bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship of systemic inflammation to prior hospitalization in adult patients with cystic fibrosis
Authors: Ngan David A , Wilcox Pearce G , Aldaabil May , Li Yuexin , Leipsic Jonathon A , Sin Don D , Man SF Paul
Published: February 2012

Background

In cystic fibrosis (CF) patients, it has been suggested that systemic inflammation may be an important risk factor for poor health outcomes. The relationship of plasma inflammatory biomarkers to lung function and hospitalization history remains largely unexplored.

Methods

This cross-sectional study included 58 consecutive, clinically stable adults from the CF Clinic at St. Paul's Hospital (Vancouver, Canada). Blood levels of interleukin (IL)-6, IL-1β, C-reactive protein (CRP), interleukin (IL)-6, IL-1β, granzyme B (GzmB), chemokine C-C motif ligand 18 (CCL18/PARC), surfactant protein D (SP-D), lipopolysaccharide (LPS)-binding protein, and soluble cluster of differentiation 14 (sCD14) were measured using enzyme-linked immunosorbent assays, and LPS levels were measured using aLimulusamebocyte lysate assay. Spirometry was also performed. Multivariable linear regression analysis was used to assess relationships of the blood biomarkers to lung function.

Results

Lung function impairment was independently associated with elevated plasma levels of CRP (P< 0.01), IL-6 (P= 0.04), IL-1β (P< 0.01), and LBP (P< 0.01). Increasing age (P< 0.01), reduced body mass index (P= 0.02), prior hospitalizations (P= 0.03), and presence ofPseudomonas aeruginosain sputum cultures (P< 0.01) were also associated with reduced lung function. Elevated concentrations of LPS in plasma were associated with a previous history of hospitalization (P< 0.05). There was a trend towards an increase in plasma IL-6 (P= 0.07) and IL-1β (P= 0.06) levels in patients who were previously hospitalized.

Conclusions

IL-6 and IL-1β are promising systemic biomarkers for lung function impairment and history of hospitalization in adult patients with CF.
On mixed boundary value problem of impulsive semilinear evolution equations of fractional order
Authors: Zhang Lihong , Wang Guotao , Song Guangxing
Published: February 2012

This article studies the existence and uniqueness of solutions for impulsive semi-linear evolution equations of fractional order α ∈ (1, 2] with mixed boundary conditions. Some standard fixed point theorems are applied to prove the main results. An illustrative example is also presented.

Mathematics Subject Classification: 26A33; 34K30; 34K45.
TRIM5α associates with proteasomal subunits in cells while in complex with HIV-1 virions
Authors: Lukic Zana , Hausmann Stéphane , Sebastian Sarah , Rucci Justin , Sastri Jaya , Robia Seth L , Luban Jeremy , Campbell Edward M
Published: February 2012

Background

The TRIM5 proteins are cellular restriction factors that prevent retroviral infection in a species-specific manner. Multiple experiments indicate that restriction activity requires accessory host factors, including E2-enzymes. To better understand the mechanism of restriction, we conducted yeast-two hybrid screens to identify proteins that bind to two TRIM5 orthologues.

Results

The only cDNAs that scored on repeat testing with both TRIM5 orthologues were the proteasome subunit PSMC2 and ubiquitin. Using co-immunoprecipitation assays, we demonstrated an interaction between TRIM5α and PSMC2, as well as numerous other proteasome subunits. Fluorescence microscopy revealed co-localization of proteasomes and TRIM5α cytoplasmic bodies. Forster resonance energy transfer (FRET) analysis indicated that the interaction between TRIM5 and PSMC2 was direct. Previous imaging experiments demonstrated that, when cells are challenged with fluorescently-labeled HIV-1 virions, restrictive TRIM5α orthologues assemble cytoplasmic bodies around incoming virion particles. Following virus challenge, we observed localization of proteasome subunits to rhTRIM5α cytoplasmic bodies that contained fluorescently labeled HIV-1 virions.

Conclusions

Taken together, the results presented here suggest that localization of the proteasome to TRIM5α cytoplasmic bodies makes an important contribution to TRIM5α-mediated restriction.
Phenotypical and functional characteristics of mesenchymal stem cells from bone marrow: comparison of culture using different media supplemented with human platelet lysate or fetal bovine serum
Authors: Azouna Nesrine Ben , Jenhani Faouzi , Regaya Zohra , Berraeis Lamia , Othman Tarek Ben , Ducrocq Elfi , Domenech Jorge
Published: February 2012

Introduction

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into several mesenchymal lineages, classically derived from bone marrow (BM) but potentially from umbilical cord blood (UCB). Although they are becoming a good tool for regenerative medicine, they usually need to be expanded in fetal bovine serum (FBS)-supplemented media. Human platelet lysate (HPL) has recently been proposed as substitute for safety reasons, but it is not yet clear how this supplement influences the properties of expanded MSCs.

Methods

In the present study, we compared the effect of various media combining autologous HPL with or without FBS on phenotypic, proliferative and functional (differentiation, cytokine secretion profile) characteristics of human BM-derived MSCs.

Results

Despite less expression of adipogenic and osteogenic markers, MSCs cultured in HPL-supplemented media fully differentiated along osteoblastic, adipogenic, chondrogenic and vascular smooth muscle lineages. The analyses of particular specific proteins expressed during osteogenic differentiation (calcium-sensing receptor (CaSR) and parathormone receptor (PTHR)) showed their decrease at D0 before any induction for MSC cultured with HPL mostly at high percentage (10%HPL). The cytokine dosage showed a clear increase of proliferation capacity and interleukin (IL)-6 and IL-8 secretion.

Conclusions

This study shows that MSCs can be expanded in media supplemented with HPL that can totally replace FBS. HPL-supplemented media not only preserves their phenotype as well as their differentiation capacity, but also shortens culture time by increasing their growth rate.
Differential contribution of dendritic cell CD1d to NKT cell-enhanced humoral immunity and CD8+ T cell activation
Authors: Joshi Sunil K , Lang Gillian A , Devera T Scott , Johnson Amy M , Kovats Susan , Lang Mark L
Published: February 2012

CD1d-restricted type I NKT cells provide help for specific antibody production. B cells, which have captured and presented a T-dependent, antigen-derived peptide on MHC class II and CD1d-binding glycolipid α-GC on CD1d, respectively, activate Th and NKT cells to elicit B cell help. However, the role of the DC CD1d in humoral immunity remains unknown. We therefore constructed mixed bone marrow chimeras containing CD1d-expressing, DTR-transgenic DCs and CD1d+ or CD1d− nontransgenic DCs. Following DT-mediated DC ablation and immunization, we observed that the primary and secondary antibody responses were equivalent in the presence of CD1d+ and CD1d− DCs. In contrast, a total ablation of DCs delayed the primary antibody response. Further experiments revealed that depletion of CD1d+ DCs blocked in vivo expansion of antigen-specific cytotoxic (CD8+) T lymphocytes. These results provide a clear demonstration that although CD1d expression on DCs is essential for NKT-enhanced CD8+ T cell expansion, it is dispensable for specific antibody production.
Colorectal and Other Cancer Risks for Carriers and Noncarriers From Families With a DNA Mismatch Repair Gene Mutation: A Prospective Cohort Study
Authors: Win Aung Ko , Young Joanne P. , Lindor Noralane M. , Tucker Katherine M. , Ahnen Dennis J. , Young Graeme P. , Buchanan Daniel D. , Clendenning Mark , Giles Graham G. , Winship Ingrid , Macrae Finlay A. , Goldblatt Jack , Southey Melissa C. , Arnold Julie , Thibodeau Stephen N. , Gunawardena Shanaka R. , Bapat Bharati , Baron John A. , Casey Graham , Gallinger Steven , Le Marchand Loïc , Newcomb Polly A. , Haile Robert W. , Hopper John L. , Jenkins Mark A.
Published: February 2012

Purpose

To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population.

Patients and Methods

We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers.

Results

Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97).

Conclusion

We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.
CoREST acts as a positive regulator of Notch signaling in the follicle cells ofDrosophila melanogaster
Authors: Domanitskaya Elena , Schüpbach Trudi
Published: February 2012

The Notch signaling pathway plays important roles in a variety of developmental events. The context-dependent activities of positive and negative modulators dramatically increase the diversity of cellular responses to Notch signaling. In a screen for mutations affecting the Drosophila melanogaster follicular epithelium, we isolated a mutation in CoREST that disrupts the Notch-dependent mitotic-to-endocycle switch of follicle cells at stage 6 of oogenesis. We show that Drosophila CoREST positively regulates Notch signaling, acting downstream of the proteolytic cleavage of Notch but upstream of Hindsight activity; the Hindsight gene is a Notch target that coordinates responses in the follicle cells. We show that CoREST genetically interacts with components of the Notch repressor complex, Hairless, C-terminal Binding Protein and Groucho. In addition, we demonstrate that levels of H3K27me3 and H4K16 acetylation are dramatically increased in CoREST mutant follicle cells. Our data indicate that CoREST acts as a positive modulator of the Notch pathway in the follicular epithelium as well as in wing tissue, and suggests a previously unidentified role for CoREST in the regulation of Notch signaling. Given its high degree of conservation among species, CoREST probably also functions as a regulator of Notch-dependent cellular events in other organisms.
Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion
Authors: Townley Anna K. , Schmidt Katy , Hodgson Lorna , Stephens David J.
Published: February 2012

Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13–Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.
Hnrpab regulates neural development and neuron cell survival after glutamate stimulation
Authors: Sinnamon John R. , Waddell Catherine B. , Nik Sara , Chen Emily I. , Czaplinski Kevin
Published: February 2012

The molecular mechanisms that govern the timing and fate of neural stem-cell differentiation toward the distinct neural lineages of the nervous system are not well defined. The contribution of post-transcriptional regulation of gene expression to neural stem-cell maintenance and differentiation, in particular, remains inadequately characterized. The RNA-binding protein Hnrpab is highly expressed in developing nervous tissue and in neurogenic regions of the adult brain, but its role in neural development and function is unknown. We raised a mouse that lacks Hnrpab expression to define what role, if any, Hnrpab plays during mouse neural development. We performed a genome-wide quantitative analysis of protein expression within the hippocampus of newborn mice to demonstrate significantly altered gene expression in mice lacking Hnrpab relative to Hnrpab-expressing littermates. The proteins affected suggested an altered pattern of neural development and also unexpectedly indicated altered glutamate signaling. We demonstrate that Hnrpab−/−neural stem and progenitor cells undergo altered differentiation patterns in culture, and mature Hnrpab−/−neurons demonstrate increased sensitivity to glutamate-induced excitotoxicity. We also demonstrate that Hnrpab nucleocytoplasmic distribution in primary neurons is regulated by developmental stage.
Rational Automata Networks: A Non-Markovian Modeling Approach
Authors: Buchholz Peter , Telek Miklós
Published: February 2012

A new class of non-Markovian models is introduced that results from the combination of stochastic automata networks and a very general class of stochastic processes, namely, rational arrival processes, which are derived from matrix exponential distributions. It is shown that the modeling formalism allows a compact representation of complex models with large state spaces. The resulting stochastic process is non-Markovian, but it can be analyzed with numerical techniques like a Markov chain, and the results at the level of the automata are stochastic distributions that can be used to compute standard performance and dependability results. The model class includes stochastic automata networks with phase-type distributed and correlated event times and also includes models that have a finite state space but cannot be represented by finite Markov chains. The paper introduces the model class, shows how the descriptor matrix can be represented in compact form, presents some example models, and outlines methods to analyze the new models.
Static Network Reliability Estimation via Generalized Splitting
Authors: Botev Zdravko I. , L'Ecuyer Pierre , Rubino Gerardo , Simard Richard , Tuffin Bruno
Published: February 2012

We propose a novel simulation-based method that exploits a generalized splitting (GS) algorithm to estimate the reliability of a graph (or network), defined here as the probability that a given set of nodes are connected, when each link of the graph fails with a given (small) probability. For large graphs, in general, computing the exact reliability is an intractable problem and estimating it by standard Monte Carlo methods poses serious difficulties, because the unreliability (one minus the reliability) is often a rare-event probability. We show that the proposed GS algorithm can accurately estimate extremely small unreliabilities and we exhibit large examples where it performs much better than existing approaches. It is also flexible enough to dispense with the frequently made assumption of independent edge failures.
Research Note—Music Blogging, Online Sampling, and the Long Tail
Authors: Dewan Sanjeev , Ramaprasad Jui
Published: February 2012

Online social media such as blogs are transforming how consumers make consumption decisions, and the music industry is at the forefront of this revolution. Based on data from a leading music blog aggregator, we analyze the relationship between music blogging and full-track sampling, drawing on theories of online social interaction. Our results suggest that intensity of music sampling is positively associated with the popularity of a blog among previous consumers and that this association is stronger in the tail than in the body of music sales distribution. At the same time, the incremental effect of music popularity on sampling is also stronger in the tail relative to the body. In the last part of the paper, we discuss the implications of our results for music sales and potential long-tailing of music sampling and sales. Put together, our analysis sheds new light on how social media are reshaping music sharing and consumption.
Indolocarbazole-based anion receptors and molecular switches
Authors: Suk Jae-min , Chae Min Kyung , Jeong Kyu-Sung
Published: February 2012

A number of indolocarbazole-based anion receptors were prepared and their anion-binding behaviors were characterized in solution and in the solid state. First, chain-length-dependent binding affinities of chloride ion were revealed using a series of indolocarbazoles that consisted of one to four indolocarbazole units. The binding affinities were steadily enhanced from monomer to dimer, then to trimer by Gibb’s free energy (–∆∆G) = 2.4 ± 0.1 kcal/mol, and then nearly saturated. Second, a water-soluble trimer folded to generate an internal helical cavity with six convergent NHs, wherein small halides bound in water in the order of Cl–(65 M–1) > F–(46 M–1), and Br–(19 M–1). Third, X-ray crystal structures clearly proved helical folding of a trimer in the presence of sulfate ion, in which left- and right-handed helices stacked alternatively. It was also shown that the selectivity of anion binding could be varied by the modification of the spacer groups connecting indolocarbazole units. Finally, we prepared chiral indolocabazole dimers that adopted helical structures by intramolecular hydrogen bonds and displayed complete inversion of the helical sense upon anion binding. The dimers gave characteristic optical readouts in a reversible manner according to chemical stimuli, thus functioning as chirooptical molecular switches.
Role of Neurokinin B in the Control of Female Puberty and Its Modulation by Metabolic Status
Authors: Navarro Víctor M. , Ruiz-Pino Francisco , Sánchez-Garrido Miguel A. , García-Galiano David , Hobbs Samuel J. , Manfredi-Lozano María , León Silvia , Sangiao-Alvarellos Susana , Castellano Juan M. , Clifton Donald K. , Pinilla Leonor , Steiner Robert A. , Tena-Sempere Manuel
Published: February 2012

Human genetic studies have revealed that neurokinin B (NKB) and its receptor, neurokinin-3 receptor (NK3R), are essential elements for normal reproduction; however, the precise role of NKB–NK3R signaling in the initiation of puberty remains unknown. We investigated here the regulation ofTac2andTacr3mRNAs (encoding NKB and NK3R, respectively) in female rats and demonstrated that their hypothalamic expression is increased along postnatal maturation. At puberty, both genes were widely expressed throughout the brain, including the lateral hypothalamic area and the arcuate nucleus (ARC)/medial basal hypothalamus, where the expression ofTacr3increased across pubertal transition. We showed that central administration of senktide (NK3R agonist) induced luteinizing hormone (LH) secretion in prepubertal and peripubertal females. Conversely, chronic infusion of an NK3R antagonist during puberty moderately delayed the timing of vaginal opening (VO) and tended to decrease LH levels. The expression of NKB and its receptor was sensitive to changes in metabolic status during puberty, as reflected by a reduction inTacr3(and, to a lesser extent,Tac2) expression in the ARC after a 48 h fast. Yet, acute LH responses to senktide in pubertal females were preserved, if not augmented, under fasting conditions, suggesting sensitization of the NKB–NK3R–gonadotropin-releasing hormone signaling pathway under metabolic distress. Moreover, repeated administration of senktide to female rats with pubertal arrest due to chronic undernutrition rescued VO (in ∼50% of animals) and potently elicited LH release. Altogether, our observations suggest that NKB–NK3R signaling plays a role in pubertal maturation and that its alterations may contribute to pubertal disorders linked to metabolic stress and negative energy balance.
Striatal α5 Nicotinic Receptor Subunit Regulates Dopamine Transmission in Dorsal Striatum
Authors: Exley Richard , McIntosh J. Michael , Marks Michael J. , Maskos Uwe , Cragg Stephanie J.
Published: February 2012

Polymorphisms in the gene for the α5 nicotinic acetylcholine receptor (nAChR) subunit are associated with vulnerability to nicotine addiction. However, the underlying normal functions of α5-containing nAChRs in the brain are poorly understood. Striatal dopamine (DA) transmission is critical to the acquisition and maintenance of drug addiction and is modulated strongly by nicotine acting at heteromeric β2-containing (β2*) nAChRs. We explored whether α5 subunits, as well as α4, α6, and β3 subunits, participate in the powerful regulation of DA release probability by β2* nAChRs in nucleus accumbens (NAc) core and in dorsal striatum [caudatoputamen (CPu)]. We detected evoked dopamine release using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal slices from mice with deletions of α4, α5, α6, or β3 subunits. We show that the nAChR subtypes that dominantly regulate dopamine transmission depend critically upon α5 subunits in the dorsal CPu in α4α5(non-α6)β2-nAChRs but not in NAc core, where α4α6β2β3-nAChRs are required. These data reveal the distinct populations of nAChRs that govern DA transmission in NAc core versus dorsal CPu. Furthermore, they indicate that α5 subunits are critical to the regulation of DA transmission by α4β2* nAChRs in regions of striatum associated with habitual and instrumental responses (dorsal CPu) rather than pavlovian associations (NAc).
Causal Links between Dorsal Medial Superior Temporal Area Neurons and Multisensory Heading Perception
Authors: Gu Yong , DeAngelis Gregory C. , Angelaki Dora E.
Published: February 2012

The dorsal medial superior temporal area (MSTd) in the extrastriate visual cortex is thought to play an important role in heading perception because neurons in this area are tuned to both optic flow and vestibular signals. MSTd neurons also show significant correlations with perceptual judgments during a fine heading direction discrimination task. To test for a causal link with heading perception, we used microstimulation and reversible inactivation techniques to artificially perturb MSTd activity while monitoring behavioral performance. Electrical microstimulation significantly biased monkeys' heading percepts based on optic flow, but did not significantly impact vestibular heading judgments. The latter result may be due to the fact that vestibular heading preferences in MSTd are more weakly clustered than visual preferences and multiunit tuning for vestibular stimuli is weak. Reversible chemical inactivation, however, increased behavioral thresholds when heading judgments were based on either optic flow or vestibular cues, although the magnitude of the effects was substantially stronger for optic flow. Behavioral deficits in a combined visual/vestibular stimulus condition were intermediate between the single-cue effects. Despite deficits in discrimination thresholds, animals were able to combine visual and vestibular cues near optimally, even after large bilateral muscimol injections into MSTd. Simulations show that the overall pattern of results following inactivation is consistent with a mixture of contributions from MSTd and other areas with vestibular-dominant tuning for heading. Our results support a causal link between MSTd neurons and multisensory heading perception but suggest that other multisensory brain areas also contribute.
Mechanisms Underlying Signal Filtering at a Multisynapse Contact
Authors: Budisantoso Timotheus , Matsui Ko , Kamasawa Naomi , Fukazawa Yugo , Shigemoto Ryuichi
Published: February 2012

Visual information must be relayed through the lateral geniculate nucleus before it reaches the visual cortex. However, not all spikes created in the retina lead to postsynaptic spikes and properties of the retinogeniculate synapse contribute to this filtering. To understand the mechanisms underlying this filtering process, we conducted electrophysiology to assess the properties of signal transmission in the Long–Evans rat. We also performed SDS-digested freeze–fracture replica labeling to quantify the receptor and transporter distribution, as well as EM reconstruction to describe the 3D structure. To analyze the impact of transmitter diffusion on the activity of the receptors, simulations were integrated. We identified that a large contributor to the filtering is the marked paired-pulse depression at this synapse, which was intensified by the morphological characteristics of the contacts. The broad presynaptic and postsynaptic contact area restricts transmitter diffusion two dimensionally. Additionally, the presence of multiple closely arranged release sites invites intersynaptic spillover, which causes desensitization of AMPA receptors. The presence of AMPA receptors that slowly recover from desensitization along with the high presynaptic release probability and multivesicular release at each synapse also contribute to the depression. These features contrast with many other synapses where spatiotemporal spread of transmitter is limited by rapid transmitter clearance allowing synapses to operate more independently. We propose that the micrometer-order structure can ultimately affect the visual information processing.
Deliberation in the Motor System: Reflex Gains Track Evolving Evidence Leading to a Decision
Authors: Selen Luc P. J. , Shadlen Michael N. , Wolpert Daniel M.
Published: February 2012

Both decision making and sensorimotor control require real-time processing of noisy information streams. Historically these processes were thought to operate sequentially: cognitive processing leads to a decision, and the outcome is passed to the motor system to be converted into action. Recently, it has been suggested that the decision process may provide a continuous flow of information to the motor system, allowing it to prepare in a graded fashion for the probable outcome. Such continuous flow is supported by electrophysiology in nonhuman primates. Here we provide direct evidence for the continuous flow of an evolving decision variable to the motor system in humans. Subjects viewed a dynamic random dot display and were asked to indicate their decision about direction by moving a handle to one of two targets. We probed the state of the motor system by perturbing the arm at random times during decision formation. Reflex gains were modulated by the strength and duration of motion, reflecting the accumulated evidence in support of the evolving decision. The magnitude and variance of these gains tracked a decision variable that explained the subject's decision accuracy. The findings support a continuous process linking the evolving computations associated with decision making and sensorimotor control.
Tamalin Is a Critical Mediator of Electroconvulsive Shock-Induced Adult Neuroplasticity
Authors: Yanpallewar Sudhirkumar U. , Barrick Colleen A. , Palko Mary Ellen , Fulgenzi Gianluca , Tessarollo Lino
Published: February 2012

The molecular mechanisms underlying the effects of electroconvulsive shock (ECS) therapy, a fast-acting and very effective antidepressant therapy, are poorly understood. Changes related to neuroplasticity, including enhanced adult hippocampal neurogenesis and neuronal arborization, are believed to play an important role in mediating the effects of ECS. Here we show a dynamic upregulation of the scaffold protein tamalin, selectively in the hippocampus of animals subjected to ECS. Interestingly, this gene upregulation is functionally significant because tamalin deletion in mice abrogated ECS-induced neurogenesis in the adult mouse hippocampus. Furthermore, loss of tamalin blunts mossy fiber sprouting and dendritic arborization caused by ECS. These data suggest an essential role for tamalin in ECS-induced adult neuroplasticity and provide new insight into the pathways that are involved in mediating ECS effects.
Neuronal Activity in the Human Subthalamic Nucleus Encodes Decision Conflict during Action Selection
Authors: Zaghloul Kareem A. , Weidemann Christoph T. , Lega Bradley C. , Jaggi Jurg L. , Baltuch Gordon H. , Kahana Michael J.
Published: February 2012

The subthalamic nucleus (STN), which receives excitatory inputs from the cortex and has direct connections with the inhibitory pathways of the basal ganglia, is well positioned to efficiently mediate action selection. Here, we use microelectrode recordings captured during deep brain stimulation surgery as participants engage in a decision task to examine the role of the human STN in action selection. We demonstrate that spiking activity in the STN increases when participants engage in a decision and that the level of spiking activity increases with the degree of decision conflict. These data implicate the STN as an important mediator of action selection during decision processes.
Hippocampal Histone Acetylation Regulates Object Recognition and the Estradiol-Induced Enhancement of Object Recognition
Authors: Zhao Zaorui , Fan Lu , Fortress Ashley M. , Boulware Marissa I. , Frick Karyn M.
Published: February 2012

Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitorin vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol (E2). We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2(5 μg/side), garcinol (1 ng/side), or E2plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of thede novomethyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2. Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor.
Regulation of Mitochondrial Transport and Inter-Microtubule Spacing by Tau Phosphorylation at the Sites Hyperphosphorylated in Alzheimer's Disease
Authors: Shahpasand Kourosh , Uemura Isao , Saito Taro , Asano Tsunaki , Hata Kenji , Shibata Keitaro , Toyoshima Yoko , Hasegawa Masato , Hisanaga Shin-ichi
Published: February 2012

The microtubule-associated protein Tau is a major component of the neurofibrillary tangles that serve as a neuropathological hallmark of Alzheimer's disease. Tau is a substrate for protein phosphorylation at multiple sites and occurs in tangles in a hyperphosphorylated state. However, the physiological functions of Tau phosphorylation or how it may contribute mechanistically to Alzheimer's pathophysiology are not completely understood. Here, we examined the function of human Tau phosphorylation at three sites, Ser199, Ser202, and Thr205, which together comprise the AT8 sites that mark abnormal phosphorylation in Alzheimer's disease. Overexpression of wild-type Tau or mutated forms in which these sites had been changed to either unphosphorylatable alanines or phosphomimetic aspartates inhibited mitochondrial movement in the neurite processes of PC12 cells as well as the axons of mouse brain cortical neurons. However, the greatest effects on mitochondrial translocation were induced by phosphomimetic mutations. These mutations also caused expansion of the space between microtubules in cultured cells when membrane tension was reduced by disrupting actin filaments. Thus, Tau phosphorylation at the AT8 sites may have meaningful effects on mitochondrial movement, likely by controlling microtubule spacing. Hyperphosphorylation of the AT8 sites may contribute to axonal degeneration by disrupting mitochondrial transport in Alzheimer's disease.
Successful Use of Bisphosphonate and Calcimimetic in Neonatal Severe Primary Hyperparathyroidism
Authors: Wilhelm-Bals Alexandra , Parvex Paloma , Magdelaine Corinne , Girardin Eric
Published: February 2012

Neonatal primary hyperparathyroidism (NPHT) is associated with an inactivating homozygous mutation of the calcium sensing receptor (CaSR). The CaSR is expressed most abundantly in the parathyroid glands and the kidney and regulates calcium homeostasis through its ability to modulate parathormone secretion and renal calcium reabsorption. NPHT leads to life threatening hypercalcemia, nephrocalcinosis, bone demineralization, and neurologic disabilities. Surgery is the treatment of choice. While waiting for surgery, bisphosphonates offer a good alternative to deal with hypercalcemia. Cinacalcet is a class II calcimimetic that increases CaSR affinity for calcium, leading to parathormone suppression and increased calcium renal excretion. At present, there is little evidence as to whether cinacalcet could improve the function of mutant CaSR in NPHT. We report a case of NPHT, treated successfully with bisphosphonates and cinacalcet after surgery failure. To our knowledge, it is the first time cinacalcet has been used for NPHT.
A Primary Care–Based, Multicomponent Lifestyle Intervention for Overweight Adolescent Females
Authors: DeBar Lynn L. , Stevens Victor J. , Perrin Nancy , Wu Philip , Pearson John , Yarborough Bobbi Jo , Dickerson John , Lynch Frances
Published: February 2012

BACKGROUND AND OBJECTIVE:

Most clinic-based weight control treatments for youth have been designed for preadolescent children by using family-based care. However, as adolescents become more autonomous and less motivated by parental influence, this strategy may be less appropriate. This study evaluated a primary care–based, multicomponent lifestyle intervention specifically tailored for overweight adolescent females.

METHODS:

Adolescent girls (N = 208) 12 to 17 years of age (mean ± SD: 14.1 ± 1.4 years), with a mean ± SD BMI percentile of 97.09 ± 2.27, were assigned randomly to the intervention or usual care control group. The gender and developmentally tailored intervention included a focus on adoptable healthy lifestyle behaviors and was reinforced by ongoing feedback from the teen’s primary care physician. Of those randomized, 195 (94%) completed the 6-month posttreatment assessment, and 173 (83%) completed the 12-month follow-up. The primary outcome was reduction in BMI z score.

RESULTS:

The decrease in BMI z score over time was significantly greater for intervention participants compared with usual care participants (−0.15 in BMI z score among intervention participants compared with −0.08 among usual care participants; P = .012). The 2 groups did not differ in secondary metabolic or psychosocial outcomes. Compared with usual care, intervention participants reported less reduction in frequency of family meals and less fast-food intake.

CONCLUSIONS:

A 5-month, medium-intensity, primary care–based, multicomponent behavioral intervention was associated with significant and sustained decreases in BMI z scores among obese adolescent girls compared with those receiving usual care.
Effect of Repeated Dietary Counseling on Serum Lipoproteins From Infancy to Adulthood
Authors: Niinikoski Harri , Pahkala Katja , Ala-Korpela Mika , Viikari Jorma , Rönnemaa Tapani , Lagström Hanna , Jokinen Eero , Jula Antti , Savolainen Markku J. , Simell Olli , Raitakari Olli T.
Published: February 2012

BACKGROUND AND OBJECTIVE:

As atherosclerosis is a lifelong process, prevention of exposure to its risk factors should start at an early age. Our aim was to study the influences of repeated low saturated fat dietary counseling on dietary intakes and lipoprotein measures from infancy to adulthood.

METHODS:

Dietary intakes (food records) and serum lipid profile were studied annually from 7 months to 19 years of age in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project), comprising 540 children in the intervention group and 522 children in the control group. Serum total and high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured and used to estimate very low-density lipoprotein–TG, intermediate-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and HDL2-C, as well as apolipoproteins A-1 and B.

RESULTS:

Compared with controls, the intervention children had a lower saturated fat intake (mean daily difference [95% confidence interval] between groups: −2.1 [−2.3, −1.9] percentage of total energy intake in boys; −1.9 [−2.1, −1.7] percentage of total energy intake in girls, both P < .001) and LDL-C concentration (difference [95% confidence interval] between groups: −0.18 [−0.26, −0.10] mmol/L, P < .001 in boys; −0.10 [−0.19, −0.01] mmol/L, P = .037 in girls), whereas HDL-C and apolipoprotein A-1 did not differ between the study groups. In boys, total cholesterol and intermediate-density lipoprotein cholesterol, very low-density lipoprotein–TG, apolipoprotein B, and TG concentrations were also lower in the intervention than in the control group, whereas no differences were found in girls.

CONCLUSIONS:

Repeated dietary counseling is effective in decreasing saturated fat intake and serum LDL-C values from infancy until 19 years of age in both genders. In boys, significant intervention effects are evident in various lipoprotein measures, indicating a more favorable lipid profile in the counseling group.
Antenatal Antecedents of Cognitive Impairment at 24 Months In Extremely Low Gestational Age Newborns
Authors: Helderman Jennifer B. , O’Shea Thomas M. , Kuban Karl C. K. , Allred Elizabeth N. , Hecht Jonathan L. , Dammann Olaf , Paneth Nigel , McElrath T. F. , Onderdonk Andrew , Leviton Alan ,   for the ELGAN study Investigators
Published: February 2012

BACKGROUND AND OBJECTIVES:

Extremely low gestational age neonates are more likely than term infants to develop cognitive impairment. Few studies have addressed antenatal risk factors of this condition. We identified antenatal antecedents of cognitive impairment determined by the Mental Development Index (MDI) portion of the Bayley Scales of Infant Development, Second Edition (BSID-II), at 24 months corrected age.

METHODS:

We studied a multicenter cohort of 921 infants born before 28 weeks of gestation during 2002 to 2004 and assessed their placentas for histologic characteristics and microorganisms. The mother was interviewed and her medical record was reviewed. At 24 months adjusted age, children were assessed with BSID-II. Multinomial logistic models were used to estimate odds ratios.

RESULTS:

A total of 103 infants (11%) had an MDI <55, and 99 infants (11%) had an MDI between 55 and 69. No associations were identified between organisms recovered from the placenta and developmental delay. Factors most strongly associated with MDI <55 were thrombosis of fetal vessels (OR 3.1; 95% confidence interval [CI] 1.2, 7.7), maternal BMI >30 (OR 2.0; 95% CI 1.1, 3.5), maternal education ≤12 years (OR 3.4; 95% CI 1.9, 6.2), nonwhite race (OR 2.2; 95% CI 1.3, 3.8), birth weight z score < −2 (OR 2.8; 95% CI 1.1, 6.9), and male gender (OR 2.7; 95% CI 1.6, 4.5).

CONCLUSIONS:

Antenatal factors, including thrombosis of fetal vessels in the placenta, severe fetal growth restriction, and maternal obesity, convey information about the risk of cognitive impairment among extremely premature newborns.
Hemodynamic Effects of Delayed Cord Clamping in Premature Infants
Authors: Sommers Ross , Stonestreet Barbara S. , Oh William , Laptook Abbot , Yanowitz Toby Debra , Raker Christina , Mercer Judith
Published: February 2012

BACKGROUND AND OBJECTIVE:

Delayed cord clamping (DCC) has been advocated during preterm delivery to improve hemodynamic stability during the early neonatal period. The hemodynamic effects of DCC in premature infants after birth have not been previously examined. Our objective was to compare the hemodynamic differences between premature infants randomized to either DCC or immediate cord clamping (ICC).

METHODS:

This prospective study was conducted on a subset of infants who were enrolled in a randomized controlled trial to evaluate the effects of DCC versus ICC. Entry criteria included gestational ages of 240 to 316 weeks. Twins and infants of mothers with substance abuse were excluded. Serial Doppler studies were performed at 6 ± 2, 24 ± 4, 48 ± 6, and 108 ± 12 hours of life. Measurements included superior vena cava blood flow, right ventricle output, middle cerebral artery blood flow velocity (BFV), superior mesenteric artery BFV, left ventricle shortening fraction, and presence of a persistent ductus arteriosus.

RESULTS:

Twenty-five infants were enrolled in the DCC group and 26 in the ICC group. Gestational age, birth weight, and male gender were similar. Admission laboratory and clinical events were also similar. DCC resulted in significantly higher superior vena cava blood flow over the study period, as well as greater right ventricle output and right ventricular stroke volumes at 48 hours. No differences were noted in middle cerebral artery BFV, mean superior mesenteric artery BFV, shortening fraction, or the incidence of a persistent ductus arteriosus.

CONCLUSIONS:

DCC in premature infants is associated with potentially beneficial hemodynamic changes over the first days of life.
Microstructural, Optical and Electrical Properties Of Post-Annealed ZnO:Al Thin Films
Authors: Charpentier Coralie , Prod’Homme Patricia , Francke Loïc , Roca i Cabarrocas Pere
Published: February 2012

Aluminum-doped zinc oxide (ZnO:Al) thin films were prepared on glass substrates by radio frequency (RF) magnetron sputtering from a ceramic mixed target ZnO:Al2O3 (1 wt.%) with a power of 250 W. Two series of samples were deposited at room temperature, the first one in pure Ar atmosphere, the second one in Ar/O2 gas mixture. Effects of post-deposition annealing treatments carried out from 400 °C to 500 °C under vacuum and in N2/H2 (5%) atmosphere have been investigated. The influence of these parameters was studied by a detailed microstructural analysis using X-Ray diffraction and Raman spectroscopy. For N2/H2 annealing process, the increase of charge carrier concentration limits the increase of the mobility while after vacuum annealing, an improvement of both electrical and optical properties was observed. The increase of the crystallinity and grain size for ZnO:Al films deposited in Ar/O2 gas mixture could explain their improvements. Resistivity was reduced down to 3.5×10-4 Ω.cm, for a mobility of 49 cm2/V.s with a vacuum annealing at 450 °C for ZnO:Al deposited in Ar/O2 gas mixture.
Time-of-Flight Technique Limits of Applicability for Thin-Films of Π-Conjugated Polymers
Authors: Cavallari Marco R. , Zanchin Vinicius R. , Amorim Cleber A. , dos Santos Gerson , Fonseca Fernando J. , Andrade Adnei M. , Mergulhão Sergio
Published: February 2012

Time of flight (ToF) is the most straightforward technique to determine polymeric semiconductor mobility for electronic applications. We demonstrate ToF limits of applicability to amorphous PPV derivatives, such as poly[2-methoxy-5-(3’,7’-dimethylloctyloxy)-1-4-phenylene vinylene] (MDMO-PPV) and poly[2-methoxy-5-(2’-ethylhexyloxy)-1-4-phenylene vinylene] (MEH-PPV), and polycrystalline poly(3-hexylthiophene) (P3HT). Hole and electron mobility (μ) in submicrometric films (200 – 500 nm) is overestimated compared to casted layers, due to reduced absorption capability, which is confirmed by Charge Extraction by Linearly Increasing Voltage (CELIV) measurements. Charge transport properties in nanometric films, such as for Field-Effect Transistors (FET), can not be studied by current-mode ToF. Hole mobility of ca. 10-5 cm2/Vs with Poole-Frenkel behavior for PPV derivatives and 10-3 cm2/Vs for P3HT is at least one order of magnitude higher than ToF results.
Oligoaniline crystals: morphology control, hierarchical assembly and structure-property relationships
Authors: Wang Yue , Tran Henry D. , Liu Jinglin , Martin David C. , Kaner Richard B.
Published: February 2012

Short-chain oligomers of aniline are attractive semi-metallic materials for applications as organic electrodes or hole-transporting layers in organic photovoltaics. However, conventionally processed oligoanilines are often amorphous, which limits their conductivities and carrier transport mobilities. Here, we report a simple solvent-exchange method that can render a variety of oligoanilines and their derivatives into crystals of different shapes and dimensions, including 1-D fibers and wires, 2-D ribbons, and 3-D plates, hollow spheres, porous sheets, and flower-like structures. Dopant ions are also simultaneously incorporated into the crystals during self-assembly, allowing them to become conducting. Mechanistic studies suggest that the higher order crystals arise from the most primitive nanofibrillar morphology via hierarchical assembly, providing insights into a general approach to control organic crystal morphologies. Selected area electron diffraction studies reveal their single crystalline nature.
Tentativas de suicídio e mortalidade por suicídio em um município no interior da Bahia
Authors: Souza Viviane dos Santos , Alves Murilo da Silva , Silva Lívia Angeli , Lino Débora Cristiane Silva Flores , Nery Adriana Alves , Casotti Cezar Augusto
Published: February 2012

Objetivo: Descrever o perfil das tentativas de suicídio e mortalidade por suicídio no município de Jequié/BA, no período entre 2006 e 2010. Método: Estudo epidemiológico descritivo. Os dados das tentativas de suicídio foram obtidos no Corpo de Bombeiros e DATASUS, enquanto aqueles referentes à mortalidade por suicídio foram coletados por meio das declarações de óbito (DOs) da 13ª Diretoria Regional de Saúde da Bahia (13ª DIRES) e complementados pelos registros do Instituto Médico Legal (IML). A análise foi feita por meio de estatística descritiva. Resultados: Nas tentativas de suicídio, a maior frequência foi na faixa etária de 20 a 39 anos (57,69%), entre indivíduos do sexo feminino (53,4%) e utilizando-se como meio a queda de altura (69,2%). Em relação ao suicídio, a taxa média de mortalidade foi de 3,19/100.000 habitantes, com maior frequência em indivíduos acima dos 40 anos (54,16%), do sexo masculino (87,5%), por meio de enforcamento (58,3%) e tendo como local de ocorrência o domicílio (83,33%). Conclusão: O município mostrou-se dentro das estatísticas da região Nordeste e abaixo das taxas nacionais de suicídio. Houve diferenciação entre as características do perfil das tentativas de suicídio e mortalidade por suicídio, especialmente segundo o sexo, faixa etária e meios utilizados.