bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notch activity in the nervous system: to switch or not switch?
Authors: Cau Elise , Blader Patrick 
Published: October 2009

AbstractThe Notch pathway is instrumental for cell fate diversification during development. Pioneer studies conducted in Drosophila and more recent work performed in vertebrates have shown that in the nervous system, Notch is reiteratively employed when cells choose between two alternative fates, a process referred to as a binary fate decision. While the early (neural versus epidermal) fate decisions mainly involve an inhibitory effect of Notch on the neural fate, late fate decisions (choice between different subtypes of neural cells) have been proposed to involve a binary switch activity whereby Notch would be instructive for one fate and inhibitory for the other. We re-examine this binary switch model in light of two recent findings made in the vertebrate nervous system. First, in the zebrafish epiphysis, Notch is required to resolve a mixed identity through the inhibition of one specific fate. Second, in the murine telencephalon, Notch regulates the competence of neural progenitors to respond to the JAK/STAT pathway, thereby allowing for the induction of an astrocyte fate. In neither case is Notch instructive for the alternative fate, but rather cooperates with another signalling pathway to coordinate binary fate choices. We also review current knowledge on the molecular cascades acting downstream of Notch in the context of neural subtype diversification, a crucial issue if one is to determine Notch function as an instructive, permissive or inhibitory signal in the various cellular contexts where it is implicated. Finally, we speculate as to how such a 'non-switch' activity could contribute to the expansion of neuronal subtype diversity.
The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans
Authors: Norris Adam D , Dyer Jamie O , Lundquist Erik A 
Published: October 2009

Abstract
Background
While many molecules involved in axon guidance have been identified, the cellular and molecular mechanisms by which these molecules regulate growth cone morphology during axon outgrowth remain to be elucidated. The actin cytoskeleton of the growth cone underlies the formation of lamellipodia and filopodia that control growth cone outgrowth and guidance. The role of the Arp2/3 complex in growth cone filopodia formation has been controversial, and other mechanisms of growth cone filopodia formation remain to be described.

Results
Here we show that mutations in genes encoding the Arp2/3 complex (arx genes) caused defects in axon guidance. Analysis of developing growth cones in vivo showed that arx mutants displayed defects in filopodia and reduced growth cone size. Time-lapse analysis of growth cones in living animals indicated that arx mutants affected the rate of growth cone filopodia formation but not filopodia stability or length. Two other actin modulatory proteins, UNC-115/abLIM and UNC-34/Enabled, that had been shown previously to affect axon guidance had overlapping roles with Arp2/3 in axon guidance and also affected the rate of filopodia initiation but not stability or length.

Conclusion
Our results indicate that the Arp2/3 complex is required cell-autonomously for axon guidance and growth cone filopodia initiation. Furthermore, they show that two other actin-binding proteins, UNC-115/abLIM and UNC-34/Enabled, also control growth cone filopodia formation, possibly in parallel to Arp2/3. These studies indicate that, in vivo, multiple actin modulatory pathways including the Arp2/3 complex contribute to growth cone filopodia formation during growth cone outgrowth.
Detailed analysis of X chromosome inactivation in a 49,XXXXX pentasomy
Authors: Moraes Lucia M , Cardoso Leila CA , Moura Vera LS , Moreira Miguel AM , Menezes Albert N , Llerena Juan C , Seuánez Héctor N 
Published: October 2009

AbstractBackgroundPentasomy X (49,XXXXX) has been associated with a severe clinical condition, presumably resulting from failure or disruption of X chromosome inactivation. Here we report that some human X chromosomes from a patient with 49,XXXXX pentasomy were functionally active following isolation in inter-specific (human-rodent) cell hybrids. A comparison with cytogenetic and molecular findings provided evidence that more than one active X chromosome was likely to be present in the cells of this patient, accounting for her abnormal phenotype.Results5-bromodeoxyuridine (BrdU)-pulsed cultures showed different patterns among late replicating X chromosomes suggesting that their replication was asynchronic and likely to result in irregular inactivation. Genotyping of the proband and her mother identified four maternal and one paternal X chromosomes in the proband. It also identified the paternal X chromosome haplotype (P), indicating that origin of this X pentasomy resulted from two maternal, meiotic non-disjunctions. Analysis of theHUMANDRECregion of the androgen receptor (AR) gene in the patient's mother showed a skewed inactivation pattern, while a similar analysis in the proband showed an active paternal X chromosome and preferentially inactivated X chromosomes carrying the 173ARallele. Analyses of 33 cell hybrid cell lines selected in medium containing hypoxanthine, aminopterin and thymidine (HAT) allowed for the identification of three maternal X haplotypes (M1, M2 and MR) and showed that X chromosomes with the M1, M2 and P haplotypes were functionally active. In 27 cell hybrids in which more than one X haplotype were detected, analysis of X inactivation patterns provided evidence of preferential inactivation.ConclusionOur findings indicated that 12% of X chromosomes with the M1 haplotype, 43.5% of X chromosomes with the M2 haplotype, and 100% of the paternal X chromosome (with the P haplotype) were likely to be functionally active in the proband's cells, a finding indicating that disruption of X inactivation was associated to her severe phenotype.
Cytokine Profiles in Human Immunodeficiency Virus‐Infected Children Treated With Highly Active Antiretroviral Therapy
Authors: Jones Brian M , Chiu Susan SS , Wong Wilfred HS , Lim Wilina WL , Lau Yu‐lung 
Published: October 2009

ContextThere have been few longitudinal studies of cytokine production in neonatally acquired HIV‐1 infection and none in Asian or Chinese children.ObjectiveTo determine whether monitoring cytokine production could contribute to the better management of pediatric patients with HIV‐1 infection.SettingClinical Immunology Laboratory and Pediatrics Department, University Hospital, Hong Kong.PatientsTen Asian and 2 Eurasian children infected with HIV‐1 by mother‐to‐child transmission were followed for up to 5 years while on treatment with highly active antiretroviral therapy (HAART).Main Outcome MeasuresNumbers of unstimulated and mitogen‐activated cytokine‐secreting cells (IFN‐gamma, interleukin [IL]‐2, IL‐4, IL‐6, IL‐10, IL‐12, and TNF‐alpha) were measured by ELISPOT assay at frequent intervals, and correlations were sought with CD4+ and CD8+ cell counts and viral loads.ResultsMitogen‐stimulated IL‐2‐secreting cells were directly associated with recovery of CD4+ cells. Correlations with viral load were found for Con A‐induced IFN‐gamma, Con A‐induced IL‐4, and unstimulated IL‐10, suggesting that these cytokines were either suppressed by high virus levels or that higher cytokine levels suppressed virus. IFN‐gamma, IL‐2‐, IL‐4‐, and IL‐12‐secreting cells induced by PHA, Con A, and/or SAC tended to increase for the first 3‐4 years of treatment but declined thereafter.ConclusionAlterations in cytokine profiles were not associated with adverse clinical events and there was little evidence to indicate that monitoring cytokine enzyme‐linked immunospots (ELISPOTs) could contribute to pediatric patient management.
Hemodynamic variables and mortality in cardiogenic shock: a retrospective cohort study
Authors: Torgersen Christian , Schmittinger Christian A , Wagner Sarah , Ulmer Hanno , Takala Jukka , Jakob Stephan M , Dünser Martin W 
Published: October 2009

Abstract
Introduction
Despite the key role of hemodynamic goals, there are few data addressing the question as to which hemodynamic variables are associated with outcome or should be targeted in cardiogenic shock patients. The aim of this study was to investigate the association between hemodynamic variables and cardiogenic shock mortality.

Methods
Medical records and the patient data management system of a multidisciplinary intensive care unit (ICU) were reviewed for patients admitted because of cardiogenic shock. In all patients, the hourly variable time integral of hemodynamic variables during the first 24 hours after ICU admission was calculated. If hemodynamic variables were associated with 28-day mortality, the hourly variable time integral of drops below clinically relevant threshold levels was computed. Regression models and receiver operator characteristic analyses were calculated. All statistical models were adjusted for age, admission year, mean catecholamine doses and the Simplified Acute Physiology Score II (excluding hemodynamic counts) in order to account for the influence of age, changes in therapies during the observation period, the severity of cardiovascular failure and the severity of the underlying disease on 28-day mortality.

Results
One-hundred and nineteen patients were included. Cardiac index (CI) (P = 0.01) and cardiac power index (CPI) (P = 0.03) were the only hemodynamic variables separately associated with mortality. The hourly time integral of CI drops <3, 2.75 (both P = 0.02) and 2.5 (P = 0.03) L/min/m2 was associated with death but not that of CI drops <2 L/min/m2 or lower thresholds (all P > 0.05). The hourly time integral of CPI drops <0.5-0.8 W/m2 (all P = 0.04) was associated with 28-day mortality but not that of CPI drops <0.4 W/m2 or lower thresholds (all P > 0.05).

Conclusions
During the first 24 hours after intensive care unit admission, CI and CPI are the most important hemodynamic variables separately associated with 28-day mortality in patients with cardiogenic shock. A CI of 3 L/min/m2 and a CPI of 0.8 W/m2 were most predictive of 28-day mortality. Since our results must be considered hypothesis-generating, randomized controlled trials are required to evaluate whether targeting these levels as early resuscitation endpoints can improve mortality in cardiogenic shock.
Facilitative Glucose Transporter 9 Expression Affects Glucose Sensing in Pancreatic β-Cells
Authors: Evans Sarah A. , Doblado Manuel , Chi Maggie M. , Corbett John A. , Moley Kelle H. 
Published: October 2009

AbstractFacilitative glucose transporters (GLUTs) including GLUT9, accelerate the facilitative diffusion of glucose across the plasma membrane. Studies in GLUT2-deficient mice suggested the existence of another GLUT in the mammalian β-cell responsible for glucose sensing. The objective of this study was to determine the expression and function of GLUT9 in murine and human β-cells. mRNA and protein expression levels were determined for both isoforms of GLUT9 in murine and human isolated islets as well as insulinoma cell lines (MIN6). Immunohistochemistry and subcellular localization were performed to localize the protein within the cell. Small interfering RNA knockdown of GLUT9 was used to determine the effect of this transporter, in the presence of GLUT2, on cell metabolism and insulin secretion in MIN6 and INS cells. In this report we demonstrate that GLUT9a and GLUT9b are expressed in pancreatic islets and that this expression localizes to insulin-containing β-cells. Subcellular localization studies indicate that mGLUT9b is found associated with the plasma membrane as well as in the high-density microsome fraction and low-density microsome fraction, whereas mGLUT9a appears to be located only in the high-density microsome and low-density microsome under basal conditions. Functionally GLUT9 appears to participate in the regulation of glucose-stimulated insulin secretion in addition to GLUT2. small interfering RNA knockdown of GLUT9 results in reduced cellular ATP levels that correlate with reductions in glucose-stimulated insulin secretion in MIN6 and INS cells. These studies confirm the expression of GLUT9a and GLUT9b in murine and human β-cells and suggest that GLUT9 may participate in glucose-sensing in β-cells.
Subclinical Hypothyroidism in Korean Preterm Infants Associated with High Levels of Iodine in Breast Milk
Authors: Chung Hye Rim , Shin Choong Ho , Yang Sei Won , Choi Chang Won , Kim Beyong Il 
Published: October 2009

Context: The dietary iodine intake of lactating women has been reported to be high in Korea.
Objectives: The aim of this study was to assess iodine balance and to determine its relationship with thyroid function in preterm infants.
Design: Thyroid functions of preterm infants born at 34 wk gestation or less were evaluated in the first (n = 31) and third (n = 19) weeks. Mothers’ breast milk (BM) and random urine samples of infants were taken on the same days for thyroid function tests.
Results: Iodine concentrations in BM were very high (198–8484 μg/liter), and one third of the infants had an iodine intake of more than 100 μg/kg per day at the third week after birth (excessive iodine intake group). At that time, the levels of TSH were positively correlated with urinary iodine (r = 0.622; P = 0.004). The frequencies of subclinical hypothyroidism were high in the excessive iodine intake group at the third and sixth weeks. The estimated daily iodine intake at the third week (51.2 ± 45.5 vs. 149.0 ± 103.8 μg/kg per day; P = 0.033), urinary iodine at the third week (913.2 ± 1179.7 vs. 1651.3 ± 1135.2 μg/liter; P = 0.051), and estimated daily iodine intake at the sixth week (32.8 ± 35.5 vs. 92.1 ± 51.2 μg/kg per day; P = 0.032) were significantly higher in infants with subclinical hypothyroidism than in controls.
Conclusions: Excessive iodine intake from BM contributed to subclinical hypothyroidism in these preterm Korean infants.
An excessive amount of iodine in breast milk causes subclinical hypothyroidism in preterm infants.
Safety and Efficacy of Quetiapine in Bipolar Depression
Authors: Bogart Gregory T , Chavez Benjamin 
Published: October 2009

Objective: To review the clinical data investigating the efficacy and safety of quetiapine in bipolar depression. Data Sources: Searches of MEDLINE and PubMed (1977–July 2009) were conducted using the key words quetiapine and bipolar depression. The references of literature found were cross-referenced. The pharmaceutical company that produces quetiapine was contacted to obtain the posters for the EMBOLDEN I and EMBOLDEN II trials. Study Selection and Data Extraction: Only double-blind, placebo-controlled trials were included for review, as well as any subanalyses of the literature that matched this criterion. Data Synthesis: There was a total of 5 double-blind, placebo-controlled trials and 5 subanalyses reviewed. The results of these data demonstrated quetiapine's efficacy in the treatment of depressive phases of bipolar disorder, including statistically significant improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS). In the trials reviewed in this article, the change in MADRS scores ranged from -15.4 to -16.94 within the quetiapine groups, and from -10.26 to -11.93 in the placebo groups. There were also statistically significant improvements in the Hamilton Anxiety Rating Scale, the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire, the Pittsburgh Sleep Quality Index, and the Sheehan Disability Scale. All of these trials had a duration of 8 weeks and therefore cannot be applied to the long-term use of quetiapine in bipolar depression. The most common adverse events were sedation, somnolence, and dry mouth. The overall dropout rates for the trials reviewed ranged from 24% to 47%. Conclusions: Based on the literature reviewed here, quetiapine appears to be a safe and efficacious short-term treatment option for bipolar depression. Patients with bipolar type I showed greater improvement on the MADRS than those with bipolar type II. Patients with a rapid-cycling disease course showed an improvement in depressive symptoms, regardless of bipolar type.
Comparative Pharmacodynamics of Intermittent and Prolonged Infusions of Piperacillin/Tazobactam Using Monte Carlo Simulations and Steady-State Pharmacokinetic Data from Hospitalized Patients
Authors: Shea Katherine M , Cheatham S Christian , Smith David W , Wack Matthew F , Sowinski Kevin M , Kays Michael B 
Published: October 2009

Background: Prolonging the infusion of a β-lactam antibiotic enhances the time in which unbound drug concentrations remain above the minimum inhibitory concentration (fT>MIC). Objective: To compare the pharmacodynamics of several dosing regimens of piperacillin/tazobactam administered by intermittent and prolonged infusion using pharmacokinetic data from hospitalized patients. Methods: Steady-state pharmacokinetic data were obtained from 13 patients who received piperacillin/tazobactam 4.5 g every 8 hours, infused over 4 hours. Monte Carlo simulations (10,000 pts.) were performed to calculate pharmacodynamic exposures at 50% fT>MIC for 4 intermittent-infusion regimens (3.375 g every 4 and 6 h, 4.5 g every 6 and 8 h) and 4 prolonged-infusion regimens (2.25 g, 3.375 g. 4.5 g, and 6.75 g every 8 h [4-h infusion]) of piperacillin/tazobactam using pharmacokinetic data for piperacillin. Cumulative fraction of response (CFR) was calculated using MIC data for 6 gram-negative pathogens (Meropenem Yearly Susceptibility Test Information Collection, 2004-2007), and probability of target attainment (PTA) was calculated at MICs ranging from 1 μg/mL to 64 μ/g/mL Results: The CFR for 3.375 g every 4 hours (intermittent infusion) and 3.375–4.5 g every 8 hours (prolonged infusion) greater than or equal to 90.3% for Escherichia coli, Serratia marcescens, and Citrobacter spp. Increasing the prolonged-infusion dose to 6.75 g improved the CFR to greater than 90% for Enterobacter spp. For every regimen evaluated, the CFR was less than 90% for Klebsiella pneumoniae and Pseudomonas aeruginosa. At an MIC of 16 μg/mL, PTA was greater than 90% for one intermittent-infusion regimen (3.375 g every 4 h) and 3 prolonged-infusion regimens (≥3.375 g every 8 h). but no regimen achieved a PTA greater than 90% at an MIC of 64 μ/g/mL. Conclusions: At doses greater than or equal to 3.375 g every 8 hours, 4-hour infusions of piperacillin/tazobactam achieved excellent target attainment with lower daily doses compared with standard regimens at MICs less than or equal to 16 μg/mL
Bendamustine-Associated Hemolytic Anemia
Authors: Glance Lisa E , Cumpston Aaron , Kanate Abraham , Remick Scot C 
Published: October 2009

Objective: To report a case of probable bendamustine-related hemolytic anemia. Case Summary: A 64-year-old white female had recently received treatment with bendamustine for stage III follicular lymphoma. After her fourth cycle, she was admitted to an outside facility with severe right upper quadrant pain across her back and findings consistent with obstructive jaundice. She was found to have pancytopenia and elevations in total bilirubin, alkaline phosphatase, and transaminase levels. A bone marrow biopsy showed no evidence of lymphoma and presence of megakaryocytes on 2 occasions. Upon transfer to West Virginia University Hospitals, her haptoglobin was found to be undetectable, total bilirubin 10.3 mg/dL (unconjugated bilirubin 4.9 mg/dL), reticulocyte count 21.4% (reticulocyte index ≥2%), alkaline phosphatase 1125 U/L, and lactate dehydrogenase 421 U/L. The peripheral smear showed evidence of spherocytes and very rare schistocytes. Based on these findings, the woman was diagnosed with hemolytic anemia secondary to bendamustine exposure. She was started on prednisone 1 mg/kg (60 mg) daily and, soon after, her platelets and hemoglobin stabilized. Discussion: Drug-induced hemolytic anemia is an acquired or extrinsic process that results in antibody-mediated red blood cell destruction. The patient was not taking any medications commonly associated with hemolytic anemia; however, her laboratory test results were consistent with hemolytic anemia. Based on bendamustine's structural similarity to fludarabine and fludarabine s association with causing hemolytic anemia, we considered exposure to bendamustine to be the most likely contributory factor for her diagnosis. According to the Naranjo probability scale, a probable likelihood was reflected in bendamustine causing the hemolytic anemia. Conclusions: Continued monitoring of postmarketing data is necessary to correlate this occurrence of hemolytic anemia with bendamustine therapy.
Thermodynamics in an icy world: The atmosphere and internal structure of Saturn's moon Titan
Authors: Heintz Andreas , Bich Eckard 
Published: October 2009

Abstract
Thermodynamic principles can be applied for describing the atmospheres and the internal structure of celestial bodies using Saturn's moon Titan as a most appropriate example. Some basic physical data of Titan such as the measured temperature and pressure on its surface, the atmospheric composition, Titan’s density and diameter, and other information allow us to predict further properties which have not been determined directly by measurements. The existence of a liquid phase covering smaller parts of the surface can be confirmed, and the composition of the liquid can be predicted. The change of temperature with the height over the surface and the appearance of clouds and rainfall in the atmosphere consisting essentially of CH4 + N2 mixtures can also be predicted. By developing a new method of calculation of atmospheric scenarios, the chemical history of Titan’s surface and atmosphere can be roughly reconstructed taking into account the known rate of methane destruction caused by radiative absorption of sunlight. Finally, some estimations concerning the material structure and the pressure behavior of Titan’s interior can be made. Only basic knowledge of thermodynamics and physics is required to understand essential features in a strange world that is more than one billion kilometers away from us.
The PPAR-γ Pro12Ala polymorphism associates with weight gain during GH-treatment in short children born small for gestational age
Authors: de Kort Sandra W K , Hokken-Koelega Anita C S 
Published: October 2009

ContextShort children born small for gestational age (SGA) have a lean phenotype with lower insulin sensitivity and higher blood pressure. GH treatment results in weight gain, and a decrease in blood pressure and insulin sensitivity. However, not all children respond in the same way. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR-γ) gene is inversely associated with body mass index (BMI), changes in BMI and the risk to develop type 2 diabetes mellitus.ObjectiveTo analyze the contribution of thePPAR-γPro12Ala polymorphism to GH induced changes in determinants of metabolic and cardiovascular disease in short SGA children.MethodsPPAR-γwas genotyped in 238 Caucasian short SGA children (mean age 7.5 years). Height, weight, blood pressure, and serum lipids were measured before start and during 4 years of GH treatment. In addition, glucose homeostasis by homeostasis model assessment insulin resistance ratio (HOMA-IR) (n=148) and by frequently sampled i.v. glucose tolerance test (n=51), and body composition by dual energy X-ray absorptiometry (n=79) were measured.ResultsAt baseline, the Ala12 allele was not associated with any determinant of metabolic and cardiovascular disease. After 4 years of GH treatment, the increase in weight for height SDS and BMI SDS was significantly greater in carriers of an Ala12 allele than in noncarriers. The change in all other parameters was not associated with Pro12Ala genotype.ConclusionThe Ala12 variant of thePPAR-γgene is associated with higher weight gain during GH treatment but not with changes in determinants of metabolic and cardiovascular diseases in Caucasian subjects born SGA.