bluuebunny/crossref_metadata_2025 huggingface dataset:
Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome: a report from the Children's Oncology Group
Authors: Maloney Kelly W. , Carroll William L. , Carroll Andrew J. , Devidas Meenakshi , Borowitz Michael J. , Martin Paul L. , Pullen Jeanette , Whitlock James A. , Willman Cheryl L. , Winick Naomi J. , Camitta Bruce M. , Hunger Stephen P.
Published: May 2010

Children with Down syndrome (DS) have an increased risk of acute lymphoblastic leukemia (ALL) and an inferior outcome. We reviewed data from 2811 children with ALL enrolled in Children's Oncology Group P9900, which included prospective testing for the major cytogenetic lesions in childhood ALL: ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL translocations and trisomies of chromosomes 4 and 10. Eighty (3%) B-precursor ALL patients had DS. Age, sex, white blood cell count, and risk group were similar between DS-ALL and non–DS-ALL but significantly more patients with DS-ALL were white (91.2% vs 76.4%, P = .001). Children with DS-ALL had lower rates of the favorable cytogenetic lesions ETV6-RUNX1 (2.5% vs 24%, P < .001) and trisomies 4 and 10 (7.7% vs 24%, P < .001). Five-year event-free (EFS) and overall survival (OS) were inferior in children with DS-ALL: 69.9% ± 8.6% versus 78.1% ± 1.2% (P = .078), and 85.8% ± 6.5% versus 90.0% ± 0.9% (P = .033). However, when children with MLL translocations, BCR-ABL1, ETV6-RUNX1, and trisomies 4 and 10 were excluded, the EFS and OS were similar for children with and without DS (EFS 68.0 %± 9.3% vs 70.5% ± 1.9%, P = .817; and OS 86.7% ± 6.7% vs 85.4% ± 1.5%; P = .852), both overall and adjusted for race. DS-ALL displays a unique spectrum of biologic subtypes with different frequencies of sentinel cytogenetic lesions having a large influence on outcome.
Constitutively active Stat5b in CD4+ T cells inhibits graft-versus-host disease lethality associated with increased regulatory T-cell potency and decreased T effector cell responses
Authors: Vogtenhuber Christine , Bucher Christoph , Highfill Steven L. , Koch Lisa K. , Goren Emily , Panoskaltsis-Mortari Angela , Taylor Patricia A. , Farrar Michael A. , Blazar Bruce R.
Published: May 2010

Overexpression of a constitutively active form of Stat5b (Stat5b-CA) increases regulatory T cells (Tregs). We show that Stat5b-CA transgenic (TG) CD4+ T cells had a markedly reduced graft-versus-host disease (GVHD) capacity versus wild-type (WT) T cells. Stat5b-CA TG versus WT CD4+ T cells had a higher proportion of Tregs, which were superior in suppressing alloresponses mediated by CD4+CD25− effector T cells (Teffs). By day 5 after transplantation, Stat5b-CA TG Tregs had expanded approximately 3-fold more than WT Tregs. Purified Stat5b-CA TG Tregs added to WT CD4+CD25− Teffs were superior on a per-cell basis for inhibiting GVHD versus WT Tregs. Surprisingly, rigorously Treg-depleted Stat5b-CA TG versus WT CD4+CD25− Teffs caused less GVHD lethality associated with diminished Teff proinflammatory and increased Th2 anti-inflammatory cytokine responses. Reduced GVHD by Stat5b-CA TG versus WT Teffs could not be explained by conversion into Tregs in day 10 posttransplantation spleen or small intestine. In addition, Stat5b-CA TG Teffs retained a graft-versus-leukemia response. These results indicate a major role for Stat5 in Treg expansion and potency along with a lesser but significant role in Teff activation and suggest a strategy of pharmacologic Stat5b up-regulation as a means of decreasing GVHD while retaining a graft-versus-leukemia effect.
A comparison of massively parallel nucleotide sequencing with oligonucleotide microarrays for global transcription profiling
Authors: Bradford James R , Hey Yvonne , Yates Tim , Li Yaoyong , Pepper Stuart D , Miller Crispin J
Published: May 2010

Background

RNA-Seq exploits the rapid generation of gigabases of sequence data by Massively Parallel Nucleotide Sequencing, allowing for the mapping and digital quantification of whole transcriptomes. Whilst previous comparisons between RNA-Seq and microarrays have been performed at the level of gene expression, in this study we adopt a more fine-grained approach. Using RNA samples from a normal human breast epithelial cell line (MCF-10a) and a breast cancer cell line (MCF-7), we present a comprehensive comparison between RNA-Seq data generated on the Applied Biosystems SOLiD platform and data from Affymetrix Exon 1.0ST arrays. The use of Exon arrays makes it possible to assess the performance of RNA-Seq in two key areas: detection of expression at the granularity of individual exons, and discovery of transcription outside annotated loci.

Results

We found a high degree of correspondence between the two platforms in terms of exon-level fold changes and detection. For example, over 80% of exons detected as expressed in RNA-Seq were also detected on the Exon array, and 91% of exons flagged as changing from Absent to Present on at least one platform had fold-changes in the same direction. The greatest detection correspondence was seen when the read count threshold at which to flag exons Absent in the SOLiD data was set to t<1 suggesting that the background error rate is extremely low in RNA-Seq. We also found RNA-Seq more sensitive to detecting differentially expressed exons than the Exon array, reflecting the wider dynamic range achievable on the SOLiD platform. In addition, we find significant evidence of novel protein coding regions outside known exons, 93% of which map to Exon array probesets, and are able to infer the presence of thousands of novel transcripts through the detection of previously unreported exon-exon junctions.

Conclusions

By focusing on exon-level expression, we present the most fine-grained comparison between RNA-Seq and microarrays to date. Overall, our study demonstrates that data from a SOLiD RNA-Seq experiment are sufficient to generate results comparable to those produced from Affymetrix Exon arrays, even using only a single replicate from each platform, and when presented with a large genome.
Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition?
Authors: van Roon Eddy HJ , van Puijenbroek Marjo , Middeldorp Anneke , van Eijk Ronald , de Meijer Emile J , Erasmus Dianhdra , Wouters Kim AD , van Engeland Manon , Oosting Jan , Hes Frederik J , Tops Carli MJ , van Wezel Tom , Boer Judith M , Morreau Hans
Published: May 2010

Background

To investigate the etiology of MLH1 promoter methylation in mismatch repair (MMR) mutation-negative early onset MSI-H colon cancer. As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer.

Methods

We studied a set of 46 MSI-H colon tumors cases with MLH1 promoter methylation which was enriched for patients with an age of onset below 50 years (n = 13). Tumors were tested for CIMP marker methylation and mutations linked to methylation: BRAF, KRAS, GADD45A and the MLH1 -93G>A polymorphism. When available, normal colon and leukocyte DNA was tested for GADD45A mutations and germline MLH1 methylation. SNP array analysis was performed on a subset of tumors.

Results

We identified two cases (33 and 60 years) with MLH1 germline promoter methylation. BRAF mutations were less frequent in colon cancer patients below 50 years relative to patients above 50 years (p-value: 0.044). CIMP-high was infrequent and related to BRAF mutations in patients below 50 years. In comparison with published controls the G>A polymorphism was associated with our cohort. Although similar distribution of the pathogenic A allele was observed in the patients with an age of onset above and below 50 years, the significance for the association was lost for the group under 50 years. GADD45A sequencing yielded an unclassified variant. Tumors from both age groups showed infrequent copy number changes and loss-of-heterozygosity.

Conclusion

Somatic or germline GADD45A mutations did not explain sporadic MSI-H colon cancer. Although germline MLH1 methylation was found in two individuals, locus-specific somatic MLH1 hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases. Our data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through somatic mutation of BRAF.
Xenon Inhibits Excitatory but Not Inhibitory Transmission in Rat Spinal Cord Dorsal Horn Neurons
Authors: Georgiev Stefan K , Furue Hidemasa , Baba Hiroshi , Kohno Tatsuro
Published: May 2010

Background:

The molecular targets for the promising gaseous anaesthetic xenon are still under investigation. Most studies identify N-methyl-D-aspartate (NMDA) receptors as the primary molecular target for xenon, but the role of α-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) receptors is less clear. In this study we evaluated the effect of xenon on excitatory and inhibitory synaptic transmission in the superficial dorsal horn of the spinal cord using in vitro patch-clamp recordings from rat spinal cord slices. We further evaluated the effects of xenon on innocuous and noxious stimuli using in vivo patch-clamp method.

Results:

In vitro, xenon decreased the amplitude and area under the curve of currents induced by exogenous NMDA and AMPA and inhibited dorsal root stimulation-evoked excitatory postsynaptic currents. Xenon decreased the amplitude, but not the frequency, of miniature excitatory postsynaptic currents. There was no discernible effect on miniature or evoked inhibitory postsynaptic currents or on the current induced by inhibitory neurotransmitters. In vivo, xenon inhibited responses to tactile and painful stimuli even in the presence of NMDA receptor antagonist.

Conclusions:

Xenon inhibits glutamatergic excitatory transmission in the superficial dorsal horn via a postsynaptic mechanism. There is no substantial effect on inhibitory synaptic transmission at the concentration we used. The blunting of excitation in the dorsal horn lamina II neurons could underlie the analgesic effect of xenon.
Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets
Authors: Mesko Bertalan , Poliskal Szilard , Szegedi Andrea , Szekanecz Zoltan , Palatka Karoly , Papp Maria , Nagy Laszlo
Published: May 2010

Background

Chronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood.

It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other.

Methods

Diseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values < 0.05).

Results

Here we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition.

Conclusions

These findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.
Two-hybrid analysis of Ty3 capsid subdomain interactions
Authors: Zhang Min , Larsen Liza SZ , Irwin Becky , Bilanchone Virginia , Sandmeyer Suzanne
Published: May 2010

Background

The yeast retrotransposon Ty3 forms stable virus-like particles. Gag3, the major structural protein, is composed of capsid, spacer and nucleocapsid domains. The capsid domain of Gag3 was previously modeled as a structure similar to retrovirus capsid.

Findings

Two-hybrid analysis was used to understand the interactions that contribute to particle assembly. Gag3 interacted with itself as predicted based on its role as the major structural protein. The N-terminal subdomain (NTD) of the capsid was able to interact with itself and with the C-terminal subdomain (CTD) of the capsid, but interacted less well with intact Gag3. Mutations previously shown to block particle assembly disrupted Gag3 interactions more than subdomain interactions.

Conclusions

The findings that the NTD interacts with itself and with the CTD are consistent with previous modeling and a role similar to that of the capsid in retrovirus particle structure. These results are consistent with a model in which the Gag3-Gag3 interactions that initiate assembly differ from the subdomain interactions that potentially underlie particle stability.
Antimicrobial anxiety: the impact of stress on antimicrobial immunity
Authors: Radek Katherine A
Published: May 2010

Review on the mechanisms behind stress-induced immune modulation of antimicrobial responses.

Leukocytes and epithelial cells are fundamental to antimicrobial immunity. Their antimicrobial responses are an evolutionarily conserved component of the innate immune system and are influenced by the host's response to external stimuli. The efficacy of host defense via antimicrobial responses derives from the ability of AMPs to rapidly identify and eradicate foreign microbes and activate proinflammatory pathways, and from the capacity of later innate and adaptive immune responses to amplify protection through distinct biochemical mechanisms. Recent advances in neuroimmunology have identified a direct link between the neuroendocrine and immune systems, where environmental stimuli are generally believed to promote a transient effect on the immune system in response to environmental challenges and are presumably brought back to baseline levels via neuroendocrine pathways. Stress is an environmental stimulus that flares from a variety of circumstances and has become engrained in human society. Small bouts of stress are believed to enhance the host's immune response; however, prolonged periods of stress can be detrimental through excess production of neuroendocrine-derived mediators that dampen immune responses to invasive pathogens. Elucidation of the mechanisms behind stress-induced immune modulation of antimicrobial responses will ultimately lead to the development of more effective therapeutic interventions for pathologic conditions. It is the intent of this review to broaden the existing paradigm of how stress-related molecules dampen immune responses through suppression of antimicrobial mechanisms, and to emphasize that bacteria can use these factors to enhance microbial pathogenesis during stress.
Sulf1A and HGF regulate satellite-cell growth
Authors: Gill Roop , Hitchins Laura , Fletcher Fenella , Dhoot Gurtej K.
Published: May 2010

The role of Sulf1A, sulfation and hepatocyte growth factor (HGF) in satellite-cell growth was examined in an in vitro model of dissociated whole skeletal muscle fibres. Pax7-positive quiescent satellite cells express little or no Sulf1A but show rapid re-expression in regenerating myoblasts and myotubes, similar to embryonic muscle and in vitro satellite cells preceding asynchronous MyoD activation. Once activated, Sulf1A and MyoD re-expression persists up to 72 hours in most satellite cells under normal culture conditions and following moderate changes in sulfation, whereas Sulf1A neutralisation by antibodies not only enhances satellite-cell proliferation but also downregulates MyoD and Pax7 expression in a large proportion of the satellite cells. The HGF exposure also induces similar but even more pronounced changes characterised by variable sulfation levels and rapid downregulation of MyoD and Pax7 without myogenin activation in a sub-set of cells. This Pax7-MyoD-myogenin-negative sub-population expresses Sulf1A and Myf5. The transfer of all such satellite-cell progenies onto gelatin-coated-substratum re-activates MyoD and Pax7 gene expression in all cells, thus detecting a distinct sub-population of satellite cells. We conclude that HGF and fine-tuned sulfation levels are major contributory factors controlling satellite-cell growth by regulating the relative activities of actively proliferating and differentiating cells.
Noradrenergic Control of Cortico-Striato-Thalamic and Mesolimbic Cross-Structural Synchrony
Authors: Dzirasa Kafui , Phillips H. Westley , Sotnikova Tatyana D. , Salahpour Ali , Kumar Sunil , Gainetdinov Raul R. , Caron Marc G. , Nicolelis Miguel A. L.
Published: May 2010

Although normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials and single-neuron activity across 10 interconnected brain areas (ventral striatum, frontal association cortex, hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute 12-fold increase in grooming. Notably, treatment with a norepinephrine precursors (l-3,4-dihydroxyphenylalanine at 100 mg/kg orl-threo-dihydroxyphenylserine at 5 mg/kg) or a selective serotonin reuptake inhibitor (fluoxetine at 20 mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE-depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striato-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.
Local Control of Postinhibitory Rebound Spiking in CA1 Pyramidal Neuron Dendrites
Authors: Ascoli Giorgio A. , Gasparini Sonia , Medinilla Virginia , Migliore Michele
Published: May 2010

Postinhibitory rebound spiking is characteristic of several neuron types and brain regions, where it sustains spontaneous activity and central pattern generation. However, rebound spikes are rarely observed in the principal cells of the hippocampus under physiological conditions. We report that CA1 pyramidal neurons support rebound spikes mediated by hyperpolarization-activated inward current (Ih), and normally masked by A-type potassium channels (KA). In both experiments and computational models,KAblockage or reduction consistently resulted in a somatic action potential upon release from hyperpolarizing injections in the soma or main apical dendrite. Rebound spiking was systematically abolished by the additional blockage or reduction ofIh. Since the density of bothKAandIhincreases in these cells with the distance from the soma, such “latent” mechanism may be most effective in the distal dendrites, which are targeted by a variety of GABAergic interneurons. Detailed computer simulations, validated against the experimental data, demonstrate that rebound spiking can result from activation of distal inhibitory synapses. In particular, partialKAreduction confined to one or few branches of the apical tuft may be sufficient to elicit a local spike following a train of synaptic inhibition. Moreover, the spatial extent and amount ofKAreduction determines whether the dendritic spike propagates to the soma. These data suggest that the plastic regulation ofKAcan provide a dynamic switch to unmask postinhibitory spiking in CA1 pyramidal neurons. This newly discovered local modulation of postinhibitory spiking further increases the signal processing power of the CA1 synaptic microcircuitry.
L-Type Voltage-Gated Ca2+Channels: A Single Molecular Switch for Long-Term Potentiation/Long-Term Depression-Like Plasticity and Activity-Dependent Metaplasticity in Humans
Authors: Wankerl Katharina , Weise David , Gentner Reinhard , Rumpf Jost-Julian , Classen Joseph
Published: May 2010

The ability of synapses to undergo persistent activity-dependent potentiation or depression [long-term potentiation (LTP)/long-term depression (LTD)] may be profoundly altered by previous neuronal activity. Although natural neuronal activity can be experimentally manipulatedin vivo, very little is known about thein vivophysiological mechanisms involved in regulating this metaplasticity in models of LTP/LTD. To examine whether Ca2+signaling may influence metaplasticityin vivoin humans, we used continuous theta burst stimulation (cTBS) (Huang et al., 2005), a noninvasive novel repetitive magnetic stimulation protocol known to induce persistent alterations of corticospinal excitability whose polarity is changed by previous voluntary motor activity. When directed to the naive motor cortex, cTBS induced long-lasting potentiation of corticospinal excitability, but depression under the influence of nimodipine (NDP), an L-type voltage-gated Ca2+channel (L-VGCC) antagonist. Both aftereffects were blocked by dextromethorphan, an NMDA receptor antagonist, supporting the notion that these bidirectional cTBS-induced alterations of corticospinal excitability map onto LTP and LTD as observed in animal studies. A short period of voluntary contraction and a small dose of NDP were each ineffective in blocking the cTBS-induced potentiation. However, when both interventions were combined, a depression was induced, and the magnitude of this depression increased with the dose of NDP. These findings suggest that Ca2+dynamics determine the polarity of LTP/LTD-like changesin vivo. L-VGCCs may act as molecular switches mediating metaplasticity induced by endogenous neuronal activation.
Sialyltransferase Regulates Nervous System Function in Drosophila
Authors: Repnikova Elena , Koles Kate , Nakamura Michiko , Pitts Jared , Li Haiwen , Ambavane Apoorva , Zoran Mark J. , Panin Vladislav M.
Published: May 2010

In vertebrates, sialylated glycans participate in a wide range of biological processes and affect the development and function of the nervous system. While the complexity of glycosylation and the functional redundancy among sialyltransferases provide obstacles for revealing biological roles of sialylation in mammals,Drosophilapossesses a sole vertebrate-type sialyltransferase,Drosophilasialyltransferase (DSiaT), with significant homology to its mammalian counterparts, suggesting thatDrosophilacould be a suitable model to investigate the function of sialylation. To explore this possibility and investigate the role of sialylation inDrosophila, we inactivated DSiaTin vivoby gene targeting and analyzed phenotypes ofDSiaTmutants using a combination of behavioral, immunolabeling, electrophysiological, and pharmacological approaches. Our experiments demonstrated that DSiaT expression is restricted to a subset of CNS neurons throughout development. We found thatDSiaTmutations result in significantly decreased life span, locomotor abnormalities, temperature-sensitive paralysis, and defects of neuromuscular junctions. Our results indicate that DSiaT regulates neuronal excitability and affects the function of a voltage-gated sodium channel. Finally, we showed that sialyltransferase activity is required for DSiaT functionin vivo, which suggests thatDSiaTmutant phenotypes result from a defect in sialylation of N-glycans. This work provided the first evidence that sialylation has an important biological function in protostomes, while also revealing a novel, nervous system-specific function of α2,6-sialylation. Thus, our data shed light on one of the most ancient functions of sialic acids in metazoan organisms and suggest a possibility that this function is evolutionarily conserved between flies and mammals.
Anatomical and Functional Connectivity of Cytoarchitectonic Areas within the Human Parietal Operculum
Authors: Eickhoff Simon B. , Jbabdi Saad , Caspers Svenja , Laird Angela R. , Fox Peter T. , Zilles Karl , Behrens Timothy E. J.
Published: May 2010

In monkeys, the somatosensory cortex on the parietal operculum can be differentiated into several distinct cortical fields. Potential human homologues for these areas have already been defined by cytoarchitectonic mapping and functional imaging experiments. Differences between the two most widely studied areas [operculum parietale (OP) 1 and OP 4] within this region particularly pertain to their connection with either the perceptive parietal network or the frontal motor areas. In the present study, we investigated differences in anatomical connection patterns probed by probabilistic tractography on diffusion tensor imaging data. Functional connectivity was then mapped by coordinate-based meta-analysis of imaging studies. Comparison between these two aspects of connectivity showed a good congruency and hence converging evidence for an involvement of these areas in matching brain networks. There were, however, also several instances in which anatomical and functional connectivity diverged, underlining the independence of these measures and the need for multimodal characterization of brain connectivity. The connectivity analyses performed showed that the two largest areas within the human parietal operculum region display considerable differences in their connectivity to frontoparietal brain regions. In particular, relative to OP 1, area OP 4 is more closely integrated with areas responsible for basic sensorimotor processing and action control, while OP 1 is more closely connected to the parietal networks for higher order somatosensory processing. These results are largely congruent with data on nonhuman primates. Differences between anatomical and functional connectivity as well as between species, however, highlight the need for an integrative view on connectivity, including comparison and cross-validation of results from different approaches.
Gambling Severity Predicts Midbrain Response to Near-Miss Outcomes
Authors: Chase Henry W. , Clark Luke
Published: May 2010

Gambling is a common recreational activity that becomes dysfunctional in a subset of individuals, with DSM “pathological gambling” regarded as the most severe form. During gambling, players experience a range of cognitive distortions that promote an overestimation of the chances of winning. Near-miss outcomes are thought to fuel these distortions. We observed previously that near misses recruited overlapping circuitry to monetary wins in a study in healthy volunteers (Clark et al., 2009). The present study sought to extend these observations in regular gamblers and relate brain responses to an index of gambling severity. Twenty regular gamblers, who varied in their involvement from recreational playing to probable pathological gambling, were scanned while performing a simplified slot machine task that delivered occasional monetary wins, as well as near-miss and full-miss nonwin outcomes. In the overall group, near-miss outcomes were associated with a significant response in the ventral striatum, which was also recruited by monetary wins. Gambling severity, measured with the South Oaks Gambling Screen, predicted a greater response in the dopaminergic midbrain to near-miss outcomes. This effect survived controlling for clinical comorbidities that were present in the regular gamblers. Gambling severity did not predict win-related responses in the midbrain or elsewhere. These results demonstrate that near-miss events during gambling recruit reward-related brain circuitry in regular players. An association with gambling severity in the midbrain suggests that near-miss outcomes may enhance dopamine transmission in disordered gambling, which extends neurobiological similarities between pathological gambling and drug addiction.
Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing Dynamics in Gonadotropin-Releasing Hormone Neurons
Authors: Lee Kiho , Duan Wen , Sneyd James , Herbison Allan E.
Published: May 2010

Gonadotropin-releasing hormone (GnRH) neurons release GnRH in a pulsatile manner to control fertility in all mammals. The mechanisms underlying burst firing in GnRH neurons, thought to contribute to pulsatile GnRH release, are not yet understood. Using minimally invasive, dual electrical–calcium recordings in acute brain slices from GnRH-Pericam transgenic mice, we find that the soma/proximal dendrites of GnRH neurons exhibit long-duration (∼10 s) calcium transients that are perfectly synchronized with their burst firing. These transients were found to be generated by calcium entry through voltage-dependent L-type calcium channels that was amplified by inositol-1,4,5-trisphosphate receptor-dependent store mechanisms. Perforated-patch current- and voltage-clamp electrophysiology coupled with mathematical modeling approaches revealed that these broad calcium transients act to control two slow afterhyperpolarization currents (sIAHP) in GnRH neurons: a quick-activating apamin-sensitive sIAHPthat regulates both intraburst and interburst dynamics, and a slow-onset UCL2077-sensitive sIAHPthat regulates only interburst dynamics. These observations highlight a unique interplay between electrical activity, calcium dynamics, and multiple calcium-regulated sIAHPs critical for shaping GnRH neuron burst firing.
Coincidence Detection and Stress Modulation of Spike Time-Dependent Long-Term Depression in the Hippocampus
Authors: Niehusmann Pitt , Seifert Gabriel , Clark Kristin , Atas Hasan C. , Herpfer Inga , Fiebich Bernd , Bischofberger Josef , Normann Claus
Published: May 2010

Associative long-term depression (LTD) in the hippocampus is a form of spike time-dependent synaptic plasticity that is induced by the asynchronous pairing of postsynaptic action potentials and EPSPs. Although metabotropic glutamate receptors (mGluRs) and postsynaptic Ca2+signaling have been suggested to mediate associative LTD, mechanisms are unclear further downstream. Here we show that either mGluR1 or mGluR5 activation is necessary for LTD induction, which is therefore mediated by group I mGluRs. Inhibition of postsynaptic phospholipase C, inositol-1,4,5-trisphosphate, and PKC prevents associative LTD. Activation of PKC by a phorbol ester causes a presynaptic potentiation of synaptic responses and facilitates LTD induction by a postsynaptic mechanism. Lithium, an inhibitor of the PKC pathway, inhibits LTD and the presynaptic and postsynaptic effects of the phorbol ester. Furthermore, LTD is sensitive to the postsynaptic application of synthetic peptides that inhibit the interaction of AMPA receptors with PDZ domains, suggesting an involvement of protein interacting with C-kinase 1 (PICK1)-mediated receptor endocytosis. Finally, enhanced PKC phosphorylation, induced by behavioral stress, is associated with enhanced LTD. Both increased PKC phosphorylation and stress-induced LTD facilitation can be reversed by lithium, indicating that this clinically used mood stabilizer may act on synaptic depression via PKC modulation. These data suggest that PKC mediates the expression of associative LTD via the PICK1-dependent internalization of AMPA receptors. Moreover, modulation of the PKC activity adjusts the set point for LTD induction in a behavior-dependent manner.
How can patients’ understanding about their surgery be improved? – Implications for everyday practice
Authors: Sobel Gábor , Langmár Zoltán , Tömösváry Zoltán , Pajor Attila , Szabó István
Published: May 2010

A pácienseink kezelésekről való tájékozottsága a megfelelő kommunikáció nagyon fontos eredménye. Az elégtelen kommunikáció félreértésekhez, aggodalomhoz és peres eljárások indításához vezethet. A betegoktatás céljából számos eszköz használható, de sebészeti beavatkozások esetében a műtétek filmre rögzítése a legmegfelelőbb.
Célkitűzés:
Vizsgálatunkban a műtéti felvételek használhatóságát kívántuk tisztázni a tájékoztatás során, a pácienseink véleménye alapján.
Betegek és módszer:
A szerzők 100, nőgyógyászati endoszkópia előtt álló pácienst kérdeztek meg, hogy beleegyeznek-e abba, hogy a műtétjükről felvétel készüljön. A szerkesztett felvételeket a kórházból való távozás előtt mutatták be a betegeknek, akik egyúttal egy kérdőívet is kitöltöttek.
Eredmények:
A csoport összes páciense beleegyezett a felvétel készítésébe, és 92 beteg kívánta a műtéti felvételt megtekinteni. A filmek átlagos hosszúsága 5 perc volt. A páciensek 88%-a gondolta úgy, hogy a felvétel megtekintése hozzásegítette őket a betegségük és a kezelés lényegének jobb megértéséhez.
Összegzés:
A szerkesztett filmfelvételek segíthetnek abban, hogy a páciensek megértsék a betegségük, illetve a kezelés lényegét. Annak ellenére, hogy ez egy időigényes tájékoztatási forma, a filmek segíthetnek továbbá abban is, hogy a családorvosok is tájékozódhassanak betegeik kezeléséről.
Epilepsy in patients with psychogenic non-epileptic seizures
Authors: Marchetti Renato Luiz , Kurcgant Daniela , Gallucci-Neto José , Von Bismark Mary Ann , Fiore Lia Arno
Published: May 2010

The aim of this study was to evaluate the frequency of epilepsy in patients who presented psychogenic non-epileptic seizures (PNES). The evaluation was carried out during intensive VEEG monitoring in a diagnostic center for epilepsy in a university hospital. The difficulties involved in reaching this diagnosis are discussed. Ninety-eight patients underwent intensive and prolonged video-electroencephalographic (VEEG) monitoring; out of these, a total of 28 patients presented PNES during monitoring. Epilepsy was defined as present when the patient presented epileptic seizures during VEEG monitoring or when, although not presenting epileptic seizures during monitoring, the patient presented unequivocal interictal epileptiform discharges. The frequency of epilepsy in patients with PNES was 50% (14 patients). Our findings suggest that the frequency of epilepsy in patients with PNES is much higher than that of previous studies, and point out the need, at least in some cases, for prolonging the evaluation of patients with PNES who have clinical histories indicating epilepsy.
Homozygotic intronic GAA mutation in three siblings with late-onset Pompe's disease
Authors: Grzesiuk Anderson Kuntz , Shinjo Sueli Mieko Oba , Silva Roseli da , Machado Marcela , Galera Marcial Francis , Marie Suely Kazue Nagahashi
Published: May 2010

Pompe's disease (PD) is a metabolic myopathy caused by the accumulation of lysosomal glycogen, secondary to acid α-glucosidase (GAA) enzyme deficiency. Childhood and late-onset forms are described, differing by the age of onset and symptoms. In this study were analyzed affected siblings with Pompe's disease (PD) and their distinct clinical and pathological presentations. METHOD: Diagnosis was performed by the clinical presentation of limb-girdle dystrophies and respiratory compromise. Confirmatory diagnoses were conducted by muscle biopsy, GAA activity measurement and by GAA gene genotyping. RESULTS: The findings suggested muscular involvement due to GAA deficiency. GAA genotyping showed they are homozygous for the c.-32-3C>A mutation. CONCLUSION: Herein we reported a family where three out of five siblings were diagnosed with late-onset PD, although it is a rare metabolic disease inherited in an autossomal recessive manner. We emphasize the importance of including this presentation within the differential diagnoses of the limb-girdle dystrophies once enzyme replacement therapy is available.
Botulinum neurotoxin type-A for primary stabbing headache: an open study
Authors: Piovesan Elcio Juliato , Teive Helio Ghizoni , Kowacs Pedro André , Silva Lucas Leite da , Werneck Lineu Cesar
Published: May 2010

Primary stabbing headache is an ultra-short headache, associated with primary headaches, more prevalent in women and with a poor response to therapy. The effect of botulinum neurotoxin type-A (BoNTA) on primary stabbing headache was investigated in 24 patients. Three patients showed complete remission. Nineteen patients showed a decrease in their primary stabbing headaches that started in the second week, and that was sustained during approximately 63 days. In two patients BoNTA showed no therapeutic effect. The BoNTA seems to be an excellent therapeutic option for primary stabbing headache.
Translation and validation into Brazilian version of the Scale of the Assessment and Rating of Ataxia (SARA)
Authors: Braga-Neto Pedro , Godeiro-Junior Clecio , Dutra Lívia Almeida , Pedroso José Luiz , Barsottini Orlando Graziani Povoas
Published: May 2010

The hereditary ataxias comprise a very large spectrum of genetically determined neurodegenerative disorders with progressive ataxia as the prominent symptom. In order to measure the severity of cerebellar ataxia in an easier and more practical way, it was proposed a new scale: the Scale for the Assessment and Rating of Ataxia (SARA). The objective of this study was to translate and validate SARA into Brazilian Portuguese. METHOD: The SARA was translated into Brazilian Portuguese, analyzed, back translated to English, and compared to the original version. It was applied to 30 patients. In addition to SARA, we applied the International Cooperative Ataxia Rating Scale (ICARS) in all subjects. RESULTS: SARA scale was translated into Brazilian version with adequate internal consistence, but a significant correlation between ICARS and SARA was not found. CONCLUSION: SARA was translated and validated into Brazilian Portuguese language, showing good reliability and validity.
Olfactory function and Parkinson's disease in Southern Brazil
Authors: Santin Ricardo , Fonseca Vicente Faraon , Bleil Cristina Birlen , Rieder Carlos R.M. , Hilbig Arlete
Published: May 2010

The idiopathic Parkinson disease (IPD) is traditionally diagnosed by motor signs, but non-motor symptoms and signs are frequent and may help in the clinical diagnosis. PURPOSE: To evaluate the olfactory function in Brazilian healthy subjects, patients with early-onset PD (EOPD) and late-onset PD (LOPD) using the Sniffin' Sticks odor-identification test (SST). METHOD: We studied 70 patients with IPD (19 EOPD and 51 LOPD) and 70 controls matched for gender, age and years of schooling. Subjects with dementia and loss of smell for other reasons were excluded. RESULTS: The SST showed a significant difference (p<0.001) between groups: control groups (12.0±0.3), EOPD (8.3±0.7), and LOPD (6.7±0.4) when the groups were adjusted for gender, age, disease duration, and years of schooling. CONCLUSION: Both groups of IPD patients presented olfactory impairments, but those whose symptoms started before 45 years-old (EOPD) had better sense of smell than the LOPD patients.
Amyotrophic lateral sclerosis: prospective study on respiratory parameters
Authors: Almeida Sara Regina Meira , Silva Luciano Bruno C. , Guerreiro Carlos Alberto M. , Nucci Anamarli
Published: May 2010

OBJECTIVE: To verify how efficient respiratory parameters are in the follow-up of subjects with amyotrophic lateral sclerosis (ALS) and to observe possible correlations between respiratory and nutritional functions. METHOD: Sixteen patients with probable or defined ALS were selected and evaluated over eight months using the following respiratory parameters: spirometry, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), arterial gasometry and pulse oximetry; and nutritional parameters such as body mass index (BMI) and percentage weight loss. RESULTS: PaCO2 was a significant parameter to follow up disease evolution (p=0.051). There was significant correlation between MIP and MEP (r: 0.83); BMI and MIP (r: 0.70); BMI and MEP (r: 0.72); pulse oximetry and forced vital capacity (r: 0.57). CONCLUSION: PaCO2 was shown to be an efficient and significant parameter in the measurement of respiratory impairment; the correlations among MIP, MEP and BMI indicated that these are significant parameters for periodic clinical evaluation.
Crecimiento en clavel estándar cv. Nelson, en suelo y en sustratos
Authors: Argüello Adriana Del Pilar Baracaldo , Ovalle Alejandra Ibagué , Roncancio Víctor Julio Flórez , Cordoba Bernardo Chaves
Published: May 2010

El cultivo de clavel en la sabana de Bogotá ha sido importante, ya que representa en la actualidad el segundo lugar de exportación en flores de corte. Recientemente, su producción en sistema de cultivo en sustrato ha aumentado debido fundamentalmente a limitantes de tipo sanitario, por lo cual es importante el estudio del crecimiento de las plantas establecidas en este sistema de cultivo. El objetivo de este estudio fue evaluar el crecimiento del clavel estándar cv. Nelson establecido en sustratos y en suelo, a segundo pico de cosecha, para lo cual, en el SENA - Centro Multisectorial de Mosquera, plantas de clavel se sometieron a los siguientes tratamientos: 100% de cascarilla de arroz quemada; 65% cascarilla de arroz quemada - 35% fibra de coco; 35% cascarilla de arroz quemada - 65% fibra de coco y suelo. En muestreos continuos se evaluaron las variables número de hojas, longitud del tallo, diámetro de tallo, número de nudos y diámetro y longitud del botón floral y se ajustaron curvas de crecimiento. Las plantas cultivadas en el tratamiento suelo presentaron mayor número de tallos. En este tratamiento los tallos florales también presentaron un mayor número de nudos y de hojas; sin embargo, fueron más cortos. Así mismo, presentaron menor diámetro de tallo y menor longitud y diámetro del botón floral; características determinantes de la calidad. Por tanto, la producción de tallos exportables de grado "select" fue significativamente inferior en el tratamiento suelo, en comparación con los demás tratamientos.
Composição de aminoácidos de gerações precoces de feijão obtidas a partir de cruzamentos com parental de alto teor de metionina
Authors: Ribeiro Nerinéia Dalfollo , Londero Patrícia Medianeira Grigoletto , Cargnelutti Filho Alberto , Jost Evandro
Published: May 2010

O objetivo deste trabalho foi avaliar a composição de aminoácidos de gerações precoces de feijão, obtidas a partir de cruzamentos com parental de alto teor de metionina, e selecionar plantas F2 para o desenvolvimento de populações segregantes com alto teor de metionina. A partir do cruzamento entre BRS Valente e IAPAR 44 foram obtidas as gerações F1, F1 recíproco, F2, F2 recíproco, retrocruzamento 1 e retrocruzamento 2. Os aminoácidos foram quantificados por cromatografia líquida de alta eficiência (CLAE) e os dados obtidos foram submetidos à análise de variância e de variáveis canônicas. Os aminoácidos - ácido aspártico, ácido glutâmico, glicina, prolina, tirosina, cisteína, metionina e treonina - apresentaram variabilidade genética. Gerações precoces com alto teor de metionina foram obtidas sem que tenha havido limitação na disponibilidade dos demais aminoácidos essenciais. As duas primeiras variáveis canônicas explicaram 99,28% da variação total dos genótipos e três grupos foram formados. Plantas da geração F2 poderão ser selecionadas pelo programa de melhoramento para o desenvolvimento de populações segregantes de feijão com alto teor de metionina.
Persistência do herbicida sulfentrazone em solo cultivado com cana-de-açúcar
Authors: Blanco Flávio Martins Garcia , Velini Edivaldo Domingues , Batista Filho Antonio
Published: May 2010

O objetivo do trabalho foi determinar o comportamento do herbicida sulfentrazone em solo franco-argilo-arenoso cultivado com cana-de-açúcar. O delineamento experimental foi o de blocos ao acaso com cinco repetições e três tratamentos de sulfentrazone (0,0; 0,6 e 1,2 kg ha-1), aplicado como pré-emergente. Foram coletadas periodicamente amostras de solo (0-10 cm), em 23 épocas entre 0 e 704 dias após o tratamento (DAT). O comportamento do herbicida sulfentrazone foi avaliado por bioensaios usando a beterraba como planta-teste, sendo determinada que para a menor dose (0,6 kg ha-1), o herbicida persistiu até 601 DAT. Para a dose de 1,2 kg ha-1, até o fim do ensaio aos 704 DAT, o herbicida ainda persistia. A persistência do herbicida sulfentrazone no solo é longa e proporcional à dose aplicada.
Enraizamento de estacas de duas cultivares de oliveira submetidas à aplicação de diferentes fertilizantes
Authors: Oliveira Marcelo Caetano de , Vieira Neto João , Oliveira Ricardo de Souza , Pio Rafael , Oliveira Nilton Caetano de , Ramos José Darlan
Published: May 2010

Estacas semilenhosas com aproximadamente 12 cm de comprimento e quatro folhas coletadas na região mediana da copa em plantas de oliveira das cultivares Ascolano 315 e Arbequina, foram preparadas, e em seguida tratadas com 3000 mg L-1 de AIB por cinco segundos. O ensaio foi realizado em estufa, com sistema de nebulização intermitente, sendo as estacas colocadas em bandejas, contendo a perlite como substrato de enraizamento. Utilizando-se delineamento inteiramente casualizado, em esquema fatorial 2 x 7, com quatro repetições, avaliaram-se as duas cultivares de oliveira e seis fertilizantes (Biofertilizante, Nippoterra, Fert Bokashi e Ativo, na proporção de 25 mL L-1 e Nutricafé e Rocksil, na proporção de 25 g L-1), além do controle sem fertilizante. Os produtos foram aplicados nas parcelas experimentais antes da estaquia, com regador manual, em dosagem única. Passados 67 dias, foi avaliada a percentagem de estacas com calo e enraizadas e o número e comprimento médio das raízes. Concluiu-se que o Biofertilizante propiciou melhores resultados, em comparação aos demais fertilizantes e que a cultivar Ascolano 315 foi a que teve melhores taxas de enraizamento.
Transporte de fósforo pela enxurrada em latossolo que recebeu lodo de esgoto
Authors: Costa Vanessa Leonel da , Maria Isabella Clerici de , Camargo Otávio Antonio de
Published: May 2010

O aporte de fósforo (P) no escoamento superficial em áreas fertilizadas está associado à eutrofização dos corpos de água. Para estudar as transferências de P para o ambiente hídrico foram avaliadoso solo, a água de enxurrada, os sedimentos e o solo de um Latossolo de textura argilosa que tem recebido aplicação de adubo mineral e de lodo de esgoto. Na enxurrada foram determinadas as concentrações de P dissolvido (inorgânico e orgânico), particulado e total. Nos sedimentos, determinaram-se os teores de P disponível e P total. No solo, além do P-Resina, foram avaliados os teores de Al, Fe e P para estimar a capacidade de adsorção de P (CAP) e o grau de saturação de P (GSP) do solo. A aplicação de lodo aumentou os teores de P no solo refletindo no aumento do GSP. Os teores de P detectados na enxurrada não se correlacionaram com o GSP e os altos teores de P no solo que recebeu lodo não contribuíram para aumentar seu transporte. As intensidades das chuvas não influenciaram as concentrações das formas de P na enxurrada onde houve aplicação de lodo de esgoto. As perdas totais de P pela erosão foram maiores na enxurrada do que nos sedimentos arrastados.