bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dorsal Raphe Modulates Sensory Responsiveness during Arousal in Zebrafish
Authors: Yokogawa Tohei , Hannan Markus C. , Burgess Harold A.
Published: October 2012

During waking behavior, animals adapt their state of arousal in response to environmental pressures. Sensory processing is regulated in aroused states, and several lines of evidence imply that this is mediated at least partly by the serotonergic system. However, there is little information directly showing that serotonergic function is required for state-dependent modulation of sensory processing. Here we find that zebrafish larvae can maintain a short-term state of arousal during which neurons in the dorsal raphe modulate sensory responsiveness to behaviorally relevant visual cues. After a brief exposure to water flow, larvae show elevated activity and heightened sensitivity to perceived motion. Calcium imaging of neuronal activity after flow revealed increased activity in serotonergic neurons of the dorsal raphe. Genetic ablation of these neurons abolished the increase in visual sensitivity during arousal without affecting baseline visual function or locomotor activity. We traced projections from the dorsal raphe to a major visual area, the optic tectum. Laser ablation of the tectum demonstrated that this structure, like the dorsal raphe, is required for improved visual sensitivity during arousal. These findings reveal that serotonergic neurons of the dorsal raphe have a state-dependent role in matching sensory responsiveness to behavioral context.
Deficiency of the Microglial Receptor CX3CR1 Impairs Postnatal Functional Development of Thalamocortical Synapses in the Barrel Cortex
Authors: Hoshiko Maki , Arnoux Isabelle , Avignone Elena , Yamamoto Nobuhiko , Audinat Etienne
Published: October 2012

Accumulative evidence indicates that microglial cells influence the normal development of brain synapses. Yet, the mechanisms by which these immune cells target maturating synapses and influence their functional development at early postnatal stages remain poorly understood. Here, we analyzed the role of CX3CR1, a microglial receptor activated by the neuronal chemokine CX3CL1 (or fractalkine) which controls key functions of microglial cells. In the whisker-related barrel field of the mouse somatosensory cortex, we show that the recruitment of microglia to the sites where developing thalamocortical synapses are concentrated (i.e., the barrel centers) occurs only after postnatal day 5 and is controlled by the fractalkine/CX3CR1 signaling pathway. Indeed, at this developmental stage fractalkine is overexpressed within the barrels and CX3CR1 deficiency delays microglial cell recruitment into the barrel centers. Functional analysis of thalamocortical synapses shows that CX3CR1 deficiency also delays the functional maturation of postsynaptic glutamate receptors which normally occurs at these synapses between the first and second postnatal week. These results show that reciprocal interactions between neurons and microglial cells control the functional maturation of cortical synapses.
Pleiotrophin Suppression of Receptor Protein Tyrosine Phosphatase-β/ζ Maintains the Self-Renewal Competence of Fetal Human Oligodendrocyte Progenitor Cells
Authors: McClain Crystal R. , Sim Fraser J. , Goldman Steven A.
Published: October 2012

Oligodendrocyte progenitor cells (OPCs) persist in human white matter, yet the mechanisms by which they are maintained in an undifferentiated state are unknown. Human OPCs differentially express protein tyrosine phosphatase receptor β/ζ (PTPRZ1) and its inhibitory ligand, pleiotrophin, suggesting the maintenance of an autocrine loop by which PTPRZ1 activity is tonically suppressed. PTPRZ1 constitutively promotes the tyrosine dephosphorylation of β-catenin and, thus, β-catenin participation in T cell factor (TCF)-mediated transcription. Using CD140a/PDGFRα-based fluorescence-activated cell sorting to isolate fetal OPCs from the fetal brain at gestational ages 16–22 weeks, we asked whether pleiotrophin modulated the expansion of OPCs and, if so, whether this was effected through the serial engagement of PTPRZ1 and β-catenin-dependent signals, such as TCF-mediated transcription. Lentiviral shRNAi knockdown of PTPRZ1 induced TCF-mediated transcription and substantially augmented GSK3β inhibition-induced TCF-reporter luciferase expression, suggesting dual regulation of β-catenin and the importance of PTPRZ1 as a tonic brake upon TCF-dependent transcription. Pharmacological inhibition of GSK3β triggered substrate detachment and initiated sphere formation, yet had no effect on either proliferation or net cell number. In contrast, pleiotrophin strongly potentiated the proliferation of CD140a+-sorted OPCs, as did PTPRZ1 knockdown, which significantly increased the total number of population doublings exhibited by OPCs before mitotic senescence. These observations suggest that pleiotrophin inhibition of PTPRZ1 contributes to the homeostatic self-renewal of OPCs and that this process is mediated by the tonic activation of β-catenin/TCF-dependent transcription.
Apolipoprotein E, Especially Apolipoprotein E4, Increases the Oligomerization of Amyloid β Peptide
Authors: Hashimoto Tadafumi , Serrano-Pozo Alberto , Hori Yukiko , Adams Kenneth W. , Takeda Shuko , Banerji Adrian Olaf , Mitani Akinori , Joyner Daniel , Thyssen Diana H. , Bacskai Brian J. , Frosch Matthew P. , Spires-Jones Tara L. , Finn Mary Beth , Holtzman David M. , Hyman Bradley T.
Published: October 2012

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder causing dementia. Massive deposition of amyloid β peptide (Aβ) as senile plaques in the brain is the pathological hallmark of AD, but oligomeric, soluble forms of Aβ have been implicated as the synaptotoxic component. The apolipoprotein E ε 4 (apoE ε4) allele is known to be a genetic risk factor for developing AD. However, it is still unknown how apoE impacts the process of Aβ oligomerization. Here, we found that the level of Aβ oligomers inAPOEε4/ε4 AD patient brains is 2.7 times higher than those inAPOEε3/ε3 AD patient brains, matched for total plaque burden, suggesting that apoE4 impacts the metabolism of Aβ oligomers. To test this hypothesis, we examined the effect of apoE on Aβ oligomer formation. Using both synthetic Aβ and a split-luciferase method for monitoring Aβ oligomers, we observed that apoE increased the level of Aβ oligomers in an isoform-dependent manner (E2 < E3 < E4). This effect appears to be dependent on the ApoE C-terminal domain. Moreover, these results were confirmed using endogenous apoE isolated from the TBS-soluble fraction of human brain, which increased the formation of Aβ oligomers. Together, these data show that lipidated apoE, especially apoE4, increases Aβ oligomers in the brain. Higher levels of Aβ oligomers in the brains ofAPOEε4/ε4 carriers compared withAPOEε3/ε3 carriers may increase the loss of dendritic spines and accelerate memory impairments, leading to earlier cognitive decline in AD.
Loss of Interleukin Receptor-Associated Kinase 4 Signaling Suppresses Amyloid Pathology and Alters Microglial Phenotype in a Mouse Model of Alzheimer's Disease
Authors: Cameron Brent , Tse Wayne , Lamb Raza , Li Xiaoxia , Lamb Bruce T. , Landreth Gary E.
Published: October 2012

Alzheimer's disease (AD) is typified by the deposition of amyloid in the brain, which elicits a robust microglial-mediated inflammatory response that is associated with disease exacerbation and accelerated progression. Microglia are the principal immune effector cells in the brain and interact with fibrillar forms of Aβ (fAβ) through a receptor complex that includes Toll-like receptors (TLR) 2/4/6 and their coreceptors. Interleukin receptor-associated kinases (IRAKs) are essential intracellular signaling molecules for transduction of TLR signals. Studies of mouse models of AD in which the individual TLRs are knocked out have produced conflicting results on roles of TLR signaling in amyloid homeostasis. Therefore, we disrupted a common downstream TLR signaling element, IRAK4. We report that microglial IRAK4 is necessaryin vitrofor fAβ to activate the canonical pro-inflammatory signaling pathways leading to activation of p38, JNK, and ERK MAP kinases and to generate reactive oxygen species.In vivothe loss of IRAK4 function results in decreased Aβ levels in a murine model of AD. This was associated with diminished microgliosis and astrogliosis in aged mice. Analysis of microglia isolated from the adult mouse brain revealed an altered pattern of gene expression associated with changes in microglial phenotype that were associated with expression of IRF transcription factors that govern microglial phenotype. Further, loss of IRAK4 function also promoted amyloid clearance mechanisms, including elevated expression of insulin-degrading enzyme. Finally, blocking IRAK function restored olfactory behavior. These data demonstrate that IRAK4 activation acts normally to regulate microglial activation status and influence amyloid homeostasis in the brain.
Motor Memory Is Encoded as a Gain-Field Combination of Intrinsic and Extrinsic Action Representations
Authors: Brayanov Jordan B. , Press Daniel Z. , Smith Maurice A.
Published: October 2012

Actions can be planned in either an intrinsic (body-based) reference frame or an extrinsic (world-based) frame, and understanding how the internal representations associated with these frames contribute to the learning of motor actions is a key issue in motor control. We studied the internal representation of this learning in human subjects by analyzing generalization patterns across an array of different movement directions and workspaces after training a visuomotor rotation in a single movement direction in one workspace. This provided a dense sampling of the generalization function across intrinsic and extrinsic reference frames, which allowed us to dissociate intrinsic and extrinsic representations and determine the manner in which they contributed to the motor memory for a trained action. A first experiment showed that the generalization pattern reflected a memory that was intermediate between intrinsic and extrinsic representations. A second experiment showed that this intermediate representation could not arise from separate intrinsic and extrinsic learning. Instead, we find that the representation of learning is based on a gain-field combination of local representations in intrinsic and extrinsic coordinates. This gain-field representation generalizes between actions by effectively computing similarity based on the (Mahalanobis) distance across intrinsic and extrinsic coordinates and is in line with neural recordings showing mixed intrinsic-extrinsic representations in motor and parietal cortices.
Autism-Associated Mutations in ProSAP2/Shank3 Impair Synaptic Transmission and Neurexin–Neuroligin-Mediated Transsynaptic Signaling
Authors: Arons Magali H. , Thynne Charlotte J. , Grabrucker Andreas M. , Li Dong , Schoen Michael , Cheyne Juliette E. , Boeckers Tobias M. , Montgomery Johanna M. , Garner Craig C.
Published: October 2012

Mutations in several postsynaptic proteins have recently been implicated in the molecular pathogenesis of autism and autism spectrum disorders (ASDs), including Neuroligins, Neurexins, and members of the ProSAP/Shank family, thereby suggesting that these genetic forms of autism may share common synaptic mechanisms. Initial studies of ASD-associated mutations in ProSAP2/Shank3 support a role for this protein in glutamate receptor function and spine morphology, but these synaptic phenotypes are not universally penetrant, indicating that other core facets of ProSAP2/Shank3 function must underlie synaptic deficits in patients with ASDs. In the present study, we have examined whether the ability of ProSAP2/Shank3 to interact with the cytoplasmic tail of Neuroligins functions to coordinate pre/postsynaptic signaling through the Neurexin–Neuroligin signaling complex in hippocampal neurons ofRattus norvegicus. Indeed, we find that synaptic levels of ProSAP2/Shank3 regulate AMPA and NMDA receptor-mediated synaptic transmission and induce widespread changes in the levels of presynaptic and postsynaptic proteins via Neurexin–Neuroligin transsynaptic signaling. ASD-associated mutations in ProSAP2/Shank3 disrupt not only postsynaptic AMPA and NMDA receptor signaling but also interfere with the ability of ProSAP2/Shank3 to signal across the synapse to alter presynaptic structure and function. These data indicate that ASD-associated mutations in a subset of synaptic proteins may target core cellular pathways that coordinate the functional matching and maturation of excitatory synapses in the CNS.
Developmental Switch in Spike Timing-Dependent Plasticity at Layers 4–2/3 in the Rodent Barrel Cortex
Authors: Itami Chiaki , Kimura Fumitaka
Published: October 2012

Sensory deprivation during the critical period induces long-lasting changes in cortical maps. In the rodent somatosensory cortex (S1), its precise initiation mechanism is not known, yet spike timing-dependent plasticity (STDP) at layer 4 (L4)–L2/3 synapses are thought to be crucial. Whisker stimulation causes “L4 followed by L2/3” cell firings, while acute single whisker deprivation suddenly reverses the sequential order in L4 and L2/3 neurons in the deprived column (Celikel et al., 2004). Reversed spike sequence then leads to long-term depression through an STDP mechanism (timing-dependent long-term depression), known as deprivation-induced suppression at L4–L2/3 synapses (Bender et al., 2006a), an important first step in the map reorganization. Here we show that STDP properties change dramatically on postnatal day 13–15 (P13–P15) in mice S1. Before P13, timing-dependent long-term potentiation (t-LTP) was predominantly induced regardless of spiking order. The induction of t-LTP required postsynaptic influx of Ca2+, an activation of protein kinase A, but not calcium/calmodulin-dependent protein kinase II. Consistent with the strong bias toward t-LTP, whisker deprivation (all whiskers in Row “D”) from P7–P12 failed to induce synaptic depression at L4–L2/3 synapses in the deprived column, but clear depression was seen if deprivation occurred after P14. Random activation of L4, L2/3 cells, as may occur in response to whisker stimulation before P13 during network formation, led to potentiation under the immature STDP rule, as predicted from the bias toward t-LTP regardless of spiking order. These findings describe a developmental switch in the STDP rule that may underlie the transition from synapse formation to circuit reorganization at L4–L2/3 synapses, both in distinct activity-dependent manners.
Hippocampal Neural Correlates for Values of Experienced Events
Authors: Lee Hyunjung , Ghim Jeong-Wook , Kim Hoseok , Lee Daeyeol , Jung MinWhan
Published: October 2012

Newly experienced events are often remembered together with how rewarding the experiences are personally. Although the hippocampus is a candidate structure where subjective values are integrated with other elements of episodic memory, it is uncertain whether and how the hippocampus processes value-related information. We examined how activity of dorsal CA1 and dorsal subicular neurons in rats performing a dynamic foraging task was related to reward values that were estimated using a reinforcement learning model. CA1 neurons carried significant signals related to action values before the animal revealed its choice behaviorally, indicating that the information on the expected values of potential choice outcomes was available in CA1. Moreover, after the outcome of the animal's goal choice was revealed, CA1 neurons carried robust signals for the value of chosen action and they temporally overlapped with the signals related to the animal's goal choice and its outcome, indicating that all the signals necessary to evaluate the outcome of an experienced event converged in CA1. On the other hand, value-related signals were substantially weaker in the subiculum. These results suggest a major role of CA1 in adding values to experienced events during episodic memory encoding. Given that CA1 neuronal activity is modulated by diverse attributes of an experienced event, CA1 might be a place where all the elements of episodic memory are integrated.
Loss of NGF-TrkA Signaling from the CNS Is Not Sufficient to Induce Cognitive Impairments in Young Adult or Intermediate-Aged Mice
Authors: Müller Markus , Triaca Viviana , Besusso Dario , Costanzi Marco , Horn Jacqueline M. , Koudelka Juraj , Geibel Mirjam , Cestari Vincenzo , Minichiello Liliana
Published: October 2012

Many molecules expressed in the CNS contribute to cognitive functions either by modulating neuronal activity or by mediating neuronal trophic support and/or connectivity. An ongoing discussion is whether signaling of nerve growth factor (NGF) through its high-affinity receptor TrkA contributes to attention behavior and/or learning and memory, based on its expression in relevant regions of the CNS such as the hippocampus, cerebral cortex, amygdala and basal forebrain. Previous animal models carrying either a null allele or transgenic manipulation ofNgforTrkahave proved difficult in addressing this question. To overcome this problem, we conditionally deletedNgforTrkafrom the CNS. Our findings confirm that NGF-TrkA signaling supports survival of only a small proportion of cholinergic neurons during development; however, this signaling is not required for trophic support or connectivity of the remaining basal forebrain cholinergic neurons. Moreover, comprehensive behavioral analysis of young adult and intermediate-aged mice lacking NGF-TrkA signaling demonstrates that this signaling is dispensable for both attention behavior and various aspects of learning and memory.
AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca2+-Permeable AMPA Receptors
Authors: Sanderson Jennifer L. , Gorski Jessica A. , Gibson Emily S. , Lam Philip , Freund Ronald K. , Chick Wallace S. , Dell'Acqua Mark L.
Published: October 2012

AMPA receptors (AMPARs) are tetrameric ion channels assembled from GluA1–GluA4 subunits that mediate the majority of fast excitatory synaptic transmission in the brain. In the hippocampus, most synaptic AMPARs are composed of GluA1/2 or GluA2/3 with the GluA2 subunit preventing Ca2+influx. However, a small number of Ca2+-permeable GluA1 homomeric receptors reside in extrasynaptic locations where they can be rapidly recruited to synapses during synaptic plasticity. Phosphorylation of GluA1 S845 by the cAMP-dependent protein kinase (PKA) primes extrasynaptic receptors for synaptic insertion in response to NMDA receptor Ca2+signaling during long-term potentiation (LTP), while phosphatases dephosphorylate S845 and remove synaptic and extrasynaptic GluA1 during long-term depression (LTD). PKA and the Ca2+-activated phosphatase calcineurin (CaN) are targeted to GluA1 through binding to A-kinase anchoring protein 150 (AKAP150) in a complex with PSD-95, but we do not understand how the opposing activities of these enzymes are balanced to control plasticity. Here, we generated AKAP150ΔPIX knock-in mice to selectively disrupt CaN anchoringin vivo. We found that AKAP150ΔPIX mice lack LTD but express enhanced LTP at CA1 synapses. Accordingly, basal GluA1 S845 phosphorylation is elevated in AKAP150ΔPIX hippocampus, and LTD-induced dephosphorylation and removal of GluA1, AKAP150, and PSD-95 from synapses are impaired. In addition, basal synaptic activity of GluA2-lacking AMPARs is increased in AKAP150ΔPIX mice and pharmacologic antagonism of these receptors restores normal LTD and inhibits the enhanced LTP. Thus, AKAP150-anchored CaN opposes PKA phosphorylation of GluA1 to restrict synaptic incorporation of Ca2+-permeable AMPARs both basally and during LTP and LTD.
The pubertal transition in 179 healthy Danish children: associations between pubarche, adrenarche, gonadarche, and body composition
Authors: Mouritsen Annette , Aksglaede Lise , Soerensen Kaspar , Hagen Casper P , Petersen J H , Main Katharina M , Juul Anders
Published: October 2012

Background

Pubertal onset is usually defined by breast development in girls and testicular growth in boys. Pubarche is defined as the attainment of pubic hair and is considered as a sign of pubertal transition. Pubarche is preceded by a gradual increase in production of adrenal androgens, DHEA and Δ4-androstenedione (Adione), a process termed adrenarche.

Objective

To study the natural course of pubertal transition and the associations with adrenarche, body fat, and linear growth.

Design and methods

A longitudinal study of 179 healthy children (89 girls) with higher socioeconomic background examined every 6 months for 5 years. Pubic hair stage, breast stage, genital stage, testicular volume (TV), height, weight, and four skinfolds were measured.

Results

In girls, median age (25th and 75th percentiles) at thelarche (B2+) was 10.1 years (9.3–10.9). In boys, median age at attaining a TV >3 ml was 11.5 years (10.9–12.0). Median age at pubarche (PH2+) was 10.9 years (10.3–11.4) in girls and 11.6 years (10.8–12.4) in boys. Only 6.8% (4/59) of the girls and 24.6% (15/61) of the boys developed pubic hair as the first isolated sign of puberty. Serum DHEAS and Adione increased with age, although the increase in Adione was most pronounced in girls. No associations between early age at thelarche/testicular growth and increased body fat (BMI and sum of four skinfolds) were observed.

Conclusion

Danish children rarely experience pubarche as the first sign of puberty. No associations between age at pubertal onset and body composition were found. Circulating levels of Adione, but not DHEAS, increased with the onset of puberty, although with large interindividual variability.
MEN1 intragenic deletions may represent the most prevalent somatic event in sporadic primary hyperparathyroidism
Authors: Alvelos Maria Inês , Vinagre João , Fonseca Elsa , Barbosa Eva , Teixeira-Gomes José , Sobrinho-Simões Manuel , Soares Paula
Published: October 2012

Objective

Primary hyperparathyroidism (pHPT) is characterised by an inappropriate over production of parathyroid hormone and it is the most frequent pathological condition of the parathyroid glands. A minority of the cases belong to familial forms, but most of them are sporadic. The genetic alterations underlying the sporadic forms of pHPT remain poorly understood. The main goal of our study is to perform the molecular characterisation of a series of sporadic pHPT cases.

Design and methods

We have studied matched blood and tumour from 24 patients with pHPT, who went to a medical appointment in Hospital Pedro Hispano. Informed consent was obtained from all individuals. TheMEN1,RETandCDKN1Bmolecular study was carried out in the germline DNA by PCR/SSCP and direct sequencing. Parathyroid tumours were further analysed by the same methods forMEN1,CDKN1BandCTNNB1genetic alterations. The multiplex ligation-dependent probe amplification technique enabled the evaluation ofMEN1gene deletions. Protein expression for menin, cyclin D1, parafibromin, p27Kip1, β-catenin and Ki-67 was conducted by immunohistochemistry.

Results

The study of parathyroid tumours detected two somaticMEN1mutations (c.249_252delGTCT and c.115_163del49bp) and revealed the presence ofMEN1intragenic deletions in 54% (13/24) of the tumours. InRETandCDKN1Bgenes only previously described, non-pathogenic variants were found. Cyclin D1 protein was overexpressed in 13% (3/24) of tumours.

Conclusions

These results suggest thatMEN1alterations, remarkably intragenic deletions, may represent the most prevalent genetic alteration in sporadic parathyroid tumours.
Early changes in carcinoembryonic antigen but not in calcitonin levels are correlated with the progression-free survival in medullary thyroid carcinoma patients treated with cytotoxic chemotherapy
Authors: Hajje G , Borget I , Leboulleux S , Chougnet C , Al Ghuzlan A , Mirghani H , Caramella C , Hartl D , Schlumberger M , Baudin E
Published: October 2012

Introduction

The prognostic value of serum calcitonin (CT) and carcinoembryonic antigen (CEA) doubling time has been recently demonstrated in medullary thyroid carcinoma (MTC) patients. No study has yet validated the surrogate role of these markers for survival during treatment. The aim of this study was to evaluate, in patients with advanced MTC treated with cytotoxic chemotherapy, the relationship between early changes of serum CT or CEA levels and progression-free survival (PFS).

Patients and methods

The files of 28 consecutive metastatic MTC patients with progressive disease, treated with cytotoxic chemotherapy in a single tertiary referral center between 2000 and 2010, were retrospectively reviewed. Serum CT and CEA measurements and radiological Response Evaluation Criteria in Solid Tumors (RECIST) evaluations were collected every 3 months. The relationship between changes in serum CT and CEA levels at 3 months, defined by an increase or a decrease of at least 20%, and PFS according to RECIST 1.0, was estimated using Kaplan–Meier curves and log-rank test.

Results

The median follow-up for the 28 patients was 68 months. According to RECIST, a partial response, a stabilization or a progression was observed in 14, 43, and 43% of cases respectively. Median PFS from the initiation of cytotoxic chemotherapy was 4.5 months. Median PFS among patients with and without significant CT increase at 3 months was 4.6 and 3.3 months respectively (P=0.75). Median PFS among patients with a significant CEA increase at 3 months was 2.7 months, whereas it was 19.1 months in patients in whom CEA did not increase (P=0.02).

Conclusion

At 3 months, an increase of serum CEA but not of CT levels appears as a valuable surrogate marker of short PFS in MTC patients treated with cytotoxic chemotherapy. A prospective validation is expected.
Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue
Authors: Pulido Marina R , Rabanal-Ruiz Yoana , Almabouada Farid , Díaz-Ruiz Alberto , Burrell María A , Vázquez María J , Castaño Justo P , Kineman Rhonda D , Luque Raúl M , Diéguez Carlos , Vázquez-Martínez Rafael , Malagón María M
Published: October 2012

There is increasing evidence that proteins associated with lipid droplets (LDs) play a key role in the coordination of lipid storage and mobilization in adipocytes. The small GTPase, RAB18, has been recently identified as a novel component of the protein coat of LDs and proposed to play a role in both β-adrenergic stimulation of lipolysis and insulin-induced lipogenesis in 3T3-L1 adipocytes. In order to better understand the role of Rab18 in the regulation of lipid metabolism in adipocytes, we evaluated the effects of age, fat location, metabolic status, and hormonal milieu onRab18expression in rodent white adipose tissue (WAT).Rab18mRNA was undetectable at postnatal day 15 (P15), but reached adult levels by P45, in both male and female rats. In adult rats,Rab18immunolocalized around LDs, as well as within the cytoplasm of mature adipocytes. A weakRab18signal was also detected in the stromal-vascular fraction of WAT. In mice, fasting significantly increased, though with a distinct time–course pattern,Rab18mRNA and protein levels in visceral and subcutaneous WAT. The expression ofRab18was also increased in visceral and subcutaneous WAT of obese mice (diet-induced,ob/ob, and New Zealand obese mice) compared with lean controls.Rab18expression in rats was unaltered by castration, adrenalectomy, or GH deficiency but was increased by hypophysectomy, as well as hypothyroidism. When viewed together, our results suggest the participation ofRab18in the regulation of lipid processing in adipose tissue under both normal and pathological conditions.
Transcatheter Aortic Valve Implantation into a Stentless Prosthetic Valve with a Low Position of the Left Main Coronary Artery
Authors: D'Ancona Giuseppe , Pasic Miralem , Dreysse Stephan , Drews Thorsten , Buz Semih , Unbehaun Axel , Kukucka Marian , Hetzer Roland
Published: October 2012

Recently during a transcatheter aortic valve implantation (TAVI), we were faced with a problem that seemed to be untreatable by TAVI. It was difficult to decide whether to perform atypical TAVI or to convert to conventional redo aortic valve surgery in an extremely high-risk patient with a degenerated stentless aortic bioprosthesis.
Extended Myectomy for Hypertrophic Obstructive Cardiomyopathy
Authors: Gao Changqing , Ren Chonglei , Xiao Cangsong , Wu Yang , Wang Gang , Liu Guopeng , Wang Yao
Published: October 2012

Background: The purpose of this study was to summarize our experience of extended ventricular septal myectomy in patients with hypertrophic obstructive cardiomyopathy (HOCM).

Methods: Thirty-eight patients (26 men, 12 women) with HOCM underwent extended ventricular septal myectomy. The mean age was 36.3 years (range, 18-64 years). Diagnosis was made by echocardiography. The mean (mean � SE) systolic gradient between the left ventricle (LV) and the aorta was 89.3 � 31.1 mm Hg (range, 50-184 mm Hg) according to echocardiographic assessments before the operations. Moderate or severe systolic anterior motion (SAM) of the anterior leaflet of the mitral valve was found in 38 cases, and mitral regurgitation was present in 29 cases. Extended ventricular septal myectomy was performed in all 38 cases. The results of the surgical procedures were evaluated intraoperatively with transesophageal echocardiography (TEE) and with transthoracic echocardiography (TTE) at 1 to 2 weeks after the operation. All patients were followed up with TTE after their operation.

Results: All patients were discharged without complications. The TEE evaluations showed that the mean systolic gradient between the LV and the aorta decreased from 94.8 � 35.6 mm Hg preoperatively to 13.6 � 10.8 mm Hg postoperatively (P = .0000) and that the mean thickness of the ventricular septum decreased from 28.3 � 7.9 mm to 11.8 � 3.2 mm (P = .0000). Mitral regurgitation and SAM were significantly reduced or eliminated. During the follow-up, all patients promptly became completely asymptomatic or complained of mild effort dyspnea only, and syncope was abolished. TTE examinations showed that the postoperative pressure gradient either remained the same or diminished.

Conclusions: Extended ventricular septal myectomy is mostly an effective method for patients with HOCM, and good surgical exposure and thorough excision of the hypertrophic septum are of paramount importance for a successful surgery.
Surgical Repair for Isolated Aortic Interruption in a Young Adult
Authors: Erkanli Korhan , Onan Burak , Akt�rk Ibrahim Faruk , Bakir Ihsan
Published: October 2012

Interrupted aortic arch (IAA), a rare congenital malformation of the aortic arch, is defined as a loss of luminal continuity between the ascending and descending portions of the aorta. It is rarely diagnosed as an isolated anomaly in adulthood. Surgical repair is feasible through a sternotomy or thoracotomy incision. In this report, we describe the surgical repair of an isolated IAA in a 29-year-old patient by performing an ascending-to-descending aortic bypass via a sternotomy with cardiopulmonary bypass.
Microsizing Using Inside Suture Placement. A Simple and Versatile Technique for Precision Adjustment of Ring Annuloplasties
Authors: Levinson Mark M. , Miller Justin
Published: October 2012

Introduction: A new and simple technique for eliminating residual leaks during mitral annuloplasty, called microsizing, is described.

Methods: Microsizing is performed by moving one or more annuloplasty sutures from the outside to the inside of the prosthetic ring. This maneuver advances discrete segments of the annulus toward the opposing leaflet by a distance equal to the thickness of the ring (approximately 3 mm). Microsizing is a simple method for precision adjustment of annular shape and size to eliminate focal gaps, regardless of the cause.

Results: A series of 63 consecutive patients with moderate to severe mitral regurgitation (MR) were repaired over a 10 year period, all with intraoperative transesophageal echocardiography guidance. No patient required valve replacement (repair success rate 100%). Concomitant (non-mitral valve) procedures were performed in 53 patients (84.1%). Fifty patients (79.3%, Group 1) underwent successful repair using traditional suture placement in the prosthetic ring. Thirteen patients (20.6%, Group 2) had one or more sutures repositioned to the inside of the ring ("micro-sized") as a new strategy to eliminate residual leaks. Mean post repair MR grade was lower when microsizing was used (0.15 for Group 2 versus 0.30 for Group 1). No micro-sized patient experienced systolic anterior motion (SAM) or mitral stenosis. There were no repairs with greater than trace MR, late ring dehiscences, recurrent regurgitation, or reoperation in the entire series. There was one death (1.6%) in a non-micro-sized patient from intra-operative abdominal hemorrhage secondary to an IABP complication.

Conclusion: Microsizing is a simple variation of suture placement that allows custom shaping of the mitral annulus by advancing selected portions toward the opposing leaflet, eliminating gaps, and improving coaptation. This technique is safe, simple, and reproducible without causing stenosis, SAM, or late failure.
Produção e qualidade de sementes do capim-mombaça em função da adubação nitrogenada
Authors: Canto Marcos Weber do , Barth Neto Armindo , Pancera Júnior Edson José , Gasparino Eliane , Boleta Vinícius Scandolara
Published: October 2012

O objetivo deste experimento foi avaliar os componentes da produção de sementes, a produtividade de sementes aparentes e puras e a qualidade de sementes do capim-mombaça (Panicum maximum, Jacq. cv. Mombaça), adubado com quatro doses de nitrogênio (0, 50, 100 e 150 kg ha-1). O delineamento experimental foi em blocos ao acaso, com quatro repetições. As variáveis analisadas foram os números de perfilhos vegetativos e com panículas, números de sementes por panícula e por área, índice de colheita, massa de mil sementes puras e a germinação de sementes. Houve efeito linear da dose de nitrogênio sobre o número de perfilhos com panículas, nos números de sementes aparentes e puras por panícula e por área, nas produtividades de sementes aparentes, puras e puras viáveis e sobre o índice de colheita. Na maior dose de N aplicada, a produtividade de sementes aparentes foi de 73 kg ha-1 e de sementes puras igual a 34 kg ha-1. Correlações significativas foram obtidas entre produtividade de sementes aparentes e puras, com a massa de perfilho com panícula, número de perfilhos com panícula, número de sementes aparentes e puras, por panícula e por área, com a matéria seca ha-1 e com o índice de colheita. A massa de mil sementes puras e a germinação de sementes não foi influenciada pela adubação nitrogenada.
Irrigação e certificação da cafeicultura na Região Centro-Oeste de São Paulo
Authors: Perdoná Marcos José , Soratto Rogério Peres , Martins Adriana Novais , Suguino Eduardo , Mancuso Mauricio Antonio Cuzato
Published: October 2012

Rentabilidade insatisfatória tem provocado diminuição paulatina do parque cafeeiro no Estado de São Paulo. Entre as alternativas para a solução deste problema, duas se destacam: a irrigação das lavouras e a certificação das propriedades. Mesmo em regiões consideradas aptas à cultura do café arábica (Coffea arabica L.), o uso da irrigação pode promover, na média dos anos, aumento de produtividade de grãos. Além disso, a certificação do produto favorece sua diferenciação no mercado e pode melhorar os resultados econômicos da atividade. Este trabalho teve por objetivo avaliar o desenvolvimento e a produtividade de cafeeiros submetidos a sistemas irrigados ou não, comparando os dados econômicos na comercialização do café certificado ou não, nas condições da Região Centro-Oeste do Estado de São Paulo. O delineamento utilizado no campo foi o de blocos ao acaso, com dois tratamentos (com e sem irrigação por gotejamento) e dez repetições. Foram calculados os custos de produção, bem como a lucratividade com a venda do produto final. A irrigação aumentou o desenvolvimento e a produtividade dos cafeeiros. Houve o retorno do investimento a partir da terceira safra. A venda de café certificado possibilitou resultados econômicos em média de 224,5% superiores ao não certificado. A irrigação aliada à venda de café certificado proporcionou saldo financeiro 1.192% superior ao café não irrigado e não certificado.
O estado da arte da avaliação de políticas públicas: conceituação e exemplos de avaliação no Brasil
Authors: Ramos Marília Patta , Schabbach Letícia Maria
Published: October 2012

A avaliação e o monitoramento são fases imprescindíveis do planejamento estatal, ocupando também espaço crescente nas pesquisas acadêmicas. Sua atualidade no debate em torno da eficácia e do impacto das políticas públicas em diferentes áreas é evidenciada pelos vários fóruns, encontros e redes de especialistas que tratam da temática, pela demanda oriunda de órgãos públicos, e pela profissionalização dessa atividade em escala internacional. O presente artigo destaca, de forma sistemática e analítica, a relevância dos processos de avaliação, sistematizando informações sobre aspectos conceituais, e o estado da arte dos estudos sobre avaliação e das práticas avaliativas de diferentes esferas de governo. O trabalho está dividido em cinco seções: na primeira, são apresentadas a conceituação de avaliação e suas principais características, na segunda são analisados os tipos de avaliação, e, na terceira, seus diversos usos. Segue, na quarta seção, uma exposição sobre as tendências dos estudos avaliativos no Brasil e no mundo e, por fim, nas conclusões são apontadas as dificuldades e as necessidades ao aprimoramento da atividade de avaliação de políticas públicas.
Estudo exploratório da eficiência dos Tribunais de Justiça estaduais brasileiros usando a Análise Envoltória de Dados (DEA)
Authors: Nogueira José Marcelo Maia , Oliveira Kátia Michelle Matos de , Vasconcelos Alan Pereira de , Oliveira Leonel Gois Lima
Published: October 2012

O objetivo deste trabalho é comparar a eficiência relativa dos Tribunais de Justiça estadual do Brasil. Trata-se de um estudo de caráter exploratório com um enfoque quantitativo e qualitativo, com pesquisa documental e bibliográfica. Foram utilizados os dados do relatório Justiça em números, edições 2007 e 2008, publicadas pelo Conselho Nacional de Justiça. Os dados foram analisados sob enfoque de um modelo orientado para outputs usando a técnica de Análise Envoltória de Dados (DEA) para análise da eficiência dos Tribunais. Verificou-se um aumento no número de tribunais que alcançaram o nível máximo da eficiência relativa entre 2007 e 2008. Alguns tribunais foram indicados como referências para os demais. É apresentada, também, a situação do Tribunal de Justiça do Estado do Ceará junto a uma análise dos fatores que precisariam ser ajustados para o alcance de sua eficiência máxima.
Gestão do conhecimento numa instituição pública de assistência técnica e extensão rural do Nordeste do Brasil
Authors: Brito Lydia Maria Pinto , Oliveira Patrícia Webber Souza de , Castro Ahiram Brunni Cartaxo de
Published: October 2012

Um dos problemas mais graves enfrentados pelas organizações públicas é a perda de conhecimento em transferências, rotatividade e aposentadorias de pessoal, pois tem como consequência a perda de know-how e capital intelectual, já que muitas informações, conhecimentos importantes e detalhes dos processos de trabalho ainda estão guardados apenas na mente das pessoas. Portanto, o objetivo deste estudo é identificar, a partir da percepção dos gestores de uma instituição pública de assistência técnica e extensão rural, a gestão do conhecimento. Para isso, utilizou-se do modelo de Diagnóstico de Gestão do Conhecimento proposto por Bukowitz e Williams (2002). A instituição estudada é um órgão de educação não formal do Nordeste do Brasil que executa políticas públicas de assistência técnica e extensão rural que beneficiam agricultores familiares. Trata-se de um estudo de caso de campo com abordagem quantitativa e método descritivo. Os dados foram registrados em planilhas eletrônicas e foram utilizadas as instruções do modelo escolhido para apuração dos resultados. Os resultados sinalizam uma contradição: uma organização que dissemina saberes para agricultores familiares não possui internamente a gestão formal do conhecimento que produz. Além disso, a instituição pesquisada é criadora de conhecimento, porém esse não é considerado seu negócio principal, por isso não gera inovação constante.
Resistência à educação a distância na educação corporativa
Authors: Albertin Alberto Luiz , Brauer Marcus
Published: October 2012

Embora a resistência às tecnologias seja um problema frequente nas empresas, as pesquisas nessa área são fragmentadas, não cumulativas e raras na literatura. O objetivo desta pesquisa foi identificar e analisar as principais dimensões de resistência à educação a distância (EAD) na educação corporativa (EC). Uma estrutura teórica que visou explicar a resistência à EAD na EC foi desenvolvida e testada. As hipóteses iniciais foram testadas e os resultados mostraram que, na amostra pesquisada, as dimensões Autoeficácia e Expectativa de Desempenho influenciam direta e positivamente a resistência à EAD na EC, e as dimensões Expectativa de Esforço, Condições Facilitadoras, Interatividade e Comunicação são construtos antecedentes à Expectativa de Desempenho. Este estudo poderá auxiliar a implantação e gestão de cursos a distância, principalmente em organizações do setor público, incluindo universidades.
Magnetic susceptibility to identify landscape segments on a detailed scale in the region of Jaboticabal, São Paulo, Brazil
Authors: Barrios Mariana dos Reis , Marques Junior José , Panosso Alan Rodrigo , Siqueira Diego Silva , La Scala Junior Newton
Published: October 2012

The agricultural potential is generally assessed and managed based on a one-dimensional vision of the soil profile, however, the increased appreciation of sustainable production has stimulated studies on faster and more accurate evaluation techniques and methods of the agricultural potential on detailed scales. The objective of this study was to investigate the possibility of using soil magnetic susceptibility for the identification of landscape segments on a detailed scale in the region of Jaboticabal, São Paulo State. The studied area has two slope curvatures: linear and concave, subdivided into three landscape segments: upper slope (US, concave), middle slope (MS, linear) and lower slope (LS, linear). In each of these segments, 20 points were randomly sampled from a database with 207 samples forming a regular grid installed in each landscape segment. The soil physical and chemical properties, CO2 emissions (FCO2) and magnetic susceptibility (MS) of the samples were evaluated represented by: magnetic susceptibility of air-dried fine earth (MS ADFE), magnetic susceptibility of the total sand fraction (MS TS) and magnetic susceptibility of the clay fraction (MS Cl) in the 0.00 - 0.15 m layer. The principal component analysis showed that MS is an important property that can be used to identify landscape segments, because the correlation of this property within the first principal component was high. The hierarchical cluster analysis method identified two groups based on the variables selected by principal component analysis; of the six selected variables, three were related to magnetic susceptibility. The landscape segments were differentiated similarly by the principal component analysis and by the cluster analysis using only the properties with higher discriminatory power. The cluster analysis of MS ADFE, MS TS and MS Cl allowed the formation of three groups that agree with the segment division established in the field. The grouping by cluster analysis indicated MS as a tool that could facilitate the identification of landscape segments and enable the mapping of more homogeneous areas at similar locations.
Digital soil mapping: strategy for data pre-processing
Authors: Caten Alexandre ten , Dalmolin Ricardo Simão Diniz , Ruiz Luis Fernando Chimelo
Published: October 2012

The region of greatest variability on soil maps is along the edge of their polygons, causing disagreement among pedologists about the appropriate description of soil classes at these locations. The objective of this work was to propose a strategy for data pre-processing applied to digital soil mapping (DSM). Soil polygons on a training map were shrunk by 100 and 160 m. This strategy prevented the use of covariates located near the edge of the soil classes for the Decision Tree (DT) models. Three DT models derived from eight predictive covariates, related to relief and organism factors sampled on the original polygons of a soil map and on polygons shrunk by 100 and 160 m were used to predict soil classes. The DT model derived from observations 160 m away from the edge of the polygons on the original map is less complex and has a better predictive performance.
Desempenho de sondas de TDR manufaturadas de diferentes comprimentos de hastes
Authors: Sant'Ana José Antonio do Vale , Coelho Eugênio Ferreira , Silva Junior João José da , Santana Junior Edvaldo Bispo , Veinromber Junior Lucio Aderito dos Anjos
Published: October 2012

A avaliação da umidade do solo com uso da reflectometria no domínio do tempo (TDR) tem sido feita a partir de sondas ou guias de onda de comprimento igual ou superior a 0,10 m, sendo poucas as informações na literatura para comprimentos inferiores. Este trabalho teve como objetivo avaliar o desempenho de sondas manufaturadas de TDR de diferentes comprimentos de hastes na estimativa da umidade do solo a partir da constante dielétrica. Foram confeccionadas guias de onda de TDR manufaturadas, com diferentes comprimentos de hastes (0,30; 0,15; 0,12; 0,10; 0,08; 0,06; e 0,04 m). No laboratório, o solo foi colocado para secagem ao ar, destorroado, passado em peneira de 2 mm e acondicionado em tubos de PVC de diâmetro de 0,196 m. Logo após a saturação, foram realizadas leituras com um reflectômetro tipo TDR até a umidade atingir valores próximos do limite inferior da disponibilidade de água do solo. As análises dos valores de umidade para os diferentes comprimentos de haste mostraram que eles tiveram efeito nas leituras de umidade do solo para os valores acima de 0,25 m³ m-3 e abaixo de 0,14 m³ m-3. As sondas com os comprimentos das hastes avaliados apresentaram leituras semelhantes para valores de umidade volumétrica constante no intervalo de 0,14 a 0,25 m³ m-3. A sonda de comprimento de haste de 0,04 m apresentou desempenho satisfatório para umidades volumétricas maiores que 0,20 m³ m-3.
Chemical and biochemical properties of Araucaria angustifolia (Bert.) Ktze. forest soils in the state of São Paulo
Authors: Carvalho Fernanda de , Moreira Fatima Maria de Souza , Cardoso Elke Jurandy Bran Nogueira
Published: October 2012

Araucaria angustifolia, commonly named Araucaria, is a Brazilian native species that is intensively exploited due to its timber quality. Therefore, Araucaria is on the list of species threatened by extinction. Despite the importance of soil for forest production, little is known about the soil properties of the highly fragmented Araucaria forests. This study was designed to investigate the use of chemical and biological properties as indicators of conservation and anthropogenic disturbance of Araucaria forests in different sampling periods. The research was carried out in two State parks of São Paulo: Parque Estadual Turístico do Alto do Ribeira and Parque Estadual de Campos de Jordão. The biochemical properties carbon and nitrogen in microbial biomass (MB-C and MB-N), basal respiration (BR), the metabolic quotient (qCO2) and the following enzyme activities: β-glucosidase, urease, and fluorescein diacetate hydrolysis (FDA) were evaluated. The sampling period (dry or rainy season) influenced the results of mainly MB-C, MB-N, BR, and qCO2. The chemical and biochemical properties, except K content, were sensitive indicators of differences in the conservation and anthropogenic disturbance stages of Araucaria forests. Although these forests differ in biochemical and chemical properties, they are efficient in energy use and conservation, which is shown by their low qCO2, suggesting an advanced stage of succession.