bluuebunny/crossref_metadata_2025 huggingface dataset:
Corticotropin-Releasing Hormone Drives Anandamide Hydrolysis in the Amygdala to Promote Anxiety
Authors: Gray J. Megan , Vecchiarelli Haley A. , Morena Maria , Lee Tiffany T.Y. , Hermanson Daniel J. , Kim Alexander B. , McLaughlin Ryan J. , Hassan Kowther I. , Kühne Claudia , Wotjak Carsten T. , Deussing Jan M. , Patel Sachin , Hill Matthew N.
Published: March 2015

Corticotropin-releasing hormone (CRH) is a central integrator in the brain of endocrine and behavioral stress responses, whereas activation of the endocannabinoid CB1 receptor suppresses these responses. Although these systems regulate overlapping functions, few studies have investigated whether these systems interact. Here we demonstrate a novel mechanism of CRH-induced anxiety that relies on modulation of endocannabinoids. Specifically, we found that CRH, through activation of the CRH receptor type 1 (CRHR1), evokes a rapid induction of the enzyme fatty acid amide hydrolase (FAAH), which causes a reduction in the endocannabinoid anandamide (AEA), within the amygdala. Similarly, the ability of acute stress to modulate amygdala FAAH and AEA in both rats and mice is also mediated through CRHR1 activation. This interaction occurs specifically in amygdala pyramidal neurons and represents a novel mechanism of endocannabinoid–CRH interactions in regulating amygdala output. Functionally, we found that CRH signaling in the amygdala promotes an anxious phenotype that is prevented by FAAH inhibition. Together, this work suggests that rapid reductions in amygdala AEA signaling following stress may prime the amygdala and facilitate the generation of downstream stress-linked behaviors. Given that endocannabinoid signaling is thought to exert “tonic” regulation on stress and anxiety responses, these data suggest that CRH signaling coordinates a disruption of tonic AEA activity to promote a state of anxiety, which in turn may represent an endogenous mechanism by which stress enhances anxiety. These data suggest that FAAH inhibitors may represent a novel class of anxiolytics that specifically target stress-induced anxiety.
The Subventricular Zone Continues to Generate Corpus Callosum and Rostral Migratory Stream Astroglia in Normal Adult Mice
Authors: Sohn Jiho , Orosco Lori , Guo Fuzheng , Chung Seung-Hyuk , Bannerman Peter , Mills Ko Emily , Zarbalis Kostas , Deng Wenbin , Pleasure David
Published: March 2015

Astrocytes are the most abundant cells in the CNS, and have many essential functions, including maintenance of blood–brain barrier integrity, and CNS water, ion, and glutamate homeostasis. Mammalian astrogliogenesis has generally been considered to be completed soon after birth, and to be reactivated in later life only under pathological circumstances. Here, by using genetic fate-mapping, we demonstrate that new corpus callosum astrocytes are continuously generated from nestin+subventricular zone (SVZ) neural progenitor cells (NPCs) in normal adult mice. These nestin fate-mapped corpus callosum astrocytes are uniformly postmitotic, express glutamate receptors, and form aquaporin-4+perivascular endfeet. The entry of new astrocytes from the SVZ into the corpus callosum appears to be balanced by astroglial apoptosis, because overall numbers of corpus callosum astrocytes remain constant during normal adulthood. Nestin fate-mapped astrocytes also flow anteriorly from the SVZ in association with the rostral migratory stream, but do not penetrate into the deeper layers of the olfactory bulb. Production of new astrocytes from nestin+NPCs is absent in the normal adult cortex, striatum, and spinal cord. Our study is the first to demonstrate ongoing SVZ astrogliogenesis in the normal adult mammalian forebrain.
Nicotinic Receptor Subtype-Selective Circuit Patterns in the Subthalamic Nucleus
Authors: Xiao Cheng , Miwa Julie M. , Henderson Brandon J. , Wang Ying , Deshpande Purnima , McKinney Sheri L. , Lester Henry A.
Published: March 2015

The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about the mechanisms of cholinergic modulation in the STN, we studied cellular and circuit aspects of nicotinic acetylcholine receptors (nAChRs) in mouse STN. We discovered two largely divergent microcircuits in the STN; these are regulated in part by either α4β2 or α7 nAChRs. STN neurons containing α4β2 nAChRs (α4β2 neurons) received more glutamatergic inputs, and preferentially innervated GABAergic neurons in the substantia nigra pars reticulata. In contrast, STN neurons containing α7 nAChRs (α7 neurons) received more GABAergic inputs, and preferentially innervated dopaminergic neurons in the substantia nigra pars compacta. Interestingly, local electrical stimuli excited a majority (79%) of α4β2 neurons but exerted strong inhibition in 58% of α7 neurons, indicating an additional diversity of STN neurons: responses to electrical stimulation. Chronic exposure to nicotine selectively affects α4β2 nAChRs in STN: this treatment increased the number of α4β2 neurons, upregulated α4-containing nAChR number and sensitivity, and enhanced the basal firing rate of α4β2 neurons bothex vivoandin vivo. Thus, chronic nicotine enhances the function of the microcircuit involving α4β2 nAChRs. This indicates chronic exposure to nicotinic agonist as a potential pharmacological intervention to alter selectively the balance between these two microcircuits, and may provide a means to inhibit substantia nigra dopaminergic neurons.
Role of the Indirect Pathway of the Basal Ganglia in Perceptual Decision Making
Authors: Wei Wei , Rubin Jonathan E. , Wang Xiao-Jing
Published: March 2015

The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed–accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond the focus of previous works on the direct and hyperdirect pathways to examine the contribution of the indirect pathway of the BG system to decision making in a biophysically based spiking network model. We find that the mechanism of adjusting the decision threshold by plasticity of the corticostriatal connections is effective, provided that the indirect pathway counterbalances the direct pathway in their projections to the output nucleus. Furthermore, in our model, changes within basal ganglia connections similar to those that arise in parkinsonism give rise to strong beta oscillations. Specifically, beta oscillations are produced by an abnormal enhancement of the interactions between the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe) in the indirect pathway, with an oscillation frequency that depends on the excitatory cortical input to the STN and the inhibitory input to the GPe from the striatum. In a parkinsonian state characterized by pronounced beta oscillations, the mean reaction time and range of threshold variation (a measure of behavioral flexibility) are significantly reduced compared with the normal state. Our work thus reveals a specific circuit mechanism for impairments of perceptual decision making associated with Parkinson's disease.
Attending to Pitch Information Inhibits Processing of Pitch Information: The Curious Case of Amusia
Authors: Zendel Benjamin Rich , Lagrois Marie-Élaine , Robitaille Nicolas , Peretz Isabelle
Published: March 2015

In normal listeners, the tonal rules of music guide musical expectancy. In a minority of individuals, known as amusics, the processing of tonality is disordered, which results in severe musical deficits. It has been shown that the tonal rules of music are neurally encoded, but not consciously available in amusics. Previous neurophysiological studies have not explicitly controlled the level of attention in tasks where participants ignored the tonal structure of the stimuli. Here, we test whether access to tonal knowledge can be demonstrated in congenital amusia when attention is controlled. Electric brain responses were recorded while asking participants to detect an individually adjusted near-threshold click in a melody. In half the melodies, a note was inserted that violated the tonal rules of music. In a second task, participants were presented with the same melodies but were required to detect the tonal deviation. Both tasks required sustained attention, thus conscious access to the rules of tonality was manipulated. In the click-detection task, the pitch deviants evoked an early right anterior negativity (ERAN) in both groups. In the pitch-detection task, the pitch deviants evoked an ERAN and P600 in controls but not in amusics. These results indicate that pitch regularities are represented in the cortex of amusics, but are not consciously available. Moreover, performing a pitch-judgment task eliminated the ERAN in amusics, suggesting that attending to pitch information interferes with perception of pitch. We propose that an impaired top-down frontotemporal projection is responsible for this disorder.
Impaired Leptomeningeal Collateral Flow Contributes to the Poor Outcome following Experimental Stroke in the Type 2 Diabetic Mice
Authors: Akamatsu Yosuke , Nishijima Yasuo , Lee Chih Cheng , Yang Shih Yen , Shi Lei , An Lin , Wang Ruikang K. , Tominaga Teiji , Liu Jialing
Published: March 2015

Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabeticdb/dbmice, which coincided with a worse stroke outcome compared with their normoglycemic counterpartdb/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, bothdb/+ anddb/dbmice underwent collateral growth 7 d after MCA stroke, althoughdb/dbmice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in thedb/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in thedb/dbmice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects.
Structure of a Single Whisker Representation in Layer 2 of Mouse Somatosensory Cortex
Authors: Clancy Kelly B. , Schnepel Philipp , Rao Antara T. , Feldman Daniel E.
Published: March 2015

Layer (L)2 is a major output of primary sensory cortex that exhibits very sparse spiking, but the structure of sensory representation in L2 is not well understood. We combined two-photon calcium imaging with deflection of many whiskers to map whisker receptive fields, characterize sparse coding, and quantitatively define the point representation in L2 of mouse somatosensory cortex. Neurons within a column-sized imaging field showed surprisingly heterogeneous, salt-and-pepper tuning to many different whiskers. Single whisker deflection elicited low-probability spikes in highly distributed, shifting neural ensembles spanning multiple cortical columns. Whisker-evoked response probability correlated strongly with spontaneous firing rate, but weakly with tuning properties, indicating a spectrum of inherent responsiveness across pyramidal cells. L2 neurons projecting to motor and secondary somatosensory cortex differed in whisker tuning and responsiveness, and carried different amounts of information about columnar whisker deflection. From these data, we derive a quantitative, fine-scale picture of the distributed point representation in L2.
Dopamine D2-Receptor Blockade Enhances Decoding of Prefrontal Signals in Humans
Authors: Kahnt Thorsten , Weber Susanna C. , Haker Helene , Robbins Trevor W. , Tobler Philippe N.
Published: March 2015

The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors,post hocanalyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs.
Early-Onset Epileptic Encephalopathy Caused by Gain-of-Function Mutations in the Voltage Sensor of Kv7.2 and Kv7.3 Potassium Channel Subunits
Authors: Miceli Francesco , Soldovieri Maria Virginia , Ambrosino Paolo , De Maria Michela , Migliore Michele , Migliore Rosanna , Taglialatela Maurizio
Published: March 2015

Mutations inKv7.2(KCNQ2) andKv7.3(KCNQ3) genes, encoding for voltage-gated K+channel subunits underlying the neuronal M-current, have been associated with a wide spectrum of early-onset epileptic disorders ranging from benign familial neonatal seizures to severe epileptic encephalopathies. The aim of the present work has been to investigate the molecular mechanisms of channel dysfunction caused by voltage-sensing domain mutations in Kv7.2 (R144Q, R201C, and R201H) or Kv7.3 (R230C) recently found in patients with epileptic encephalopathies and/or intellectual disability. Electrophysiological studies in mammalian cells transfected with human Kv7.2 and/or Kv7.3 cDNAs revealed that each of these four mutations stabilized the activated state of the channel, thereby producing gain-of-function effects, which are opposite to the loss-of-function effects produced by previously found mutations. Multistate structural modeling revealed that the R201 residue in Kv7.2, corresponding to R230 in Kv7.3, stabilized the resting and nearby voltage-sensing domain states by forming an intricate network of electrostatic interactions with neighboring negatively charged residues, a result also confirmed by disulfide trapping experiments. Using a realistic model of a feedforward inhibitory microcircuit in the hippocampal CA1 region, an increased excitability of pyramidal neurons was found upon incorporation of the experimentally defined parameters for mutant M-current, suggesting that changes in network interactions rather than in intrinsic cell properties may be responsible for the neuronal hyperexcitability by these gain-of-function mutations. Together, the present results suggest that gain-of-function mutations in Kv7.2/3 currents may cause human epilepsy with a severe clinical course, thus revealing a previously unexplored level of complexity in disease pathogenetic mechanisms.
Homer Protein–Metabotropic Glutamate Receptor Binding Regulates Endocannabinoid Signaling and Affects Hyperexcitability in a Mouse Model of Fragile X Syndrome
Authors: Tang Ai-Hui , Alger Bradley E.
Published: March 2015

The Fmr1 knock-out mouse model of fragile X syndrome (Fmr1−/y) has an epileptogenic phenotype that is triggered by group I metabotropic glutamate receptor (mGluR) activation. We found that a membrane-permeable peptide that disrupts mGluR5 interactions with long-form Homers enhanced mGluR-induced epileptiform burst firing in wild-type (WT) animals, replicating the early stages of hyperexcitability inFmr1−/y. The peptide enhanced mGluR-evoked endocannabinoid (eCB)-mediated suppression of inhibitory synapses, decreased it at excitatory synapses in WTs, but had no effect on eCB actions inFmr1−/y. At a low concentration, the mGluR agonist did not generate eCBs at excitatory synapses but nevertheless induced burst firing in bothFmr1−/yand peptide-treated WT slices. This burst firing was suppressed by a cannabinoid receptor antagonist. We suggest that integrity of Homer scaffolds is essential for normal mGluR–eCB functioning and that aberrant eCB signaling resulting from disturbances of this molecular structure contributes to the epileptic phenotype ofFmr1−/y.
Obesity Is Associated with Decreased μ-Opioid But Unaltered Dopamine D2Receptor Availability in the Brain
Authors: Karlsson Henry K. , Tuominen Lauri , Tuulari Jetro J. , Hirvonen Jussi , Parkkola Riitta , Helin Semi , Salminen Paulina , Nuutila Pirjo , Nummenmaa Lauri
Published: March 2015

Neurochemical pathways involved in pathological overeating and obesity are poorly understood. Although previous studies have shown increased μ-opioid receptor (MOR) and decreased dopamine D2receptor (D2R) availability in addictive disorders, the role that these systems play in human obesity still remains unclear. We studied 13 morbidly obese women [mean body mass index (BMI), 42 kg/m2] and 14 nonobese age-matched women, and measured brain MOR and D2R availability using PET with selective radioligands [11C]carfentanil and [11C]raclopride, respectively. We also used quantitative meta-analytic techniques to pool previous evidence on the effects of obesity on altered D2R availability. Morbidly obese subjects had significantly lower MOR availability than control subjects in brain regions relevant for reward processing, including ventral striatum, insula, and thalamus. Moreover, in these areas, BMI correlated negatively with MOR availability. Striatal MOR availability was also negatively associated with self-reported food addiction and restrained eating patterns. There were no significant differences in D2R availability between obese and nonobese subjects in any brain region. Meta-analysis confirmed that current evidence for altered D2R availability in obesity is only modest. Obesity appears to have unique neurobiological underpinnings in the reward circuit, whereby it is more similar to opioid addiction than to other addictive disorders. The opioid system modulates motivation and reward processing, and low μ-opioid availability may promote overeating to compensate decreased hedonic responses in this system. Behavioral and pharmacological strategies for recovering opioidergic function might thus be critical to curb the obesity epidemic.
Movement-Related Discharge in the Macaque Globus Pallidus during High-Frequency Stimulation of the Subthalamic Nucleus
Authors: Zimnik Andrew J. , Nora Gerald J. , Desmurget Michel , Turner Robert S.
Published: March 2015

Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an “informational lesion,” whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism.
Axonal and Schwann Cell BACE1 Is Equally Required for Remyelination of Peripheral Nerves
Authors: Hu Xiangyou , Hu Jinxuan , Dai Lu , Trapp Bruce , Yan Riqiang
Published: March 2015

Inhibition of β-site APP cleaving enzyme 1 (BACE1) is being pursued as a therapeutic target for treating patients with Alzheimer's disease because BACE1 is the sole β-secretase for generating β-amyloid peptide. Knowledge regarding the other cellular functions of BACE1 is therefore critical for the safe use of BACE1 inhibitors in human patients. BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination in injured sciatic nerves. Since BACE1 is expected to be ubiquitously expressed, we asked whether axonal or Schwann cell BACE1 is required for optimal remyelination. By swapping sciatic nerve segments from BACE1-null mice with the corresponding wild-type nerve segments or vice versa, we tested how a deficiency of BACE1 in Schwann cells or axons affects remyelination. Our results show that BACE1 in axons and Schwann cells is similarly important for remyelination of regenerated axons. Nerve injury induces BACE1 transcription and protein levels are elevated in Schwann cells. Expression of type I neuregulin 1 (Nrg1), rather than type III Nrg1, was induced by Schwann cells, and the abolished Nrg1 cleavage in BACE1-null Schwann cells contributed to decreased remyelination of regenerated axons. Hence, this study is the first to demonstrate the equal importance of axonal and Schwann cell BACE1 for remyelination of injured nerves.
Modeling X-Linked Ancestral Origins in Multiparental Populations
Authors: Zheng Chaozhi
Published: March 2015

The models for the mosaic structure of an individual’s genome from multiparental populations have been developed primarily for autosomes, whereas X chromosomes receive very little attention. In this paper, we extend our previous approach to model ancestral origin processes along two X chromosomes in a mapping population, which is necessary for developing hidden Markov models in the reconstruction of ancestry blocks for X-linked quantitative trait locus mapping. The model accounts for the joint recombination pattern, the asymmetry between maternally and paternally derived X chromosomes, and the finiteness of population size. The model can be applied to various mapping populations such as the advanced intercross lines (AIL), the Collaborative Cross (CC), the heterogeneous stock (HS), the Diversity Outcross (DO), and the Drosophila synthetic population resource (DSPR). We further derive the map expansion, density (per Morgan) of recombination breakpoints, in advanced intercross populations with L inbred founders under the limit of an infinitely large population size. The analytic results show that for X chromosomes the genetic map expands linearly at a rate (per generation) of two-thirds times 1 – 10/(9L) for the AIL, and at a rate of two-thirds times 1 – 1/L for the DO and the HS, whereas for autosomes the map expands at a rate of 1 – 1/L for the AIL, the DO, and the HS.
A Multipurpose, High-Throughput Single-Nucleotide Polymorphism Chip for the Dengue and Yellow Fever Mosquito, Aedes aegypti
Authors: Evans Benjamin R , Gloria-Soria Andrea , Hou Lin , McBride Carolyn , Bonizzoni Mariangela , Zhao Hongyu , Powell Jeffrey R
Published: March 2015

The dengue and yellow fever mosquito, Aedes aegypti, contributes significantly to global disease burden. Genetic study of Aedes aegypti is essential to understanding its evolutionary history, competence as a disease vector, and the effects and efficacy of vector control methods. The prevalence of repeats and transposable elements in the Aedes aegypti genome complicates marker development and makes genome-wide genetic study challenging. To overcome these challenges, we developed a high-throughput genotyping chip, Axiom_aegypti1. This chip screens for 50,000 single-nucleotide polymorphisms present in Aedes aegypti populations from around the world. The array currently used genotypes 96 samples simultaneously. To ensure that these markers satisfy assumptions commonly made in many genetic analyses, we tested for Mendelian inheritance and linkage disequilibrium in laboratory crosses and a wild population, respectively. We have validated more than 25,000 of these markers to date, and expect this number to increase with more sampling. We also present evidence of the chip’s efficacy in distinguishing populations throughout the world. The markers on this chip are ideal for applications ranging from population genetics to genome-wide association studies. This tool makes rapid, cost-effective, and comparable genotype data attainable to diverse sets of Aedes aegypti researchers, from those interested in potential range shifts due to climate change to those characterizing the genetic underpinnings of its competence to transmit disease.
Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation
Authors: Yadav Anupama , Radhakrishnan Aparna , Bhanot Gyan , Sinha Himanshu
Published: March 2015

Antagonistic pleiotropy (AP), the ability of a gene to show opposing effects in different phenotypes, has been identified in various life history traits and complex disorders, indicating its fundamental role in balancing fitness over the course of evolution. It is intuitive that natural selection might maintain AP to allow organisms phenotypic flexibility in different environments. However, despite several attempts, little evidence exists for its role in adaptation. We performed a meta-analysis in yeast to identify the genetic basis of AP in bi-parental segregants, natural isolates, and a laboratory strain genome-wide deletion collection, by comparing growth in favorable and stress conditions. We found that whereas AP was abundant in the synthetic populations, it was absent in the natural isolates. This finding indicated resolution of trade-offs, i.e., mitigation of trade-offs over evolutionary history, probably through accumulation of compensatory mutations. In the deletion collection, organizational genes showed AP, suggesting ancient resolutions of trade-offs in the basic cellular pathways. We find abundant AP in the segregants, greater than estimated in the deletion collection or observed in previous studies, with IRA2, a negative regulator of the Ras/PKA signaling pathway, showing trade-offs across diverse environments. Additionally, IRA2 and several other Ras/PKA pathway genes showed balancing selection in isolates of S. cerevisiae and S. paradoxus, indicating that multiple alleles maintain AP in this pathway in natural populations. We propose that during AP resolution, retaining the ability to vary signaling pathways such as Ras/PKA, may provide organisms with phenotypic flexibility. However, with increasing organismal complexity AP resolution may become difficult. A partial resolution of AP could manifest as complex human diseases, and the inability to resolve AP may play a role in speciation. Our findings suggest that testing a universal phenomenon like AP across multiple experimental systems may elucidate mechanisms underlying its regulation and evolution.
Genetic and Genomic Toolbox of Zea mays
Authors: Nannas Natalie J , Dawe R Kelly
Published: March 2015

Maize has a long history of genetic and genomic tool development and is considered one of the most accessible higher plant systems. With a fully sequenced genome, a suite of cytogenetic tools, methods for both forward and reverse genetics, and characterized phenotype markers, maize is amenable to studying questions beyond plant biology. Major discoveries in the areas of transposons, imprinting, and chromosome biology came from work in maize. Moving forward in the post-genomic era, this classic model system will continue to be at the forefront of basic biological study. In this review, we outline the basics of working with maize and describe its rich genetic toolbox.
Structural Tuning Using a Novel Membrane Reactor for Carbon Nanotube Synthesis
Authors: Sheppard Dane J. K. , Chibante L. P. Felipe
Published: March 2015

Carbon nanotubes come in many varieties, with chemical, mechanical, and electrical properties depending on carbon nanotube (CNT) structural morphology. In order to provide a platform for CNT structural tuning, a membrane reactor was designed and constructed. This reactor provided more intimate gas-catalyst contact by decoupling the carbon feedstock gas from carrier gas in a chemical vapour deposition (CVD) environment using an asymmetric membrane and a macroporous membrane. Growth using this membrane reactor demonstrated normalized yield improvements of ∼300% and ∼1000% for the asymmetric and macroporous membrane cases, respectively, over standard CVD methods. To illustrate the possibility for control, growth variation with time was successfully demonstrated by growing vertically aligned multi-walled CNTs to heights of 0.71 mm, 1.36 mm, and 1.84 mm after growth for 15, 30, and 60 minutes in a commercial thermal CVD reactor. To demonstrate CNT diameter control via catalyst particle size, dip coating and spray coating methods were explored using ferrofluid and Fe(NO3)3 systems. CNT diameter was demonstrated to increase with increasing particle size, yielding CNT like growth with diameters ranging from 15 -150 nm. Demonstration of these dimensions of control coupled with the dramatic efficiency increases over growth in a commercialized CVD reactor establish this new reactor technology as a starting point for further research into CNT structural tuning.
Home care: An opportunity for physiotherapy?
Authors: Parsons John , Mathieson Sean , Parsons Matthew
Published: March 2015

Remaining physically active in later life is critical to maintaining independence in activities of daily living and is a major contributor to overall health status amongst older people. Traditionally a key focus of physiotherapy has been on maintaining functional capacity and mobility. However, the health and disability sector is a constantly evolving entity. Clinicians from a number of disciplines, including physiotherapy, need to be flexible, responsive and innovative and maximise cost benefit for the service funder. Nicholls et al. (2009) highlighted the imperative need for physiotherapists to investigate innovative models that align with current and future policy and health care reforms. Over the past 15 years there has been an increased emphasis on supporting older people to remain living at home. This article describes New Zealand and international evidence relating to the optimisation of the potential role of physiotherapy in providing rehabilitation expertise into the provision of home care for older people.
Mortalidade por doença meningocócica no Município de São Paulo, Brasil: características e preditores
Authors: Masuda Eliana Tiemi , Carvalhanas Telma Regina Marques Pinto , Fernandes Rachel Maria Borelli Paradella , Casagrande Silvana Tadeu , Okada Paula Suzuki , Waldman Eliseu Alves
Published: March 2015

O estudo objetiva descrever a magnitude, as características da mortalidade e da letalidade por doença meningocócica e investigar preditores de óbito por essa causa, no Município de São Paulo, Brasil, de 1986 a 2004. Utilizou-se a regressão logística múltipla não condicional para a investigação dos preditores de óbitos. Foram estudados 10.087 casos de doença meningocócica no município. A taxa anual média de mortalidade foi de 1,0/100 mil habitantes/ano, variando de 0,2 a 1,8; a letalidade foi de 20,5% com grandes diferenças segundo idade, sorogrupo e tipo de hospital. Os preditores de óbito por doença meningocócica foram idade, especialmente as faixas etárias de um a dois anos e de 40 anos ou mais e o sorogrupo W. Os resultados obtidos podem contribuir para a elaboração de políticas públicas com foco na organização da assistência hospitalar e elaboração de protocolos que promovam a maior efetividade do tratamento e a aplicação de estratégias de vacinação que diminuam a incidência nos grupos de maior risco para óbito por doença meningocócica.
Going open source: some lessons learned from the development of OpenRecLink
Authors: Camargo Jr. Kenneth Rochel de , Coeli Claudia Medina
Published: March 2015

Record linkage is the process of identifying and merging records across different databases belonging to the same entity. The health sector is one of the pioneering areas of record linkage techniques applications. In 1998 we began the development of a software package, called RecLink that implemented probabilistic record linkage techniques. In this article we report the development of a new, open-source version of that program, now named OpenRecLink. The aim of this article is to present the main characteristics of the new version and some of the lessons learned during its development. The new version is a total rewrite of the program, based on three goals: (1) to migrate to a free and open source software (FOSS) platform; (2) to implement a multiplatform version; (3) to implement the support for internationalization. We describe the tools that we adopted, the process of development and some of the problems encountered.
Epidemiology of high blood pressure among the Kaingang people on the Xapecó Indigenous Land in Santa Catarina State, Brazil, 2013
Authors: Bresan Deise , Bastos João Luiz , Leite Maurício Soares
Published: March 2015

This cross-sectional study describes the prevalence of high blood pressure (HBP; measured at one setting, and suggestive of a clinical diagnosis of arterial hypertension) and mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) and their associations with socio-demographic and anthropometric variables among 355 Kaingang adults (≥ 20 years) on the Xapecó Indigenous Land in Brazil. Weight, height, waist circumference (WC), SBP, and DBP were measured and socio-demographic data were collected. Prevalence of HBP was 53.2% (95%CI: 45.3; 61.1) in men and 40.7% (95%CI: 33.8; 47.6) in women. In women, age and WC were directly associated with HBP; age was associated with SBP and schooling with DBP. In men, HBP was statistically associated with high body mass index (BMI) and tile floor in the home (as a socioeconomic proxy); BMI and WC were associated with SBP; BMI and WC were associated with DBP. The study highlights the need for measures to control risk factors for HBP, especially due to its relevance for cardiovascular diseases and their consequences.
Qualidade de vida e AIDS sob a ótica de pessoas vivendo com o agravo: contribuição preliminar da abordagem estrutural das representações sociais
Authors: Costa Tadeu Lessa da , Oliveira Denize Cristina de , Formozo Gláucia Alexandre
Published: March 2015

Trata-se de estudo descritivo, qualitativo, tendo por objetivos: identificar o conteúdo e a estrutura das representações sociais da qualidade de vida e da AIDS entre pessoas com a doença e analisar as relações estruturais entre tais representações. Os sujeitos foram 103 pessoas soropositivas de município norte fluminense, Brasil. Empregou-se técnica de evocação livre e hierarquizada de palavras aos termos indutores "AIDS" e "qualidade de vida da pessoa que tem AIDS", com análise pelo software EVOC. Foram identificados, como provável núcleo central da representação da AIDS, preconceito, tratamento, família e medicações e, para a qualidade de vida, os mesmos componentes, acrescidos de boa alimentação e trabalho. Assim, elaborou-se hipótese de interação representacional do tipo coordenada, em conjunção, com encaixamento entre as duas representações, com implicações para a apropriação simbólica e avaliação da qualidade de vida pelas pessoas vivendo com a doença. Esses achados consistem em subsídios para abordagens coletivas e individuais em saúde para melhoria da qualidade de vida desse grupo.
Blackberry (Rubus spp.): influence of ripening and processing on levels of phenolic compounds and antioxidant activity of the 'Brazos' and 'Tupy' varieties grown in Brazil
Authors: Zielinski Acácio Antonio Ferreira , Goltz Caroline , Yamato Maira Akemi Casagrande , Ávila Suelen , Hirooka Elisa Yoko , Wosiacki Gilvan , Nogueira Alessandro , Demiate Ivo Mottin
Published: March 2015

Fruits from temperate and tropical climates which have high levels of antioxidant compounds are the source of numerous studies concerning the correlation with benefits to human health. The objectives of this study were to quantify the anthocyanins and phenolic compounds and also to measure the antioxidant activity (ferric reducing antioxidant power - FRAP) of blackberries from two varieties grown in southern Brazil ('Brazos' and 'Tupy') at three stages of ripening; unripe, semi-ripe, ripe and their products (pulp and fermented products). During fruit ripening it was observed that weight, size, diameter and sugars increase significantly and acidity decreased significantly. The anthocyanin content ranged from 4.19 (semi-ripe 'Tupy' variety) to 205.75mg 100g-1 (ripe 'Brazos' variety). The highest levels of phenolic compounds were observed for the unripe fruit of both varieties, while antioxidant activity showed no significant difference during the ripening stages. The studied pulp showed a high content of phenolic compounds (ten times higher than that found in the ripe fruits). The anthocyanin content and antioxidant activity did not show the same increase due to the degradation of anthocyanins caused by the heat treatment that was used. The alcoholic fermented beverage made from blackberries remained stable (total phenolic compounds and antioxidant activity) during two years of storage, but the in third year a significant reduction in antioxidant activity was observed. These results can be important for establishing the shelf life of this kind of product made with blackberry
Perdas de nitrogênio do solo e resposta do pessegueiro à adição de composto orgânico
Authors: Sete Paula Beatriz , Melo George Wellington Bastos de , Oliveira Bruno Salvador , Freitas Rafael Fernando , Magro Renan Dal , Ambrosini Vitor Gabriel , Trapp Talita , Comin Jucinei José , Gatiboni Luciano Colpo , Brunetto Gustavo
Published: March 2015

A aplicação de composto orgânico no solo pode incrementar a produção de pêssego, porém parte do N pode ser perdido por lixiviação e volatilização. O trabalho objetivou avaliar o estado nutricional das plantas, a produção de pêssego, a lixiviação de formas de N no solo e a volatilização de N-NH3 em um pomar de pessegueiro com a adição de composto orgânico produzido a partir de resíduos de agroindústrias de suco, resíduos de abatedouro de aves e serragem. O pomar foi implantado em 2009 e, em julho de 2010, 2011 e 2012, foram aplicados 0, 3, 6, 12 e 24L de composto por m2 e avaliaram-se os teores totais de nutrientes nas folhas e a produção. Em 2012, usando lisímetros instalados a 20 e a 40cm de profundidade, avaliaram-se as formas de N lixiviadas na solução percolada nos tratamentos 0 e 24L de composto. Usando câmeras coletoras, foi avaliada a volatilização de N-NH3 em todos os tratamentos até 478h depois da deposição do composto no solo. A aplicação de composto na superfície do solo incrementou o teor de K e N nas folhas completas, aumentando a produção de frutos. A aplicação de composto no florescimento aumentou a concentração de nitrato na solução do solo, somente na profundidade de 20cm. A emissão de amônia aumentou com o incremento da dose de composto aplicado, especialmente e nos períodos de maior temperatura
Detecção da tolerância de diferentes espécies de capim-colchão a herbicidas inibidores do fotossistema II utilizando a técnica da fluorescência
Authors: Tropaldi Leandro , Velini Edivaldo Domingues , Carbonari Caio Antonio , Araldi Rosilaine , Corniani Natália , Girotto Marcelo , Silva Ilca Puertas de Freitas e
Published: March 2015

Este estudo teve como objetivo investigar a tolerância ou susceptibilidade das espécies de capim-colchão (Digitaria ciliaris, D. horizontalis e D. nuda) a herbicidas inibidores do fotossistema II (FSII), por meio da técnica da fluorescência, utilizando a taxa de transferência de elétrons do FSII como indicador. Para isso, foi conduzido um experimento em esquema fatorial 3x6, com três espécies de capim-colchão e seis tratamentos (ametryn, hexazinone, diuron+hexazinone, amicarbazone, diuron, tebuthiuron e testemunha) aplicados em pós-emergência. Foi monitorada a taxa de transporte de elétrons (ETR) do FSII em intervalos de tempo crescente e aferida a massa seca das plantas aos 21 dias após a aplicação. A partir dos dados da ETR, calculou-se um valor numérico representativo da taxa de inativação da ETR. Os resultados demonstraram que todas as espécies de capim-colchão estudadas são susceptíveis aos herbicidas ametryn e hexazinone (valores da taxa de inativação da ETR superiores a 10.000). Os herbicidas diuron e tebuthiuron apresentaram menores taxas de inativação da ETR para a D. nuda (3.585 e 3.497, respectivamente) e maiores para as espécies D. ciliaris e D. horizontalis (acima de 10.000), enquanto que o herbicida amicarbazone apresentou valor intermediário para D. nuda (7.967). O monitoramento da ETR foi eficiente para verificar a atuação dos herbicidas nas diferentes espécies estudadas
Ricardo Bruno: history, social processes and health practices
Authors: Ayres José Ricardo de Carvalho Mesquita
Published: March 2015

This essay has the objective of revisiting the intellectual output of Ricardo Bruno Mendes-Gonçalves (1946-1996), Professor of the Department of Preventive Medicine of the Faculty of Medicine of the University of São Paulo and one of the theoreticians who participated in the construction of the field of Brazilian Collective Health during the years 1970-1990. On the basis of brief biographical and bibliographical information, as well as relevant aspects regarding the historical context in which his output is located, I examine the principal works of the author, their effects on the lines of investigation of investigation of his students and his legacy of contributions and challenges for Collective Health. I highlight the genesis and development of his Theory of the Health Work Process and its impact on the understanding and empirical investigation of the socio-historical dimensions of health practices and on the reconstruction of knowledge and technologies in the context of the Brazilian Health Sector Reform. In particular, I highlight his concern with the ethical perspective of academic praxis and in this sense, with hope as a human value which is historically objectified and intersubjectively constructed.
Barriers to the involvement of the elderly in public services to promote physical activity
Authors: Ribeiro Renato Mendonça , Tribess Sheilla , Santos Andrêza Soares dos , Pinto Lélia Lessa Teixeira , Ribeiro Maria da Conceição Lopes , Roza Liliane Beatriz , Virtuoso Júnior Jair Sindra
Published: March 2015

The aim of this study was to examine the sociodemographic, health and behavioural characteristics related to non-participation of elderly people in activities offered by the program PROETI Health of Uberaba, Minas Gerais state. Observational study, case-control design with pairing 1:1 and sample composed of 220 elderly 60-80 years. Binary Logistic Regression was used to identify the sociodemographic, health and behavioral factors associated with non-engagement of non-users to the program. After hierarchical analysis, the non-engagement of the elderly in the program activities was associated with depressive symptoms, insufficient physical activity in the domain of leisure and reduced self-efficacy for performing moderate or vigorous physical activity. The characteristics identified in this study should receive priority attention in the formulation of community programs targeted at promoting physical activity for elderly people.
Indicadores nutricionais combinados e fatores associados em população Quilombola no Sudoeste da Bahia, Brasil
Authors: Soares Daniela Arruda , Barreto Sandhi Maria
Published: March 2015

Este estudo estimou a prevalência de duas combinações de indicadores nutricionais: Índice de Massa Corporal (IMC) + Circunferência da Cintura (CC) e IMC + Razão Cintura Estatura (RCE), e investigou os fatores associados em adultos Quilombolas. Amostra aleatória em dois estágios de 739 adultos ≥ 20 anos, residentes em Comunidades Quilombolas em Vitória da Conquista (BA), em 2011. Risco combinado IMC + RCE incluiu os indivíduos que simultaneamente apresentaram IMC ≥ 25,0Kg/m2 ou ≥ 27,0Kg/m2, se idade ≥ 60 anos e RCE ≥ 0,5. O risco IMC + RCE incluiu indivíduos com IMC elevado que também apresentavam CC ≥ 80cm, se mulher, ou ≥ 94cm, se homem. As prevalências dos indicadores nutricionais combinados foram de 35,3% (IMC + RCE) e 26,8% (IMC + CC). Sexo feminino e hipertensão aumentaram a chance para os dois indicadores enquanto que o estado civil não casado diminuiu esta chance. O indicador IMC + RCE foi maior na faixa etária de 40 a 59 anos e o indicador IMC + CC foi mais frequente na faixa de 40 a 49 anos. A baixa escolaridade elevou o indicador IMC + RCE, enquanto assistir televisão por mais de duas horas por dia, o indicador IMC + CC. A elevada prevalência de risco nutricional para DCNT, especialmente de obesidade central, confirmou a necessidade de ações de promoção de dieta saudável e saúde.
Death in hospital and at home: population and health policy influences in Londrina, State of Paraná, Brazil (1996-2010)
Authors: Marcucci Fernando Cesar Iwamoto , Cabrera Marcos Aparecido Sarria
Published: March 2015

An aging population and epidemiological transition involves prolonged terminal illnesses and an increased demand for end-stage support in health services, mainly in hospitals. Changes in health care and government health policies may influence the death locations, making it possible to remain at home or in an institution. The scope of this article is to analyze death locations in the city of Londrina, State of Paraná, from 1996 to 2010, and to verify the influence of population and health policy changes on these statistics. An analysis was conducted into death locations in Londrina in Mortality Information System (SIM) considering the main causes and locations of death. There was an increase of 28% in deaths among the population in general, though 48% for the population over 60 years of age. There was an increase of deaths in hospitals, which were responsible for 70% of the occurrences, though death frequencies in others locations did not increase, and deaths in the home remained at about 18%. The locations of death did not change during this period, even with health policies that broadened care in other locations, such as the patient´s home. The predominance of hospital deaths was similar to other Brazilian cities, albeit higher than in other countries.