bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Folic Acid Combined with Fluoxetine in Patients with Major Depression on Plasma Homocysteine and Vitamin B12, and Serotonin Levels in Lymphocytes
Authors: Resler Gustavo , Lavie Renée , Campos Julio , Mata Salvador , Urbina Mary , García Alberto , Apitz Rafael , Lima Lucimey
Published: August 2008

Objective(s): Folic acid, a micronutrient supporting the natural defense system, may elevate antidepressant responses, although the lymphocyte serotonergic system has not been explored in folate-supplemented depressed patients. Methods: Twenty-seven patients were randomly assigned to groups receiving fluoxetine (20 mg) and folic acid (10 mg/day) or fluoxetine and placebo for 6 weeks. Clinical outcome was assessed according to the Hamilton Depression Rating Scale (HDRS) at the beginning, during and at the end of treatment. Blood samples were taken, plasma was separated, and lymphocytes were obtained by density gradient centrifugation with Ficoll/Hypaque and differential adhesion to plastic dishes. Fifteen healthy subjects served as controls. Plasma folate, homocysteine and vitamin B12, and serotonin concentration in lymphocytes were determined by HPLC. The HDRS score was significantly lower in patients receiving fluoxetine and folic acid compared with those receiving fluoxetine and placebo after 6 weeks of treatment (7.43 ± 1.65 vs. 11.43 ± 1.31, respectively; p = 0.04). Plasma homocysteine statistically significant decreased after folic acid (p = 0.02), but no significant changes were observed in vitamin B12. Results: Serotonin was significantly reduced after fluoxetine either with folate (p = 0.03) or placebo (p = 0.01) probably by the effect of transporter blockade. 5-Hydroxyindoleacetic acid was lower in lymphocytes of patients receiving folate (p = 0.04), indicating a reduced turnover rate, thus accumulating serotonin in the cells. A significant negative correlation was noted between homocysteine and folate. No significant correlations were present among biochemical parameters and depression severity. Conclusion: Modifications due to treatment with fluoxetine and folic acid may alter lymphocyte function in depression probably indirectly by reducing homocysteine levels and directly on lymphocytes by modifying the serotonergic system.
Overexpression of Tyrosine Kinase B Protein as a Predictor for Distant Metastases and Prognosis in Gastric Carcinoma
Authors: Zhang Yong , Fujiwara Yoshiyuki , Doki Yuichiro , Takiguchi Shuji , Yasuda Takushi , Miyata Hiroshi , Yamazaki Makoto , Ngan Chew Yee , Yamamoto Hirofumi , Ma Qingyong , Monden Morito
Published: August 2008

Objective: Tyrosine kinase B (TrkB) is associated with aggressive behavior and poor prognosis in various cancers. Here we examined the association between TrkB expression and distant metastases/prognosis in gastric carcinoma (GC). Patients and Methods: We analyzed TrkB expression in 161 GC patients by immunohistochemistry and Western blot analysis. The correlation of TrkB mRNA and protein expression levels was examined in 10 patients by RT-PCR assay. Results: TrkB expression was of level 1 in 97 (60.2%) and level 2 in 64 (39.8%) patients. Patients with level 2 expression had a significantly higher incidence of distant metastases (p < 0.0001), well-differentiated tumors (p < 0.005), deeper depth of invasion (p < 0.005) and poorer disease-free and overall survival (p < 0.0001 each) compared to patients with level 1. Multivariate analysis identified the level of TrkB expression as an independent prognostic factor for both disease-free and overall survival (p < 0.01 and p < 0.0001, respectively). Both lymph node metastasis (odds ratio = 10.7) and TrkB expression (odds ratio = 9.3) were independent predictors of distant metastases. Conclusion: A high level of TrkB expression was observed in well-differentiated GC subtypes and is a predictor for distant metastases and prognosis in GC.
Platelet Chemokines in Vascular Disease
Authors: Gleissner Christian A. , von Hundelshausen Philipp , Ley Klaus
Published: August 2008

Platelets are a rich source of different chemokines and express chemokine receptors. CXCL4 is highly abundant in platelets and involved in promoting monocyte arrest from rolling and monocyte differentiation to macrophages. CXCL4 can also associate with CCL5 and amplify its effect on monocytes. The megakaryocyte
CXCL7
gene product is proteolytically cleaved into the strong neutrophil chemoattractant, NAP-2, which has also been implicated in repair cell homing to vascular lesions. Platelet adhesion can induce release of CCL2 and CXCL8 from endothelial cells. Conversely, the chemokines CCL17, CCL22, and CXCL12 made by other cells amplify platelet activation. Platelet chemokines enhance recruitment of various hematopoietic cells to the vascular wall, fostering processes such as neointima formation, atherosclerosis, and thrombosis, but also vessel repair and regeneration after vascular injury.
Statins Use a Novel Nijmegen Breakage Syndrome-1–Dependent Pathway to Accelerate DNA Repair in Vascular Smooth Muscle Cells
Authors: Mahmoudi Melli , Gorenne Isabelle , Mercer John , Figg Nicola , Littlewood Trevor , Bennett Martin
Published: August 2008

Although the hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are widely used in atherosclerosis to reduce serum cholesterol, statins have multiple other effects, including direct effects on cells of the vessel wall. Recently, DNA damage, including telomere shortening, has been identified in vascular smooth muscle cells (VSMCs) in human atherosclerosis. Although statins reduce DNA damage in vitro, the mechanisms by which they might protect DNA integrity in VSMCs are unknown. We show that human atherosclerotic plaque VSMCs exhibit increased levels of double-stranded DNA breaks and basal activation of DNA repair pathways involving ataxia telangiectasia–mutated (ATM) and the histone H2AX in vivo and in vitro. Oxidant stress induced DNA damage and activated DNA repair pathways in VSMCs. Statin treatment did not reduce oxidant stress or DNA damage but markedly accelerated DNA repair. Accelerated DNA repair required both the Nijmegen breakage syndrome (NBS)-1 protein and the human double minute protein Hdm2, accompanied by phosphorylation of Hdm2, dissociation of NBS-1 and Hdm2, inhibition of NBS-1 degradation, and accelerated phosphorylation of ATM. Statin treatment reduced VSMC senescence and telomere attrition in culture, accelerated DNA repair and reduced apoptosis in vivo after irradiation, and reduced ATM/ATR (ATM and Rad3-related) activity in atherosclerosis. We conclude that statins activate a novel mechanism of accelerating DNA repair, dependent on NBS-1 stabilization and Hdm2. Statin treatment may delay cell senescence and promote DNA repair in atherosclerosis.
Financial Misrepresentation: Antecedents and Performance Effects
Authors: Harris Jared D.
Published: August 2008

This doctoral thesis examines the influence of relative performance and managerial incentives on corporate financial misrepresentation, and then tests the relationship between misrepresentation and subsequent operating performance, including the moderating effects of change in board composition and Chief Executive Officer (CEO) turnover. Using a hand-collected data set from several archival sources of company records, the study includes a combination of estimation techniques, including categorical dependent variable and fixed-effect methods, all conducted using a matched sample of misrepresenting and nonmisrepresenting firms. The author draws several important conclusions from the empirical analyses. First, CEO incentive pay and poor relative performance increase the likelihood of misrepresentation. Second, misrepresentation impairs subsequent operating performance, although this negative effect can be partially offset by CEO replacement and increased board independence. The study advances our academic understanding of corporate misconduct and contributes to academic theory across research literatures, including strategic management, organization theory, and business ethics.
Asia in the Debate on Russian Identity
Authors: Pandey Sanjay Kumar
Published: August 2008

The issue of Russian identity—whether Russia belongs to Europe or Asia or is unique and distinct—has been debated for nearly three centuries within and outside Russia. Though Russia's relation with Europe was central to the debate, Asia also figured prominently in it. The article tries to examine Asia's role in the shaping of Russian identity. The issue has acquired further importance in the recent years as post-Soviet Russia is faced with the task of defining its place in the present day world.
Validation of the Arabic Humor Styles Questionnaire in a Community Sample of Lebanese in Lebanon
Authors: Taher Dana , Kazarian Shahe S. , Martin Rod A.
Published: August 2008

The Humor Styles Questionnaire (HSQ) is a measure of two potentially beneficial (affiliative and self-enhancing) and two potentially detrimental (self-defeating and aggressive) humor styles. Validation of the Arabic translation of the HSQ in the Lebanese culture, in which the self is construed as interdependent and in-group relatedness is seen as the primary determinant of well-being, indicates that four humor styles exist in the Lebanese context but that aggressive humor is less clearly distinct in this case, that self-defeating humor may be less clearly maladaptive for the interdependent self of the Lebanese, and that the four humor styles are not as strong predictors of psychological and social well-being in the Lebanese context as they are in the West. The findings suggest conceptual rethinking of humor styles in cultural contexts in which the self is construed as interdependent.
Maternal Regulation Strategies in the United States and Turkey: A Brief Report
Authors: Çatay Zeynep , Allen Rhianon , Samstag Lisa Wallner
Published: August 2008

This study examines the cultural and socioeconomic differences in the regulation strategies of Euro-American and Turkish mothers. Participants are interviewed about how they would manage their children's problem behaviors under hypothetical scenarios. American mothers are found to rely more extensively on appeals to their own authority and on rules, whereas Turkish mothers employ appeals to consequences and other-oriented strategies to a greater degree. Higher socioeconomic status (SES) mothers use strategies that emphasize decision-making capacities more frequently.
The misuse/abuse of antihistamine antiemetic medication (cyclizine) by cancer patients
Authors: Bailey F , Davies A
Published: August 2008

Cyclizine is an antihistamine, which is frequently used to manage nausea and vomiting in cancer patients. Antihistamines can be drugs of misuse/abuse, and the article describes four cancer patients who developed such problems after receiving parenteral cyclizine within the inpatient unit of a cancer centre. The article also briefly reviews the literature on the misuse/abuse of cyclizine and other antihistamines.
Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users
Authors: Ramaekers JG , Kauert G , Theunissen EL , Toennes SW , Moeller MR
Published: August 2008

Abstract

Performance impairment during Δ9-tetrahydrocannabinol (THC) intoxication has been well described in occasional cannabis users. It is less clear whether tolerance develops to the impairing effects of THC in heavy users of cannabis. The aim of the present study was to assess neurocognitive performance during acute THC intoxication in occasional and heavy users. Twenty-four subjects (12 occasional cannabis users and 12 heavy cannabis users) participated in a double-blind, placebo-controlled, two-way mixed model design. Both groups received single doses of THC placebo and 500 μg/kg THC by smoking. Performance tests were conducted at regular intervals between 0 and 8 h after smoking, and included measures of perceptual motor control (critical tracking task), dual task processing (divided attention task), motor inhibition (stop signal task) and cognition (Tower of London). THC significantly impaired performance of occasional cannabis users on critical tracking, divided attention and the stop signal task. THC did not affect the performance of heavy cannabis users except in the stop signal task, i.e. stop reaction time increased, particularly at high THC concentrations. Group comparisons of overall performance in occasional and heavy users did not reveal any persistent performance differences due to residual THC in heavy users. These data indicate that cannabis use history strongly determines the behavioural response to single doses of THC.
Electrophysiological effects of the co-administration of escitalopram and bupropion on rat serotonin and norepinephrine neurons
Authors: Ghanbari R. , El Mansari M. , Blier P.
Published: August 2008

Clinical studies indicate that addition of bupropion to selective serotonin (5-HT) reuptake inhibitors (SSRIs) provides incremental benefit over SSRI monotherapy in depression. This study was designed to investigate the effects of co-administration of bupropion with escitalopram on the firing rate of 5-HT and norepinephrine (NE) neurons in anesthetized rats. Escitalopram (10 mg/kg/day × 2 days), given via subcutaneously (s.c.) implanted minipumps, decreased the firing of 5-HT and NE neurons by 70% and 55%, respectively. The firing of 5-HT neurons, unlike that of NE neurons, recovered after the 14-day escitalopram regimen. Bupropion, injected once daily (30 mg/kg/day, s.c. × 2 days), did not increase 5-HT firing but decreased that of NE by 55%. After 14 days of repeated bupropion administration, 5-HT firing was increased by 50%, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited by 60% after 2 days, but partially recovered after 14 days. The responsiveness of 5-HT1Aautoreceptors was significantly attenuated in the combination-treated rats after 2 days, indicating an early desensitization. These results provide support for contributions from 5-HT and NE mechanisms for enhanced effectiveness of combination of SSRI and bupropion treatment.
Efficacy and tolerability of duloxetine in the treatment of patients with borderline personality disorder: a pilot study
Authors: Bellino S. , Paradiso E. , Bozzatello P. , Bogetto F.
Published: August 2008

Guidelines of the American Psychiatric Association for borderline personality disorder (BPD) indicate selective serotonin reuptake inhibitors and the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine for treating affective dysregulation and impulsive behavioural dyscontrol symptoms. The SNRI duloxetine has been studied in patients with major depression, generalized anxiety disorder and fibromyalgia, showing particular efficacy on somatic complaints. This study investigates duloxetine in the treatment of patients with BPD. Eighteen outpatients with a DSM-IV-TR diagnosis of BPD were treated with open-label duloxetine, 60 mg/day, for 12 weeks. Patients were assessed at baseline, week 4 and 12 with the CGI Severity item, the BPRS, the HAM-D, the HAM-A, the SOFAS, the BPD Severity Index (BPDSI) and the HSCL-90-Somatization Subscale (HSCL-90 SOM). Adverse effects were evaluated using the Dosage Record Treatment Emergent Symptom Scale. Statistics were performed with the analysis of variance. Significant P values were ≤0.05. Fourteen patients completed the study. Four patients (22.2%) discontinued treatment in the first 4 weeks because of non-compliance. A significant change was found for: BPRS, HAM-D, SOFAS, BPDSI total score and items ‘impulsivity’, ‘outbursts of anger’ and ‘affective instability’ and HSCL-90 SOM. Adverse effects were mild headache and nausea. Initial results suggest that duloxetine is an effective and well-tolerated treatment for BPD, with positive effects on somatic symptoms.
Institutional Balancing and International Relations Theory: Economic Interdependence and Balance of Power Strategies in Southeast Asia
Authors: Kai He
Published: August 2008

This study integrates elements of neorealist and neoliberal theories with a model of institutional balancing that identifies the conditions under which this form of soft balancing occurs. Institutional balancing, i.e. countering pressures or threats through initiating, utilizing, and dominating multilateral institutions, is a new realist strategy for states to pursue security under anarchy. The interplay between the distribution of capabilities and strong economic interdependence shapes states' decisions on when and how to employ this strategy. Historical examples include: inclusive and exclusive efforts by Third World states and the superpowers to organize voting blocs in the UN during the Cold War; inclusive institutional balancing of ASEAN states to constrain China and ensure US support in the ASEAN Regional Forum (ARF) after the Cold War; exclusive institutional balancing of ASEAN states against the US in the ASEAN Plus Three (APT) summit after the Southeast Asian financial crisis. These examples illustrate the logic of institutional balancing under the conditions of bipolarity, incipient multipolarity, and unipolarity.
Framing the Anti-War Protests in the Global Village
Authors: Zengjun Peng
Published: August 2008

/ This study compared newspaper coverage of anti-war protests in three countries based on the theoretical framework of framing. News stories in The New York Times, The Times and the People's Daily over a period of six months were analyzed in terms of news selection, prominence, sourcing pattern, frames, themes and overall favorability toward the protestors. Results show significant differences not only in coverage between contrasting media systems (US and Britain vs China), but also between comparable media systems (US vs Britain). Reasons for these differences and theoretical implications are explored.
Expression of the Transcriptional Repressor ATF3 in Gonadotrophs Is Regulated by Egr-1, CREB, and ATF2 after Gonadotropin-Releasing Hormone Receptor Stimulation
Authors: Mayer Sabine I. , Dexheimer Verena , Nishida Eisuke , Kitajima Shigetaka , Thiel Gerald
Published: August 2008

Stimulation of GnRH receptors enhances expression of activating transcription factor (ATF) 3 in a pituitary gonadotroph cell line. The signaling pathway requires elevated cytosolic Ca2+ levels and activation of ERK and c-Jun N-terminal protein kinase. The signaling cascade was blocked by overexpression of either MAPK phosphatase (MKP)-1 or MAPK phosphatase-5 that dephosphorylate nuclear ERK and c-Jun N-terminal protein kinase. In addition, ATF3 biosynthesis was impaired after lentiviral-mediated expression of a constitutively active mutant of calcineurin A. Thus, MKP-1, MKP-5, and calcineurin may function as shut-off devices for GnRH receptor signaling. Expression of dominant-negative mutants of early growth response protein (Egr)-1, cAMP response element binding protein (CREB), and ATF2 blocked the biosynthesis of ATF3, indicating that these transcription factors connect the intracellular signaling cascade elicited by activation of GnRH receptors with transcription of the ATF3 gene. This view was corroborated by chromatin immunoprecipitation experiments revealing that Egr-1 and the phosphorylated forms of CREB and ATF2 bound to the 5′-upstream region of the ATF3 gene in buserelin-stimulated gonadotrophs. Together the data indicate that the ATF3 gene is a bona fide target gene of Egr-1, CREB, and ATF2 in gonadotrophs. Moreover, we show that in gonadotrophs ATF3 bound to its own promoter under physiological conditions. The analysis of a lentiviral-transmitted ATF3 promoter/luciferase reporter gene, embedded into the chromatin of the cells, revealed that ATF3 blocked the activity of its own promoter. We additionally identified the chromogranin B gene as bona fide target gene of ATF3 in gonadotrophs.
Suppression of Basal Spontaneous Gonadotropin-Releasing Hormone Neuronal Activity during Lactation: Role of Inhibitory Effects of Neuropeptide Y
Authors: Xu Jing , Kirigiti Melissa A. , Cowley Michael A. , Grove Kevin L. , Smith M. Susan
Published: August 2008

Increased neuropeptide Y (NPY) activity drives the chronic hyperphagia of lactation and may contribute to the suppression of GnRH activity. The majority of GnRH neurons are contacted by NPY fibers, and GnRH cells express NPY Y5 receptor (Y5R). Therefore, NPY provides a neurocircuitry for information about food intake/energy balance to be directly transmitted to GnRH neurons. To investigate the effects of lactation on GnRH neuronal activity, hypothalamic slices were prepared from green fluorescent protein-GnRH transgenic rats. Extracellular loose-patch recordings determined basal GnRH neuronal activity from slices of ovariectomized control and lactating rats. Compared with controls, hypothalamic slices from lactating rats had double the number of quiescent GnRH neurons (14.51 ± 2.86 vs. 7.04 ± 2.84%) and significantly lower firing rates of active GnRH neurons (0.25 ± 0.02 vs. 0.37 ± 0.03 Hz). To study the NPY-postsynaptic Y5R system, whole-cell current-clamp recordings were performed in hypothalamic slices from control rats to examine NPY/Y5R antagonist effects on GnRH neuronal resting membrane potential. Under tetrodotoxin treatment, NPY hyperpolarized GnRH neurons from −56.7 ± 1.94 to −62.1 ± 1.83 mV; NPY’s effects were blocked by Y5R antagonist. To determine whether increased endogenous NPY tone contributes to GnRH neuronal suppression during lactation, hypothalamic slices were treated with Y5R antagonist. A significantly greater percentage of GnRH cells were activated in slices from lactating rats (52%) compared with controls (28%). These results suggest that: 1) basal GnRH neuronal activity is suppressed during lactation; 2) NPY can hyperpolarize GnRH neurons via postsynaptic Y5R; and 3) increased inhibitory NPY tone during lactation is a component of the mechanisms responsible for suppression of GnRH neuronal activity.

Neuropeptide Y (NPY) directly hyperpolarizes GnRH neurons via postsynaptic NPY Y5 receptor. Increased inhibitory NPY tone during lactation is an important component of the suppression of GnRH neuronal activity.
The effects of short-term antioxidant supplementation on oxidative stress and flight performance in adult budgerigars Melopsittacus undulatus
Authors: Larcombe S. D. , Tregaskes C. A. , Coffey J. S. , Stevenson A. E. , Alexander L. , Arnold K. E.
Published: August 2008

Antioxidants are known to play an important role in quenching reactive oxygen species (ROS), thus ameliorating oxidative stress. Since increased metabolism associated with exercise can increase oxidative stress, dietary antioxidants may be a limiting factor in determining aspects of physical performance. Here we tested whether oxidative stress associated with flight exercise of captive adult budgerigars, Melopsittacus undulatusdiffered after they received a diet containing either enhanced (EQ) or reduced levels (RQ) of a nutritional supplement (Nutrivit®) rich in antioxidants for 4 weeks. We also assessed differences in take-off escape time, a potential fitness-determining physiological capability. Oxidative stress was measured in two ways: comet assay to measure DNA damage; and analysis of malondialdehyde(MDA), a by-product of lipid peroxidation. Flight exercise appeared to increase oxidative stress. Moreover, birds had a higher percentage of intact DNA (fewer alkali labile sites) in one comet measure and lower levels of MDA after an EQ diet than after an RQ diet. We found no difference in flight performance between the two diets. Our results suggested that birds exerted maximum effort in escape flights, regardless of diet. However, this was at a cost of increased oxidative stress post-flight when on a reduced quality diet,but not when on an enhanced, antioxidant-rich diet. We suggest that dietary antioxidants may prove important in reducing exercise-related costs through multiple physiological pathways. Further work is necessary to fully understand the effects of antioxidants and oxidative stress on exercise performance in the longer term.
Bile salts are effective taste stimuli in channel catfish
Authors: Rolen S. H. , Caprio J.
Published: August 2008

Bile salts are known olfactory stimuli for teleosts, but only a single report has indicated that the taste system of a fish was sensitive to this class of stimuli. Here, gustatory responses of the channel catfish, Ictalurus punctatus, to four bile salts that included taurine-,glycine- and non-conjugated compounds along with three stimulatory amino acids as a comparison were investigated using extracellular electrophysiological techniques. Integrated multiunit responses were obtained from the branch of the facial nerve innervating taste buds on the maxillary barbel. Bile salts were shown to be highly effective facial taste stimuli, with estimated electrophysiological thresholds for three of the four tested bile salts of approximately 10–11 mol l–1 to 10–10 mol l–1, slightly lower by 1–2 log units than those to amino acids in the same species. Although the sensitivity of the facial taste system of the channel catfish to bile salts is high, the relative magnitude of the response to suprathreshold concentrations of bile salts was significantly less than that to amino acids. Multiunit cross-adaptation experiments indicate that bile salts and amino acids bind to relatively independent receptor sites; however, nerve-twig data and single-fiber recordings suggest that both independent and shared neural pathways exist for the transmission of bile salt and amino acid information to the primary gustatory nucleus of the medulla.
The physiology of the midgut ofLutzomyia longipalpis(Lutz and Neiva 1912): pH in different physiological conditions and mechanisms involved in its control
Authors: Santos Vânia C. , Araujo Ricardo N. , Machado Luciane A. D. , Pereira Marcos H. , Gontijo Nelder F.
Published: August 2008

Nutrient digestion and absorption after blood feeding are important events for Lutzomyia longipalpis, which uses these nutrients to produce eggs. In this context, the pH inside the digestive tract is an important physiological feature as it can markedly influence the digestive process as well as interfere with Leishmania development in infected phlebotomines. It was described previously that unfed females have an acidic midgut (pH 6). In this study, the pH inside the midgut of blood-fed females was measured. The abdominal midgut (AM) pH varied from 8.15±0.31 in the first 10 h post-blood meal to 7.7±0.17 after 24 h. While the AM was alkaline during blood digestion, the pH in the thoracic midgut (TM) remained acidic (5.5–6.0). In agreement with these findings, the enzymeα-glucosidase, which has an optimum pH of 5.8, is mainly encountered in the acidic TM. The capacity of unfed females to maintain the acidic intestinal pH was also evaluated. Our results showed the presence of an efficient mechanism that maintains the pH almost constant at about 6 in the midgut, but not in the crop. This mechanism is promptly interrupted in the AM by blood ingestion. RT-PCR results indicated the presence of carbonic anhydrase in the midgut cells, which apparently is required to maintain the pH at 6 in the midgut of unfed females. Investigations on the phenomenon of alkalization observed after blood ingestion indicated that two mechanisms are involved: in addition to the alkalization promoted by CO2 volatilization there is a minor contribution from a second mechanism not yet characterized. Some inferences concerning Leishmania development and pH in the digestive tube are presented.
Determination of Trace Elements and Correction of Mass Spectral Interferences in Superalloy Analyzed by Glow Discharge Mass Spectrometry
Authors: Xing Yu , Xiaojia Li , Haizhou Wang
Published: August 2008

Mass spectral interference was investigated systematically during the determination of trace elements in superalloy by glow discharge mass spectrometry (GD-MS); moreover the main mass spectral interference and interference level of isotopes were provided in detail. According to the mass spectral interference of elements, different methods were selected for interference correction. The effects of mass spectral interference were removed efficiently by using correction methods such as selecting isotopes without interference, matching sample matrices and deducing interference with multivariable linear regression. The determination results of three superalloy samples show that trace elements such as B, Mg, Ga, As, Ag, In, Sn, Sb, Te, Tl, Pb and Bi were determined successfully after interference correction.
Automated Neutral Loss and Data Dependent Energy Resolved “Pseudo MS3” for the Targeted Identification, Characterization and Quantitative Analysis of Methionine-Containing Peptides
Authors: Froelich Jennifer M. , Kaplinghat Suchitra , Reid Gavin E.
Published: August 2008

A strategy involving the fixed-charge sulfonium ion derivatization, stable isotope labeling, capillary high-performance liquid chromatography and automated data dependent neutral loss scan mode tandem mass spectrometry (MS/MS) and “pseudo multiple mass spectrometry (MS3)” product ion scans in a triple quadrupole mass spectrometer has been developed for the “targeted” gas-phase identification, characterization and quantitative analysis of low abundance methionine-containing peptides present within complex protein digests. Selective gas-phase “enrichment” and identification is performed via neutral loss scan mode MS/MS, by low energy collision-induced dissociation of the derivatized methionine side chain, resulting in the formation of a single characteristic product ion. Structural characterization of identified peptides is then achieved by automatically subjecting the characteristic neutral loss product ion to further dissociation by data dependent product ion scan mode pseudo MS3 under higher collision energy conditions. Quantitative analysis is achieved by measurement of the abundances of characteristic product ions formed by sequential neutral loss scan mode MS/MS experiments from “light” (12C) and “heavy” (13C) stable isotope encoded fixed-charge derivatized peptides. In contrast to MS-based quantitative analysis strategies, the neutral loss scan mode MS/MS method employed here was able to achieve accurate quantification for individual peptides at levels as low as 100fmol and at abundance ratios ranging from 0.1 to 10, present within a complex protein digest.
Identification of specific let-7 microRNA binding complexes in Caenorhabditis elegans
Authors: Chan Shih-Peng , Ramaswamy Gopalakrishna , Choi Eun-Young , Slack Frank J.
Published: August 2008

Little is known about the protein complexes required for microRNA formation and function. Here we used native gel electrophoresis to identify miRNA ribonucleoprotein complexes (miRNPs) in Caenorhabditis elegans. Our data reveal multiple distinct miRNPs that assemble on the let-7 miRNA in vitro. The formation of these complexes is affected but not abolished by alg-1 or alg-2 null mutations. The largest complex (M*) with an estimated molecular mass of >669 kDa cofractionates with the known RISC factors ALG-1, VIG-1, and TSN-1. The M* complex and two complexes, M3 and M4, with similar molecular weights of ∼500 kDa, also assemble on all other miRNAs used in our experiments. Two smaller complexes, M1 (∼160 kDa) and M2 (∼250 kDa), assemble on the members of the let-7 miRNAs family but not lin-4 or mir-234, and their formation is highly dependent on specific sequences in the 5′ seed region of let-7. Moreover, an unidentified protein, p40, which only appears in the M1 and M2 complexes, was detected by UV triggered cross-linking to let-7 but not to lin-4. The cross-linking of p40 to let-7 is also dependent on the let-7 sequence. Another unidentified protein, p13, is detected in all let-7 binding complexes and lin-4 cross-linked products. Our data suggest that besides being present in certain large miRNPs with sizes similar to reported RISC, the let-7 miRNA also assembles with specific binding proteins and forms distinct small complexes.
Effects of Spatially Varying Selection on Nucleotide Diversity and Linkage Disequilibrium: Insights From Deer Mouse Globin Genes
Authors: Storz Jay F , Kelly John K
Published: August 2008

An important goal of population genetics is to elucidate the effects of natural selection on patterns of DNA sequence variation. Here we report results of a study to assess the joint effects of selection, recombination, and gene flow in shaping patterns of nucleotide variation at genes involved in local adaptation. We first describe a new summary statistic, Zg, that measures the between-sample component of linkage disequilibrium (LD). We then report results of a multilocus survey of nucleotide diversity and LD between high- and low-altitude populations of deer mice, Peromyscus maniculatus. The multilocus survey included two closely linked α-globin genes, HBA-T1 and HBA-T2, that underlie adaptation to different elevational zones. The primary goals were to assess whether the α-globin genes exhibit the hallmarks of spatially varying selection that are predicted by theory (i.e., sharply defined peaks in the between-population components of nucleotide diversity and LD) and to assess whether peaks in diversity and LD may be useful for identifying specific sites that distinguish selectively maintained alleles. Consistent with theoretical expectations, HBA-T1 and HBA-T2 were characterized by highly elevated levels of diversity between populations and between allele classes. Simulation and empirical results indicate that sliding-window analyses of Zg between allele classes may provide an effective means of pinpointing causal substitutions.
Quantitative Trait Loci Affecting Phenotypic Plasticity and the Allometric Relationship of Ovariole Number and Thorax Length in Drosophila melanogaster
Authors: Bergland Alan O , Genissel Anne , Nuzhdin Sergey V , Tatar Marc
Published: August 2008

Environmental factors during juvenile growth such as temperature and nutrition have major effects on adult morphology and life-history traits. In Drosophila melanogaster, ovary size, measured as ovariole number, and body size, measured as thorax length, are developmentally plastic traits with respect to larval nutrition. Herein we investigated the genetic basis for plasticity of ovariole number and body size, as well the genetic basis for their allometric relationship using recombinant inbred lines (RILs) derived from a natural population in Winters, California. We reared 196 RILs in four yeast concentrations and measured ovariole number and body size. The genetic correlation between ovariole number and thorax length was positive, but the strength of this correlation decreased with increasing yeast concentration. Genetic variation and genotype-by-environment (G × E) interactions were observed for both traits. We identified quantitative trait loci (QTL), epistatic, QTL-by-environment, and epistatic-by-environment interactions for both traits and their scaling relationships. The results are discussed in the context of multivariate trait evolution.
A Male-Specific Fatty Acid ω-Hydroxylase, SXE1, Is Necessary for Efficient Male Mating in Drosophila melanogaster
Authors: Fujii Shinsuke , Toyama Akemi , Amrein Hubert
Published: August 2008

In Drosophila, sexual differentiation, physiology, and behavior are thought to be mediated by numerous male- and female-specific effector genes whose expression is controlled by sex-specifically expressed transcriptional regulators. One such downstream effector gene, sex-specific enzyme 1 (sxe1, cyp4d21), has been identified in a screen for genes with sex-biased expression in the head. Sxe1 was also identified in another screen as a circadian regulated gene. Here, we analyzed the spatial and temporal regulation of sxe1 and identified a function for this gene in male courtship. We show that male-specific transcriptional regulator DSXM and the clock genes are necessary for cycling of sxe1 mRNA during the diurnal cycle. Similar to sxe1 mRNA, expression of SXE1 protein oscillates in a diurnal fashion, with highest protein levels occurring around midnight. SXE1 protein expression is restricted to nonneuronal cells associated with diverse sensory bristles of both the chemo- and mechanosensory systems. Suppression or knockout of sxe1 significantly reduces mating success throughout the diurnal cycle. Finally, the metabolomic profile of wild-type and sxe1 mutant males revealed that sxe1 likely functions as a fatty acid ω-hydroxylase, suggesting that male courtship and mating success is mediated by small compounds generated by this enzyme.
Maintenance of Mitochondrial DNA by the Caenorhabditis elegans ATR Checkpoint Protein ATL-1
Authors: Mori Chihiro , Takanami Takako , Higashitani Atsushi
Published: August 2008

Here we show that inactivation of the ATR-related kinase ATL-1 results in a significant reduction in mitochondrial DNA (mtDNA) copy numbers in Caenorhabditis elegans. Although ribonucleotide reductase (RNR) expression and the ATP/dATP ratio remained unaltered in atl-1 deletion mutants, inhibition of RNR by RNAi or hydroxyurea treatment caused further reductions in mtDNA copy number. These results suggest that ATL-1 functions to maintain mtDNA independently of RNR.
Second-Order Moments of Segregating Sites Under Variable Population Size
Authors: Živković Daniel , Wiehe Thomas
Published: August 2008

The identification of genomic regions that have been exposed to positive selection is a major challenge in population genetics. Since selective sweeps are expected to occur during environmental changes or when populations are colonizing a new habitat, statistical tests constructed on the assumption of constant population size are biased by the co-occurrence of population size changes and selection. To delimit this problem and gain better insights into demographic factors, theoretical results regarding the second-order moments of segregating sites, such as the variance of segregating sites, have been derived. Driven by emerging genomewide surveys, which allow the estimation of demographic parameters, a generalized version of Tajima's D has been derived that takes into account a previously estimated demographic scenario to test single loci for traces of selection against the null hypothesis of neutral evolution under variable population size.
Human Amniotic Fluid Stem Cells Can Integrate and Differentiate into Epithelial Lung Lineages
Authors: Carraro Gianni , Perin Laura , Sedrakyan Sargis , Giuliani Stefano , Tiozzo Caterina , Lee Jooeun , Turcatel Gianluca , De Langhe Stijn P. , Driscoll Barbara , Bellusci Saverio , Minoo Parviz , Atala Anthony , De Filippo Roger Edward , Warburton David
Published: August 2008

A new source of stem cells has recently been isolated from amniotic fluid; these amniotic fluid stem cells have significant potential for regenerative medicine. These cells are multipotent, showing the ability to differentiate into cell types from each embryonic germ layer. We investigated the ability of human amniotic fluid stem cells (hAFSC) to integrate into murine lung and to differentiate into pulmonary lineages after injury. Using microinjection into cultured mouse embryonic lungs, hAFSC can integrate into the epithelium and express the early human differentiation marker thyroid transcription factor 1 (TTF1). In adult nude mice, following hyperoxia injury, tail vein-injected hAFSC localized in the distal lung and expressed both TTF1 and the type II pneumocyte marker surfactant protein C. Specific damage of Clara cells through naphthalene injury produced integration and differentiation of hAFSC at the bronchioalveolar and bronchial positions with expression of the specific Clara cell 10-kDa protein. These results illustrate the plasticity of hAFSC to respond in different ways to different types of lung damage by expressing specific alveolar versus bronchiolar epithelial cell lineage markers, depending on the type of injury to recipient lung.

Disclosure of potential conflicts of interest is found at the end of this article.
Study on control of micro-pollutants by BAC filtration
Authors: Zhang Z. H. , Shao L.
Published: August 2008

The objective of this research was to evaluate removal efficiency of micro-pollutants in a BAC filter that followed ozonation for long term operation. The experimental results showed that after continuous operation for one year BAC filter still maintained a removal of 15 ∼ 20% for CODMn and 20 ∼ 30% of removal for UV254. Correlative analysis based on lots of data found that empty bed contact time (EBCT) instead of flow rate could obviously impact on removal effect of micro-pollutants in BAC filter. And the optimal relationship between EBCT and removal effect of micro-pollutants for BAC filter was logarithm. On the other hand, long term running of BAC filter proved that there was a good removal of chloroform formation potential, but the removal of brominated trihalomethane formation potential decline with further bromization, even there appeared to be formation of bromoform in BAC filter.
Cardiac Findings in Fetal and Pediatric Autopsies: A Five-Year Retrospective Review
Authors: Grant Elena K. , Evans Margaret J.
Published: August 2008

This review aims to determine the spectrum of cardiac findings in our fetal and pediatric postmortem population and provide an analysis of associated extracardiac malformations and genetic abnormalities. Pediatric autopsy reports from 2003 to 2007 inclusive were reviewed and cases with cardiac pathology selected for analysis. Over the 5-year period, 119 cases (10.8%) with abnormal cardiac findings were identified from a total of 1102 postmortem examinations. Of these cardiac cases, 42% were after termination of pregnancy for fetal anomaly, 29% after fetal demise, 14% after neonatal unit death, 3% after hospital inpatient death, and 11% after sudden unexpected death. Structural abnormality cases numbered 107 (90%), with ventricular septal defect as the most common individual defect. Nonstructural abnormality cases, such as myocarditis, numbered 12 (10%). Extracardiac malformations were identified in 78%. Chromosome or gene aberrations were detected in 37%. This review highlights the potential benefit of introducing routine fetal anomaly scanning, the need for cardiac pathology training for pediatric pathologists, and the importance of examination of the heart and associated vessels in all cases to provide parents with as much information as possible and aid identification of the etiology and associations of cardiac pathology.
Juvenile Myelomonocytic Leukemia: Report of Seven Cases and Review of Literature
Authors: Urs Latha , Qualman Stephen J. , Kahwash Samir B.
Published: August 2008

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive, clonal hematopoietic disorder of childhood with features of both myelodysplasia (thrombocytopenia, anemia) and myeloproliferation (leukocytosis, monocytosis). In most cases there is marrow hypercellularity, splenomegaly, and extramedullary involvement. In 1997 an international consensus on terminology was reached and guidelines/criteria for diagnosis were proposed. A recent World Health Organization classification described the current diagnostic criteria of JMML. Although the diagnosis of JMML has been facilitated, it can be challenging, especially in the early stages or when it 1st presents as an extramedullary tumor. We report a series of 7 cases diagnosed over a period of 10 years (from January 1, 1996, to December 31, 2005). Two cases had interesting associated findings that would potentially lead to delay in diagnosis or misdiagnosis. Two other cases had extramedullary involvement with symptoms referable to the organs of involvement at presentation. Clinical and pathologic findings are summarized with a review of relevant literature.
Meaning of Caring to 7 Novice Physical Therapists During Their First Year of Clinical Practice
Authors: Greenfield Bruce H , Anderson Adam , Cox Brittany , Tanner Michelle Coryell
Published: August 2008

Background and Purpose

Caring has been identified as a rules-based approach to good patient care, as a core value in physical therapist professional behavior, as a part of experienced and expert practice, as a virtue, and as a moral orientation. Previous research showed that experienced and expert female physical therapists value compassion and caring in clinical practice. However, little is known about how novice physical therapists care for their patients. The purpose of this study was to explore the meaning of caring from the perspectives of novice physical therapists.

Subjects

Seven novice physical therapists (with less than 1 year of clinical experience) working in either an outpatient or an inpatient facility were recruited.

Methods

A qualitative method (phenomenology) was used, with data being obtained from retrospective interviews of the novice physical therapists regarding their experiences in the clinic.

Results

Three common themes relating to the nature of caring emerged: learning to care (with the following subthemes: barriers to caring, the “difficult” patient, finding a balance, and time constraints), patients as subjects, and the culture of the clinic.

Discussion and Conclusion

The novice physical therapists in this study expressed difficulty in dealing with difficult patients, with time management, and with balancing their professional and personal lives. However, despite the barriers to caring, many of these participants viewed caring not just as a rules-based approach but as a core value and, in some cases, a moral orientation that guided their first year of clinical practice. The findings suggest that caring requires certain skills and attitudes that accrue over time and that physical therapist education programs should integrate learning experiences (including clinical experiences) throughout the curriculum that foster caring behaviors in order to prepare students for the first-year transition in the clinic. In addition, experienced clinicians should appreciate how their clinic's culture and their behaviors can help model caring attitudes in novice physical therapists.
Veterinary Medicine Is Public Health
Authors: Blackwell Michael J. , Leap Rebecca L.
Published: August 2008

The symposium Partnerships for Preparedness: Future Directions of Schools of Public Health and Colleges of Veterinary Medicine documents the importance of further integration between the fields of veterinary medicine and public health to protect our nation from public-health emergencies. Current areas targeted for improved collaboration include academic programs, public policy, workforce training, and research.