed a reduction in histamine release after stimulation with antigen in vitrowhen compared with fragments obtained from nondiabetic sensitized rats. Optical microscopy analysis revealed that the dorsal skin of diabetic rats showed a marked reduction in dermis thickness, as compared with that seen in normal animals. A significant decrease in the number of skin mast cells was also noted, a phenomenon that paralleled with the reduction in the expression of extracellular matrix components laminin, fibronectin and collagen. Administration of insulin into diabetic rats restored basal mast cell numbers as well as the levels of laminin, fibronectin and collagen. Conclusions: Our findings show that alloxan diabetes induces downregulation of the skin allergic inflammatory response in rats, and this was correlated with reduction in local mast cell numbers and expression of extracellular matrix components. Lastly, these alterations were reversed with insulin treatment.
Nestin Expression Reflects Formation, Revascularization and Reinnervation of New Myofibers in Regenerating Rat Hind Limb Skeletal Muscles
Authors: Čížková Dana , Soukup Tomáš , Mokrý Jaroslav
Published: July 2008

This work provides a comprehensive view of expression and distribution patterns of the intermediate filament nestin in rat regenerating skeletal muscles. Regeneration was induced by heterochronous isotransplantation of extensor digitorum longus (EDL) or soleus muscles from 15-day-old rats into the EDL muscle of adult female inbred Lewis rats. Recipients were sacrificed by anesthetic overdose and the host muscles with the graft were excised after 7-, 16-, 21- and 29-day survival, fixed in 10% formalin solution and immunohistochemically stained. In the regenerating skeletal muscle maximal nestin expression was observed in newly formed myoblasts and myotubes and it decreased in the course of skeletal myofiber development. We demonstrate the phenomenon of a peripheral concentration of nestin expression within the differentiating myofibers called ‘lateralization’, which may represent a mechanism of nestin elimination during the development of skeletal myofibers. Furthermore, nestin has been detected in newly formed endothelial cells of blood vessels growing into the regenerated area and also in peripheral nerves innervating the graft as well as the host muscle. In conclusion, according to our results, nestin represents an ideal marker for skeletal muscle regeneration, as its expression reflects processes of development, revascularization and reinnervation of new myofibers.
Global Birth Hypoxia Increases the Neonatal Testosterone Surge in the Rat
Authors: Boksa Patricia , Zhang Ying
Published: July 2008

Background/Aims: Global birth hypoxia in rats has been shown to produce long-term changes in central nervous system functions, known to be influenced by neonatal testosterone secretion. Birth hypoxia alters levels of several circulating hormones, but it is unknown if it affects neonatal testosterone. Methods: Using a rat model of acute global hypoxia during cesarean section (C-section) birth, this study tested whether birth hypoxia affects neonatal testosterone. We then evaluated whether the observed hypoxia-induced changes in neonatal testosterone may be mediated via N-methyl-D-aspartate (NMDA) receptor activation and/or altered luteinizing hormone (LH), adrenocorticotropic hormone (ACTH) or corticosterone levels. Longer-term effects of birth hypoxia on testosterone-related function were also assessed. Results: Rats born by C-section + 15 min of anoxia had significantly higher plasma testosterone at 2 and 3 h after birth compared to controls born either vaginally or by C-section. Administration of an NMDA receptor antagonist at birth increased neonatal testosterone in both anoxic pups and controls. Pups exposed to birth anoxia under hypothermic conditions also showed increased neonatal testosterone. Circulating LH, follicle-stimulating hormone and corticosterone in neonates, and testosterone at adulthood were unaffected by birth hypoxia. However, plasma ACTH was significantly increased in anoxic neonates at 2 h after birth. Birth condition had no effect on anogenital distance or juvenile play behavior. Conclusion: It is concluded that birth hypoxia augments plasma testosterone during the critical period of the neonatal testosterone surge, by a mechanism that is independent of NMDA-mediated LH secretion, but may involve increased circulating ACTH.
Activity of Exporters of Escherichia coli in Corynebacterium glutamicum, and Their Use to Increase L-Threonine Production
Authors: Diesveld Ramon , Tietze Nadine , Fürst Oliver , Reth Alexander , Bathe Brigitte , Sahm Hermann , Eggeling Lothar
Published: July 2008

L-Threonine is an important biotechnological product and Corynebacterium glutamicum is able to synthesize and accumulate this amino acid to high intracellular levels. We here use four exporters of Escherichia coli and show that three of them operate in C. glutamicum, with RhtA and RhtC being the most effective. Whereas RhtA was unspecific, resulting in L-homoserine together with L-threonine excretion, this was not the case with RhtC. Expression of rhtC reduced the intracellular L-threonine concentration from 140 to 11 mM and resulted in maximal excretion rates of 11.2 nmol min–1 mg–1 as compared to 2.3 nmol min–1 mg–1 obtained without rhtC expression. In combination with an ilvA mutation generated and introduced into the chromosome, an accumulation of up to 54 mML-threonine was achieved as compared to 21 mM obtained with the ancestor strain. This shows that expression of rhtC is the pivotal point for industrial relevant L-threonine production with C. glutamicum, and might encourage in general the use of heterologous exporters in the field of white biotechnology to make full use of biosynthesis pathways.
Density-Dependent Shift of Transforming Growth Factor-Beta-1 from Inhibition to Stimulation of Vascular Smooth Muscle Cell Growth Is Based on Unconventional Regulation of Proliferation, Apoptosis and Contact Inhibition
Authors: Hneino Mohammad , Bouazza Lamia , Bricca Giampiero , Li Jacques Yuan , Langlois Dominique
Published: July 2008

Background: TGF-β shifts from inhibition to stimulation of vascular smooth muscle cell (vSMC) growth when cell density increases. How proliferation and apoptosis contribute to this shift is still unknown. Methods: In sparse and confluent V8 vSMC treated or not with TGF-β1 (1 ng/ml) for 3 days, cell number, mitotic activity, cell-cycle-regulatory protein levels, caspase-3 and phosphoinositide 3-kinase (PI3-K) activities were studied. Results: In TGF-β1-treated cells, (i) the growth curve rose constantly compared to controls, reaching post-confluent densities; (ii) mitotic activity, which was constant at all cell densities, was lower than in sparse but higher than in contact-inhibited control cells, and (iii) apoptosis occurred at sparse densities only. The mechanism of proliferation control by TGF-β1 was very unconventional in V8 vSMCs: (i) p15INK4b and cyclin D levels were similar in cells treated or not with TGF-β1, and (ii) p27Kip1 levels remained very low even at high densities while cyclin E levels were not markedly decreased. TGF-β1-induced apoptosis in sparse cultures and its reversal in dense cultures were inversely correlated to PI3-K activation. Conclusions: TGF-β1 slowed sparse V8 vSMC growth by inhibiting proliferation and inducing apoptosis. TGF-β1-treated confluent vSMCs escaped contact inhibition and kept growing through unconventional regulation of p27Kip1, cyclin E and suppression of apoptosis.
Brain-Specific Expression of Vascular Endothelial Growth Factor 146 Correlates with the Blood-Brain Barrier Induction in Quail Embryos
Authors: Ikeda Eiji , Takubo Keiyo , Kodama Takahide , Okada Yasunori
Published: July 2008

Homeostasis of the neural environment is indispensable for the normal functioning of neural cells, and is maintained by the blood-brain barrier (BBB). The BBB is induced during embryonic development. The present study aimed to clarify the molecular mechanisms of BBB induction in neural tissues. Using an in vivo model of BBB induction that is based on xenograft transplantation between quail and chick embryos, we showed that the gene expression in developing brain cells is appropriately regulated to generate the neural microenvironment for endothelial cells to form the neural tissue-specific vascular structure with a BBB function. Vascular endothelial growth factor (VEGF) is a factor controlling vascular proliferation as well as vascular permeability, and is known to be produced by developing brain cells. In the present study, we show that the isoforms of VEGF produced by developing quail brain cells change with close temporal correlation to the BBB induction. Among four isoforms, VEGF122 and VEGF166 were expressed constitutively during the course of embryonic development, while the expressions of VEGF146 and VEGF190 were upregulated after the differentiation of endothelial cells to BBB-forming cells had begun. Furthermore, through investigation into developing extracranial tissues, the changes in VEGF isoform expression, especially the upregulation of VEGF146 expression, were shown to be specific for brain tissues that contain the blood vessels with BBB properties. These results suggest that the expression of VEGF isoforms by brain cells is developmentally regulated for the achievement of brain development including the BBB induction.
Inadequate Blood Glucose Control Is Associated With In-Hospital Mortality and Morbidity in Diabetic and Nondiabetic Patients Undergoing Cardiac Surgery
Authors: Ascione R. , Rogers C.A. , Rajakaruna C. , Angelini G.D.
Published: July 2008

Background—

Derangement of glucose metabolism after surgery is not specific to patients with diabetes mellitus. We investigated the effect of different degrees of blood glucose control (BGC) on clinical outcomes after cardiac surgery.

Methods and Results—

We analyzed 8727 adults operated on between April 1996 and March 2004. The highest blood glucose level recorded over the first 60 hours postoperatively was used to classify patients as having good (<200 mg/dL), moderate (200 to 250 mg/dL), or poor (>250 mg/dL) BGC; 7547 patients (85%) had good, 905 (10%) had moderate, and 365 (4%) had poor BGC. Patients with inadequate BGC were more likely to present with advanced New York Heart Association class, congestive heart failure, hypertension, renal dysfunction, and ejection fraction <50% (
P
≤0.001). We found that 52% of patients with poor, 31% with moderate, and 8% with good BGC had diabetes mellitus. Inadequate BGC, but not diabetes mellitus (
P
=0.79), was associated with in-hospital mortality (good, 1.8%; moderate, 4.2%; poor, 9.6%; adjusted odds ratio: poor versus good BGC, 3.90 [95% confidence interval, 2.47 to 6.15]; moderate versus good BGC, 1.68 [95% confidence interval, 1.25 to 2.25]). Inadequate BGC also was associated with postoperative myocardial infarction (eg, odds ratio, poor versus good BGC: 2.73 [95% confidence interval, 1.74 to 4.26]) and with pulmonary and renal complications in patients without known diabetes mellitus (eg, odds ratio, poor versus good BGC: 2.27 [95% confidence interval, 1.65 to 3.12] and 2.82 [95% confidence interval, 1.54 to 5.14] respectively).

Conclusions—

More than 50% of patients with moderate to poor BGC after cardiac surgery were not previously identified as diabetic. Inadequate postoperative BGC is a predictor of in-hospital mortality and morbidity.
Heritability and Genome-Wide Linkage in US and Australian Twins Identify Novel Genomic Regions Controlling Chromogranin A
Authors: O'Connor Daniel T. , Zhu Gu , Rao Fangwen , Taupenot Laurent , Fung Maple M. , Das Madhusudan , Mahata Sushil K. , Mahata Manjula , Wang Lei , Zhang Kuixing , Greenwood Tiffany A. , Shih Pei-an Betty , Cockburn Myles G. , Ziegler Michael G. , Stridsberg Mats , Martin Nicholas G. , Whitfield John B.
Published: July 2008

Background—

Chromogranin A (CHGA) triggers catecholamine secretory granule biogenesis, and its catestatin fragment inhibits catecholamine release. We approached catestatin heritability using twin pairs, coupled with genome-wide linkage, in a series of twin and sibling pairs from 2 continents.

Methods and Results—

Hypertensive patients had elevated CHGA coupled with reduction in catestatin, suggesting diminished conversion of precursor to catestatin. Heritability for catestatin in twins was 44% to 60%. Six hundred fifteen nuclear families yielded 870 sib pairs for linkage, with significant logarithm of odds peaks on chromosomes 4p, 4q, and 17q. Because acidification of catecholamine secretory vesicles determines CHGA trafficking and processing to catestatin, we genotyped at positional candidate
ATP6N1
, bracketed by peak linkage markers on chromosome 17q, encoding a subunit of vesicular H
+
-translocating ATPase. The minor allele diminished CHGA secretion and processing to catestatin. The
ATP6N1
variant also influenced blood pressure in 1178 individuals with the most extreme blood pressure values in the population. In chromaffin cells, inhibition of H
+
-ATPase diverted CHGA from regulated to constitutive secretory pathways.

Conclusions—

We established heritability of catestatin in twins from 2 continents. Linkage identified 3 regions contributing to catestatin, likely novel determinants of sympathochromaffin exocytosis. At 1 such positional candidate (
ATP6N1
), variation influenced CHGA secretion and processing to catestatin, confirming the mechanism of a novel
trans
-QTL for sympathochromaffin activity and blood pressure.
Cardiovascular Risk Factors and the Metabolic Syndrome in Pediatric Nonalcoholic Fatty Liver Disease
Authors: Schwimmer Jeffrey B. , Pardee Perrie E. , Lavine Joel E. , Blumkin Aaron K. , Cook Stephen
Published: July 2008

Background—

Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in children, is associated with obesity and insulin resistance. However, the relationship between NAFLD and cardiovascular risk factors in children is not fully understood. The objective of this study was to determine the association between NAFLD and the presence of metabolic syndrome in overweight and obese children.

Methods and Results—

This case-control study of 150 overweight children with biopsy-proven NAFLD and 150 overweight children without NAFLD compared rates of metabolic syndrome using Adult Treatment Panel III criteria. Cases and controls were well matched in age, sex, and severity of obesity. Children with NAFLD had significantly higher fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure than overweight and obese children without NAFLD. Subjects with NAFLD also had significantly lower high-density lipoprotein cholesterol than controls. After adjustment for age, sex, race, ethnicity, body mass index, and hyperinsulinemia, children with metabolic syndrome had 5.0 (95% confidence interval, 2.6 to 9.7) times the odds of having NAFLD as overweight and obese children without metabolic syndrome.

Conclusions—

NAFLD in overweight and obese children is strongly associated with multiple cardiovascular risk factors. The identification of NAFLD in a child should prompt global counseling to address nutrition, physical activity, and avoidance of smoking to prevent the development of cardiovascular disease and type 2 diabetes.
Transcriptomic Biomarkers for Individual Risk Assessment in New-Onset Heart Failure
Authors: Heidecker Bettina , Kasper Edward K. , Wittstein Ilan S. , Champion Hunter C. , Breton Elayne , Russell Stuart D. , Kittleson Michelle M. , Baughman Kenneth L. , Hare Joshua M.
Published: July 2008

Background—

Prediction of prognosis remains a major unmet need in new-onset heart failure (HF). Although several clinical tests are in use, none accurately distinguish between patients with poor versus excellent survival. We hypothesized that a transcriptomic signature, generated from a single endomyocardial biopsy, could serve as a novel prognostic biomarker in HF.

Methods and Results—

Endomyocardial biopsy samples and clinical data were collected from all patients presenting with new-onset HF from 1997 to 2006. Among a total of 350 endomyocardial biopsy samples, 180 were identified as idiopathic dilated cardiomyopathy. Patients with phenotypic extremes in survival were selected: good prognosis (event-free survival for at least 5 years; n=25) and poor prognosis (events [death, requirement for left ventricular assist device, or cardiac transplant] within the first 2 years of presentation with HF symptoms; n=18). We used human U133 Plus 2.0 microarrays (Affymetrix) and analyzed the data with significance analysis of microarrays and prediction analysis of microarrays. We identified 46 overexpressed genes in patients with good versus poor prognosis, of which 45 genes were selected by prediction analysis of microarrays for prediction of prognosis in a train set (n=29) with subsequent validation in test sets (n=14 each). The biomarker performed with 74% sensitivity (95% CI 69% to 79%) and 90% specificity (95% CI 87% to 93%) after 50 random partitions.

Conclusions—

These findings suggest the potential of transcriptomic biomarkers to predict prognosis in patients with new-onset HF from a single endomyocardial biopsy sample. In addition, our findings offer potential novel therapeutic targets for HF and cardiomyopathy.
Hypoxia-Inducible Factor-1 Is Central to Cardioprotection
Authors: Eckle Tobias , Köhler David , Lehmann Rainer , El Kasmi Karim C. , Eltzschig Holger K.
Published: July 2008

Background—

Ischemic preconditioning provides strong cardioprotection from ischemia, but its molecular mechanisms remain unknown. Convincing evidence confirms a central role of hypoxia-inducible factor (HIF)-1 in mammalian oxygen homeostasis. Thus, we pursued HIF-1 as a central component of cardioprotection by ischemic preconditioning.

Methods and Results—

Murine studies of in situ preconditioning revealed a robust activation of cardiac HIF-1α. Moreover, in vivo small interfering RNA repression of cardiac HIF-1α resulted in abolished cardioprotection by ischemic preconditioning. In contrast, pretreatment with the HIF activator dimethyloxalylglycine was associated with cardioprotection similar to that of ischemic preconditioning itself. Finally, selective small interfering RNA repression of prolylhydroxylase 2 resulted in significant activation of HIF-1α and attenuated myocardial infarct sizes (0.44±0.09-fold). As an end point of HIF-dependent cardioprotection, we defined the role of A2B adenosine receptor (A2BAR) signaling. Although the cardiac A2BAR was induced with HIF activation, HIF-dependent cardioprotection was abolished in

A2BAR
−/−

mice.

Conclusion—

Taken together, these studies provide evidence for a critical role of HIF-1 in ischemic preconditioning via enhancing purinergic signaling pathways.
Comparison of Thrombolysis Followed by Broad Use of Percutaneous Coronary Intervention With Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Acute Myocardial Infarction
Authors: Danchin Nicolas , Coste Pierre , Ferrières Jean , Steg Philippe-Gabriel , Cottin Yves , Blanchard Didier , Belle Loïc , Ritz Bernard , Kirkorian Gilbert , Angioi Michael , Sans Philippe , Charbonnier Bernard , Eltchaninoff Hélène , Guéret Pascal , Khalife Khalife , Asseman Philippe , Puel Jacques , Goldstein Patrick , Cambou Jean-Pierre , Simon Tabassome
Published: July 2008

Background—

Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI.

Methods and Results—

This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (
P
=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively.

Conclusions—

When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.
Genomic Association Analysis Suggests Chromosome 12 Locus Influencing Antihypertensive Response to Thiazide Diuretic
Authors: Turner Stephen T. , Bailey Kent R. , Fridley Brooke L. , Chapman Arlene B. , Schwartz Gary L. , Chai High Seng , Sicotte Hugues , Kocher Jean-Pierre , Rodin Andréi S. , Boerwinkle Eric
Published: July 2008

We conducted a genome-wide association study to identify novel genes influencing diastolic blood pressure (BP) response to hydrochlorothiazide, a commonly prescribed thiazide diuretic preferred for the treatment of high BP. Affymetrix GeneChip Human Mapping 100K Arrays were used to measure single nucleotide polymorphisms across the 22 autosomes in 194 non-Hispanic black subjects and 195 non-Hispanic white subjects with essential hypertension selected from opposite tertiles of the race- and sex-specific distributions of age-adjusted diastolic BP response to hydrochlorothiazide (25 mg daily, PO, for 4 weeks). The black sample consisted of 97 “good” responders (diastolic BP response [mean±SD]=−18.3±4.2 mm Hg; age=47.1±6.1 years; 51.5% women) and 97 “poor” responders (diastolic BP response=−0.18±4.3; age=47.4±6.5 years; 51.5% women). Haplotype trend regression identified a region of chromosome 12q15 in which haplotypes constructed from 3 successive single nucleotide polymorphisms (rs317689, rs315135, and rs7297610) in proximity to lysozyme (
LYZ
), YEATS domain containing 4 (
YEATS4
), and fibroblast growth receptor substrate 2 (
FRS2
) were significantly associated with diastolic BP response (nominal
P
=2.39×10
−7
; Bonferroni corrected
P
=0.024; simulated experiment-wise
P
=0.040). Genotyping of 35 additional single nucleotide polymorphisms selected to “tag” linkage disequilibrium blocks in these genes provided corroboration that variation in
LYZ
and
YEATS4
was associated with diastolic BP response in a statistically independent data set of 291 black subjects and in the sample of 294 white subjects. These results support the use of genome-wide association analyses to identify novel genes influencing antihypertensive drug responses.
Increased Myeloperoxidase in the Placenta and Circulation of Women With Preeclampsia
Authors: Gandley Robin E. , Rohland Jennifer , Zhou Yan , Shibata Eiji , Harger Gail F. , Rajakumar Augustine , Kagan Valerian E. , Markovic Nina , Hubel Carl A.
Published: July 2008

Myeloperoxidase (MPO) is a hemoprotein normally released from activated monocytes and neutrophils. Traditionally viewed as a microbicidal enzyme, MPO also induces low-density lipoprotein oxidation, activates metalloproteinases, and oxidatively consumes endothelium-derived NO. The elevated plasma MPO level is a risk factor for myocardial events in patients with coronary artery disease. Patients with preeclampsia display evidence of the inflammation and endothelial dysfunction associated with oxidative stress in the circulation, vasculature, and placenta. We hypothesized that MPO levels in the circulation and placental extracts from women with preeclampsia would be greater than levels in women with normal pregnancies. Placental extracts were prepared from placental villous biopsies from preeclamptic (n=27) and control (n=43) placentas. EDTA plasma samples were obtained from gestationally age-matched preeclamptic and control normal pregnancies. MPO concentrations were measured by ELISA. Immunohistochemistry was used to determine MPO localization in the placenta. MPO levels in placental extracts from women with preeclampsia were significantly higher than the levels in normal control subjects (546±62 versus 347±32 ng/mL;
P
=0.025). MPO was found in the floating villi and basal plate of placentas with a greater staining in the basal plates from preeclampsia placentas compared with normal pregnancies. Plasma MPO levels were 3-fold higher in patients with preeclampsia compared with normal control subjects (36.6±7.6 versus 11.0±3.1 ng/mL;
P
=0.003). In conclusion, MPO levels are significantly increased in the circulation and placenta of women with preeclampsia. We speculate that MPO may contribute to the oxidative damage reported in the endothelium and placenta of women with preeclampsia.
Quantitative Determination of Triglyceride by Photoactivated CdSe/ZnS Quantum Dots Through Fluorescence Assay
Authors: Huang Chin-Ping , Li Yaw-Kuen , Chen Teng-Ming
Published: July 2008

The quantitative detection of triglycerides is an important issue for health inspection of metabolic disorders and for food and oil-refining industries. Many methods have been designed to approach this target, in which multiple reactions catalyzed by enzymes are normally coupled consecutively.
In this study, we demonstrated a simple assay system containing lipase and photoactivated luminescent CdSe/ZnS quantum dots (QDs) for the quantitative detection of triglycerides. Photoactivated CdSe/ZnS QDs function as a sensitive "indicator" to reveal the minute acidity change of the assay
system resulting from the enzymatic hydrolysis of triglycerides. By controlling the initial buffer condition of the assay system at 5, 10, or 20 mM phosphate buffer at pH 8.0, respectively, the quenching ratio of the QDs fluorescence intensity monitored at the maximum photoluminescence showed
a linear correlation with the concentration of the examined triglyceride in the range of 0.02–6, 0.2–10, or 2–20 mM, respectively. The assay system also provides a convenient way to estimate triglyceride concentration by visualizing the color change of the QDs fluorescence.
As compared to most of the existing methods, the system reported herein possessed many advantages, including simplicity, low cost, high flexibility, and high sensitivity. Furthermore, no complicated chemical modification or enzyme immobilization is needed.
Spin-Polarized Scanning Tunneling Spectroscopy of Self-Organized Nanoscale Co Islands on Au(111) Surfaces
Authors: Schouteden K. , Muzychenko D. A. , Van Haesendonck C.
Published: July 2008

Magnetic monolayer and bilayer Co islands of only a few nanometer in size were grown by atomic deposition on atomically flat Au(111) films. The islands were studied in situ by scanning tunneling microscopy (STM) and spectroscopy at low temperatures. Spin-resolved tunneling spectroscopy,
using an STM tip with a magnetic coating, revealed that the Co islands exhibit a net magnetization perpendicular to the substrate surface due to the presence of spin-polarized d-states. A random distribution of islands with either upward or downward pointing magnetization was observed,
without any specific correlation of magnetization orientation with island size or island height.
Interaction between Coastal Upwelling and Local Winds at Cabo Frio, Brazil: An Observational Study
Authors: Franchito Sergio H. , Oda Tania O. , Rao V. Brahmananda , Kayano Mary T.
Published: July 2008

The relationships between coastal upwelling and local winds at Cabo Frio (Brazil) are studied using SST and time series of surface wind for a 10-yr period (1971–80). The results show that the seasonal variations of SST and local winds are closely related. Sea-breeze circulation is intensified by the enhancement of the land–sea temperature gradient due to cold water upwelling near the coast; coastal upwelling, in turn, is associated with strong northeasterlies. This result confirms the conclusions of earlier modeling studies. Interannual variability is also apparent in the results. During the period from 1971 to 1980, the highest SST values occur during the years 1972–73 (strong El Niño event) and the lowest occur in 1977 (moderate El Niño event). This suggests some possible effects of atmospheric teleconnections on South Atlantic SSTs. However, a record longer than 10 yr is needed to confirm the connection with El Niño and La Niña events. Time–frequency analyses of the SST and zonal wind series for 1975–77 are done using Morlet wavelet analysis. The global wavelet spectra for these variables show strong peaks at 24 and 157 h (approximately 6.6 days). These analyses also indicate that the sea breeze occurs at Cabo Frio almost year-round and confirm the relationships with the coastal upwelling in the region.
Strategies for Evaluating Quality Assurance Procedures
Authors: Durre Imke , Menne Matthew J. , Vose Russell S.
Published: July 2008

The evaluation strategies outlined in this paper constitute a set of tools beneficial to the development and documentation of robust automated quality assurance (QA) procedures. Traditionally, thresholds for the QA of climate data have been based on target flag rates or statistical confidence limits. However, these approaches do not necessarily quantify a procedure’s effectiveness at detecting true errors in the data. Rather, as illustrated by way of an “extremes check” for daily precipitation totals, information on the performance of a QA test is best obtained through a systematic manual inspection of samples of flagged values combined with a careful analysis of geographical and seasonal patterns of flagged observations. Such an evaluation process not only helps to document the effectiveness of each individual test, but, when applied repeatedly throughout the development process, it also aids in choosing the optimal combination of QA procedures and associated thresholds. In addition, the approach described here constitutes a mechanism for reassessing system performance whenever revisions are made following initial development.
Process-Oriented Analysis of Environmental Conditions Associated with Precipitation Fog Events in the New York City Region
Authors: Tardif Robert , Rasmussen Roy M.
Published: July 2008

An analysis of the environmental conditions associated with precipitation fog events is presented using 20 yr of historical observations taken in a region centered on New York, New York. The objective is to determine the preferred weather scenarios and identify physical processes influencing the formation of fog during precipitation. Salient synoptic-scale features are identified using NCEP–NCAR reanalyses. Local environmental parameters, such as wind speed and direction, temperature, and humidity, are analyzed using surface observations, while the vertical structure of the lower atmosphere is examined using available rawinsonde data. The analysis reveals that precipitation fog mostly occurs as a result of the gradual lowering of cloud bases as continuous light rain or light drizzle is observed. Such scenarios occur under various synoptic weather patterns in areas characterized by large-scale uplift, differential temperature advection, and positive moisture advection. Precipitation fog onset typically occurs with winds from the northeast at inland locations and onshore flow at coastal locations, with flows from the south to southwest aloft. A majority of the cases showed the presence of a sharp low-level temperature inversion resulting from differential temperature advection or through the interaction of warm air flowing over a cold surface in onshore flow conditions. This suggests a common scenario of fog formation under moistening conditions resulting from precipitation evaporating into colder air near the surface. A smaller number of events formed with cooling of the near-saturated or saturated air. Evidence is also presented of the possible role of shear-induced turbulent mixing in the production of supersaturation and fog formation during precipitation.
Does an August Singularity Exist in the Northern Rockies of the United States?
Authors: Soulé Peter T. , Knapp Paul A.
Published: July 2008

Climatic singularities offer a degree of orderliness to notable meteorological events that are typically characterized by significant temporal variability. Significant deviations from normal daily maximum temperatures that occur following the passage of a strong midlatitude cyclone in mid- to late August in the northern Rocky Mountains of the United States are recognized in the local culture as the “August Singularity.” Daily standardized maximum temperature anomalies for August–October were examined for eight climate stations in Montana and Idaho as indicators of major midlatitude storms. The data indicate that a single-day negative maximum temperature singularity exists for 13 August. Further, a 3-day singularity event exists for 24–26 August. It is concluded that the concept of an August Singularity in the northern Rockies is valid, because the high frequency of recorded negative maximum temperature anomalies suggests that there are specific time intervals during late summer that are more likely to experience a major midlatitude storm. The principal benefit to society for the August Singularity is that the reduced temperatures help in the efforts to control wildfires that are common this time of year in the northern Rockies.
The Impact of Aerosols on the Summer Rainfall Frequency in China
Authors: Choi Yong-Sang , Ho Chang-Hoi , Kim Jinwon , Gong Dao-Yi , Park Rokjin J.
Published: July 2008

The authors investigate the short-term relationship between aerosol concentrations and summer rainfall frequency in China using the daily surface observations of particulate matters with a diameter of less than 10 μm (PM10) mass concentration, rainfall, and satellite-observed cloud properties. Results in this study reveal that on the time scale of a few days aerosol concentration is positively correlated with the frequency of moderate-rainfall (10–20 mm day−1) days but is negatively correlated with the frequency of light-rainfall (<5 mm day−1) days. Satellite observations of cloud properties show that higher aerosol concentrations are positively correlated with the increase in mixed cloud amount, cloud effective radius, cloud optical depth, and cloud-top heights; this corresponds to the decrease in low-level liquid clouds and the increase in midlevel ice–mixed clouds. Based on this analysis, the authors hypothesize that the increase in aerosol concentration results in the increase in summer rainfall frequency in China via enhanced ice nucleation in the midtroposphere. However, over the past few decades, observations show an increasing long-term trend in aerosol concentration but decreasing trends in summer rainfall frequency and relative humidity (RH) in China. Despite the short-term positive relationship between summer rainfall frequency and aerosol concentration found in this study, the long-term variations in summer rainfall frequency in China are mainly determined by other factors including RH variation possibly caused by global and regional climate changes. A continuous decrease in RH resulting in less summer rainfall frequency may further enhance aerosol concentrations in the future in conjunction with the increase in the anthropogenic emissions.
Coexistence of Equatorial Coupled Modes of ENSO*
Authors: Bejarano Luis , Jin Fei-Fei
Published: July 2008

To study the regimes of leading ocean–atmosphere coupled modes of relevance to the El Niño–Southern Oscillation (ENSO) phenomenon, a comprehensive eigenmode analysis of an intermediate coupled model linearized with respect to an array of basic states is performed. Different kinds of leading modes are found to coexist and become unstable under wide ranges of basic states and parameter conditions. In particular, the two most important modes have periods of around 4 and 2 yr. They are referred to as the quasi-quadrennial (QQ) and the quasi-biennial (QB) modes, respectively. The positive coupled feedback destabilizes and quantizes the near-continuous spectrum for the low-frequency modes of the upper-ocean dynamics, giving rise to these leading modes with distinct periodicities. The primary mechanism for the phase transition of the QQ mode is due to the slow oceanic dynamic adjustment of equatorial heat content, which is consistent with the simple conceptual recharge oscillator, whereas anomalous advection of sea surface temperature by equatorial zonal current anomalies plays a dominant role in the phase transition of the QB mode. The coexistence of these ENSO-like coupled modes under the present climate conditions may provide an explanation for the observed rich variations in ENSO behaviors.
On the Role of Atmospheric Teleconnections in Climate
Authors: Tsonis Anastasios A. , Swanson Kyle L. , Wang Geli
Published: July 2008

In a recent application of networks to 500-hPa data, it was found that supernodes in the network correspond to major teleconnection. More specifically, in the Northern Hemisphere a set of supernodes coincides with the North Atlantic Oscillation (NAO) and another set is located in the area where the Pacific–North American (PNA) and the tropical Northern Hemisphere (TNH) patterns are found. It was subsequently suggested that the presence of atmospheric teleconnections make climate more stable and more efficient in transferring information. Here this hypothesis is tested by examining the topology of the complete network as well as of the networks without teleconnections. It is found that indeed without teleconnections the network becomes less stable and less efficient in transferring information. It was also found that the pattern chiefly responsible for this mechanism in the extratropics is the NAO. The other patterns are simply a linear response of the activity in the tropics and their role in this mechanism is inconsequential.
Variability and Trend of North West Australia Rainfall: Observations and Coupled Climate Modeling
Authors: Shi Ge , Cai Wenju , Cowan Tim , Ribbe Joachim , Rotstayn Leon , Dix Martin
Published: July 2008

Since 1950, there has been an increase in rainfall over North West Australia (NWA), occurring mainly during the Southern Hemisphere (SH) summer season. A recent study using twentieth-century multimember ensemble simulations in a global climate model forced with and without increasing anthropogenic aerosols suggests that the rainfall increase is attributable to increasing Northern Hemisphere aerosols. The present study investigates the dynamics of the observed trend toward increased rainfall and compares the observed trend with that generated in the model forced with increasing aerosols.

It is found that the observed positive trend in rainfall is projected onto two modes of variability. The first mode is associated with an anomalously low mean sea level pressure (MSLP) off NWA instigated by the enhanced sea surface temperature (SST) gradients toward the coast. The associated cyclonic flows bring high-moisture air to northern Australia, leading to an increase in rainfall. The second mode is associated with an anomalously high MSLP over much of the Australian continent; the anticyclonic circulation pattern, over northern Australia, determines that when rainfall is anomalously high, west of 130°E, rainfall is anomalously low east of this longitude. The sum of the upward trends in these two modes compares well to the observed increasing trend pattern.

The modeled rainfall trend, however, is generated by a different process. The model suffers from an equatorial cold-tongue bias: the tongue of anomalies associated with El Niño–Southern Oscillation extends too far west into the eastern Indian Ocean. Consequently, there is an unrealistic relationship in the SH summer between Australian rainfall and eastern Indian Ocean SST: the rise in SST is associated with increasing rainfall over NWA. In the presence of increasing aerosols, a significant SST increase occurs in the eastern tropical Indian Ocean. As a result, the modeled rainfall increase in the presence of aerosol forcing is accounted for by these unrealistic relationships. It is not clear whether, in a model without such defects, the observed trend can be generated by increasing aerosols. Thus, the impact of aerosols on Australian rainfall remains an open question.