bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of severe unilateral cerebellar hypoplasia
Authors: PORETTI ANDREA , LIMPEROPOULOS CATHERINE , ROULET‐PEREZ ELIANE , WOLF NICOLE I , RAUSCHER CHRISTIAN , PRAYER DANIELA , MÜLLER ANITA , WEISSERT MARKUS , KOTZAERIDOU URANIA , DU PLESSIS ADRE J , HUISMAN THIERRY A G M , BOLTSHAUSER EUGEN
Published: October 2009

Aim  Complete or subtotal absence of one cerebellar hemisphere is exceptional; only single cases have been described. We aimed to assess the long‐term outcome in children with severe unilateral cerebellar hypoplasia (UCH).

Method  As part of a retrospective study we describe neuroimaging features, clinical findings, and cognitive outcomes of seven children with UCH (five males, two females; age at first magnetic resonance imaging [MRI]: median 1y 3mo, range 9d–8y 10mo; age at latest follow‐up: median 6y 6mo, range 2y 3mo–14y 11mo).

Results  One child had abnormalities on prenatal MRI at 21 weeks’ gestation. The left cerebellar hemisphere was affected in five children, and the right hemisphere in two children. The vermis was involved in five children. The volume of the posterior fossa was variable. At the latest follow‐up, neurological findings included truncal ataxia and muscular hypotonia in five children, limb ataxia in three patients, and head nodding in two patients. Three children had learning disability*, five had speech and language disorders, and one had a severe behavioural disorder.

Interpretation  Severe UCH is a residual change after a disruptive prenatal cerebellar insult, most likely haemorrhagic. The outcome is variable, ranging from almost normal development to marked developmental impairment. Ataxia is a frequent but not a leading sign. It seems that involvement of the cerebellar vermis is often, but not consistently, associated with a poorer cognitive outcome, whereas an intact vermis is associated with normal outcome and no truncal ataxia.
Alcohol Stimulates Activation of Snail, Epidermal Growth Factor Receptor Signaling, and Biomarkers of Epithelial–Mesenchymal Transition in Colon and Breast Cancer Cells
Authors: Forsyth Christopher B. , Tang Yueming , Shaikh Maliha , Zhang Lijuan , Keshavarzian Ali
Published: October 2009

Background:  Alcohol consumption is associated with the risk of progressive cancers including colon and breast cancer. The mechanisms for the alcohol‐induced aggressive behavior of these epithelial cancer cells have not been fully identified. Epithelial–mesenchymal transition (EMT) is a developmental program recently shown to play a role in cancer progression and metastases. We hypothesized that alcohol might promote cancer progression by inducing EMT in cancer cells and tested this hypothesis by assessing alcohol‐stimulated changes in phenotypic markers of EMT as well as the EMT transcription factor Snail and its related cell signaling.

Methods:  Colon and breast cancer cell lines and a normal intestinal epithelial cell line were tested as well as colonic mucosal biopsy samples from alcoholic subjects. Cells were treated with alcohol and assessed for EMT‐related changes using immunofluorescent microscopy, western blotting, reporter assays, RT‐PCR, and knockdown of Snail with siRNA.

Results:  We show alcohol upregulated the signature EMT phenotypic marker vimentin as well as matrix metalloprotease (MMP)‐2, MMP‐7, and MMP‐9 and cell migration in colon and breast cancer cells—all characteristics of EMT. Alcohol also stimulated nuclear localization of Snail phosphorylated at Ser246, transcription from a Snail reporter plasmid, and Snail mRNA expression by RT‐PCR. Snail siRNA knockdown prevented alcohol‐stimulated vimentin expression. In vivo, Snail expression was significantly elevated in colonic mucosal biopsies from alcoholics. Also, we found alcohol stimulated activation of epidermal growth factor receptor (EGFR) signaling and an EGFR inhibitor blocked alcohol‐induced cell migration and Snail mRNA expression.

Conclusions:  Collectively, our data support a novel mechanism for alcohol promoting cancer progression through stimulating the EMT program in cancer cells via an EGFR‐Snail mediated pathway. This study reveals new pathways for alcohol‐mediated promotion of cancer that could be targeted for therapy or prevention of alcohol‐related cancers.
Glycine Receptors Involved in Acamprosate’s Modulation of Accumbal Dopamine Levels: An In Vivo Microdialysis Study
Authors: Chau PeiPei , Stomberg Rosita , Fagerberg Anne , Söderpalm Bo , Ericson Mia
Published: October 2009

Background:  Glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) have been suggested to be involved in the positive reinforcing and dopamine elevating effects of ethanol. Recent studies have also shown that ethanol high‐preferring rats substantially decrease their ethanol intake when treated with a glycine transporter 1 inhibitor (ORG 25935). Acamprosate, a drug used for relapse prevention in treatment of alcohol dependence, has also been demonstrated to elevate extracellular dopamine levels in the nAc. However, the underlying mechanism of action of acamprosate is not fully understood. Here we investigated whether acamprosate interferes with a neuronal circuitry that previously has been demonstrated to be involved in the dopamine elevating effects of ethanol and taurine.

Methods:  In vivo microdialysis in freely moving rats was used to assess accumbal dopamine levels before and during local (nAc) or systemic administration of acamprosate.

Results:  Perfusion of 0.5 mM acamprosate in the nAc significantly increased dopamine levels. Pretreatment either with 10 μM strychnine in the nAc or 100 μM mecamylamine in the VTA, completely antagonized the acamprosate‐induced elevation of accumbal dopamine levels. Also, systemic acamprosate administration elevated accumbal dopamine output, an effect that was abolished by local (nAc) pretreatment with 10 μM strychnine.

Conclusions:  These results suggest that both systemic and local application of acamprosate elevate extracellular dopamine levels in the nAc by activating accumbal GlyRs, and, secondarily, tegmental nAChRs.
Glycine Receptors in the Nucleus Accumbens Involved in the Ethanol Intake‐Reducing Effect of Acamprosate
Authors: Chau PeiPei , Höifödt‐Lidö Helga , Löf Elin , Söderpalm Bo , Ericson Mia
Published: October 2009

Background:  We have previously demonstrated that strychnine‐sensitive glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area are involved in mediating ethanol (EtOH)‐induced elevation of dopamine in the rat mesolimbic dopamine system. This neuronal circuitry was also demonstrated to mediate dopamine elevation in the nAc after both taurine, an endogenous agonist of GlyRs, and acamprosate, a synthetic derivate of homotaurine. The aim of this study was to investigate whether the EtOH intake‐reducing effect of acamprosate involves accumbal GlyRs.

Methods:  For this purpose, we used a voluntary EtOH consumption model where EtOH medium‐ and high‐preferring rats were implanted with guide cannulae in the nAc. The animals received daily injections of acamprosate or 0.9% NaCl before accessing a bottle of 6% EtOH and a bottle of water. After 2 days, a microinjection of strychnine or vehicle preceded the daily systemic injection and bottle‐access period.

Results:  Acamprosate, but not saline, decreased EtOH intake. Pretreatment with Ringer in the nAc did not influence EtOH intake in saline or acamprosate‐treated animals. Pretreatment with strychnine had no effect on EtOH intake in saline‐treated animals, whereas it completely reversed the EtOH intake‐reducing effect of acamprosate.

Conclusions:  Based on current and previous results, we suggest that acamprosate primarily interacts with accumbal GlyRs and secondarily with ventral tegmental nAChRs, in a similar manner to that previously observed with EtOH and taurine. The interaction between acamprosate and GlyRs does not only influence dopamine output in the nAc but also EtOH consumption, giving further support for our hypothesis that GlyRs are of importance in EtOH reinforcement.
Alcohol Up‐Regulates TLR2 Through a NO/cGMP Dependent Pathway
Authors: Bailey Kristina L , Sisson Joseph H. , Romberger Debra J. , Robinson James E. , Wyatt Todd A.
Published: October 2009

Background:  Heavy alcohol consumption is associated with severe bronchitis. This is likely related to increased inflammation in the airways of alcohol abusers. Toll‐like receptor 2 (TLR2) is an important mediator of inflammation in the airway epithelium. TLR2 initiates an inflammatory cascade in response to gram‐positive bacteria. We have previously shown that alcohol up‐regulates TLR2 in the airway epithelium. However, the mechanism of alcohol‐mediated up‐regulation of TLR2 has not been identified.

Methods:  A human airway epithelial cell line, 16HBE14o−, was exposed to biologically relevant concentrations of alcohol (100 mM) in the presence and absence of Nω‐Nitro‐l‐arginine methyl ester hydrochloride, a nitric oxide (NO) synthase inhibitor; and Rp‐8‐Br‐cGMP‐S, an antagonist analogue of cGMP. TLR2 was measured using real‐time PCR and Western blots. In addition, 16HBE14o− cells were incubated with sodium nitroprusside (SNP), an NO donor, and 8‐Br‐cGMP, a cGMP analogue. TLR2 was measured using real‐time PCR.

Results:  N
ω‐Nitro‐l‐arginine methyl ester hydrochloride blocked the alcohol‐mediated up‐regulation of TLR2. This indicates that NO plays a key role in alcohol’s up‐regulation of TLR2. SNP, a NO donor, up‐regulated TLR2. Rp‐8‐Br‐CGMP‐S attenuated alcohol’s up‐regulation of TLR2, suggesting that NO was working through cGMP/PKG. 8‐Br‐cGMP up‐regulated TLR2, also demonstrating the importance of cGMP/PKG.

Conclusions:  Alcohol up‐regulates TLR2 through a NO/cGMP/PKG dependent pathway in the airway epithelium. This is an important observation in the understanding how alcohol modulates airway inflammation. In addition, this is the first time that cyclic nucleotides have been shown to play a role in the regulation of TLR2.
Alcohol, Cocaine, and Brain Stimulation‐Reward in C57Bl6/J and DBA2/J Mice
Authors: Fish Eric W. , Riday Thorfinn T. , McGuigan Megan M. , Faccidomo Sara , Hodge Clyde W. , Malanga C. J.
Published: October 2009

Background: Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self‐stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward. These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine.

Methods: Male C57 and DBA mice were implanted with unipolar stimulating electrodes in the lateral hypothalamus and conditioned to spin a wheel for reinforcement by the delivery of rewarding electrical stimulation (i.e., brain stimulation‐reward or BSR). Using the curve‐shift method, the BSR threshold (θ0) was determined immediately before and after oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol concentration (BAC) was measured to determine the influence of alcohol metabolism on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0, 30.0 mg/kg) or saline intraperitoneally.

Results: In C57 mice, the 0.6 g/kg dose of alcohol lowered BSR thresholds by about 20%, during the rising (up to 40 mg/dl), but not falling, phase of BAC. When given to the DBA mice, alcohol lowered BSR thresholds over the entire dose range; the largest reduction was by about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was more potent in DBA mice than in C57 mice as revealed by a leftward shift in the cocaine dose–response curve. For both alcohol and cocaine, effects on BSR threshold were dissociable from effects on operant response rates.

Conclusions: In C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechanisms of brain reward. The DBA mice are more sensitive to the reward‐potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique.
CB1 Receptor Blockade Decreases Ethanol Intake and Associated Neurochemical Changes in Fawn‐Hooded Rats
Authors: Femenía Teresa , García‐Gutiérrez María S. , Manzanares Jorge
Published: October 2009

Background: This study was undertaken to identify the neurochemical changes underlying the attenuation of voluntary ethanol intake induced by the cannabinoid CB1 receptor antagonist AM251 in fawn‐hooded rats.

Methods: Rats were exposed to the 2‐bottle‐choice paradigm (ethanol 10% v/v or water) for 15 days. After this period, rats received AM251 (3 to 6 mg/kg, i.p.) or vehicle.

Results: Voluntary ethanol intake decreased (30%) with the administration of incremental dosages of AM251 (3 mg/kg, 5 days and 6 mg/kg, 5 days) in rats with acquired high preferring ethanol consumption (>3.5 g of ethanol/kg/d). Ethanol intake significantly decreased proopiomelanocortin expression in the arcuate nucleus (38.31%) and μ‐opioid‐DAMGO‐stimulated [35S]‐GTPγ binding in the caudate‐putamen (40%), nucleus accumbens core (AccC) (32.87%), and shell (AccS) (34.21%). Moreover, ethanol intake increased tyrosine hydroxylase (TH) gene expression in the substantia nigra (24%) and ventral tegmental area (23%) and corticotrophin‐releasing gene expression in the paraventricular hypothalamic nucleus (41.6%). The reduction of ethanol intake induced by AM251 was associated with blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. Interestingly, treatment with AM251 reduced (20%) TH gene expression in rats drinking only water. In this respect, the action of AM251 in reducing TH gene expression may not be specific.

Conclusion: Taken together, these results revealed that blockade of cannabinoid CB1 receptors (CB1r) decreased voluntary ethanol intake in ethanol‐habituated rats by normalizing the neurochemical alterations induced by ethanol.
Heavy Episodic Drinking and Alcohol Consumption in French Colleges: The Role of Perceived Social Norms
Authors: França Lionel Riou , Dautzenberg Bertrand , Reynaud Michel
Published: October 2009

Background:  The effect of normative perceptions (social norms) on heavy episodic drinking (HED) behavior is well known in the U.S. college setting, but little work is available in other cultural contexts. The objective of this study is therefore to assess whether social norms of alcohol use are related to HED in France, taking account of other influential predictors.

Methods:  A cross‐sectional survey was carried out among 731 second‐year university students in the Paris region to explore the role of 29 potential alcohol use risk factors. The probability of heavy episodic drinking and the frequency of HED among heavy episodic drinkers were modeled independently. Monthly alcohol consumption was also assessed.

Results:  Of the students, 56% overestimate peer student prevalence of HED (37% for alcohol drinking prevalence). HED frequency rises with perceived peer student prevalence of HED. Other social norms associated with HED are perceived friends’ approval of HED (increasing both HED probability and HED frequency) and perceived friend prevalence of alcohol drinking (increasing HED probability only). Cannabis and tobacco use, academic discipline, gender, and the number of friends are also identified as being associated with HED.

Conclusions:  Overestimation of peer student prevalence is not uncommon among French university students. Furthermore, perceived peer student prevalence of HED is linked to HED frequency, even after adjusting for other correlates. Interventions correcting misperceived prevalences of HED among peer students have therefore the potential to reduce the frequency of HED in this population.
Recipient‐derived HPA‐1a antibodies: a cause of prolonged thrombocytopenia after unrelated donor stem cell transplantation
Authors: Lucas Geoff , Culliford Steven , Green Frances , Sidra Gamal , Calvert Anthony , Green Ann , Harrison Penny , Harvey John , Allen Dave , Smillie David , Masurekar Ashish , Marks David , Russell Nigel , Massey Edwin
Published: October 2009

BACKGROUND:Patients with human platelet antigen (HPA) specific antibodies in cases of neonatal alloimmune thrombocytopenia and platelet (PLT) refractoriness derive clinical benefit from the use of HPA‐selected PLTs.

STUDY DESIGN AND METHODS:This study describes three patients with underlying diagnoses of acute myeloid leukemia, chronic lymphocytic leukemia, and myelodysplasia, respectively, who underwent allogeneic bone marrow transplantation (BMT) with unrelated donors matched at the HLA‐A, B, C, Dr, and DQ loci but who failed to achieve an adequate PLT count. Investigation using PLT immunofluorescence test, monoclonal antibody immobilization of PLT antigens assay, and genotyping revealed the presence of recipient‐derived HPA‐1a antibodies.

RESULTS:In two patients, anti‐HPA‐1a was detected post‐BMT and in the third patient, anti‐HPA‐1a was detected during pre‐BMT chemotherapy. Despite apparent 100% engraftment of donor cells, the patients' PLT counts failed to recover 9‐10 months posttransplant. The patients remained PLT‐transfusion dependent and failed to achieve satisfactory increments following random donor or HLA‐matched PLT transfusions. After the identification of HPA‐1a antibodies, the patients were supported by HPA‐1a(‐) PLTs and satisfactory posttransfusion PLT increments were obtained. These cases illustrate that HPA‐1a antibodies may remain detectable for 10 months following apparently successful donor engraftment and the disappearance of recipient‐derived HLA antibodies. The prolonged persistence of recipient‐derived PLT‐specific antibodies following BMT has to our knowledge not been described previously.

CONCLUSION:HPA‐1a antibodies were associated with protracted PLT‐transfusion dependence and significant hemorrhagic complications. Appropriate and timely laboratory investigation for HPA‐specific antibodiesfollowed by transfusion support with HPA‐selected PLTs provided the cornerstone of the hemostatic management in these cases.
First‐Principles Calculation and Proton Transfer in TiO2‐Modified Porous Glass
Authors: Araki Takanobu , Daiko Yusuke , Mineshige Atsushi , Kobune Masafumi , Toyoda Noriaki , Yamada Isao , Yazawa Tetsuo
Published: October 2009

Porous glasses (PGs) with 4 nm in diameter pores were prepared utilizing a spinodal‐type phase separation of Na2O–B2O3–SiO2 glass, and their surface was modified using titanium tetraisopropoxide. Fourier transform infrared measurements revealed that the absorbance for strong hydrogen‐bonding OH groups increased after the modification. Bond overlap population (BOP), which is directly related to the strength of the covalent bond, between O and H of OH groups were calculated using density functional theory and first‐principles calculations. BOPs decreased by the introduction of Ti atoms on pores. The proton conductivity at 80°C and 90% relative humidity of the titania‐modified PG was about five times higher than that of unmodified PG.
Direct Scanning Electron Microscopy Imaging of Ferroelectric Domains After Ion Milling
Authors: Grüner Daniel , Shen Zhijian
Published: October 2009

A method for directly observing the ferroelectric domain structure by scanning electron microscopy after argon ion milling has been established. Its advantages are exemplified by exposing the domain structure in three widely used ferroelectric ceramics, BaTiO3, (Na,K)NbO3, and Pb(Ti,Zr)O3. Stable high‐resolution images revealing domains with widths <30 nm have been obtained. The domain contrast is caused by electron channeling and is strongly dependent on the sample tilt angle. Owing to a strain‐ and defect‐free surface generated by gentle ion milling, pronounced orientation contrast is observed.
The Identification of a Human Skull Recovered from an eBay Sale
Authors: Seidemann Ryan M. , Stojanowski Christopher M. , Rich Fredrick J.
Published: October 2009

Abstract: A human skull seized by the State of Louisiana from an eBay sale is analyzed. Bioarchaeological analyses of age‐at‐death, sex, and population affinity suggest the individual represented by the skull was a middle‐aged Native American female. The presence of intentional cranial modification independently supports the population affinity assessment while confounding the metric analyses. However, no further specificity as to population affinity could be inferred using existing methods and comparative databases. Sedimentological and palynological analyses were attempted to redress this impasse. The presence of fine‐grained charcoal, abundant fungal remains, and small angular quartz grains suggestive of burial in loess, as well as the lack of pollen, pteridophyte spores, and microscopic algae, suggest a likely upland burial location from somewhere in the lower Mississippi Valley. The sedimentological and palynological analyses, while not conclusive, show promise for use in future affiliation analyses of human remains recovered during the course of forensic investigations. The results are reviewed within the broader context of the legal debate over the repatriation of human remains.
Morbidity Involving the Hallucinogenic Designer Amines MDA and 2C‐I*
Authors: Drees Julia C. , Stone Judy A. , Wu Alan H. B.
Published: October 2009

Abstract:  A case is presented of a 39‐year‐old woman who suffered severe debilitation because of a hemorrhagic stroke in the context of substance abuse. The patient presented to the emergency room with rapidly diminishing mental status, hypertension, and vasoconstriction; her friends provided a history of ingestion of cocaine, 3,4‐methylenedioxymethamphetamine (MDMA), and 2C‐I, a novel designer amine. A multi‐targeted LC‐MS/MS method for sympathomimetic amines and related drugs in urine detected and quantified 2C‐I and MDA, while ruling out MDMA. The cause of the stroke was determined to be an underlying cerebrovascular abnormality called Moyamoya, secondary to substance abuse. In clinical laboratories, gas chromatography–mass spectrometry or liquid chromatography–tandem mass spectrometry (LC‐MS/MS) confirmation of a positive amphetamine immunoassay is usually directed only towards amphetamine, methamphetamine, MDMA and MDA. This report demonstrates the utility of testing for a wider menu of compounds using LC‐MS/MS in order to better characterize the prevalence and toxicities of novel amines such as 2C‐I.
Preservation of TSPO by chronic intermittent hypobaric hypoxia confers antiarrhythmic activity
Authors: Li Jun , Xu Jiahong , Xiao Junjie , Zhang Hong , Liang Dandan , Liu Yi , Zhang Yangyang , Liu Ying , Wen Wei , Hu Yaer , Yu Zhuo , Yan Biao , Jiang Bing , Zhou Zhao‐Nian , Chen Yi‐Han
Published: October 2009

Abnormal activation of mitochondrial translocator protein (TSPO) contributes to arrhythmogenesis during cardiac metabolic compromise; however, its role in the antiarrhythmic activities of chronic hypoxia adaptation remains unclear. Our results demonstrated that 80% of normoxic rats developed ischaemic VF, whereas this condition was seldom observed in rats with 14 days of chronic intermittent hypobaric hypoxia (CIHH). TSPO stimulation or inhibition affected the arrhythmias incidence in normoxic rats, but did not change the CIHH‐mediated antiarrhythmic effects. Abrupt and excessive elevation of TSPO activity was positively linked to ischaemic VF, and CIHH preserved TSPO activity during ischaemia. The preservation of TSPO activity by CIHH also contributed to the maintenance of intracellular Ca homeostasis. These results suggest that the blunt sensitivity of TSPO to ischaemic stress may be responsible for the antiarrhythmic effects by CIHH.
Lipid droplet growth by fusion: insights from freeze‐fracture imaging
Authors: Robenek Horst , Severs Nicholas J.
Published: October 2009

An understanding of how lipid droplets grow in the cell is important to current human health issues. Homotypic fusion of small lipid droplets to create larger ones is one proposed mechanism though the evidence for this process continues to be debated. By applying the technique of freeze‐fracture electron microscopy to cells that have been stimulated to accumulate lipid droplets, we here present images which suggest that at least some large lipid droplets may indeed result from amalgamation of multiple smaller ones. These visual data add significantly to the notion that fusion contributes to lipid droplet growth.
Tissue inhibitor of metalloproteinases‐1‐induced scattered liver metastasis is mediated by host‐derived urokinase‐type plasminogen activator
Authors: Schrötzlmair Florian , Kopitz Charlotte , Halbgewachs Birgit , Lu Fei , Algül Hana , Brünner Nils , Gänsbacher Bernd , Krüger Achim
Published: October 2009

Paradoxically, not only proteinases but also their inhibitors can correlate with bad prognosis of cancer patients, underlining the evolving concept of the protease web as the complex interplay between proteinases, their inhibitors and effector molecules. Elevated levels of tissue inhibitor of metalloproteinases‐1 (TIMP‐1) render the liver more susceptible to metastasis by triggering urokinase plasminogen activator (uPA) expression as well as hepatocyte growth factor (HGF) signalling, thereby leading to the fatal scattered infiltration of metastasizing tumour cells throughout the parenchyma of the target organ. Here, we investigated whether host uPA is a crucial protagonist for the TIMP‐1‐induced modulation of a pro‐metastatic microenvironment in the liver. Indeed, in livers of uPA‐ablated mice elevated TIMP‐1 levels did not trigger HGF signalling and did not promote metastasis of a murine T‐lymphoma cell line. In contrast, lack of tumour cell‐derived uPA induced by gene silencing did not interfere with this pro‐metastatic pathway. Furthermore, host uPA was necessary for the recruitment of neutrophilic granulocytes and the associated increase of HGF in livers with elevated TIMP‐1 levels. This newly identified co‐operation between TIMP‐1 and host uPA suggests that therapies, simultaneously interfering with pro‐ and anti‐proteolytic pathways may be beneficial for patients with metastatic disease.
Sensing, physiological effects and molecular response to elevated CO2 levels in eukaryotes
Authors: Sharabi Kfir , Lecuona Emilia , Helenius Iiro Taneli , Beitel Greg J. , Sznajder Jacob Iasha , Gruenbaum Yosef
Published: October 2009

CO2 transport into cells

CO2 sensing in cells and organisms

Physiological effects of elevated CO2

Molecular response to elevated CO2 levels

Carbon dioxide (CO2) is an important gaseous molecule that maintains biosphere homeostasis and is an important cellular signalling molecule in all organisms. The transport of CO2 through membranes has fundamental roles in most basic aspects of life in both plants and animals. There is a growing interest in understanding how CO2 is transported into cells, how it is sensed by neurons and other cell types and in understanding the physiological and molecular consequences of elevated CO2 levels (hypercapnia) at the cell and organism levels. Human pulmonary diseases and model organisms such as fungi, C. elegans, Drosophila and mice have been proven to be important in understanding of the mechanisms of CO2 sensing and response.
Cooperation of adapter molecules in proximal signaling cascades during allergic inflammation
Authors: Kambayashi Taku , LaRosa David F. , Silverman Michael A. , Koretzky Gary A.
Published: October 2009

Summary:  Activation of mast cells through their high‐affinity immunoglobulin E receptor (FcεRI) plays an important role in allergic disorders. Other mast cell‐activating stimuli, such as Toll‐like receptor (TLR) ligands, synergize with FcεRI to enhance allergic inflammation. Thus, there is much interest in understanding how signaling occurs downstream of these receptors. One key event for FcεRI‐mediated mast cell activation is the inducible formation of multimolecular proximal signaling complexes. These complexes are nucleated by adapter proteins, scaffolds that localize various signaling molecules through their multiple molecule‐binding domains. Here we review recent findings in proximal signaling cascades with an emphasis on how adapter molecules cooperate with each other to generate an optimal signal in mast cells, and we discuss how signals crosstalk between FcεRI and TLRs in enhancing mast cell activation. Deciphering the molecular mechanisms leading to mast cell activation will hopefully bring new ideas for the development of novel therapeutics to control allergic diseases.
Adapters in the organization of mast cell signaling
Authors: Alvarez‐Errico Damiana , Lessmann Eva , Rivera Juan
Published: October 2009

Summary:  Mast cells are pivotal in innate immunity and play an important role in amplifying adaptive immunity. Nonetheless, they have long been known to be central to the initiation of allergic disorders. This results from the dysregulation of the immune response whereby normally innocuous substances are recognized as non‐self, resulting in the production of IgE antibodies to these ‘allergens’. Preformed and newly synthesized inflammatory (allergic) mediators are released from the mast cell following allergen‐mediated aggregation of allergen‐specific IgE bound to the high‐affinity receptors for IgE (FcεRI). Thus, the process by which the mast cell is able to interpret the engagement of FcεRI into the molecular events necessary for release of their allergic mediators is of considerable therapeutic interest. Unraveling these molecular events has led to the discovery of a functional class of proteins that are essential in organizing activated signaling molecules and in coordinating and compartmentalizing their activity. These so‐called ‘adapters’ bind multiple signaling proteins and localize them to specific cellular compartments, such as the plasma membrane. This organization is essential for normal mast cell responses. Here, we summarize the role of adapter proteins in mast cells focusing on the most recent advances toward understanding how these molecules work upon FcεRI engagement.
Comprehending the complex connection between PKCβ, TAK1, and IKK in BCR signaling
Authors: Shinohara Hisaaki , Kurosaki Tomohiro
Published: October 2009

Summary:  The transcription factor nuclear factor‐κB (NF‐κB) contributes to many events in the immune system. Characterization of NF‐κB has facilitated our understanding of immune cell differentiation, survival, proliferation, and effector functions. Intense research continues to elucidate the role of NF‐κB, which is shared in several receptor signaling pathways, such as Toll‐like receptors, the tumor necrosis factor receptor, and antigen receptors. The specificity of cellular responses emanating from stimulation of these receptors is determined by post‐translational modification, or ‘fine tuning’, which regulates spatiotemporal dynamics of downstream signaling. Understanding the fine tuning mechanisms of NF‐κB activation is crucial for insights into biological regulation and for understanding how cellular signaling pathways are tightly regulated to guide different cell fates. In this review, we focus on recent advances that illuminate the fine tuning mechanisms of NF‐κB activation by BCR signaling and have increased our comprehension of complex signal systems.
A Dominant Negative Mutant of Pma1 Interferes with the Folding of the Wild Type Enzyme
Authors: Eraso Pilar , Mazón María J. , Portillo Francisco
Published: October 2009

Misfolded proteins are usually arrested in the endoplasmic reticulum (ER) and degraded by the ER‐associated degradation (ERAD) machinery. Several mutant alleles of PMA1, the gene coding for the plasma membrane H +‐ATPase, render misfolded proteins that are subjected to ERAD. A subset of misfolded PMA1 mutants exhibits a dominant negative effect on yeast growth since, when co‐expressed with the wild type allele, both proteins are retained in the ER and degraded. We have used a PMA1‐D378T dominant lethal allele to analyse the mechanism underlying the retention of the wild type enzyme by the dominant negative mutant. A genetic screen was performed for isolation of intragenic suppressors of PMA1‐D378T allele. This analysis pointed to transmembrane helix 10 (TM10) as an important element in the establishment of the dominant lethality. Deletion of the TM10 was able to suppress not only the PMA1‐D378T but all the dominant lethal alleles tested. Biochemical analyses suggest that dominant lethal proteins obstruct, through TM10, the correct folding of the wild type enzyme leading to its retention and degradation by ERAD.
Spiral Coating of the Endothelial Caveolar Membranes as Revealed by Electron Tomography and Template Matching
Authors: Lebbink Misjaël N. , Jiménez Nuria , Vocking Karin , Hekking Liesbeth H. , Verkleij Arie J. , Post Jan A.
Published: October 2009

Caveolae are invaginations of the plasma membrane involved in multiple cellular processes, including transcytosis. In this paper we present an extensive 3‐D electron tomographic study of the endothelial caveolar system in situ. Analysis of large cellular volumes of (high‐pressure frozen, freeze‐substituted and epon‐embedded) human umbilical vein endothelial cells (HUVECs) provided a notable view on the architecture of the caveolar system that comprises – as confirmed by 3‐D immunolabeling for caveolin of ‘intact’ cells –bona fide caveolae, free plasmalemmal vesicles, racemose invaginations and free multi‐caveolar bodies. Application of template matching to tomograms allowed the 3‐D localization of caveolar membrane coatings in a robust manner. In this way we observed that bona fide endothelial caveolae, cryofixed and embedded in their cellular context, show a spiral organization of the coating as shown in the past for chemically fixed and freeze‐etched caveolae from fibroblasts. Meticulous 3‐D analysis further revealed that the coatings are distributed in triads of spirals over the caveolar bulb and neck. Remarkably, this coating distribution is consistently present over the membranes of the other members of the caveolar system in HUVECs. The novel observations that we present clarify the ultrastructural complexity of the ‘intact’ caveolar system, setting a detailed morphological basis for its functional diversity.
Effects of feeding level of milk replacer on body growth, plasma metabolite and insulin concentrations, and visceral organ growth of suckling calves
Authors: KAMIYA Mitsuru , MATSUZAKI Masatoshi , ORITO Hideki , KAMIYA Yuko , NAKAMURA Yoshi‐nori , TSUNEISHI Eisaku
Published: October 2009

The objective was to evaluate effects of feeding level of milk replacer on body growth, plasma metabolite and insulin concentrations, and allometric growth of visceral organs in suckling calves. Holstein bull calves (n = 8; 3–4 days of age) were fed either a low amount (average 0.63 kgDM/day, LM) or high amount (average 1.15 kgDM/day, HM) of high protein milk replacer until they were slaughtered at 6 weeks of age. Body weight (BW) at 4, 5, and 6 weeks of age, feed intake, average daily gain, and feed efficiency were higher in the HM than LM calves. The HM group had higher plasma glucose at 3 and 4 weeks of age and insulin levels after the age of 4 weeks compared with LM calves whereas no effect was detected on plasma nonesterified fatty acid or urea nitrogen concentrations. The HM calves had greater empty body weight (EBW), viscera‐free BW and most of the organs dissected than LM calves. Relative weights (% of EBW) of liver, spleen, kidneys, and internal fat were higher, whereas head and large intestine was lower in HM than LM calves. The results suggest that increased milk feeding levels would accelerate the growth of the body and specific organs.
Positive Marital Quality, Acculturative Stress, and Child Outcomes Among Mexican Americans
Authors: Leidy Melinda S. , Parke Ross D. , Cladis Mina , Coltrane Scott , Duffy Sharon
Published: October 2009

Previous research suggests that the quality of parents' relationships can influence their children's adjustment, but most studies have focused on the negative effects of marital conflict for children in White middle‐class families. The current study focuses on the potential benefits of positive marital quality for children in working‐class first generation Mexican American families using observational and self‐report data. This study examined the links between positive marital quality and child internalizing and externalizing behaviors 1 year later when the child was in sixth grade (N = 134 families). Positive marital quality was negatively correlated with child internalizing behaviors. Parent acculturative stress was found to mediate the relationship between positive marital quality and child internalizing behaviors in sixth grade.
Effects of Welfare Participation on Marriage
Authors: Teitler Julien O. , Reichman Nancy E. , Nepomnyaschy Lenna , Garfinkel Irwin
Published: October 2009

We investigated the widely held premise that welfare participation causes women to refrain from marriage. Using data from the Fragile Families and Child Wellbeing Study (N = 3,219), we employed an event history approach to study transitions to marriage among mothers who have had a nonmarital birth. We found that welfare participation reduces the likelihood of transitioning to marriage (hazard ratio is 0.67, p <.01), but only while the mother is receiving benefits. Once the mother leaves welfare, past receipt has little effect on marriage. We infer that the negative association between welfare participation and subsequent marriage reflects temporary economic disincentives rather than an erosion of values.
Family Structure History: Links to Relationship Formation Behaviors in Young Adulthood
Authors: Ryan Suzanne , Franzetta Kerry , Schelar Erin , Manlove Jennifer
Published: October 2009

Using data from three waves of the National Longitudinal Study of Adolescent Health (N = 4, 667), we examined the intergenerational link between parental family structure history and relationship formation in young adulthood. We investigated (a) whether parental family structure history is associated with young adults' own relationship formation behaviors, (b) which dimensions of family structure history are most predictive of children's later relationship formation behaviors, and (c) if the association between family structure history and young adulthood relationship formation differs by gender. Our findings provide evidence of an intergenerational link between parent relationship histories and their offspring's own relationship formation behaviors in young adulthood over and above confounding factors.
Stepfamily Formation: Implications for Adolescent Ties to Mothers, Nonresident Fathers, and Stepfathers
Authors: King Valarie
Published: October 2009

This study examines how the entrance of a stepfather influences adolescent ties to mothers and nonresident fathers and how prior ties to each biological parent influence the development of stepfather‐stepchild ties. Data come from 1,753 adolescents in the National Longitudinal Study of Adolescent Health who lived with a single mother in Wave 1 who remained single, cohabited, or married by Wave 2, approximately 1 year later. Stepfamily formation had little consequence for adolescent‐nonresident father ties. Adolescent‐mother closeness, however, declined when cohabiting, but not married, stepfathers entered the household. Close ties to married stepfathers were more likely to develop when adolescents were closer to their mothers before stepfather entry. Prior ties to nonresident fathers were unrelated to stepfather‐stepchild ties.
The Social Relations Model in Family Studies: A Systematic Review
Authors: Eichelsheim Veroni I. , Deković Maja , Buist Kirsten L. , Cook William L.
Published: October 2009

The Social Relations Model (SRM) allows for examination of family relations on three different levels: the individual level (actor and partner effects), the dyadic level (relationship effects), and the family level (family effect). The aim of this study was to present a systematic review of SRM family studies and identify general patterns in the results. Results of reanalyses of 17 data sets showed that characteristics of the person who reports on the relationship and the unique characteristics of the relationship were most important explanations of differences in family relationships. The present systematic review contributes to a better understanding of who is driving relationship outcomes in families and provides suggestions concerning the application of the SRM to family data.
Economic Well‐Being in Salvadoran Transnational Families: How Gender Affects Remittance Practices
Authors: Abrego Leisy
Published: October 2009

This article examines how migrant parents' gender affects transnational families' economic well‐being. Drawing on 130 in‐depth interviews with Salvadoran immigrants in the United States and adolescent and young adult children of migrants in El Salvador, I demonstrate that the gender of migrant parents centrally affects how well their families are faring. Gender structurally differentiates immigrant parents' experiences through labor market opportunities in the United States. Simultaneously, gendered social expectations inform immigrants' approaches to parental responsibilities and remitting behaviors. Remittances—the monies parents send—directly shape children's economic well‐being in El Salvador. I find that even though immigrant mothers are structurally more disadvantaged than immigrant fathers, mother‐away families are often thriving economically because of mothers' extreme sacrifices.
Household Composition Among Elders in Sub‐Saharan Africa in the Context of HIV/AIDS
Authors: Zimmer Zachary
Published: October 2009

Cross‐sectional and repeated surveys from household components of Demographic and Health Surveys in sub‐Saharan Africa were examined to determine whether household composition indicators for older adults (N = 52,573), involving offspring and grandchildren, correlated with national levels of AIDS mortality. One in 4 was living with a grandchild whose own parents were absent. Absence was a result of residence elsewhere and parents being deceased. Older adults in countries with a high accumulation of AIDS mortality were more likely to live in a skip‐generation household and with a double‐orphaned grandchild and less likely to live in a 3‐generation household. Change in living arrangements toward skip generation and a double orphaned household was experienced in countries with high accumulation of AIDS mortality.
Dark matter dominated dwarf disc galaxy Segue 1
Authors: Xiang-Gruess Meng , Lou Yu-Qing , Duschl Wolfgang J.
Published: October 2009

Several observations reveal that dwarf galaxy Segue 1 has a dark matter (DM) halo at least ∼200 times more massive than its visible baryon mass of only ∼103 M⊙. The baryon mass is dominated by stars with perhaps an interstellar gas mass of ≲13 M⊙. Regarding Segue 1 as a dwarf disc galaxy by its morphological appearance of long stretch, we invoke the dynamic model of Xiang-Gruess, Lou & Duschl (XLD) to estimate its physical parameters for possible equilibria with and without an isopedically magnetized gas disc. We estimate the range of DM mass and compare it with available observational inferences. Due to the relatively high stellar velocity dispersion compared to the stellar surface mass density, we find that a massive DM halo would be necessary to sustain disc equilibria. The required DM halo mass agrees grossly with observational inferences so far. For an isopedic magnetic field in a gas disc, the ratio f between the DM and baryon potentials depends strongly on the magnetic field strength. Therefore, a massive DM halo is needed to counteract either the strong stellar velocity dispersion and rotation of the stellar disc or the magnetic Lorentz force in the gas disc. By the radial force balances, the DM halo mass increases for faster disc rotation.
Simulation of dark lanes in post-flare supra-arcade
Authors: Costa A. , Elaskar S. , Fernández C. A. , Martínez G.
Published: October 2009

We integrate the magnetohydrodynamics (MHD) ideal equations to simulate dark void sunwardly moving structures in post-flare supra-arcades. We study the onset and evolution of the internal plasma instability to compare with observations and to gain insight into physical processes and characteristic parameters of these phenomena. The numerical approach uses a finite-volume Harten–Yee total variation diminishing (TVD) scheme to integrate the 1D 1/2 MHD equations specially designed to capture supersonic flow discontinuities. The integration is performed in both directions, the sunward radial one and the transverse to the magnetic field. For the first time, we numerically reproduce observational dark voids described in Verwichte et al. We show that the dark tracks are plasma vacuums generated by the bouncing and interfering of shocks and expansion waves, upstream an initial slow magnetoacoustic shock produced by a localized deposition of energy modelled with a pressure perturbation. The same pressure perturbation produces a transverse to the field or perpendicular magnetic shock giving rise to non-linear waves that compose the kink-like plasma void structures, with the same functional sunward decreasing phase speed and constancy with height of the period, as those determined by the observations.
Discovery of a magnetic field in the O9 sub-giant star HD 57682 by the MiMeS Collaboration
Authors: Grunhut J. H. , Wade G. A. , Marcolino W. L. F. , Petit V. , Henrichs H. F. , Cohen D. H. , Alecian E. , Bohlender D. , Bouret J. C. , Kochukhov O. , Neiner C. , St Louis N. , Townsend R. H. D.
Published: October 2009

We report the detection of a strong, organized magnetic field in the O9IV star HD 57682, using spectropolarimetric observations obtained with ESPaDOnS at the 3.6 m Canada–France–Hawaii Telescope within the context of the Magnetism in Massive Stars (MiMeS) Large Programme. From the fitting of our spectra using non local thermodynamic equilibrium model atmospheres, we determined that HD 57682 is a 17+19−9M⊙ star with a radius of 7.0+2.4−1.8R⊙ and a relatively low mass loss rate of 1.4+3.1−0.95× 10−9M⊙yr−1. The photospheric absorption lines are narrow, and we use the Fourier transform technique to infer v sini= 15 ± 3 kms−1. This v sini implies a maximum rotational period of 31.5d, a value qualitatively consistent with the observed variability of the optical absorption and emission lines, as well as the Stokes V profiles and longitudinal field. Using a Bayesian analysis of the velocity resolved Stokes V profiles to infer the magnetic field characteristics, we tentatively derive a dipole field strength of 1680+134−356G. The derived field strength and wind characteristics imply a wind that is strongly confined by the magnetic field.
Partners in the Spiritual Dance: Learning Clients’ Steps While Minding All Our Toes
Authors: Keeling Margaret L. , Dolbin‐MacNab Megan L. , Ford James , Perkins Susan N.
Published: October 2009

We present four case illustrations highlighting the complex interplay of therapists’ and clients’ spirituality in therapy. Complexity, in these cases, results from (a) degrees of similarity and difference, both real and perceived, between clients’ and therapists’ spiritual beliefs and practices; (b) degrees of spiritual disclosure; (c) characteristics of the therapeutic relationship; and (d) geographic and cultural influences. Practicing therapists and therapist training programs can benefit from addressing how therapist and client spirituality intersect and influence therapy, how both similarity and difference present obstacles and opportunities, and how ambiguity and assumptions can contribute to misunderstandings. We believe that both the therapist’s and the client’s spiritualities are key influences in therapy that can contribute to the frustration, and the growth, of clients and therapists alike.