bluuebunny/crossref_metadata_2025_split huggingface dataset:
SATB2 interacts with chromatin‐remodeling molecules in differentiating cortical neurons
Authors: Gyorgy Andrea B. , Szemes Marianna , De Juan Romero Camino , Tarabykin Victor , Agoston Denes V. 
Published: March 2008

AbstractDuring our search for developmental regulators of neuronal differentiation, we identified special AT‐rich sequence‐binding protein (SATB)2 that is specifically expressed in the developing rat neocortex and binds to AT‐rich DNA elements. Here we investigated whether the regulatory function of SATB2 involves chromatin remodeling at the AT‐rich DNA site. In‐vitro and in‐vivo assays using a DNA affinity pre‐incubation specificity test of recognition and chromatin immunoprecipitation showed that SATB2 specifically binds to histone deacetylase 1 and metastasis‐associated protein 2, members of the nucleosome‐remodeling and histone deacetylase complex. Double immunohistochemistry showed that, in the developing rat neocortex, SATB2 is coexpressed with both proteins. Using a cell culture model, we showed that trichostatin A treatment, which blocks the activities of histone deacetylases, reverses the AT‐rich dsDNA‐dependent repressor effect of SATB2. These findings suggested that the molecular regulatory function of SATB2 involves modification of the chromatin structure. Semi‐quantitative chromatin immunoprecipitation analysis of cortices from SATB2 mutant and wild‐type animals indicated that, in the knock‐out brains, SATB2 is replaced in the chromatin‐remodeling complex by AU‐rich element RNA binding protein 1, another AT‐rich DNA binding protein also expressed in differentiating cortical neurons. These results suggested that an altered chromatin structure, due to the presence of different AT‐rich DNA binding proteins in the chromatin‐remodeling complex, may contribute to the developmental abnormalities observed in the SATB2 mutant animals. These findings also raised the interesting possibility that SATB2, along with other AT‐rich DNA binding proteins, is involved in mediating epigenetic influences during cortical development.
Contextual integration the unusual way: a magnetoencephalographic study of responses to semantic violation in individuals with autism spectrum disorders
Authors: Braeutigam Sven , Swithenby Stephen J. , Bailey Anthony J. 
Published: March 2008

AbstractAutism is a neurodevelopmental disorder associated with deficits in language and social communication. Behavioural studies indicate abnormal semantic organization in individuals with autism, but little is known about the neural mechanism underlying the processing of language in context. Magnetoencephalography was used to record neural responses in 11 able adults with autism spectrum disorders reading meaningful sentences and sentences ending with a semantically incongruous word (e.g. ‘He sent a photo to the trumpet’). Spatially extended evoked signals at 400 ms (N4) and 750 ms (LPC), as well as synchronized gamma‐oscillations, provided clear evidence for specific neuronal processes sensitive to sentence context that differed in individuals with autism compared with typically developing individuals (11 healthy volunteers). Amongst other differences, N4 responses following incongruous words were weaker over left temporal cortices, whereas LPC responses to incongruous words and long‐latency gamma‐oscillations following congruous words were stronger over central and prefrontal regions in individuals with autism compared with the control group. Also, incongruous words elicited long‐lasting gamma‐oscillations above 40 Hz in the clinical group, but not in typically developing subjects. These findings may indicate unusual strategies for resolving semantic ambiguity in autism. Moreover, the observed gamma‐band responses provide evidence for sustained cortical synchronization across segregated areas in individuals with autism, contrary to claims that a general deficit in either temporal binding or long‐range connectivity may explain autism.
Ro5‐4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats
Authors: Mills Charles , Makwana Milan , Wallace Adam , Benn Susanna , Schmidt Helmut , Tegeder Irmgard , Costigan Michael , Brown Robert H , Raivich Gennadij , Woolf Clifford J. 
Published: March 2008

AbstractThe translocator protein (18 kDa; TSPO), formerly known as the peripheral benzodiazepine receptor, is an outer mitochondrial membrane protein that associates with the mitochondrial permeability transition pore to regulate both steroidogenesis and apoptosis. TSPO expression is induced in adult dorsal root ganglion (DRG) sensory neurons after peripheral nerve injury and a TSPO receptor ligand, Ro5‐4864, enhances DRG neurite growth in vitro and axonal regeneration in vivo. We have now found that TSPO is induced in neonatal motor neurons after peripheral nerve injury and have evaluated its involvement in neonatal and adult sensory and motor neuron survival, and in adult motor neuron regeneration. The TSPO ligand Ro5‐4864 rescued cultured neonatal DRG neurons from nerve growth factor withdrawal‐induced apoptosis and protected neonatal spinal cord motor neurons from death due to sciatic nerve axotomy. However, Ro5‐4864 had only a small neuroprotective effect on adult facial motor neurons after axotomy, did not delay onset or prolong survival in SOD1 mutant mice, and failed to protect adult DRG neurons from sciatic nerve injury‐induced death. In contrast, Ro5‐4864 substantially enhanced adult facial motor neuron nerve regeneration and restoration of function after facial nerve axotomy. These data indicate a selective sensitivity of neonatal sensory and motor neurons to survival in response to Ro5‐4864, which highlights that survival in injured immature neurons cannot necessarily predict success in adults. Furthermore, although Ro5‐4864 is only a very weak promoter of survival in adult neurons, it significantly enhances regeneration and functional recovery in adults.
Neuronal field potential in acute hippocampus slice recorded with transistor and micropipette electrode
Authors: Stangl Christian , Fromherz Peter 
Published: March 2008

AbstractArrays of planar electrodes are often applied to record spatial patterns of neuronal field potentials in acute brain slices. The approach is hampered by layers of inactive tissue caused by the cutting process and also by a film of bath electrolyte that may exist between the slice and the substrate. To address this issue, we used a micropipette electrode to measure the vertical profile of evoked field potentials across acute slices from mouse hippocampus. In this way, we found that the signal due to an excitatory postsynaptic potential (EPSP) at the bottom of the slice was about 40% of the maximum at its centre. The vertical profile was matched by a volume‐conductor model with proper boundary conditions. Simultaneously, voltage transients caused by EPSPs were measured with a field‐effect transistor in the substrate. The transistor signals were in agreement with the evoked field potentials at the bottom of the slice. The study demonstrates: (i) that the loss of signal amplitude from the centre of a slice to the bottom is modest, despite an inactive tissue layer; and (ii) that in principle, planar sensors are able to record the field potential at the bottom of a slice. The results raise questions about the small voltages that are often observed with planar metal electrodes and about the reconstruction of the neuronal activity from field potentials at the bottom of acute slices using current‐source density analysis.
Personality‐dependent dissociation of absolute and relative loss processing in orbitofrontal cortex
Authors: Fujiwara Juri , Tobler Philippe N. , Taira Masato , Iijima Toshio , Tsutsui Ken‐Ichiro 
Published: March 2008

AbstractA negative outcome can have motivational and emotional consequences on its own (absolute loss) or in comparison to alternative, better, outcomes (relative loss). The consequences of incurring a loss are moderated by personality factors such as neuroticism and introversion. However, the neuronal basis of this moderation is unknown. Here we investigated the neuronal basis of loss processing and personality with functional magnetic resonance imaging in a choice task. We separated absolute and relative financial loss by sequentially revealing the chosen and unchosen outcomes. With increasing neuroticism, activity in the left lateral orbitofrontal cortex (OFC) preferentially reflected relative rather than absolute losses. Conversely, with increasing introversion, activity in the right lateral OFC preferentially reflected absolute rather than relative losses. These results suggest that personality affects loss‐related processing through the lateral OFC, and propose a dissociation of personality dimension and loss type on the neuronal level.
Developmental regulation of the morphology of mouse retinal horizontal cells by visual experience
Authors: Lee Eun‐Jin , Padilla Monica , Merwine David K. , Grzywacz Norberto M. 
Published: March 2008

AbstractVisual deprivation during development alters the normal refinement of connections, neurotransmitter expression and physiological function in the retina. We investigated the effects of different forms of visual experience on the anatomy of retinal neurons in the mouse. Although it is generally assumed that outer retinal cells are not affected morphologically by visual experience, we found changes in the outer retinas of animals reared with light but no contrast. In postnatal day 30 animals reared in control, dark and high‐contrast environments, horizontal‐cell processes ramified normally in the outer plexiform layer. However, in postnatal day 30 no‐contrast‐reared retinas, horizontal‐cell processes emerged from the outer plexiform layer and ramified in the inner nuclear layer. Similar sprouting processes of horizontal cells were found in a mouse model of retinitis pigmentosa. In conclusion, our data show that a lack of contrast during development alters the morphology of horizontal cells and may thus affect normal visual processing. This effect may be relevant for young patients with cloudy vision (e.g. cataract).
Activation of dopamine D1‐like receptors in nucleus accumbens is critical for the acquisition, but not the expression, of nutrient‐conditioned flavor preferences in rats
Authors: Touzani Khalid , Bodnar Richard , Sclafani Anthony 
Published: March 2008

AbstractThe present study investigated the role of dopamine neurotransmission within the nucleus accumbens (NAc) in flavor preference learning induced by the postoral consequences of carbohydrates. In Experiment 1, rats fitted with a gastric catheter were trained with a flavor (CS+) paired with intragastric (IG) infusions of 8% glucose and a different flavor (CS–) paired with IG water infusions. The CS+ preference was then evaluated in two‐bottle preference tests following bilateral injection of the dopamine D1‐like receptor antagonist SCH23390 into the NAc shell at total doses of 0, 12, 24 and 48 nmol. SCH23390 produced dose‐related reductions in CS+ intake but did not block the CS+ preference except at the highest dose, which also greatly suppressed the CS intakes. In Experiment 2, new rats were injected daily in the NAc shell with either saline or SCH23390 (12 nmol), 10 min prior to training sessions with CS+ with IG glucose and CS– with IG water. In the two‐bottle preference tests, the drug‐treated rats, unlike the control rats, did not significantly prefer the CS+ (61 vs. 83% preference). In Experiment 3, new rats were trained with the same procedures as Experiment 2, except that brain injections were in the NAc core. In contrast to control rats, SCH‐treated rats failed to prefer the CS+ to the CS– in two‐bottle tests (55% vs. 89% preference). These results demonstrate that D1‐like receptors in the NAc shell and core are greatly involved in the acquisition, but less so in the expression, of a flavor preference conditioned by postingestive effects of glucose.
Effects of blood sample volume on hematocrit in critically ill children and neonates
Authors: LISTER PAULA , PETERS MARK J , PETROS ANDY J 
Published: March 2008

SummaryBackground:  There are no studies correlating the volume of blood taken from children and hematocrit (Hct) stability, relating those changes to duration of stay, severity of illness or weight. Earlier studies in neonates suggest that repeated sampling results in a drop in Hct.Aim:  To characterize the changes in Hct in children of all ages admitted to intensive care over a 5‐day period following routine blood volume sampling.Methods:  We undertook an open prospective observational study. Eligible children were recruited sequentially and data recorded for 5 days following admission. The bedside nurse recorded the daily volume of blood samples taken and transfusions given. Daily Hct was noted from the routine full blood count. The relationship between changes in Hct and blood sample volume and transfusion requirement was studied.Results:  There were no differences in mean Hct on admission at end of the study (P = 0.69, n = 30) nor in the median blood volume sampled between transfused and nontransfused groups (7.5 ml·kg−1 vs 7.9 ml·kg−1, P = 0.88). The largest blood sample volumes were taken on admission and from the smallest patients.Conclusion:  We have quantitated the change in Hct and size of blood volume taken for routine laboratory studies. We suggest that children can tolerate 0.25 ml·kg−1·day−1 blood sampling without a fall in Hct and sampling can be tailored to the individual child according to the admission Hct.
Combination of the insulin sensitizer, pioglitazone, and the long‐acting GLP‐1 human analog, liraglutide, exerts potent synergistic glucose‐lowering efficacy in severely diabetic ZDF rats
Authors: Larsen P. J. , Wulff E. M. , Gotfredsen C. F. , Brand C. L. , Sturis J. , Vrang N. , Knudsen L. B. , Lykkegaard K. 
Published: March 2008

Objective:  Severe insulin resistance and impaired pancreatic β‐cell function are pathophysiological contributors to type 2 diabetes, and ideally, antihyperglycaemic strategies should address both.Research Design and Methods:  Therapeutic benefits of combining the long‐acting human glucagon‐like peptide‐1 (GLP‐1) analog, liraglutide (0.4 mg/kg/day), with insulin sensitizer, pioglitazone (10 mg/kg/day), were assessed in severely diabetic Zucker diabetic fatty rats for 42 days. Impact on glycaemic control was assessed by glycated haemoglobin (HbA1C) at day 28 and by oral glucose tolerance test at day 42.Results:  Liraglutide and pioglitazone synergistically improved glycaemic control as reflected by a marked decrease in HbA1C (liraglutide + pioglitazone: 4.8 ± 0.3%; liraglutide: 8.8 ± 0.6%; pioglitazone: 7.9 ± 0.4%; vehicle: 9.7 ± 0.3%) and improved oral glucose tolerance at day 42 (area under the curve; liraglutide + pioglitazone: 4244 ± 445 mmol/l × min; liraglutide: 7164 ± 187 mmol/l × min; pioglitazone: 7430 ± 446 mmol/l × min; vehicle: 8093 ± 139 mmol/l × min). A 24‐h plasma glucose profile at day 38 was significantly decreased only in the liraglutide + pioglitazone group. In addition, 24‐h insulin profile was significantly elevated only in the liraglutide + pioglitazone group. Liraglutide significantly decreased food intake alone and in combination with pioglitazone, while pioglitazone alone increased cumulated food intake. As a result, rats on liraglutide alone gained significantly less weight than vehicle‐treated rats, whereas rats on pioglitazone alone gained significantly more body weight than vehicle‐treated rats. However, combination therapy with liraglutide and pioglitazone caused the largest weight gain, probably reflecting marked improvement of energy balance because of reduction of glucosuria.Conclusions:  Combination therapy with insulinotropic GLP‐1 agonist liraglutide and insulin sensitizer, pioglitazone, improves glycaemic control above and beyond what would be expected from additive effects of the two antidiabetic agents.
BRAIN DEATH AND ITS ENTANGLEMENTS
Authors: Haque Omar Sultan 
Published: March 2008

ABSTRACTThe Islamic philosophical, mystical, and theological sub‐traditions have each made characteristic assumptions about the human person, including an incorporation of substance dualism in distinctive manners. Advances in the brain sciences of the last half century, which include a widespread acceptance of death as the end of essential brain function, require the abandonment of dualistic notions of the human person that assert an immaterial and incorporeal soul separate from a body. In this article, I trace classical Islamic notions of death and the soul, the modern definition of death as “brain death,” and some contemporary Islamic responses to this definition. I argue that a completely naturalistic account of human personhood in the Islamic tradition is the best and most viable alternative for the future. This corporeal monistic account of Muslim personhood as embodied consciousness incorporates the insights of pre‐modern Muslim thinkers yet rehabilitates their characteristic mistakes and thus has the advantages of neuroscientific validity and modern relevance in trans‐cultural ethical discourse; it also helps to alleviate organ shortages in countries with majority Muslim populations, a serious ethical impasse of recent years.
A Flexible Marginal Modelling Strategy for Non-Monotone Missing Data
Authors: Jansen Ivy , Molenberghs Geert 
Published: March 2008

SummaryMuch research has been devoted to modelling strategies for longitudinal data with missingness, recently especially within the missingness not at random context. In this paper, the relatively unexplored but practically highly relevant domain of non-monotone missingness with multivariate ordinal responses is broached. For this, a dedicated version of the multivariate Dale model is formulated. Furthermore, we also assess the sensitivity of these models to their assumptions, by using the technique of global influence.
Lopinavir/ritonavir monotherapy as maintenance treatment in HIV‐infected individuals with virological suppression: results from a pilot study in Brazil
Authors: Sprinz E , Bay MB , Lazzaretti RK , Jeffman MW , Mattevi VS 
Published: March 2008

ObjectiveThe aim of the study was to evaluate the possibility of using lopinavir/ritonavir (LPV/RTV) alone as maintenance therapy in HIV‐infected individuals with virological suppression.DesignThis was a single‐armed single‐centre pilot trial.MethodsAsymptomatic HIV‐infected patients on highly active antiretroviral therapy (HAART) including LPV/RTV, and with plasma HIV RNA <40 copies/mL for at least 6 months, were enrolled in the study, during which they continued with LPV/RTV alone. The intention was to recruit 25 patients to be followed for 2 years. Viral failure was defined as two consecutive HIV RNA measurements >40 copies/mL. Nadir and baseline CD4 cell counts, highest ever HIV RNA load, time with undetectable viraemia before monotherapy, number of previous antiretroviral (ARV) regimens, and gene polymorphism at CYP3A4 and CYP3A5 were evaluated.ResultsAll patients (27) completed the study. Their median age was 43 years, and 66% were men. Ten patients (37%) failed to maintain virological suppression (the median time to HIV rebound was 10.5 months, with a range of 4–23 months). One patient developed full resistance to LPV and another developed neurocognitive impairment while on LPV/RTV which improved after HAART reintroduction. There were no differences between failures and nonfailures according to the analysed parameters. Patients with viral failure were successfully resuppressed.ConclusionsLPV/RTV maintenance therapy was associated with 37% failure, a higher than expected failure rate. In order to ensure that unnecessary risks are not being taken in patients on LPV/RTV, this finding should be further evaluated in large randomized trials for longer periods of follow‐up.
Presentation, diagnosis and management of tuberculosis in HIV‐infected children in the UK
Authors: Cohen JM , Whittaker E , Walters S , Lyall H , Tudor‐Williams G , Kampmann B 
Published: March 2008

ObjectivesManagement of HIV‐infected children with tuberculosis (TB) is challenging. The objective of this study was to assess current treatment and outcomes in a resource‐rich setting in the era of highly active antiretroviral therapy (HAART).MethodsA retrospective case‐note review of coinfected children was carried out in a large UK‐based HIV family clinic.ResultsOf 328 HIV‐infected children, 18 were diagnosed and treated for active TB.TB presentation led to HIV diagnosis in eight of these 18 children. TB was confirmed microbiologically in 33% of children. Fifteen of the 18 children presented with pulmonary TB, and three with extrapulmonary TB (EPTB). Immunological status at TB diagnosis did not predict EPTB. The mean CD4 T‐cell count at TB presentation was 402 cells/μL (mean CD4 percentage 16%), with a range of 0–790 cells/μL (0–34%). In seven children concurrently treated with HAART and anti‐tuberculous therapy (ATT), therapeutic drug monitoring (TDM) guided management. No immune reconstitution disease occurred. There was one death, unrelated to TB, 2 years after completion of ATT.ConclusionsAn HIV test should be considered in all children diagnosed with TB, especially if there are epidemiological risk factors. Our experience shows that, even with deferral of HAART in concurrently infected children, good therapeutic responses to ATT can be achieved. Where necessary, TDM guiding concurrent HAART and ATT can facilitate good clinical and virological responses.
Predictors (0–10 months) of psychopathology at age 1½ years – a general population study in The Copenhagen Child Cohort CCC 2000*
Authors: Skovgaard A.M. , Olsen E.M. , Christiansen E. , Houmann T. , Landorph S.L. , Jørgensen T. ,   the CCC 2000* Study Group
Published: March 2008

Background:  Epidemiological studies of mental health problems in the first years of life are few. This study aims to investigate infancy predictors of psychopathology in the second year of life.Methods:  A random general population sample of 210 children from the Copenhagen Child Birth Cohort CCC 2000 was investigated by data from National Danish registers and data collected prospectively from birth in a general child health surveillance programme. Mental health outcome at 1½ years was assessed by clinical and standardised measures including the Child Behavior Check List 1½–5 (CBCL 1½–5), Infant Toddler Symptom Check List (ITSCL), Checklist for Autism in Toddlers (CHAT), Bayley Scales of Infant Development (BSID II), Mannheim Eltern Interview (MEI), Parent Child Early Relational Assessment (PC ERA) and Parent Infant Relationship Global Assessment Scale (PIR‐GAS), and disordered children were diagnosed according to the International Classification of Diseases (ICD‐10) and Diagnostic Classification Zero to Three (DC: 0–3).Results:  Deviant language development in the first 10 months of life predicted the child having any disorder at 1½ years, OR 3.3 (1.4–8.0). Neuro‐developmental disorders were predicted by deviant neuro‐cognitive functioning, OR 6.8 (2.2–21.4), deviant language development, OR 5.9 (1.9–18.7) and impaired social interaction and communication, OR 3.8 (1.3–11.4). Unwanted pregnancy and parents’ negative expectations of the child recorded in the first months of the child's life were significant predictors of relationship disturbances at 1½ years.Conclusions:  Predictors of neuro‐developmental disorders and parent–child relationship disturbances can be identified in the first 10 months of life in children from the general population.