bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early risk indicators of internalizing problems in late childhood: a 9‐year longitudinal study
Authors: Ashford Janka , Smit Filip , Van Lier Pol A.C. , Cuijpers Pim , Koot Hans M. 
Published: March 2008

Background:  Longitudinal studies on risk indicators of internalizing problems in childhood are in short supply, but could be valuable to identify target groups for prevention.Methods:  Standardized assessments of 294 children’s internalizing problems at the age of 2–3 years (parent report), 4–5 years (parent and teacher report) and 11 years (parent and teacher) were available in addition to risk indicators from the child, family and contextual domain.Results:  Low socioeconomic status, family psychopathology at child age 2–3, parenting stress at child age 4–5 years, and parents’ reports of child internalizing problems at age 4–5 years were the strongest predictors of internalizing problems at the age of 11. If these early risk factors were effectively ameliorated through preventive interventions, up to 57% of internalizing cases at age 11 years could be avoided.Conclusions:  Predictors from as early as 2–5 years of age are relevant for identifying children at risk of internalizing problems in late childhood. The methodological approach used in this study can help to identify children who are most in need of preventive interventions and help to assess the potential health gain and efficiency of such interventions.
Self/nonself perception and recognition mechanisms in plants: a comparison of self‐incompatibility and innate immunity
Authors: Sanabria Natasha , Goring Daphne , Nürnberger Thorsten , Dubery Ian 
Published: March 2008

SummaryAnalyses of emerging concepts indicate that parallels exist between self‐incompatibility and pathogen recognition. In the case of surveillance of ‘nonself’, plant immune responses are triggered either by pattern recognition receptors (PRRs) that detect conserved pathogen‐associated molecular patterns (PAMPs) or by resistance (R) proteins recognizing isolate‐specific pathogen effectors. PAMP detection is an important component of innate immunity in plants and serves as an early warning system for the presence of potential pathogens and activation of plant defense mechanisms. In the Brassicaceae, the recognition of ‘self’ and self‐incompatibility are components of a receptor‐ligand based mechanism that utilizes an S receptor kinase (SRK) to perceive and reject ‘self’‐pollen. SRK is an S‐domain receptor‐like kinase (RLK), which in turn is part of the RLK family, some members of which represent PRRs involved in the detection of PAMPs. S‐domain RLKs also occur in species that do not exhibit self‐incompatibility and are up‐regulated in response to wounding, PAMPs and pathogen recognition. Although evolution may have driven expansion of certain RLK families to serve roles in particular physiological processes, this may not exclude these receptor types from functioning in different programs. Recent findings on self/nonself recognition are reviewed and conceptual and mechanistic links between microbial recognition and self‐incompatibility are discussed.
P300 amplitude age reductions are not caused by latency jitter
Authors: Walhovd Kristine B. , Rosquist Hannah , Fjell Anders M. 
Published: March 2008

AbstractStudies of the event‐related potentials (ERPs) P3a/P3b have given insights into age effects on cognitive processes in the brain, and it has been established that latency increases and amplitude decreases with age. However, if latency jitter, that is, variation in single trial latencies, is larger in elderly than in younger participants, this may create an artificial age–amplitude correlation. The aim of this article is to test whether correction for latency jitter affects the P3a/P3b age correlations. One hundred thirty‐three healthy adults (20–88 years old) went through a 3‐stimuli visual oddball paradigm. Latency jitter was corrected by use of a Maximum Likelihood Estimation method. The results showed that corrections for latency jitter did not significantly affect the correlations between P3a/P3b and age. It is concluded that previous reports of amplitude reduction as a function of age seem to be valid regardless of whether latency jitter correction has been applied.
Preliminary evidence that morning vaccination is associated with an enhanced antibody response in men
Authors: Phillips Anna C. , Gallagher Stephen , Carroll Douglas , Drayson Mark 
Published: March 2008

AbstractVariation in response to vaccination, particularly in vulnerable groups, provides a strong rationale for developing vaccine adjuvants. If there were consistent diurnal variation in immune response, this could inform a simple intervention for enhancing vaccine efficacy. Data from two studies are presented examining morning versus afternoon vaccine administration; in the first, hepatitis A vaccine was administered to young adults, and in the second, influenza vaccine to older community‐based adults. Men, but not women, vaccinated in the morning mounted a better peak antibody response to both hepatitis A and the A/Panama influenza strain. These results indicate that it would be worthwhile testing this effect in a large randomized control trial with vaccination during time periods representing the extremes of hormonal and cytokine diurnal rhythms.
Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration
Authors: Ramesh Babu J. , Lamar Seibenhener M. , Peng Junmin , Strom Anna‐Lena , Kemppainen Robert , Cox Nancy , Zhu Haining , Wooten Michael C. , Diaz‐Meco María T. , Moscat Jorge , Wooten Marie W. 
Published: March 2008

AbstractThe signaling adapter p62 plays a coordinating role in mediating phosphorylation and ubiquitin‐dependent trafficking of interacting proteins. However, there is little known about the physiologic role of this protein in brain. Here, we report age‐dependent constitutive activation of glycogen synthase kinase 3β, protein kinase B, mitogen‐activated protein kinase, and c‐Jun‐N‐terminal kinase in adult p62−/− mice resulting in hyperphosphorylated tau, neurofibrillary tangles, and neurodegeneration. Biochemical fractionation of p62−/− brain led to recovery of aggregated K63‐ubiquitinated tau. Loss of p62 was manifested by increased anxiety, depression, loss of working memory, and reduced serum brain‐derived neurotrophic factor levels. Our findings reveal a novel role for p62 as a chaperone that regulates tau solubility thereby preventing tau aggregation. This study provides a clear demonstration of an Alzheimer‐like phenotype in a mouse model in the absence of expression of human genes carrying mutations in amyloid‐beta protein precursor, presenilin, or tau. Thus, these findings provide new insight into manifestation of sporadic Alzheimer disease and the impact of obesity.
FK506 binding protein 12 differentially accelerates fibril formation of wild type alpha‐synuclein and its clinical mutants A30P or A53T
Authors: Gerard Melanie , Debyser Zeger , Desender Linda , Baert Johan , Brandt Inger , Baekelandt Veerle , Engelborghs Yves 
Published: March 2008

AbstractAggregation of alpha‐synuclein (α‐SYN) plays a key role in Parkinson’s disease. We have previously shown that aggregation of α‐SYNin vitrois accelerated by addition of FK506 binding proteins (FKBP) and that this effect can be counteracted by FK506, a specific inhibitor of these enzymes. In this paper, we investigated in detail the effect of FKBP12 on early aggregation and on fibril formation of wild‐type, A53T and A30P α‐SYN. FKBP12 has a much smaller effect on the fibril formation of these two clinical mutants α‐SYN. Using an inactive enzyme, we were able to discriminate between catalytic and non‐catalytic effects that differentially influence the two processes. A model explaining non‐linear concentration dependencies is proposed.
In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation
Authors: Weinger Jason G. , Gohari Pouyan , Yan Ying , Backer Jonathan M. , Varnum Brian , Shafit‐Zagardo Bridget 
Published: March 2008

AbstractAxl is a receptor tyrosine kinase implicated in cell survival following growth factor withdrawal and other stressors. The binding of Axl’s ligand, growth arrest‐specific protein 6 (Gas6), results in Axl autophosphorylation, recruitment of signaling molecules, and activation of downstream survival pathways. Pull‐down assays and immunoprecipitations using wildtype and mutant Axl transfected cells determined that Axl directly binds growth factor receptor‐bound protein 2 (Grb2) at pYVN and the p85 subunit of phosphatidylinositol‐3 kinase (PI3 kinase) at two pYXXM sites (pY779 and pY821). Also, p85 can indirectly bind to Axl via an interaction between p85’s second proline‐rich region and the N‐terminal SH3 domain of Grb2. Further, Grb2 and p85 can compete for binding at the pY821VNM site. Gas6‐stimulation of Axl‐transfected COS7 cells recruited activated PI3 kinase and phosphorylated Akt. An interaction between Axl, p85 and Grb2 was confirmed in brain homogenates, enriched populations of O4+ oligodendrocytes, and O4− flow‐through prepared from day 10 mouse brain, indicating that cells with active Gas6/Axl signal through Grb2 and the PI3 kinase/Akt pathways.
Distinct changes in neuronal and astrocytic amino acid neurotransmitter metabolism in mice with reduced numbers of synaptic vesicles
Authors: Bogen Inger Lise , Risa Øystein , Haug Kristin H. , Sonnewald Ursula , Fonnum Frode , Walaas S. Ivar 
Published: March 2008

AbstractThe relations between glutamate and GABA concentrations and synaptic vesicle density in nerve terminals were examined in an animal model with 40–50% reduction in synaptic vesicle numbers caused by inactivation of the genes encoding synapsin I and II. Concentrations and synthesis of amino acids were measured in extracts from cerebrum and a crude synaptosomal fraction by HPLC and 13C nuclear magnetic resonance spectroscopy (NMRS), respectively. Analysis of cerebrum extracts, comprising both neurotransmitter and metabolic pools, showed decreased concentration of GABA, increased concentration of glutamine and unchanged concentration of glutamate in synapsin I and II double knockout (DKO) mice. In contrast, both glutamate and GABA concentrations were decreased in crude synaptosomes isolated from synapsin DKO mice, suggesting that the large metabolic pool of glutamate in the cerebral extracts may overshadow minor changes in the transmitter pool. 13C NMRS studies showed that the changes in amino acid concentrations in the synapsin DKO mice were caused by decreased synthesis of GABA (20–24%) in cerebral neurons and increased synthesis of glutamine (36%) in astrocytes. In a crude synaptosomal fraction, the glutamate synthesis was reduced (24%), but this reduction could not be detected in cerebrum extracts. We suggest that lack of synaptic vesicles causes down‐regulation of neuronal GABA and glutamate synthesis, with a concomitant increase in astrocytic synthesis of glutamine, in order to maintain normal neurotransmitter concentrations in the nerve terminal cytosol.
Immunoproteasome responds to injury in the retina and brain
Authors: Ferrington Deborah A. , Hussong Stacy A. , Roehrich Heidi , Kapphahn Rebecca J. , Kavanaugh Shannon M. , Heuss Neal D. , Gregerson Dale S. 
Published: March 2008

AbstractIt is well known that immunoproteasome generates peptides for MHC Class I occupancy and recognition by cytotoxic T lymphocytes (CTL). The present study focused on evidence for alternative roles for immunoproteasome. Retina and brain were analyzed for expression of immunoproteasome subunits using immunohistochemistry and western blotting under normal conditions and after injury/stress induced by CTL attack on glia (brain) or neurons (retina). Normal retina expressed substantial levels of immunoproteasome in glia, neurons, and retinal pigment epithelium. The basal level of immunoproteasome in retina was two‐fold higher than in brain; CTL‐induced retinal injury further up‐regulated immunoproteasome expression. Immunoproteasome up‐regulation was also observed in injured brain and corresponded with expression in Purkinje cells, microglia, astrocytes, and oligodendrocytes. These results suggest that the normal environment of the retina is sufficiently challenging to require on‐going expression of immunoproteasome. Further, immunoproteasome up‐regulation with retinal and brain injury implies a role in neuronal protection and/or repair of damage.
Vertical imbalance induced by prism‐ballasted soft toric contact lenses fitted unilaterally
Authors: Nilsson M. , Stevenson S. B. , Leach N. , Bergmanson J. P. , Brautaset R. L. 
Published: March 2008

AbstractFitting a prism‐ballasted soft toric contact lens unilaterally may potentially induce a vergence error that the subject cannot compensate. In the present study, a prism‐ballasted (1.5Δ base down) soft toric contact lens was fitted in the right eye only of 10 subjects with normal binocular vision. The effect on binocular vision was evaluated by measuring vertical phoria adaptation and vertical fixation disparity adaptation. The results show that the vertical vergence error induced was well compensated and fully adapted to. However, care might be needed when fitting these lenses unilaterally in subjects with vertical phoria‐related problems.
Clinical and experimental findings in Acanthamoeba keratitis with Heidelberg Retina Tomograph III‐RCM
Authors: Chen Zhang , Shijing Deng , Zhiqun Wang , Ran Li , Xuguang Sun 
Published: March 2008

AbstractPurpose:  To observe Acanthamoeba cysts and trophozoites in the corneal tissue of patients and rabbits with Acanthamoeba keratitis (AK), using the Heidelberg Retina Tomograph III Rostock‐cornea‐module (HRTIII‐RCM).Methods:  Eight eyes of seven patients with clinical and laboratory diagnosis of AK, presenting to the Beijing Institute of Ophthalmology between July and December 2006, were included in this study. The laboratory diagnosis in all cases was established by a cytological analysis and culture of the corneal scraping. The scanning with HRTIII‐RCM was performed on all the patients. Acanthamoeba cysts and trophozoites in the corneas of three rabbits were observed with the HRTIII‐RCM after a suspension of trophozoites was injected into the corneal stromal layer of the rabbits.Results:  Acanthamoeba cysts or trophozoites were observed with the HRTIII‐RCM in the corneas of all the patients. The size and shape of Acanthamoeba in the tissue of the rabbit corneas was consistent with that in the patients’ eyes. The Acanthamoeba cyst presented a round high‐contrast particle, 15–20 μm in diameter, with a double wall. In contrast, the trophozoite presented an irregular high‐contrast particle, without an apparent wall, 25–40 μm in diameter and with a round conspicuous nucleus.Conclusions:  HRTIII‐RCM is a useful non‐invasive clinical technique to help to diagnose and monitor the response of AK to therapy.
PE2I: A Radiopharmaceutical forIn vivoExploration of the Dopamine Transporter
Authors: Emond Patrick , Guilloteau Denis , Chalon Sylvie 
Published: March 2008

The membrane dopamine transporter (DAT) has a pivotal role in the regulation of dopamine (DA) neurotransmission involved in a number of physiological functions and brain disorders. Molecular imaging techniques, such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT), are relevant tools to explore the DAT, and we developed the cocaine derivative N‐(3‐iodopro‐2E‐enyl)‐2β‐carbomethoxy‐3β‐(4′‐methylphenyl) nortropane (PE2I) that has proved to be a very potent radiopharmaceutical to image the DAT by these techniques.Several methods are available to obtain PE2I labeled with iodine‐123 or ‐125, carbon‐11 and tritium. The pharmacological properties of PE2I have demonstrated that it has good affinity for the DAT (4 nM) and is one of the most selective DAT ligands. [125I]PE2I characterized postmortem in human brains has revealed very intense and selective binding in the basal ganglia.Ex vivoautoradiography in rats has shown that high level of [125I]PE2I accumulates in the striatum and also in the substantia nigra and ventral tegmental area. [125I]PE2I accumulation in the rat striatum is rapid, high, and selective, providing a maximum striatum/cerebellum ratio of 10 during the first 30 min post injection. Using SPECT or PET, rapid, high, and selective accumulation of PE2I was found in the caudate nucleus and putamen in monkeys, whereas rapid wash out from the cerebellum was observed.In vivoinvestigations in healthy humans have demonstrated that PE2I has high striatal uptake, low nonspecific binding, low radiation exposure, and a fairly short scanning time.A number of findings in various animal models of Parkinson's disease in rats and monkeys have demonstrated the high efficacy of PE2I for detection of reduction in the density of DAT, thus showing the potential value of PE2I for early diagnosis and evaluation of treatment of this disease. The excellent properties of PE2I are basis for the development of new DAT tracers for use in future PET explorations using fluor‐18.
A Haplotype of the DRD1 Gene Is Associated With Alcohol Dependence
Authors: Batel P. , Houchi H. , Daoust M. , Ramoz N. , Naassila M. , Gorwood P. 
Published: March 2008

Background:  The D1 dopamine receptor has been involved in a number of brain functions, including motor control, inattentive symptoms and reward and reinforcement mechanisms. Indeed, DRD1 antagonists may reduce cocaine‐seeking behavior and the acquisition of cocaine‐cue associations. The D1.1/r4532 marker of the DRD1 gene has been associated with a large set of phenotypes including addictive behaviors, but none with alcohol dependence per se.Methods:  We analyzed a population of 134 patients with alcohol dependence, also assessing more homogeneous (severe) phenotypes, comparing this sample with a healthy control population, assessing two SNPs within the DRD1 gene in order to depict the role of DRD1 polymorphisms and haplotypes.Results:  The T allele of the rs686 polymorphism within DRD1 gene was significantly more frequent in patients with alcohol dependence (p = 0.0008), with a larger excess for patients with severe dependence (p = 6 × 10−6), and even more for patients with severe complications such as withdrawal seizures (p = 7 × 10−7). A specific haplotype rs686*T‐rs4532*G within the DRD1 gene was significantly more precisely associated with alcohol dependence in our sample (p = 5 × 10−6).Conclusions:  Even though chance finding cannot be ruled out, convergent evidence is given that the DRD1 gene is a susceptibility gene in alcohol dependence, regarding the fact that relying on more homogeneous phenotypes (i.e., more severe patients) and more informative genetic markers (i.e., haplotypes) reinforce the initial association.
Ethanol Induces Apoptotic Death of β‐Endorphin Neurons in the Rat Hypothalamus by a TGF‐β1‐Dependent Mechanism
Authors: Kuhn Peter , Sarkar Dipak K. 
Published: March 2008

Background:  We have previously shown that developing β‐endorphin neurons, in the arcuate nucleus of the hypothalamus become increasingly apoptotic when exposed to ethanol. As in the previous study we have observed an involvement in transforming growth factor beta 1 (TGF‐β1) in mediation of the apoptotic process, the present study was conducted to determine the ethanol‐induced changes in this apoptotic regulatory peptide signaling in the arcuate nucleus of the hypothalamus of neonatal rats.Methods:  Pups were exposed to 11.34% ethanol in a milk‐based diet or control diet on postnatal day (PND) 3 to PND7. Two hours after the last daily feeding, brains were collected and frozen in liquid nitrogen for analysis of various apoptosis regulatory proteins in the arcuate tissue by Western blots. Some animals were fixed in 4% paraformaldehyde and analyzed immunohistochemically.Results:  Ethanol exposure increased apoptotic death of β‐endorphin neurons in the arcuate nucleus of the hypothalamus. The cell death was associated with an increase in the tissue levels of TGF‐β1 in the mediobasal hypothalamus. This was correlated with a reduction in the arcuate level of retinoblastoma protein (Rb) phosphorylation. The reduced level of Rb phosphorylation was associated with an increased protein level of the cyclin dependent kinase inhibitor p27/kip but with a decreased protein level of cyclin dependent kinase 4 and cyclin D3. In addition, the apoptotic cell death was positively correlated with the level of Bclxs but negatively correlated with the level of the Bcl2.Conclusions:  These results suggest that ethanol exposure increases TGF‐β1 signaling involving Bcl2 and Rb repression that may lead to apoptotic death of cells including β‐endorphin neurons in the arcuate nucleus of the hypothalamus.
Improving transfusion safety: implementation of a comprehensive computerized bar code–based tracking system for detecting and preventing errors
Authors: Askeland R.W. , McGrane S. , Levitt J.S. , Dane S.K. , Greene D.L. , VandeBerg J.A. , Walker K. , Porcella A. , Herwaldt L.A. , Carmen L.T. , Kemp J.D. 
Published: March 2008

BACKGROUND: To transfuse blood products safely, health care workers must accurately identify patients, blood samples, and the blood components. A comprehensive bar code–based computerized tracking system was developed and implemented to identify and prevent transfusion errors.STUDY DESIGN AND METHODS: A data network, wireless devices, and bar‐coded labels were pilot tested before the system was introduced hospitalwide. The system provided a complete audit trail for all transactions. Data from before and after implementation were analyzed.RESULTS: Incident reports decreased from a mean of 41.5 reports per month in the 6 months before the system was implemented to a mean of 7.2 reports per month after implementation. The blood sample rejection rate decreased from 1.82 percent to a mean of 0.17 percent after implementation. Errors detected by the new system were sorted into misscans, skipped steps, wrong steps, and prevented identification errors (PIEs). Misscans and skipped steps were the most common errors in the first 10 months after implementation. During the final transfusion step, PIEs occurred at the rate of about one per month and scans were omitted approximately 1 percent of the time. Therefore, it is estimated that mistransfusions could occur about once every 100 months on average with the new system.CONCLUSIONS: The bar code–based computerized tracking system detected and prevented identification and matching errors, thereby reducing the proportion of blood samples rejected and increasing patient safety.