bluuebunny/crossref_metadata_2025 huggingface dataset:
An improved label propagation algorithm based on node importance and random walk for community detection
Authors: Ma Tianren , Xia Zhengyou
Published: May 2017

Currently, with the rapid development of information technology, the electronic media for social communication is becoming more and more popular. Discovery of communities is a very effective way to understand the properties of complex networks. However, traditional community detection algorithms consider the structural characteristics of a social organization only, with more information about nodes and edges wasted. In the meanwhile, these algorithms do not consider each node on its merits.

Label propagation algorithm (LPA) is a near linear time algorithm which aims to find the community in the network. It attracts many scholars owing to its high efficiency. In recent years, there are more improved algorithms that were put forward based on LPA. In this paper, an improved LPA based on random walk and node importance (NILPA) is proposed. Firstly, a list of node importance is obtained through calculation. The nodes in the network are sorted in descending order of importance. On the basis of random walk, a matrix is constructed to measure the similarity of nodes and it avoids the random choice in the LPA. Secondly, a new metric IAS (importance and similarity) is calculated by node importance and similarity matrix, which we can use to avoid the random selection in the original LPA and improve the algorithm stability.

Finally, a test in real-world and synthetic networks is given. The result shows that this algorithm has better performance than existing methods in finding community structure.
Hybrid Uncertain Analysis for Exterior Acoustic Field Prediction with Interval Random Parameters
Authors: Chen Ning , Yu Dejie , Xia Baizhan , Beer Michael
Published: May 2017

For exterior acoustic field problems that lack sufficient information to construct precise probability distributions, an interval random model is introduced to deal with the uncertain parameters. In the interval random model, the probability variables are employed to treat the uncertain parameters, whereas some distribution parameters of random variables are modeled as interval variables instead of precise values. Based on the interval random model, the interval random finite element equation for exterior acoustic fields is established and a hybrid uncertain analysis method is presented to solve the exterior acoustic field problem with interval random variables. In the presented method, by temporarily neglecting the uncertainties of interval variables, a first-order stochastic perturbation method is adopted to calculate the expectation and the variance of the response vector. According to the monotonicity of the expectation and variance of the response vector with respect to the interval variables, the lower and upper bounds of the expectation and variance of the response vector can be calculated by the vertex method. In addition, in order to ensure accuracy of the proposed method, the subinterval technique is introduced and investigated. The numerical example of a square flexible shell model is presented to demonstrate the effectiveness of the proposed method.
Syntheses and PDT activity of new mono- and di-conjugated derivatives of chlorin e6
Authors: Chen Hui , Humble Stewart W. , Jinadasa R. G. Waruna , Zhou Zehua , Nguyen Alex L. , Vicente M. Graça H. , Smith Kevin M.
Published: May 2017

Syntheses of three new chlorin e6 conjugates for PDT of tumors are reported. One of the new compounds 17 is conjugated with lysine at the 131-position, but the others are mono-conjugated 14 or diconjugated 15 with the non-amino acid species ethanolamine. Cellular experiments with the three new compounds and previously synthesized non-amino acid 152-conjugates (7–10), 131-monoconjugates 14, 16, and a 131,152-diconjugate 12 are reported. In vitro cytotoxicity experiments show that the 131-conjugates are more toxic than the 152-conjugates, and the most toxic derivative (dark- and photo-toxicity) is the 131-ethylenediamine conjugate 11. The most useful PDT photosentitizers appear to be the ethanolamine derivatives, conjugated at the 152- and the 131,152-positions; these show high phototoxicity but relatively low dark toxicity compared with 11, and also the highest dark/photo cytotoxicity ratios.
Managing Water Scarcity at a River Basin Scale with Economic Instruments
Authors: Gómez Gómez Carlos Mario , Pérez-Blanco C. D. , Adamson David , Loch Adam
Published: May 2017

This paper presents a conceptual framework for both assessing the role of economic instruments, and reshaping them in order to enhance their contribution to the goals of managing water scarcity. Water management problems stem from the mismatch between a multitude of individual decisions, on the one hand, and the current and projected status of water resources on the other. Economics can provide valuable incentives that drive individual decisions, and can design efficient instruments to address water governance problems in a context of conflicting interests and relevant transaction costs. Yet, instruments such as water pricing or trading are mostly based on general principles of welfare economics that are not readily applicable to assets as complex as water. A flaw in welfare economic approaches lies in the presumption that economic instruments may be good or bad on their own (e.g., finding the “right” price). This vision changes radically when we focus on the problem, instead of the instrument. In this paper, we examine how economic instruments to achieve welfare-enhancing water resource outcomes can realize their full potential in basin-scale management contexts. We follow a political economy perspective that views conflicts between public and private interest as the main instrumental challenge of water management. Our analysis allows us to better understand the critical importance of economic instruments for reconciling individual actions towards collective ambitions of water efficiency, equity and sustainability with lessons for later-adopting jurisdictions. Rather than providing panaceas, the successful design and implementation of economic instruments as key river basin management arrangements involves high transaction costs, wide institutional changes and collective action at different levels.
Early Diverging Fungi: Diversity and Impact at the Dawn of Terrestrial Life
Authors: Berbee Mary L. , James Timothy Y. , Strullu-Derrien Christine
Published: May 2017

As decomposers or plant pathogens, fungi deploy invasive growth and powerful carbohydrate active enzymes to reduce multicellular plant tissues to humus and simple sugars. Fungi are perhaps also the most important mutualistic symbionts in modern ecosystems, transporting poorly soluble mineral nutrients to plants and thus enhancing the growth of vegetation. However, at their origin over a billion years ago, fungi, like plants and animals, were unicellular marine microbes. Like the other multicellular kingdoms, Fungi evolved increased size, complexity, and metabolic functioning. Interactions of fungi with plants changed terrestrial ecology and geology and modified the Earth's atmosphere. In this review, we discuss the diversification and ecological roles of the fungi over their first 600 million years, from their origin through their colonization of land, drawing on phylogenomic evidence for their relationships and metabolic capabilities and on molecular dating, fossils, and modeling of Earth's paleoclimate.
Regulation of Cell Polarity in Motility and Cell Division inMyxococcus xanthus
Authors: Schumacher Dominik , Søgaard-Andersen Lotte
Published: May 2017

Rod-shaped Myxococcus xanthus cells are polarized with proteins asymmetrically localizing to specific positions. This spatial organization is important for regulation of motility and cell division and changes over time. Dedicated protein modules regulate motility independent of the cell cycle, and cell division dependent on the cell cycle. For motility, a leading-lagging cell polarity is established that is inverted during cellular reversals. Establishment and inversion of this polarity are regulated hierarchically by interfacing protein modules that sort polarized motility proteins to the correct cell poles or cause their relocation between cell poles during reversals akin to a spatial toggle switch. For division, a novel self-organizing protein module that incorporates a ParA ATPase positions the FtsZ-ring at midcell. This review covers recent findings concerning the spatiotemporal regulation of motility and cell division in M. xanthus and illustrates how the study of diverse bacteria may uncover novel mechanisms involved in regulating bacterial cell polarity.
Mood, the Circadian System, and Melanopsin Retinal Ganglion Cells
Authors: Lazzerini Ospri Lorenzo , Prusky Glen , Hattar Samer
Published: May 2017

The discovery of a third type of photoreceptors in the mammalian retina, intrinsically photosensitive retinal ganglion cells (ipRGCs), has had a revolutionary impact on chronobiology. We can now properly account for numerous non-vision-related functions of light, including its effect on the circadian system. Here, we give an overview of ipRGCs and their function as it relates specifically to mood and biological rhythms. Although circadian disruptions have been traditionally hypothesized to be the mediators of light's effects on mood, here we present an alternative model that dispenses with assumptions of causality between the two phenomena and explains mood regulation by light via another ipRGC-dependent mechanism.
Skin Color and Colorism: Global Research, Concepts, and Measurement
Authors: Dixon Angela R. , Telles Edward E.
Published: May 2017

We examine a vast, interdisciplinary, and increasingly global literature concerning skin color and colorism, which are related to status throughout the world. The vast majority of research has investigated Western societies, where color and colorism have been closely related to race and racism. In Latin America, the two sets of concepts have particularly overlapped. In the rest of the world, particularly in Asia, color and colorism have also been important but have evolved separately from the relatively new concepts of race and racism. In recent years, however, color consciousness and white supremacy appear to have been increasingly united, globalized, and commodified, as exemplified by the global multibillion-dollar skin-lightening industry. Finally, we document the growing methodological attention to measurements of skin color and social science data that incorporate skin color measures.
Explicating Divided Approaches to Gentrification and Growing Income Inequality
Authors: Brown-Saracino Japonica
Published: May 2017

Contemporary sociology offers competing images of the breadth and consequences of gentrification. One subset presents gentrification as a nearly unstoppable force that plays a prominent role in the spatial reorganization of urban life; another presents it as less monolithic and less momentous for marginalized residents, particularly racial minorities. Although neither camp is methodologically homogenous, more qualitative scholars, typically relying on micro-level analyses of individual neighborhoods, tend to present gentrification as increasingly endemic, advanced, and consequential, whereas more quantitative scholars, typically relying on macro analyses, tend to present it in less dire terms. These competing images of gentrification originate in the fact that each subset of research asks different questions, employs distinct methods, and produces particular answers. Exacerbating and partially driving these divergences are different responses to an anxiety within and beyond the academy about broader spatial and economic shifts, such as growing income inequality.
The Second Demographic Transition Theory: A Review and Appraisal
Authors: Zaidi Batool , Morgan S. Philip
Published: May 2017

References to the second demographic transition (SDT) have increased dramatically in the past two decades. The SDT predicts unilinear change toward very low fertility and a diversity of union and family types. The primary driver of these changes is a powerful, inevitable, and irreversible shift in attitudes and norms in the direction of greater individual freedom and self-actualization. First, we describe the origin of this framework and its evolution over time. Second, we review the empirical fit of the framework to major changes in demographic and family behavior in the United States, the West, and beyond. As has been the case for other unilinear, developmental theories of demographic or family change, the SDT failed to predict many contemporary patterns of change and difference. Finally, we review previous critiques and identify fundamental weaknesses of this perspective, and we provide brief comparisons to selected alternative approaches.
Measuring osmosis and hemolysis of red blood cells
Authors: Goodhead Lauren K. , MacMillan Frances M.
Published: May 2017

Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the cell’s interior. The selectively permeable nature of the cell membrane allows the movement of some solutes and prevents the movement of others. This has important consequences for cell volume and the integrity of the cell and, as a result, is of utmost clinical importance, for example in the administration of isotonic intravenous infusions. The concepts of osmolarity and tonicity are often confused by students as impermeant isosmotic solutes such as NaCl are also isotonic; however, isosmotic solutes such as urea are actually hypotonic due to the permeant nature of the membrane. By placing red blood cells in solutions of differing osmolarities and tonicities, this experiment demonstrates the effects of osmosis and the resultant changes in cell volume. Using hemoglobin standard solutions, where known concentrations of hemoglobin are produced, the proportion of hemolysis and the effect of this on resultant hematocrit can be estimated. No change in cell volume occurs in isotonic NaCl, and, by placing blood cells in hypotonic NaCl, incomplete hemolysis occurs. By changing the bathing solution to either distilled water or isosmotic urea, complete hemolysis occurs due to their hypotonic effects. With the use of animal blood in this practical, students gain useful experience in handling tissue fluids and calculating dilutions and can appreciate the science behind clinical scenarios.
Long non-coding RNA NEAT1 promotes hepatocellular carcinoma cell proliferation through the regulation of miR-129-5p-VCP-IκB
Authors: Fang Luo , Sun Jiao , Pan Zongfu , Song Yu , Zhong Like , Zhang Yiwen , Liu Yujia , Zheng Xiaowei , Huang Ping
Published: May 2017

Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays an important role in the pathogenesis and development of several types of cancer. However, the functional mechanism of NEAT1 in hepatocellular carcinoma (HCC) remains unclear. NEAT1 and microRNA (miR)-129-5p expression in HCC tissues and cell lines was quantified by means of quantitative PCR. The effects of NEAT1 expression inhibition or upregulation in HCC cell lines were analyzed in terms of cell viability and apoptosis. Biological software was used to predict the binding sites of NEAT1 and miR-129-5p. The expression of the miR-129-5p target molecules valosin-containing protein (VCP) and IκB was detected using Western blotting. The effect of NEAT1 on tumor growth was observed in mouse models of transplanted hepatoma. In the present study, it was concluded that the expression of NEAT1 was significantly increased in the HCC tissues and cell lines. Meanwhile, after downregulating NEAT1 expression in HepG2/Huh7 cell lines, the cell viability was significantly lowered, whereas the corresponding rate of apoptosis was significantly increased. Additionally, it was found that the NEAT1 and miR-129-5p expression showed a negative correlation in HCC tissues. It was further proved that there was a certain negative regulatory mechanism between NEAT1 and miR-129-5p, which was related to the expression of VCP and IκB. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited tumor growth. The study concluded that the overexpression of NEAT1 inhibited the expression of miR-129-5p by regulating VCP/IκB, thereby promoting the proliferation of HCC cells. This study provides new insights into the pathogenesis of HCC, as well as identifying new target genes for diagnosis and treatment.

NEW & NOTEWORTHY The results provide strong evidence that upregulated NEAT1 promotes the proliferation of cancer cells in hepatocellular carcinoma (HCC) and this regulatory mechanism depends on the microRNA (miR)-129-5p-valosin-containing protein-IκB axis. The study also indicates that NEAT1 could be a potential therapeutic target for HCC.
Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart
Authors: Thapa Dharendra , Zhang Manling , Manning Janet R. , Guimarães Danielle A. , Stoner Michael W. , O’Doherty Robert M. , Shiva Sruti , Scott Iain
Published: May 2017

Lysine acetylation is a reversible posttranslational modification and is particularly important in the regulation of mitochondrial metabolic enzymes. Acetylation uses acetyl-CoA derived from fuel metabolism as a cofactor, thereby linking nutrition to metabolic activity. In the present study, we investigated how mitochondrial acetylation status in the heart is controlled by food intake and how these changes affect mitochondrial metabolism. We found that there was a significant increase in cardiac mitochondrial protein acetylation in mice fed a long-term high-fat diet and that this change correlated with an increase in the abundance of the mitochondrial acetyltransferase-related protein GCN5L1. We showed that the acetylation status of several mitochondrial fatty acid oxidation enzymes (long-chain acyl-CoA dehydrogenase, short-chain acyl-CoA dehydrogenase, and hydroxyacyl-CoA dehydrogenase) and a pyruvate oxidation enzyme (pyruvate dehydrogenase) was significantly upregulated in high-fat diet-fed mice and that the increase in long-chain and short-chain acyl-CoA dehydrogenase acetylation correlated with increased enzymatic activity. Finally, we demonstrated that the acetylation of mitochondrial fatty acid oxidation proteins was decreased after GCN5L1 knockdown and that the reduced acetylation led to diminished fatty acid oxidation in cultured H9C2 cells. These data indicate that lysine acetylation promotes fatty acid oxidation in the heart and that this modification is regulated in part by the activity of GCN5L1.

NEW & NOTEWORTHY Recent research has shown that acetylation of mitochondrial fatty acid oxidation enzymes has greatly contrasting effects on their activity in different tissues. Here, we provide new evidence that acetylation of cardiac mitochondrial fatty acid oxidation enzymes by GCN5L1 significantly upregulates their activity in diet-induced obese mice.
Immediate and delayed potentiating effects of tumor necrosis factor-α on TRPV1 sensitivity of rat vagal pulmonary sensory neurons
Authors: Hsu Chun-Chun , Lin You Shuei , Lin Ruei-Lung , Lee Lu-Yuan
Published: May 2017

We studied acute effects of tumor necrosis factor-α (TNFα) on the sensitivity of isolated rat vagal pulmonary sensory neurons. Our results showed the following. First, a brief pretreatment with a low dose of TNFα (1.44 nM, 9 min) enhanced the sensitivity of transient receptor potential vanilloid type 1 (TRPV1) receptors in these neurons in two distinct phases: the inward current evoked by capsaicin was amplified (Δ = 247%) immediately following the TNFα pretreatment, which gradually declined toward control and then increased again reaching another peak (Δ = 384%) after 60–90 min. Second, the immediate phase of this potentiating effect of TNFα was completely abolished by a pretreatment with a selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, whereas the delayed potentiation was only partially attenuated. Third, in sharp contrast, TNFα did not generate any potentiating effect on the responses to non-TRPV1 chemical activators of these neurons. Fourth, the selectivity of the TNFα action on TRPV1 was further illustrated by the responses to acid (pH 6.0); TNFα did not affect the rapid transient current mediated by acid-sensing ion channels but significantly augmented the slow sustained current mediated by TRPV1 in the same neurons. Fifth, in anesthetized rats, a similar pattern of acute sensitizing effects of TNFα on pulmonary C-fiber afferents and the involvement of COX-2 were also clearly shown. In conclusion, a brief pretreatment with TNFα induced both immediate and delayed potentiating effects on the TRPV1 sensitivity in pulmonary sensory neurons, and the production of COX-2 arachidonic acid metabolites plays a major role in the immediate sensitizing effect of TNFα.
Biomarkers of exposure to new and emerging tobacco delivery products
Authors: Schick Suzaynn F. , Blount Benjamin C. , Jacob Peyton , Saliba Najat A. , Bernert John T. , El Hellani Ahmad , Jatlow Peter , Pappas R. Steven , Wang Lanqing , Foulds Jonathan , Ghosh Arunava , Hecht Stephen S. , Gomez John C. , Martin Jessica R. , Mesaros Clementina , Srivastava Sanjay , St. Helen Gideon , Tarran Robert , Lorkiewicz Pawel K. , Blair Ian A. , Kimmel Heather L. , Doerschuk Claire M. , Benowitz Neal L. , Bhatnagar Aruni
Published: May 2017

Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.
Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATPchannel function
Authors: Wang Xinrui , Fitts Robert H.
Published: May 2017

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K+(KATP) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6–8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca2+transient durations reflected the changes in APD, while Ca2+transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β1-AR blocker atenolol, but not the β2-AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β1-AR. At 10 Hz, the KATPchannel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β1-AR responsiveness and KATPchannel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca2+influx; during exercise, an increase in KATPchannel activity would shorten APD and, thus, protect the heart against Ca2+overload or inadequate filling.

NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca2+transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the β-adrenergic receptor agonist dose-response curve rightward compared with controls by reducing β1-adrenergic receptor responsiveness and that, at the high activation rate, myocytes from trained animals showed higher KATPchannel function.
Ontogeny of myosin isoform expression and prehensile function in the tail of the gray short-tailed opossum (Monodelphis domestica)
Authors: Thomas Dylan R. , Chadwell Brad A. , Walker Gary R. , Budde Julio E. , VandeBerg John L. , Butcher Michael T.
Published: May 2017

Terrestrial opossums use their semiprehensile tail for grasping nesting materials as opposed to arboreal maneuvering. We relate the development of this adaptive behavior with ontogenetic changes in myosin heavy chain (MHC) isoform expression from 21 days to adulthood. Monodelphis domestica is expected to demonstrate a progressive ability to flex the distal tail up to age 7 mo, when it should exhibit routine nest construction. We hypothesize that juvenile stages (3–7 mo) will be characterized by retention of the neonatal isoform (MHC-Neo), along with predominant expression of fast MHC-2X and -2B, which will transition into greater MHC-1β and -2A isoform content as development progresses. This hypothesis was tested using Q-PCR to quantify and compare gene expression of each isoform with its protein content determined by gel electrophoresis and densitometry. These data were correlated with nesting activity in an age-matched sample of each age group studied. Shifts in regulation of MHC gene transcripts matched well with isoform expression. Notably, mRNA for MHC-Neo and -2B decrease, resulting in little-to-no isoform translation after age 7 mo, whereas mRNA for MHC-1β and -2A increase, and this corresponds with subtle increases in content for these isoforms into late adulthood. Despite the tail remaining intrinsically fast-contracting, a critical growth period for isoform transition is observed between 7 and 13 mo, correlating primarily with use of the tail during nesting activities. Functional transitions in MHC isoforms and fiber type properties may be associated with muscle “tuning” repetitive nest remodeling tasks requiring sustained contractions of the caudal flexors.

NEW & NOTEWORTHY Little is understood about skeletal muscle development as it pertains to tail prehensility in mammals. This study uses an integrative approach of relating both MHC gene and protein expression with behavioral and morphometric changes to reveal a predominant fast MHC expression with subtle isoform transitions in caudal muscle across ontogeny. The functional shifts observed are most notably correlated with increased tail grasping for nesting activities.
A2Adenosine Receptors Inhibit Calcium Influx Through L-Type Calcium Channels in Rod Photoreceptors of the Salamander Retina
Authors: Stella Salvatore L. , Bryson Eric J. , Thoreson Wallace B.
Published: May 2017

Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca2+currents ( ICa) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca2+channels that regulate the release ofl-glutamate. In the retina, adenosine is released in the dark when l-glutamate release is maximal. We tested whether adenosine inhibits ICaand intracellular Ca2+increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both ICaand the [Ca2+]iincrease evoked by depolarization in a dose-dependent manner with ∼25% inhibition at 50 μM. An A2-selective agonist, ( N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, ( R)- N6-(1-methyl-2-phenylethyl)adenosine and N6-2-(4-aminophenyl)ethyladenosine, also inhibited ICaand depolarization-induced [Ca2+]iincreases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both ICaand the depolarization-evoked [Ca2+]iincrease in rods. The results suggest that activation of A2receptors stimulates PKA to inhibit L-type Ca2+channels in rods resulting in a decreased Ca2+influx that should suppress glutamate release.
Independent Representations of Limb Axis Length and Orientation in Spinocerebellar Response Components
Authors: Poppele R. E. , Bosco G. , Rankin A. M.
Published: May 2017

Dorsal spinocerebellar tract (DSCT) neurons transmit sensory signals to the cerebellum that encode global hindlimb parameters, such as the hindlimb end-point position and its direction of movement. Here we use a population analysis approach to examine further the characteristics of DSCT neuronal responses during continuous movements of the hind foot. We used a robot to move the hind paw of anesthetized cats through the trajectories of a step or a figure-8 footpath in a parasagittal plane. Extracellular recordings from 82 cells converted to cycle histograms provided the basis for a principal-component analysis to determine the common features of the DSCT movement responses. Five principal components (PCs) accounted for about 80% of the total variance in the waveforms across units. The first two PCs accounted for about 60% of the variance and they were highly robust across samples. We examined the relationship between the responses and limb kinematic parameters by correlating the PC waveforms with waveforms of the joint angle and limb axis trajectories using multivariate linear regression models. Each PC waveform could be at least partly explained by a linear relationship to joint-angle trajectories, but except for the first PC, they required multiple angles. However, the limb axis parameters more closely related to both the first and second PC waveforms. In fact, linear regression models with limb axis length and orientation trajectories as predictors explained 94% of the variance in both PCs, and each was related to a particular linear combination of position and velocity. The first PC correlated with the limb axis orientation and orientation velocity trajectories, whereas second PC with the length and length velocity trajectories. These combinations were found to correspond to the dynamics of muscle spindle responses. The first two PCs were also most representative of the data set since about half the DSCT responses could be at least 85% accounted for by weighted linear combinations of these two PCs. Higher-order PCs were unrelated to limb axis trajectories and accounted instead for different dynamic components of the responses. The findings imply that an explicit and independent representation of the limb axis length and orientation may be present at the lowest levels of sensory processing in the spinal cord.
Sound-Level-Dependent Representation of Frequency Modulations in Human Auditory Cortex: A Low-Noise fMRI Study
Authors: Brechmann André , Baumgart Frank , Scheich Henning
Published: May 2017

Recognition of sound patterns must be largely independent of level and of masking or jamming background sounds. Auditory patterns of relevance in numerous environmental sounds, species-specific vocalizations and speech are frequency modulations (FM). Level-dependent activation of the human auditory cortex (AC) in response to a large set of upward and downward FM tones was studied with low-noise (48 dB) functional magnetic resonance imaging at 3 Tesla. Separate analysis in four territories of AC was performed in each individual brain using a combination of anatomical landmarks and spatial activation criteria for their distinction. Activation of territory T1b (including primary AC) showed the most robust level dependence over the large range of 48–102 dB in terms of activated volume and blood oxygen level dependent contrast (BOLD) signal intensity. The left nonprimary territory T2 also showed a good correlation of level with activated volume but, in contrast to T1b, not with BOLD signal intensity. These findings are compatible with level coding mechanisms observed in animal AC. A systematic increase of activation with level was not observed for T1a (anterior of Heschl's gyrus) and T3 (on the planum temporale). Thus these areas might not be specifically involved in processing of the overall intensity of FM. The rostral territory T1a of the left hemisphere exhibited highest activation when the FM sound level fell 12 dB below scanner noise. This supports the previously suggested special involvement of this territory in foreground-background decomposition tasks. Overall, AC of the left hemisphere showed a stronger level-dependence of signal intensity and activated volume than the right hemisphere. But any side differences of signal intensity at given levels were lateralized to right AC. This might point to an involvement of the right hemisphere in more specific aspects of FM processing than level coding.
Conditions Sufficient for Nonsynaptic Epileptogenesis in the CA1 Region of Hippocampal Slices
Authors: Bikson Marom , Baraban Scott C. , Durand Dominique M.
Published: May 2017

Nonsynaptic mechanisms exert a powerful influence on seizure threshold. It is well-established that nonsynaptic epileptiform activity can be induced in hippocampal slices by reducing extracellular Ca2+ concentration. We show here that nonsynaptic epileptiform activity can be readily induced in vitro in normal (2 mM) Ca2+ levels. Those conditions sufficient for nonsynaptic epileptogenesis in the CA1 region were determined by pharmacologically mimicking the effects of Ca2+ reduction in normal Ca2+ levels. Increasing neuronal excitability, by removing extracellular Mg2+ and increasing extracellular K+ (6–15 mM), induced epileptiform activity that was suppressed by postsynaptic receptor antagonists [d-(−)-2-amino-5-phosphonopentanoic acid, picrotoxin, and 6,7-dinitroquinoxaline-2,3-dione] and was therefore synaptic in nature. Similarly, epileptiform activity induced when neuronal excitability was increased in the presence of KCaantagonists (verruculogen, charybdotoxin, norepinephrine, tetraethylammonium salt, and Ba2+) was found to be synaptic in nature. Decreases in osmolarity also failed to induce nonsynaptic epileptiform activity in the CA1 region. However, increasing neuronal excitability (by removing extracellular Mg2+ and increasing extracellular K+) in the presence of Cd2+, a nonselective Ca2+channel antagonist, or veratridine, a persistent sodium conductance enhancer, induced spontaneous nonsynaptic epileptiform activity in vitro. Both novel models were characterized using intracellular and ion-selective electrodes. The results of this study suggest that reducing extracellular Ca2+ facilitates bursting by increasing neuronal excitability and inhibiting Ca2+ influx, which might, in turn, enhance a persistent sodium conductance. Furthermore, these data show that nonsynaptic mechanisms can contribute to epileptiform activity in normal Ca2+ levels.
Acute Effect of an Incision on Mechanosensitive Afferents in the Plantar Rat Hindpaw
Authors: Hämäläinen Minna M. , Gebhart G. F. , Brennan Timothy J.
Published: May 2017

The purpose of this study was to examine which primary afferent fibers are sensitized to mechanical stimuli after an experimental surgical incision to the glabrous skin of the rat hindpaw. Afferent fibers teased from the L5dorsal root or the tibial nerve were recorded in anesthetized rats. The mechanical response properties of each fiber were characterized before and 45 min after an incision (or sham procedure) within the mechanical receptive field. Sensitization is characterized by an expansion of the mechanical receptive field, an increase in background activity, an increase in response magnitude, or a decrease in response threshold. After incision, the background activity and response properties of Aβ-fibers ( n = 9) to mechanical stimuli were unchanged. Four of 13 mechanosensitive Aδ-fibers exhibited sensitization after the incision; response threshold decreased, response magnitude increased, or receptive field size increased. Background activity of Aδ-fibers was not increased by the incision. Sensitization was observed in 4 of 18 mechanosensitive C-fibers 45 min after the incision. Background activity of C-fibers was not increased by the incision. In a group of mechanically insensitive afferent fibers (MIAs), 3 of 7 Aδ-fibers and 4 of 10 C-fibers sensitized 45 min after incision. Response threshold was decreased in only 2 of 17 MIAs; receptive field size increased in 7 of 17 MIAs. Aβ-fibers did not sensitize after the incision, and only 8 of 31 (26%) mechanosensitive Aδ- and C-fibers gave evidence of sensitization. In a group of MIA Aδ- and C-fibers, a greater percentage of 17 fibers studied (41%) were sensitized after incision. In this model, the principal effect of an incision, when examined 45 min after the insult, is an increase in receptive field size of the afferents, particularly those characterized as MIAs. To the extent that the mechanical hyperalgesia characterized in the same model is initiated in the periphery, it would appear that spatial summation of modestly increased response magnitude is important to the development of hyperalgesia.
Background Noise Improves Gap Detection in Tonically Inhibited Inferior Colliculus Neurons
Authors: Wilson Willard W. , Walton Joseph P.
Published: May 2017

Single units in the inferior colliculus (IC) in the C57Bl/6 inbred mouse strain were tested for their temporal processing ability as measured by their minimum gap threshold (MGT), the shortest silent interval in an ongoing white-noise stimulus which a unit could encode. After ascertaining the MGT in quiet, units were re-tested in various levels of background noise. The focus of this report is on two types of tonically responding units found in the IC. Tonically inhibited (TI) units encoded gaps poorly in quiet and low levels of background noise as compared with tonically excited (TE) units. In quiet, the MGTs of TI units were about an order of magnitude longer than the MGTs typical of TE units. Paradoxically, gap encoding was improved in high levels of background noise for TI units. This result is unexpected from the traditional viewpoint that noise necessarily degrades signal processing and is inconsistent with psychophysical observations of diminished speech and gap detection processing in noisy environments. We believe the improved feature detection described here is produced by the adaptation of inhibitory input. Continuous background noise would diminish the inhibitory efficacy of the gap stimulus by increasing the latency to the onset of inhibition and decreasing its duration. This would allow more spontaneous activity to “bleed through” the silent gap, thus signaling its presence. Improved feature detection in background noise resulting from inhibitory adaptation would seem an efficient neural mechanism and one that might be generally useful in other signal detection tasks.
Contribution of Presynaptic Na+ Channel Inactivation to Paired-Pulse Synaptic Depression in Cultured Hippocampal Neurons
Authors: He Yejun , Zorumski Charles F. , Mennerick Steven
Published: May 2017

Paired-pulse depression (PPD) of synaptic transmission is important for neuronal information processing. Historically, depletion of the readily releasable pool of synaptic vesicles has been proposed as the major component of PPD. Recent results suggest, however, that other mechanisms may be involved in PPD, including inactivation of presynaptic voltage-dependent sodium channels (NaChs), which may influence coupling of action potentials to transmitter release. In hippocampal cultures, we have examined the potential role and relative contribution of presynaptic NaCh inactivation in excitatory postsynaptic current (EPSC) PPD. Based on current- and voltage-clamp recordings from somas, our data suggest that NaCh inactivation could potentially participate in PPD. Paired stimulation of somatic action potentials (20- to 100-ms interval) results in subtle changes in action potential shape that are mimicked by low concentrations of tetrodotoxin (TTX) and that appear to be generated by a combination of fast and slow recovery from NaCh inactivation. Dilute concentrations of TTX dramatically depress glutamate release. However, we find evidence for only minimal contribution of NaCh inactivation to EPSC PPD under basal conditions. Hyperpolarization of presynaptic elements to speed recovery from inactivation or increasing the driving force on Na+ ions through active NaChs had minimal effects on PPD while more robustly reversing the effects of pharmacological NaCh blockade. On the other hand, slight depolarization of the presynaptic membrane potential, by elevating extracellular [K+]o, significantly increased PPD and frequency-dependent depression of EPSCs during short trains of action potentials. The results suggest that NaCh inactivation is poised to modulate EPSC amplitude with small tonic depolarizations that likely occur with physiological or pathophysiological activity.
Functional Organization of the Pallid Bat Auditory Cortex: Emphasis on Binaural Organization
Authors: Razak Khaleel A. , Fuzessery Zoltan M.
Published: May 2017

This report maps the organization of the primary auditory cortex of the pallid bat in terms of frequency tuning, selectivity for behaviorally relevant sounds, and interaural intensity difference (IID) sensitivity. The pallid bat is unusual in that it localizes terrestrial prey by passively listening to prey-generated noise transients (1–20 kHz), while reserving high-frequency (<30 kHz) echolocation for obstacle avoidance. The functional organization of its auditory cortex reflects the need for specializations in echolocation and passive sound localization. Best frequencies were arranged tonotopically with a general increase in the caudolateral to rostromedial direction. Frequencies between 24 and 32 kHz were under-represented, resulting in hypertrophy of frequencies relevant for prey localization and echolocation. Most neurons (83%) tuned <30 kHz responded preferentially to broadband or band-pass noise over single tones. Most neurons (62%) tuned >30 kHz responded selectively or exclusively to the 60- to 30-kHz downward frequency-modulated (FM) sweep used for echolocation. Within the low-frequency region, neurons were placed in two groups that occurred in two separate clusters: those selective for low- or high-frequency band-pass noise and suppressed by broadband noise, and neurons that showed no preference for band-pass noise over broadband noise. Neurons were organized in homogeneous clusters with respect to their binaural response properties. The distribution of binaural properties differed in the noise- and FM sweep-preferring regions, suggesting task-dependent differences in binaural processing. The low-frequency region was dominated by a large cluster of binaurally inhibited neurons with a smaller cluster of neurons with mixed binaural interactions. The FM sweep-selective region was dominated by neurons with mixed binaural interactions or monaural neurons. Finally, this report describes a cortical substrate for systematic representation of a spatial cue, IIDs, in the low-frequency region. This substrate may underlie a population code for sound localization based on a systematic shift in the distribution of activity across the cortex with sound source location.
Ionic Basis of the Resting Membrane Potential and Action Potential in the Pharyngeal Muscle of Caenorhabditis elegans
Authors: Franks Christopher J. , Pemberton Darrel , Vinogradova Irina , Cook Alan , Walker Robert J. , Holden-Dye Lindy
Published: May 2017

The pharynx of C. elegans is a rhythmically active muscle that pumps bacteria into the gut of the nematode. This activity is maintained by action potentials, which qualitatively bear a resemblance to vertebrate cardiac action potentials. Here, the ionic basis of the resting membrane potential and pharyngeal action potential has been characterized using intracellular recording techniques. The resting membrane potential is largely determined by a K+permeability, and a ouabain-sensitive, electrogenic pump. As previously suggested, the action potential is at least partly dependent on voltage-gated Ca2+ channels, as the amplitude was increased as extracellular Ca2+ was increased, and decreased by L-type Ca2+ channel blockers verapamil and nifedipine. Barium caused a marked prolongation of action potential duration, suggesting that a calcium-activated K+ current may contribute to repolarization. Most notably, however, we found that action potentials were abolished in the absence of external Na+. This may be due, at least in part, to a Na+-dependent pacemaker potential. In addition, the persistence of action potentials in nominally free Ca2+, the inhibition by Na+ channel blockers procaine and quinidine, and the increase in action potential frequency caused by veratridine, a toxin that alters activation of voltage-gated Na+channels, point to the involvement of a voltage-gated Na+ current. Voltage-clamp analysis is required for detailed characterization of this current, and this is in progress. Nonetheless, these observations are quite surprising in view of the lack of any obvious candidate genes for voltage-gated Na+ channels in the C. elegans genome. It would therefore be informative to re-evaluate the data from these homology searches, with the aim of identifying the gene(s) conferring this Na+, quinidine, and veratridine sensitivity to the pharynx.