bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol Attenuates Spatial Memory Deficits and Increases mGlu1a Receptor Expression in the Hippocampus of Rats Exposed to Prenatal Stress
Authors: Van Waes Vincent , Enache Mihaela , Zuena Annarita , Mairesse Jérôme , Nicoletti Ferdinando , Vinner Elisabeth , Lhermitte Michel , Maccari Stefania , Darnaudéry Muriel
Published: April 2009

Background:  Although it is generally believed that chronic ethanol consumption impairs learning and memory, results obtained in experimental animals are not univocal, and there are conditions in which ethanol paradoxically improves cognitive functions. In the present work, we investigated the effects of prenatal stress and of chronic ethanol exposure during adulthood on spatial memory in rats.

Methods:  Rats were subjected to a prenatal stress delivered as 3 daily 45‐minute sections of restraint stress to the mothers during the last 10 days of pregnancy (PRS rats). After 7 months of ethanol exposure (ethanol 10%, oral intake), memory performances were evaluated in a spatial discrimination test in control and PRS male rats. Then, the oxidative damages and the expression of metabotropic glutamate (mGlu) receptors were assessed in their hippocampus.

Results:  Chronic ethanol exposure resulted in a reduced performance in a spatial recognition task in control animals. Unexpectedly, however, the same treatment attenuated spatial memory deficits in rats that had been subjected to prenatal stress. This paradigm of ethanol administration did not produce detectable signs of oxidative damage in the hippocampus in either unstressed or PRS rats. Interestingly, ethanol intake resulted in differential effects in the expression of mGlu receptor subtypes implicated in mechanisms of learning and memory. In control rats, ethanol intake reduced mGlu2/3 and mGlu5 receptor levels in the hippocampus; in PRS rats, which exhibited a constitutive reduction in the levels of these mGlu receptor subtypes, ethanol increased the expression of mGlu1a receptors but did not change the expression of mGlu2/3 or mGlu5 receptors.

Conclusion:  Our findings support the idea that stress‐related events occurring before birth have long‐lasting effects on brain function and behavior, and suggest that the impact of ethanol on cognition is not only dose‐ and duration‐dependent, but also critically influenced by early life experiences.
Ethanol‐Responsive Genes (Crtam, Zbtb16, and Mobp) Located in the Alcohol‐QTL Region of Chromosome 9 Are Associated With Alcohol Preference in Mice
Authors: Weng Julia , Symons Melissa N. , Singh Shiva M.
Published: April 2009

Background:  Previously, our group identified cytotoxic and regulatory T‐cell molecule (Crtam), zinc finger and BTB domain containing 16 (Zbtb16), and myelin‐associated oligodendrocytic basic protein (Mobp) as ethanol‐responsive genes in the mouse brain by gene expression profiling. In this study, we used a genetic co‐segregation analysis to assess the association of Crtam, Zbtb16, and Mobp with the alcohol preference (AP) phenotype in the alcohol‐preferring C57BL/6J (B6) and alcohol avoiding DBA/2J (D2) strains of mice.

Methods:  Semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) was used to confirm previous microarray analysis results that Crtam, Zbtb16, and Mobp brain mRNA levels in the B6 and D2 strains are altered by ethanol treatment. The association of the 3 genes with AP was assessed in a F2 population (n = 427) derived from the reciprocal crosses involving the B6 and D2 strains. Each F2 individual was assessed for their AP using the 2 bottle choice test and genotyped for Crtam, Zbtb16, and Mobp single nucleotide polymorphisms (SNPs) that differ between B6 and D2 mice.

Results:  Semi‐quantitative RT‐PCR analysis confirmed that Crtam, Zbtb16, and Mobp are ethanol‐responsive genes. The SNP analyses show that alleles of the 3 genes co‐segregate with the AP phenotype in F2 mice, where individuals homozygous for the B6 allele have higher AP than those homozygous for the D2 allele. Also, the Crtam–Zbtb16 loci that are tightly linked and the Mobp locus act in an additive fashion in determining the relative AP phenotype.

Conclusion:  Our results are consistent with the hypothesis that Crtam, Zbtb16, and Mobp may be involved in AP in mice. The nature of this association remains to be established and may reflect a direct effect of these genes or an indirect effect caused by linked genes on mouse chromosome 9.
Three‐Year Chemical Dependency and Mental Health Treatment Outcomes Among Adolescents: The Role of Continuing Care
Authors: Sterling Stacy , Chi Felicia , Campbell Cynthia , Weisner Constance
Published: April 2009

Background:  Few studies have examined the effects of treatment factors, including the types of services [chemical dependency (CD), psychiatric, or both], on long‐term outcomes among adolescents following CD treatment, and whether receiving continuing care may contribute to better outcomes. This study examines the effect of the index CD and ongoing CD and psychiatric treatment episodes, 12‐step participation, and individual characteristics such as CD and mental health (MH) severity and gender, age, and ethnicity, on 3‐year CD and MH outcomes.

Methods:  Participants were 296 adolescents aged 13 to 18 seeking treatment at 4 CD programs of a nonprofit, managed care, integrated health system. We surveyed participants at intake, 1 year, and 3 years, and examined survey and administrative data, and CD and psychiatric utilization.

Results:  At 3 years, 29.7% of the sample reported total abstinence from both alcohol and drugs (excluding tobacco). Compared with girls, boys had only half the odds of being abstinent (OR = 0.46, p = 0.0204). Gender also predicted Externalizing severity at 3 years (coefficients 18.42 vs. 14.77, p < 0.01). CD treatment readmission in the second and third follow‐up years was related to abstinence at 3 years (OR = 0.24, p = 0.0066 and OR = 3.33, p = 0.0207, respectively). Abstinence at 1 year predicted abstinence at 3 years (OR = 4.11, p < 0.0001). Those who were abstinent at 1 year also had better MH outcomes (both lower Internalizing and Externalizing scores) than those who were not (11.75 vs. 15.55, p = 0.0012 and 15.13 vs. 18.06, p = 0.0179, respectively).

Conclusions:  A CD treatment episode resulting in good 1‐year CD outcomes may contribute significantly to both CD and MH outcomes 3 years later. The findings also point to the value of providing a continuing care model of treatment for adolescents.
Effect of Antibiotic Guidelines on Outcomes of Hospitalized Patients with Nursing Home–Acquired Pneumonia
Authors: El Solh Ali A. , Akinnusi Morohunfolu E. , Alfarah Ziad , Patel Anil
Published: April 2009

OBJECTIVES: To compare the 2003 community‐acquired pneumonia (CAP) guideline and the 2005 healthcare‐associated pneumonia (HCAP) guideline on time to clinical stability, length of hospital stay, and mortality in nursing home patients hospitalized for pneumonia.

DESIGN: Retrospective study.

SETTING: Three tertiary‐care hospitals.

PARTICIPANTS: Three hundred thirty‐four nursing home patients.

MEASUREMENTS: Patients were classified according to the antibiotic regimens they received based on the 2003 CAP guideline or the 2005 HCAP guideline. Time to clinical stability, time to switch therapy, and mortality were evaluated in an intention‐to‐treat analysis. A multivariate survival model using propensity analysis was used to adjust for heterogeneity between the two groups.

RESULTS: Of the 334 patients, 258 (77%) were treated according to the 2003 HCAP guideline. Time to clinical stability did not differ between those treated according to the 2003 CAP or the 2005 HCAP guidelines. Only the Pneumonia Severity Index (P=.006) and multilobar involvement (P=.005) were significantly associated with delay in achieving clinical stability. Adjusted in‐hospital and 30‐day mortality were comparable in both cohorts (odds ratio (OR)=0.87, 95% confidence interval (CI)=0.49–1.34, and OR=0.79, 95% CI=0.42–1.31, respectively), although time to switch therapy and length of stay were longer for those treated according to the 2005 HCAP guideline.

CONCLUSION: In hospitalized nursing home patients with pneumonia, treatment with an antibiotic regimen according to the 2003 CAP guideline achieved comparable time to clinical stability and in‐hospital and 30‐day mortality with a regimen based on the 2005 HCAP guideline.
Healthy Older Adults Better Tolerate Sleep Deprivation Than Young Adults
Authors: Duffy Jeanne F. , Willson Hannah J. , Wang Wei , Czeisler Charles A.
Published: April 2009

OBJECTIVES: To determine whether healthy aging is associated with increased sleepiness and whether healthy older adults experience more sleepiness when acutely sleep deprived.

DESIGN: A 5‐day inpatient circadian rhythm–sleep study consisting of 3 baseline nights followed by an extended 26‐hour wake episode under constant conditions.

SETTING: Intensive Physiological Monitoring Unit, General Clinical Research Center, Brigham and Women's Hospital.

PARTICIPANTS: Thirty‐seven healthy participants without medical, psychological, or sleep disorders: 26 young (7 women, 19 men; mean age 21.9±3.3, range 18–29) and 11 “young‐old” adults (3 women, 8 men; mean age 68.1±3.6, range 65–76).

INTERVENTION: An extended 26‐hour wake episode under constant conditions.

MEASUREMENTS: Electroencephalographic‐verified wakefulness, slow eye movements, sustained attention, subjective sleepiness.

RESULTS: During the first 16 hours corresponding to the usual waking day, both groups rated themselves as alert and had similar levels of vigilance and little evidence of sleepiness. As the wake episode continued, the older subjects were less impaired, showing faster reaction times, fewer performance lapses and attentional failures, and less frequent unintentional sleep episodes than the younger subjects.

CONCLUSION: This small study suggests that excessive sleepiness is not normal in healthy older adults. Symptoms of excessive sleepiness in this population, including reliance on caffeine to maintain alertness, should be evaluated and treated. Further study is needed to determine whether daytime sleepiness in middle‐old (75–84 years) and old‐old (≥85) adults is normal or is instead associated with sleep restriction, undiagnosed sleep disorders, medication side effects, mood disorders, or other medical disorders that disrupt sleep.
Deficiency of Testosterone Associates with the Substrate of Atrial Fibrillation in the Rat Model
Authors: TSUNEDA TAKAYUKI , YAMASHITA TAKESHI , KATO TAKESHI , SEKIGUCHI AKIKO , SAGARA KOUICHI , SAWADA HITOSHI , AIZAWA TADANORI , FU LONG‐TAI , FUJIKI AKIRA , INOUE HIROSHI
Published: April 2009

Background: Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF.

Methods and Results: We examined the electrophysiological properties of the atria in isolated‐perfused hearts of sham‐operated male (SM), female (SF), orchiectomized male with and without administration of testosterone (ORCH‐T and ORCH), and ovariectomized female (OVX) Sprague‐Dawley rats. An electrophysiological study revealed that repetitive atrial responses induced by electrical stimuli significantly increased in ORCH rats without changes in other electrophysiological properties and were abolished by administration of testosterone. To investigate the underlying mechanisms, we evaluated the expression level of calcium‐handling proteins. In ORCH rats, the immunoreactive protein level of ryanodine receptor type 2 (RyR2) and sodium–calcium exchanger significantly increased as compared with SM and ORCH‐T rats without alterations in the level of FK506‐binding protein (FKBP12.6), sarcoendoplasmic reticulum Ca‐ATPase, and phospholamban. Immunoprecipitation analysis demonstrated decreased binding of FKBP12.6 to RyR2 in ORCH rats, which was prevented by testosterone. In contrast, the expression levels of these proteins showed no significant differences between SF and OVX rats.

Conclusion: Deficiency of testosterone was arrhythmogenic in rat atria possibly through less binding of FKBP12.6 to RyR2, which could induce feasible calcium leakage from the sarcoendoplasmic reticulum. These results would explain, at least in part, the increase in the prevalence of AF in accordance with the decline of testosterone particularly in elderly men.
Structural Adjustment, Spatial Imaginaries, and “Piracy” in Guatemala's Apparel Industry
Authors: Thomas Kedron
Published: April 2009

This article examines how urban violence influences the everyday lives of Guatemalan Maya entrepreneurs who make nontraditional clothing to sell in highland markets and Guatemala City. How urban space is imagined and experienced among apparel producers reflects a process of class differentiation linked to Guatemala's entrance into international trade and legal agreements. Realities of uneven access and unequal resource distribution allow some producers to take advantage of formal markets and official networks in the capital city, while others avoid the city streets out of fear. Such inequalities are obscured when entrepreneurs who benefit from urban connections talk about relative success in terms of a moral division between those who engage in brand piracy and those who do not. In line with an official discourse that blames “pirates,” gangs, and other marginalized groups for the country's social and economic ills, apparel producers who do not copy popular brands often view those who do as immoral and illegal. The case study presented here is fruitful ground for theorizing how cultural representations of urban space influence market strategies and moral logics amidst processes of economic and legal restructuring.
Industrial Anthropology in Argentina
Authors: Giniger Nuria Inés
Published: April 2009

This paper examines the history and practice of industrial anthropology in Argentina. The development of this subfield is discussed in the context of Argentina's recent history and research institutions.
Transnational Migration, the Lost Girls of Sudan and Global “Care work”: A Photo Essay
Authors: DeLuca Laura
Published: April 2009

This essay explores the work lives of a group of Sudanese refugees known popularly as the Lost Girls of Sudan. Like other women from the Global South, the Lost Girls often work in the care work sector as maids, babysitters, nannies, preschool attendants, food service workers, nurses, personal care attendants for elderly and disabled people. The article also explores the U.S. refugee policy of self‐sufficiency.
The neurocognitive performance of drug‐free and medicated euthymic bipolar patients do not differ
Authors: Goswami U. , Sharma A. , Varma A. , Gulrajani C. , Ferrier I. N. , Young A. H. , Gallagher P. , Thompson J. M. , Moore P. B.
Published: April 2009

Objective:  Although it is established that euthymic bipolar patients have neurocognitive deficits, the influence of medication on their cognitive performance is uncertain and requires investigation.

Method:  Neuropsychological tests of executive function, memory and attention were performed on 44 prospectively verified, euthymic bipolar I patients, 22 of whom were drug‐free. Residual mood symptom effects were controlled statistically using ancova.

Results:  Drug‐free and medicated patients differed only in delayed verbal recall (Rey AVLT list A7, drug‐free > medicated), and perseverations during the five‐point test (drug‐free > medicated). When residual mood symptoms were controlled statistically, differences between drug‐free and medicated subjects became insignificant. Medication effect sizes were modest. Significant correlations were found between residual depression scores and measures of verbal learning.

Conclusion:  Medications did not have any significant influence on neurocognitive performance, suggesting that neurocognitive deficits are an integral part of bipolar disorder.
Stroke in children: inherited and acquired factors and age‐related variations in the presentation of 48 paediatric patients
Authors: Del Balzo Francesca , Spalice Alberto , Ruggieri Martino , Greco Filippo , Properzi Enrico , Iannetti Paola
Published: April 2009

Aim:  Stroke is relatively rare in children and the clinical presentation of paediatric stroke is often subtle. Numerous predisposing risk factors are known, and these can be both inherited and acquired. They include cardiac disease, vascular abnormalities, endothelial damage, infectious diseases, collagen tissue diseases, certain inborn errors of metabolism and anticardiolipin antibody, lupus anticoagulant and deficiencies of protein C, protein S, antithrombin or plasminogen. In addition, abnormal activated protein C resistance (or Factor V Leiden), Factor II G20219A variant, and the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR C677T) need to be considered.

Methods:  To explore the prevalence of different predisposing conditions in paediatric stroke patients, we evaluated 48 patients, including subjects with ischaemic and haemorrhagic stroke subtypes.

Results:  Only 7 out of 48 (14.5%) had no recognizable risk factors: the majority of paediatric stroke patients had pre‐existing risk factors that predisposed to the condition. The major genetic risk factor in our series of patients was homozygosity for the MTHFR C677T mutation (7 out of 48 patients); three more patients were found to be heterozygous for the Factor V Leiden mutation. Acquired predisposing conditions were present in 23 out of 48 patients and included pulmunar stenosis, head trauma, hyperlipidaemia and varicella infection. A total of 17 patients had both genetic and acquired predisposing factors.

Conclusion:  Our results emphasize that multiple predisposing risk factors commonly predispose to paediatric stroke. In addition, the primary clinical presentation appeared to differ between the older and younger children: hemiparesis was the typical presentation in children <1 year of age while seizure predominated in older children.
Pathways of Sexual Desire
Authors: Pfaus James G.
Published: April 2009

Introduction

Sexual desire is controlled by brain systems involved in sexual excitation and inhibition. Hypoactive sexual desire disorder (HSDD) may result from hypofunctional excitation, hyperfunctional inhibition, or some mix of the two.

Aim

This study aimed to identify neurochemical and neuroanatomical systems involved in sexual excitation and inhibition, their role during normal, and hypoactive sexual expressions.

Methods

A comprehensive review of the human and animal literature is made, and a theory surrounding the ways that HSDD can be manifested and treated is presented.

Main Outcome Measures

Drug effects and neural systems derived largely from rat studies that are involved in the stimulation of sexual desire (excitatory system) vs. the stimulation of sexual reward, sedation, and satiety (inhibitory system).

Results

Brain dopamine systems (incertohypothalamic and mesolimbic) that link the hypothalamus and limbic system appear to form the core of the excitatory system. This system also includes melanocortins, oxytocin, and norepinephrine. Brain opioid, endocannabinoid, and serotonin systems are activated during periods of sexual inhibition, and blunt the ability of excitatory systems to be activated.

Conclusions

Drugs that stimulate the activation of hypothalamic dopamine or that blunt endocannabinoid or serotonin release and/or postsynaptic binding may be effective in stimulating sexual desire in animals and humans. The characterization of how those drugs work will help generate a rational approach to drug development in the treatment of HSDD.
COMPOSITION PROPERTIES, PHYSICOCHEMICAL CHARACTERISTICS AND SHELF LIFE OF WHOLE MILK AFTER THERMAL AND THERMO‐SONICATION TREATMENTS
Authors: BERMÚDEZ‐AGUIRRE DANIELA , MAWSON RAYMOND , VERSTEEG KEES , BARBOSA‐CÁNOVAS GUSTAVO V.
Published: April 2009

Raw whole milk (RM) was pasteurized with heat‐pasteurized milk (TT) and thermo‐sonication (US) treatments. Batch pasteurization was used for TT and 36, 72, 108 and 120 µm of the ultrasound wave intensity (24 kHz, 400 W); in addition, the heat conditions were applied together for US. Apparent protein content of US milk decreased; butter fat content was increased by US treatment. Proximal analysis showed the presence of added water in US milk and a decrease of nonfat solids, whereas pH was decreased for US milk, lactic acid was increased and density was decreased from RM to US; also, the color of US milk was whiter. The tested parameters for the TT samples were often intermediate between RM and US samples. Statistical analysis showed a significant difference (P < 0.05) among all treatments. After 16 days, US samples (4C) did not show mesophilic growth higher than 2 log; pH, acidity and color remained constant.

PRACTICAL APPLICATIONS

Thermo‐sonication (US) is an available method that can improve some sensorial and quality milk characteristics such as color and appearance, while at the same time, ultrasound pasteurizes the product. Minor changes in nutritional properties of milk (i.e., protein content) have been reported after US, with the advantage of extending the shelf life of the product for more than 16 days at 4C without the use of intensive heat treatments. This is a potential technology for use in research and development of new and current products in the dairy industry.
STUDY OF SOLIDS LEACHED DURING RICE COOKING USING THE TRANSMITTANCE AT 650 NM
Authors: MORAWICKI RUBÉN O. , SIEBENMORGEN TERRY , CHO MI JIN
Published: April 2009

The objective of this research was to develop a method to predict the amount of total solids leached during rice cooking using light transmittance at 650 nm with an ultraviolet‐visible spectrometer. Rice was cooked in excess water for different durations, the transmittance was measured, and the solids were determined gravimetrically after evaporation of the water. Results of leached solids obtained gravimetrically showed a good correlation with the logarithm of the transmittance (R2 = 0.9731), thus indicating the feasibility of the method. As a result, calibration curves were developed using rice starch and rice flour as standards. Calibration curves generated with rice starch has shown to overpredict the amount of solids leached. When rice flour was used, the method predicted that the solids leached with an average error of 2.3%, with a minor tendency towards underprediction.

PRACTICAL APPLICATIONS

During the industrial production of instant rice, important amounts of solids leach out from the rice, producing yield loss and high biochemical oxygen demand (BOD) waste streams. A quick method to estimate the leaching potential of different rice varieties would be important to adjust processing parameters and minimize leaching. The results presented in this study show that the transmittance at 650 nm can be used to estimate the solids leached during rice cooking. Still, the successful implementation of this method depends on the finding of suitable standards.
EFFECT OF BLANCHING ON STORAGE STABILITY OF HAZELNUT MEAL
Authors: CAM SEHRIBAN , KILIC MERAL
Published: April 2009

Influence of blanching on storage stability of hazelnut meal was investigated under accelerated storage conditions. Meals were obtained from unblanched and blanched hazelnut kernels, and stored at a relative humidity of 60% at 30C for 50 days. Total free fatty acid content, concentrations of individual free fatty acids, peroxide value and oil stability index were measured in the hazelnut meal samples during storage. No significant difference was found between peroxide values of the samples, however, the values of both samples increased during storage time. The concentrations of free fatty acids increased because of the activity of lipase in both meals, but the levels were lower in the blanched sample. Oil stability index of the unblanched sample was lower than that of the blanched sample. Blanching treatment was found to improve the oxidative stability of hazelnut meal, possibly because of partial inactivation of deteriorative enzymes.

PRACTICAL APPLICATIONS

Hazelnut meal is a product obtained from hazelnut which is used as an ingredient in various food products. Hazelnut meal is more prone to degradation and quality loss during storage via oxidation compared with the whole counterpart. Stability of whole hazelnut has been studied to a great extent in the literature, but there is a scarcity of information regarding stability of processed hazelnut. In addition, there is no information in the literature about the amount of individual free fatty acids in hazelnut where the amounts of total free fatty acids have been reported extensively. This study provides data for quality and stability of hazelnut meal during storage which could be used by the food industry.
EFFICACY OF SOUR WHEY AS A SHELF‐LIFE ENHANCER: USE IN ANTIOXIDATIVE EDIBLE COATINGS OF BEEF STEAK*
Authors: HAQUE ZAHUR U. , SHON JINHAN , WILLIAMS J. BYRON
Published: April 2009

Sour whey powder (SWP) based edible coatings, with and without carboxymethyl cellulose (CMC), were used to reduce oxidative degradation of cut beef steak stored at 2C for 5 days. Comparison was with calcium caseinate (CC) and soy protein isolate (SPI). Colorimetric measurements showed the mean of the color consistency index for L*, a*and b*scales of SWP to be highest with (18.3) and without CMC (19.8). Control gave a significantly lower value of 10.6. The percent inhibition of thiobarbituric acid reactive substances (TBARS) compared to control was 40.9, 38.9 and 48.9%, respectively for CC, SPI and SWP. In the same order, this value increased to 51.9, 45.1 and 59.2% when CMC was added to the coating. The peroxide value was also significantly reduced by SWP. Oxidative degradation as reflected by an increase in carbonyls and decrease in sulfhydryls was also reduced by SWP and it was better at this than the other proteins. Moisture barrier property of SWP based coating was the best and CMC significantly enhanced this property of CC and SPI though they did not fare well by themselves. Data show that SWP can effectively be used to extend quality and shelf life of beef steak.

PRACTICAL APPLICATIONS

In 2006, the U.S.A. produced more than 11.95 million metric tons of beef. Most of this was consumed as hamburger meat and steaks. Unfortunately, once the animal is slaughtered, meat undergoes oxidative degradation. Retail cut meats are particularly susceptible. Various antioxidative coatings have been tried with varying levels of success. The industry is keen for inexpensive and natural means. Recently, we successfully used sour whey, a byproduct of cottage cheese and/or caseinate manufacture, as natural antioxidative coating to extend shelf life of cut vegetables and apples. This part of our study investigates its efficacy in reducing oxidative degradation of retail cut beef steaks.
Introduction to Luther's Theology in Global Context
Authors: Helmer Christine
Published: April 2009

Luther's theology has for the past two centuries been interpreted in the categories of German Protestant thought. As the paradigmatic ‘Reformer’, however, Luther transcends the geographical and historical restrictions of his own sixteenth‐century German context, so that his person and work emerge as inspirations of freedom in global context. This essay looks at Luther's theology of freedom by treating its reception in distinct contexts. The particularities of freedom as ‘justification’ spoken by ‘the word’ is a characteristic feature of German Protestantism. Freedom is interpreted in its Nordic and North American contexts in less ‘word‐focused’ and more philosophical‐theological concepts as well as in complex dialogue with late medieval thought. Contemporary feminist and liberation theologians take Luther's message into the global context of oppression and violence, seeing in Luther constructive potential for addressing economic and political injustice. The ‘global Luther’ opens up new possibilities for understanding Luther's theology in terms of experience, emotions, and reason.
Met amplification and tumor progression in Cdkn2a‐deficient melanocytes
Authors: VanBrocklin Matthew W. , Robinson James P. , Whitwam Todd , Guilbeault Adam R. , Koeman Julie , Swiatek Pamela J. , Vande Woude George F. , Khoury Joseph D. , Holmen Sheri L.
Published: April 2009

While many genetic alterations have been identified in melanoma, the relevant molecular events that contribute to disease progression are poorly understood. Most primary human melanomas exhibit loss of expression of the CDKN2A locus in addition to activation of the canonical mitogen‐activated protein kinase signaling pathway. In this study, we used a Cdkn2a‐deficient mouse melanocyte cell line to screen for secondary genetic events in melanoma tumor progression. Upon investigation, intrachromosomal gene amplification of Met, a receptor tyrosine kinase implicated in melanoma progression, was identified in Cdkn2a‐deficient tumors. RNA interference targeting Met in these tumor cells resulted in a significant delay in tumor growth in vivo compared with the control cells. MET expression is rarely detected in primary human melanoma but is frequently observed in metastatic disease. This study validates a role for Met activation in melanoma tumor progression in the context of Cdkn2a deficiency.
Frequent mutations in the MITF pathway in melanoma
Authors: Cronin Julia C. , Wunderlich John , Loftus Stacie K. , Prickett Todd D. , Wei Xiaomu , Ridd Katie , Vemula Swapna , Burrell Allison S. , Agrawal Neena S. , Lin Jimmy C. , Banister Carolyn E. , Buckhaults Phillip , Rosenberg Steven A. , Bastian Boris C. , Pavan William J. , Samuels Yardena
Published: April 2009

Microphthalmia‐associated transcription factor (MITF) is involved in melanocyte cell development, pigmentation and neoplasia. To determine whether MITF is somatically mutated in melanoma, we compared the sequence of MITF from primary and metastatic lesions to patient‐matched normal DNA. In the 50 metastatic melanoma tumor lines analysed, we discovered four samples that had genomic amplifications of MITF and four that had MITF mutations in the regions encoding the transactivation, DNA binding or basic, helix‐loop‐helix domains. Sequence analysis for SOX10, a transcription factor, which both acts upstream of MITF and synergizes with MITF, identified an additional three samples with frameshift or nonsense mutations. Microphthalmia‐associated transcription factor and SOX10 were found to be mutated in a mutually exclusive fashion, possibly suggesting disruption in a common genetic pathway. Taken together we found that over 20% of the metastatic melanoma cases had alterations in the MITF pathway. We show that the MITF pathway is also altered in primary melanomas: 2/26 demonstrated mutations in MITF and 6/55 demonstrated mutations in SOX10. Our findings suggest that altered MITF function during melanomagenesis can be achieved by MITF amplification, MITF single base substitutions or by mutation of its regulator SOX10.
Activation by Ca2+/calmodulin of an exogenous myosin light chain kinase in mouse arteries
Authors: Raina H. , Zacharia J. , Li M. , Wier W. G.
Published: April 2009

Activation of myosin light chain kinase (MLCK) and other kinases was studied in the arteries of transgenic mice that express an optical fluorescence resonance energy transfer (FRET) MLCK activity biosensor. Binding of Ca2+/calmodulin (Ca2+/CaM) induces an increase in MLCK activity and a change in FRET. After exposure to high external [K+], intracellular [Ca2+] (fura‐2 ratio or fluo‐4 fluorescence) and MLCK activity both increased rapidly to an initial peak and then declined, rapidly at first and then very slowly. After an initial peak (‘phasic’) force was constant or increased slowly (termed ‘tonic’ force). Inhibition ofrho‐kinase (Y‐27632) decreased tonic force more than phasic, but had little effect on [Ca2+] and MLCK activation. Inhibition of PKCα and PKCβ with Gö6976 had no effect. KN‐93, an inhibitor of CaMK II, markedly reduced force, MLCK FRET and [Ca2+]. Applied during tonic force, forskolin caused a rapid decrease in MLCK FRET ratio and force, but no change in Ca2+, suggesting a cAMP mediated decrease in affinity of MLCK for Ca2+/CaM. However, receptor (β‐adrenergic) activated increases in cAMP during KCl were ineffective in causing relaxation, changes in [Ca2+], or MLCK FRET. At the same tonic force, MLCK FRET ratio activated by α1‐adrenoceptors was ∼60% of that activated by KCl. In conclusion, MLCK activity of arterial smooth muscle during KCl‐induced contraction is determined primarily by Ca2+/CaM.Rho‐kinase is activated, by unknown mechanisms, and increases ‘Ca2+sensitivity’ significantly. Forskolin mediated increases in cAMP, but not receptor mediated increases in cAMP cause a rapid decrease in the affinity of MLCK for Ca2+/CaM.
Stretch‐stimulated glucose uptake in skeletal muscle is mediated by reactive oxygen species and p38 MAP‐kinase
Authors: Chambers Melissa A. , Moylan Jennifer S. , Smith Jeffrey D. , Goodyear Laurie J. , Reid Michael B.
Published: April 2009

Alternatives to the canonical insulin‐stimulated pathway for glucose uptake are exercise‐ and exogenous reactive oxygen species (ROS)‐stimulated glucose uptake. We proposed a model wherein mechanical loading, i.e. stretch, stimulates production of ROS to activate AMP‐activated kinase (AMPK) to increase glucose uptake. Immunoblotting was used to measure protein phosphorylation; the fluorochrome probe 2′7′‐dichlorofluorescin diacetate was used to measure cytosolic oxidant activity and 2‐deoxy‐d[1,2‐3H]glucose was used to measure glucose uptake. The current studies demonstrate that stretch increases ROS, AMPKα phosphorylation and glucose transport in murine extensor digitorum longus (EDL) muscle (+121%, +164% and +184%, respectively; P < 0.05). We also demonstrate that stretch‐induced glucose uptake persists in transgenic mice expressing an inactive form of the AMPKα2 catalytic subunit in skeletal muscle (+173%; P < 0.05). MnTBAP, a superoxide dismutase (SOD) mimetic, N‐acteyl cysteine (NAC), a non‐specific antioxidant, ebselen, a glutathione mimetic, or combined SOD plus catalase (ROS‐selective scavengers) all decrease stretch‐stimulated glucose uptake (P < 0.05) without changing basal uptake (P > 0.16). We also demonstrate that stretch‐stimulated glucose uptake persists in the presence of the phosphatidylinositol 3‐kinase (PI3‐K) inhibitors wortmannin and LY294001 (P < 0.05) but is diminished by the p38‐MAPK inhibitors SB203580 and A304000 (P > 0.99). These data indicate that stretch‐stimulated glucose uptake in skeletal muscle is mediated by a ROS‐ and p38 MAPK‐dependent mechanism that appears to be AMPKα2‐ and PI3‐K‐independent.
Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia
Authors: Casas‐Pruneda Griselda , Reyes Juan Pablo , Pérez‐Flores Gabriela , Pérez‐Cornejo Patricia , Arreola Jorge
Published: April 2009

Mouse parotid acinar cells express P2X4 and P2X7 receptors (mP2X4R and mP2X7R) whose physiological function remains undetermined. Here we show that mP2X4R expressed in HEK‐293 cells do not allow the passage of tetraethylammonium (TEA+) and promote little, if any, ethidium bromide (EtBr) uptake when stimulated with ATP or BzATP. In contrast, mP2X7R generates slowly decaying TEA+ current, sustained Na+ current and promotes robust EtBr uptake. However, ATP‐activated TEA+ current from acinar cells was unlike that generated by mP2X7R or mP2X4R. Functional interactions between mP2X4R and mP2X7R were investigated in HEK cells co‐transfected with different mP2X4 : mP2X7 cDNA ratios and using solutions containing either TEA+ or Na+ ions. Co‐expressed channels generated a TEA+ current that displayed faster decay during ATP stimulation than mP2X7R alone. Moreover, cells transfected with a 2 : 1 cDNA ratio displayed decaying kinetics similar to those observed in acinar cells. Concentration–response curves in Na+‐containing solutions were constructed for heterologously expressed mP2X4R, mP2X7R and mP2X4R:mP2X7R co‐expressions as well as acinar cells. The EC50 values determined were 11, 220, 434 and 442 μm, respectively. Na+ currents generated by expressing mP2X4R or mP2X7R alone were potentiated by ivermectin (IVM). In contrast, IVM potentiation in acinar cells and HEK cells co‐expressing P2X4 and P2X7 (1 : 1 or 2 : 1 cDNA ratios) was seen only when the ATP concentration was lowered from 5 to 0.03 mm. Taken together our observations indicate a functional interaction between murine P2X7 and P2X4 receptors. Such interaction might occur in acinar cells to shape the response to extracellular ATP in salivary epithelia.
Jugular venous overflow of noradrenaline from the brain: a neurochemical indicator of cerebrovascular sympathetic nerve activity in humans
Authors: Mitchell David A. , Lambert Gavin , Secher Niels H. , Raven Peter B. , Van Lieshout Johannes , Esler Murray D.
Published: April 2009

A novel neurochemical method was applied for studying the activity of sympathetic nerves in the human cerebral vascular system. The aim was to investigate whether noradrenaline plasma kinetic measurements made with internal jugular venous sampling reflect cerebrovascular sympathetic activity. A database was assembled of fifty‐six healthy subjects in whom total body noradrenaline spillover (indicative of whole body sympathetic nervous activity), brain noradrenaline spillover and brain lipophlic noradrenaline metabolite (3,4‐dihydroxyphenolglycol (DHPG) and 3‐methoxy‐4‐hydroxyphenylglycol (MHPG)) overflow rates were measured. These measurements were also made following ganglion blockade (trimethaphan, n= 6), central sympathetic inhibition (clonidine, n= 4) and neuronal noradrenaline uptake blockade (desipramine, n= 13) and in a group of patients (n= 9) with pure autonomic failure (PAF). The mean brain noradrenline spillover and brain noradrenaline metabolite overflow in healthy subjects were 12.5 ± 1.8, and 186.4 ± 25 ng min−1, respectively, with unilateral jugular venous sampling for both. Total body noradrenaline spillover was 605.8 ng min−1± 34.4 ng min−1. As expected, trimethaphan infusion lowered brain noradrenaline spillover (P= 0.03), but perhaps surprisingly increased jugular overflow of brain metabolites (P= 0.01). Suppression of sympathetic nervous outflow with clonidine lowered brain noradrenaline spillover (P= 0.004), without changing brain metabolite overflow (P= 0.3). Neuronal noradrenaline uptake block with desipramine lowered the transcranial plasma extraction of tritiated noradrenaline (P= 0.001). The PAF patients had 77% lower brain noradrenaline spillover than healthy recruits (P= 0.06), indicating that in them sympathetic nerve degeneration extended to the cerebral circulation, but metabolites overflow was similar to healthy subjects (P= 0.3). The invariable discordance between noradrenline spillover and noradrenaline metabolite overflow from the brain under these different circumstances indicates that the two measures arise from different sources, i.e. noradrenaline spillover originates from the cerebral vasculature outside the blood–brain barrier, and the noradrenaline metabolites originate primarily from brain noradrenergic neurons. We suggest that measurements of transcranial plasma noradrenaline spillover have utility as a method for assessing the sympathetic nerve activity of the cerebral vasculature.
Organizational role for pubertal androgens on adult hypothalamic‐pituitary‐adrenal sensitivity to testosterone in the male rat
Authors: Evuarherhe O. , Leggett J. D. , Waite E. J. , Kershaw Y. M. , Atkinson H. C. , Lightman S. L.
Published: April 2009

The inhibitory effect of androgens on the hypothalamic‐pituitary‐adrenal (HPA) axis in basal and stress conditions in adult male rats is well documented. Major sex‐related neuroendocrine changes take place during puberty. There is a robust rise in production and secretion of gonadal steroids, which is thought to underlie numerous neural and behavioural changes brought on after puberty. The present study investigated the effect of the pubertal rise in gonadal steroid levels on the subsequent adult corticosterone profile, particularly the sensitivity of the adult HPA axis to testosterone. Animals were castrated either prepubertally (28 days) or in adulthood (11 weeks) and adult animals were subsequently treated with subcutaneous implants containing either testosterone or cholesterol. Using an automated blood sampling system, blood was collected from each freely moving, conscious rat every 10 min (i) over a 24 h period; (ii) in response to 10 min of noise stress, and (iii) following an immunological challenge with lipopolysaccharide (LPS). Analysis revealed that testosterone treatment did not significantly affect overall corticosterone release over the 24 h period in adult animals castrated before puberty in contrast to animals castrated in adulthood in which testosterone significantly suppressed corticosterone secretion. Following either a noise stress or LPS injection, testosterone treatment did not affect the hypothalamic or adrenal stress response in animals castrated prepubertally. Testosterone significantly suppressed the corticotrophin‐releasing hormone and arginine vasopressin mRNA as well as the corticosterone response to LPS in castrated animals that had had their testes intact over puberty. These data provide evidence that puberty is a critical organizational period during which rising levels of gonadal steroids programme the sensitivity of the adult HPA axis to gonadal steroids in adulthood.
Postnatal early overnutrition changes the leptin signalling pathway in the hypothalamic–pituitary–thyroid axis of young and adult rats
Authors: Rodrigues Ananda Lages , De Moura Egberto Gaspar , Fonseca Passos Magna Cottini , Potente Dutra Sheila Cristina , Lisboa Patricia Cristina
Published: April 2009

Postnatal early overnutrition (EO) is a risk factor for obesity in adult life. Rats raised in a small litter can develop hyperinsulinaemia, hyperphagia, hyperleptinaemia and hypertension as adults. Since leptin regulates the hypothalamic–pituitary–thyroid axis and the metabolism of thyroid hormones, we studied the leptin signalling pathway in pituitary and thyroid glands of the postnatal EO model. To induce EO, at the third day of lactation the litter size was reduced to three pups per litter (SL group). In control litters (NL group), the litter size was adjusted to 10 pups per litter. Body weight and food intake were monitored. Rat offspring were killed at 21 (weaning) and 180 days old (adulthood). Plasma thyroid hormones, thyroid‐stimulating hormone (TSH) and leptin were measured by radioimmunoassay. Proteins of the leptin signalling pathway were analysed by Western blotting. Body weight of offspring in the SL group was higher from the seventh day of lactation (+33%, P < 0.05) until 180 days old (+18%, P < 0.05). Offspring in the SL group showed higher visceral fat mass at 21 and 180 days old (+176 and +52%, respectively, P < 0.05), but plasma leptin was higher only at 21 days (+88%, P < 0.05). The SL offspring showed higher plasma TSH, 3,5,3′‐triiodothronine (T3) and thyroxine (T4) at 21 days (+60, +91 and +68%, respectively, P < 0.05), while the opposite was observed at 180 days regarding thyroid hormones (T3, −10%; and T4, −30%, P < 0.05), with no difference in TSH levels. In hypothalamus, no change was observed in the leptin signalling pathway at 21 days. However, lower janus thyrosine kinase 2 (JAK2) and phosphorilated‐signal transducer and activator of transcription‐3 (p‐STAT3) content were detected in adulthood. In pituitary, the SL group presented higher leptin receptors (Ob‐R), JAK2 and p‐STAT3 content at 21 days and lower JAK2 and STAT3 content at 180 days old. In contrast, in thyroid, the Ob‐R expression was lower in young SL rats, while the adult SL group presented higher Ob‐R and JAK2 content. We showed that postnatal EO induces short‐ and long‐term effects upon the hypothalamic–pituitary–thyroid axis. These changes may help to explain future development of metabolic and endocrine dysfunctions, such as metabolic syndrome and hypothyroidism.
Modulation of internal model formation during force field‐induced motor learning by anodal transcranial direct current stimulation of primary motor cortex
Authors: Hunter Timothy , Sacco Paul , Nitsche Michael A. , Turner Duncan L.
Published: April 2009

Human subjects can quickly adapt and maintain performance of arm reaching when experiencing novel physical environments such as robot‐induced velocity‐dependent force fields. Using anodal transcranial direct current stimulation (tDCS) this study showed that the primary motor cortex may play a role in motor adaptation of this sort. Subjects performed arm reaching movement trials in three phases: in a null force field (baseline), in a velocity‐dependent force field (adaptation; 25 N s m−1) and once again in a null force field (de‐adaptation). Active or sham tDCS was directed to the motor cortex representation of biceps brachii muscle during the adaptation phase of the motor learning protocol. During the adaptation phase, the global error in arm reaching (summed error from an ideal trajectory) was similar in both tDCS conditions. However, active tDCS induced a significantly greater global reaching (overshoot) error during the early stage of de‐adaptation compared to the sham tDCS condition. The overshoot error may be representative of the development of a greater predictive movement to overcome the expected imposed force. An estimate of the predictive, initial movement trajectory (signed error in the first 150 ms of movement) was significantly augmented during the adaptation phase with active tDCS compared to sham tDCS. Furthermore, this increase was linearly related to the change of the overshoot summed error in the de‐adaptation process. Together the results suggest that anodal tDCS augments the development of an internal model of the novel adapted movement and suggests that the primary motor cortex is involved in adaptation of reaching movements of healthy human subjects.
Direct evidence of nitric oxide release from neuronal nitric oxide synthase activation in the left ventricle as a result of cervical vagus nerve stimulation
Authors: Brack Kieran E. , Patel Vanlata H. , Mantravardi Rajkumar , Coote John H. , Ng G. Andre
Published: April 2009

Information regarding vagal innervation in the cardiac ventricle is limited and the direct effect of vagal stimulation on ventricular myocardial function is controversial. We have recently provided indirect evidence that the anti‐fibrillatory effect of vagus nerve stimulation on the ventricle is mediated by nitric oxide (NO). The aim of this study was to provide direct evidence for the release of nitric oxide in the cardiac ventricle during stimulation of the efferent parasympathetic fibres of the cervical vagus nerve. The isolated innervated rabbit heart was employed with the use of the NO fluorescent indicator 4,5‐diaminofluorescein diacetate (DAF‐2 DA) during stimulation of the cervical vagus nerves and acetylcholine perfusion in the absence and presence of the non‐specific NO synthase inhibitor NG‐nito‐l‐arginine (l‐NNA) and the neuronal NO synthase selective inhibitor 1‐(2‐trifluormethylphenyl)imidazole (TRIM). Using the novel fluorescence method in the beating heart, we have shown that NO‐dependent fluorescence is increased by 0.92 ± 0.26, 1.20 ± 0.30 and 1.91 ± 0.27% (during low, medium and high frequency, respectively) in the ventricle in a stimulation frequency‐dependent manner during vagus nerve stimulation, with comparable increases seen during separate stimulation of the left and right cervical vagus nerves. Background fluorescence is reduced during perfusion with l‐NNA and the increase in fluorescence during high frequency vagal stimulation is inhibited during perfusion with both l‐NNA (1.97 ± 0.35% increase before l‐NNA, 0.00 ± 0.02% during l‐NNA) and TRIM (1.78 ± 0.18% increase before TRIM, −0.11 ± 0.08% during TRIM). Perfusion with 0.1 μm acetylcholine increased NO fluorescence by 0.76 ± 0.09% which was blocked by l‐NNA (change of 0.00 ± 0.03%) but not TRIM (increase of 0.82 ± 0.21%). Activation of cardiac parasympathetic efferent nerve fibres by stimulation of the cervical vagus is associated with NO production and release in the ventricle of the rabbit, via the neuronal isoform of nitric oxide synthase.