bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression plasticity evolves in response to colonization of freshwater lakes in threespine stickleback
Authors: Morris Matthew R. J. , Richard Romain , Leder Erica H. , Barrett Rowan D. H. , Aubin‐Horth Nadia , Rogers Sean M. 
Published: May 2014

AbstractPhenotypic plasticity is predicted to facilitate individual survival and/or evolve in response to novel environments. Plasticity that facilitates survival should both permit colonization and act as a buffer against further evolution, with contemporary and derived forms predicted to be similarly plastic for a suite of traits. On the other hand, given the importance of plasticity in maintaining internal homeostasis, derived populations that encounter greater environmental heterogeneity should evolve greater plasticity. We tested the evolutionary significance of phenotypic plasticity in coastalBritishColumbian postglacial populations of threespine stickleback (Gasterosteus aculeatus) that evolved under greater seasonal extremes in temperature after invading freshwater lakes from the sea. Two ancestral (contemporary marine) and two derived (contemporary freshwater) populations of stickleback were raised near their thermal tolerance extremes, 7 and 22 °C. Gene expression plasticity was estimated for more than 14 000 genes. Over five thousand genes were similarly plastic in marine and freshwater stickleback, but freshwater populations exhibited significantly more genes with plastic expression than marine populations. Furthermore, several of the loci shown to exhibit gene expression plasticity have been previously implicated in the adaptive evolution of freshwater populations, including a gene involved in mitochondrial regulation (PPARAa). Collectively, these data provide molecular evidence that highlights the importance of plasticity in colonization and adaptation to new environments.
Genome diversity in Brachypodium distachyon: deep sequencing of highly diverse inbred lines
Authors: Gordon Sean P. , Priest Henry , Des Marais David L. , Schackwitz Wendy , Figueroa Melania , Martin Joel , Bragg Jennifer N. , Tyler Ludmila , Lee Cheng‐Ruei , Bryant Doug , Wang Wenqin , Messing Joachim , Manzaneda Antonio J. , Barry Kerrie , Garvin David F. , Budak Hikmet , Tuna Metin , Mitchell‐Olds Thomas , Pfender William F. , Juenger Thomas E. , Mockler Todd C. , Vogel John P. 
Published: May 2014

SummaryBrachypodium distachyon is small annual grass that has been adopted as a model for the grasses. Its small genome, high‐quality reference genome, large germplasm collection, and selfing nature make it an excellent subject for studies of natural variation. We sequenced six divergent lines to identify a comprehensive set of polymorphisms and analyze their distribution and concordance with gene expression. Multiple methods and controls were utilized to identify polymorphisms and validate their quality. mRNA‐Seq experiments under control and simulated drought‐stress conditions, identified 300 genes with a genotype‐dependent treatment response. We showed that large‐scale sequence variants had extremely high concordance with altered expression of hundreds of genes, including many with genotype‐dependent treatment responses. We generated a deep mRNA‐Seq dataset for the most divergent line and created a de novo transcriptome assembly. This led to the discovery of >2400 previously unannotated transcripts and hundreds of genes not present in the reference genome. We built a public database for visualization and investigation of sequence variants among these widely used inbred lines.
Respiratory modulation of muscle sympathetic nerve activity in obstructive sleep apnoea
Authors: Fatouleh Rania , McKenzie David K. , Macefield Vaughan G. 
Published: May 2014

New Findings
What is the central question of this study?
Muscle sympathetic nerve activity (MSNA) is increased in obstructive sleep apnoea (OSA), leading to hypertension. Is this due to an increase in respiratory–sympathetic coupling, as has been demonstrated in the spontaneously hypertensive rat?
What is the main finding and its importance?
Using direct microelectrode recordings of MSNA in hypertensive OSA patients and normotensive control subjects, we show that the magnitude of respiratory modulation is not increased in OSA, arguing against an amplified respiratory–sympathetic coupling as the underlying cause of the neurogenic hypertension, although the temporal coupling of MSNA to respiration was stronger in OSA.
Obstructive sleep apnoea (OSA) is associated with elevated muscle sympathetic nerve activity (MSNA) during normoxic daytime wakefulness, leading to hypertension. We tested the hypothesis that respiratory–sympathetic coupling, postulated to be the underlying cause of neurogenic hypertension, is increased in OSA. Muscle sympathetic nerve activity, blood pressure, ECG and respiration were recorded in 21 normotensive control subjects and 21 newly diagnosed patients with OSA before and after 6 and 12 months of treatment with continuous positive airway pressure. Muscle sympathetic nerve activity was recorded via tungsten microelectrodes inserted percutaneously into the peroneal nerve. Cardiac and respiratory modulation of MSNA was quantified from the cross‐correlation histograms constructed between the sympathetic spikes and either ECG or respiration. Muscle sympathetic nerve activity was significantly elevated in newly diagnosed OSA patients compared with control subjects (53 ± 2 versus 28 ± 2 bursts min−1). There was a significant fall in MSNA after 6 months of continuous positive airway pressure (37 ± 2 bursts min−1), with no further change after 12 months (37 ± 2 bursts min−1). There were no significant differences in the magnitude of respiratory modulation of MSNA between the OSA patients and control subjects (40 ± 3.1 versus 39 ± 3.4%). However, when considering the normalized temporal profile there were changes in the respiratory patterning of MSNA in OSA, with more activity occurring in postinspiration and less in inspiration and expiration. This was largely reversed following long‐term continuous positive airway pressure.
The degree of acute descending control of spinal nociception in an area of primary hyperalgesia is dependent on the peripheral domain of afferent input
Authors: Drake Robert A. R. , Hulse Richard P. , Lumb Bridget M. , Donaldson Lucy F. 
Published: May 2014

Key points
Acute inflammation engages various descending control systems in the brain that alter the resulting inflammatory pain, usually by inhibiting it.
In this study we looked at the differences in inhibition of acute (up to 3 h) inflammatory pain from smooth (glabrous) and hairy skin in the rat hind foot.
In hairy skin, inflammatory pain is rapidly inhibited by descending systems that release noradrenaline, but not opiates, into the spinal cord.
In glabrous skin, neither descending noradrenergic nor opioidergic controls affect inflammatory pain.
These results tell us that the controls on the spinal processing of cutaneous inflammatory pain differ according to the skin type affected.
AbstractDescending controls of spinal nociceptive processing play a critical role in the development of inflammatory hyperalgesia. Acute peripheral nociceptor sensitization drives spinal sensitization and activates spino–supraspinal–spinal loops leading to descending inhibitory and facilitatory controls of spinal neuronal activity that further modify the extent and degree of the pain state. The afferent inputs from hairy and glabrous skin are distinct with respect to both the profile of primary afferent classes and the degree of their peripheral sensitization. It is not known whether these differences in afferent input differentially engage descending control systems to different extents or in different ways. Injection of complete Freund's adjuvant resulted in inflammation and swelling of hairy hind foot skin in rats, a transient thermal hyperalgesia lasting <2 h, and longlasting primary mechanical hyperalgesia (≥7 days). Much longer lasting thermal hyperalgesia was apparent in glabrous skin (1 h to >72 h). In hairy skin, transient hyperalgesia was associated with sensitization of withdrawal reflexes to thermal activation of either A‐ or C‐nociceptors. The transience of the hyperalgesia was attributable to a rapidly engaged descending inhibitory noradrenergic mechanism, which affected withdrawal responses to both A‐ and C‐nociceptor activation and this could be reversed by intrathecal administration of yohimbine (α‐2‐adrenoceptor antagonist). In glabrous skin, yohimbine had no effect on an equivalent thermal inflammatory hyperalgesia. We conclude that acute inflammation and peripheral nociceptor sensitization in hind foot hairy skin, but not glabrous skin, rapidly activates a descending inhibitory noradrenergic system. This may result from differences in the engagement of descending control systems following sensitization of different primary afferent classes that innervate glabrous and hairy skin.
Nociceptive primary afferents: they have a mind of their own
Authors: Carlton Susan M. 
Published: May 2014

AbstractNociceptive primary afferents have three surprising properties: they are highly complex in their expression of neurotransmitters and receptors and most probably participate in autocrine and paracrine interactions; they are capable of exerting tonic and activity‐dependent inhibitory control over incoming nociceptive input; they can generate signals in the form of dorsal root reflexes that are transmitted antidromically out to the periphery and these signals can result in neurogenic inflammation in the innervated tissue. Thus, nociceptive primary afferents are highly complicated structures, capable of modifying input before it is ever transmitted to the central nervous system and capable of altering the tissue they innervate.
Diet‐dependent modulation of gastro‐oesphageal vagal afferent mechanosensitivity by endogenous nitric oxide
Authors: Kentish Stephen J. , O'Donnell Tracey A. , Wittert Gary A. , Page Amanda J. 
Published: May 2014

Key points
Nitric oxide (NO) is an important signalling molecule found in the gastrointestinal tract, which can modulate the mechanosensitivity of gastro‐oesophageal vagal afferents.
It is known that the effects of NO on food intake depend on feeding status, but the effect of NO on gastro‐oesophageal vagal afferents in different feeding conditions is unknown.
We show that in the fed state endogenous NO inhibits mucosal afferents through a pathway involving nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
In mice fasted overnight endogenous NO potentiates the response of mucosal stroking‐ and tension‐sensitive afferents to mechanical stimuli via a mechanism involving hyperpolarisation‐activated cyclic nucleotide‐gated 3 (HCN3) channels.
These results show the role of NO in the peripheral modulation of gastro‐oesophageal vagal afferents is dynamic and dependent on feeding status.
AbstractNeuronal nitric oxide (NO) plays an important role in gastric motor activity and modulates the mechanosensitivity of gastro‐oesophageal vagal afferents. Effects of NO on food intake are dependent on feeding status. We sought to determine the effect of NO on gastro‐oesophageal vagal afferent activity in the normally fed and food‐restricted states and the second messenger pathways mediating these effects. Eight week old female C56BL/6 mice were fed ad libitum or food restricted for 14 h. An in vitro preparation was used to determine the functional effects of NO and the second messenger pathways involved. Expression of NO signal transduction molecules in vagal afferents was determined by reverse‐transcription polymerase chain reaction (RT‐PCR). Endogenous NO and the NO donor S‐nitroso‐N‐acetylpenicillamine (SNAP) inhibited vagal mucosal afferent responses to tactile stimuli in mice fed ad libitum. After a 14 h fast endogenous NO and SNAP potentiated tension and mucosal afferent responses to mechanical stimulation. The excitatory effect of NO was blocked by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin. After a 14 h fast expression of NADPH oxidase 2 (NOX2) mRNA in whole nodose ganglia was significantly reduced and the excitatory effect of NO on gastro‐oesophageal vagal afferents was lost. Under fasting conditions the inhibitory effect of NO was blocked with the hyperpolarisation‐activated cyclic nucleotide‐gated (HCN) channel blocker ivabradine and mRNA expression of HCN3 in the nodose ganglia was elevated. In conclusion, the role of NO in the peripheral modulation of gastro‐oesophageal vagal afferents is dynamic and dependent on feeding status.
Cholinergic circuit modulation through differential recruitment of neocortical interneuron types during behaviour
Authors: Poorthuis Rogier B. , Enke Leona , Letzkus Johannes J. 
Published: May 2014

AbstractAcetylcholine is a crucial neuromodulator for attention, learning and memory. Release of acetylcholine in primary sensory cortex enhances processing of sensory stimuli, and many in vitro studies have pinpointed cellular mechanisms that could mediate this effect. In contrast, how cholinergic modulation shapes the function of intact circuits during behaviour is only beginning to emerge. Here we review recent data on the recruitment of identified interneuron types in neocortex by cholinergic signalling, obtained with a combination of genetic targeting of cell types, two‐photon imaging and optogenetics. These results suggest that acetylcholine release during basal forebrain stimulation, and during physiological recruitment of the basal forebrain, can strongly and rapidly influence the firing of neocortical interneurons. In contrast to the traditional view of neuromodulation as a relatively slow process, cholinergic signalling can thus rapidly convey time‐locked information to neocortex about the behavioural state of the animal and the occurrence of salient sensory stimuli. Importantly, these effects strongly depend on interneuron type, and different interneuron types in turn control distinct aspects of circuit function. One prominent effect of phasic acetylcholine release is disinhibition of pyramidal neurons, which can facilitate sensory processing and associative learning.
Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic skeletal muscle
Authors: Tan Nhi , Lansman Jeffry B. 
Published: May 2014

Key points
Loss of the cytoskeletal protein dystrophin leads to muscle degeneration in Duchenne muscular dystrophy. The mdx mouse lacks dystrophin but muscle disease is mild, in part because upregulation of utrophin compensates for dystrophin. Evidence suggests that Ca2+ entry through mechanosensitive (MS) ion channels contributes to disease pathogenesis, but the role of utrophin in regulating Ca2+ entry has not been studied.
Depletion of utrophin in mdx mice produces a gene dose‐dependent increase in MS channel open probability, single‐channel conductance in some patches, and an increase in the pressure required to MS channels. The overall effect of loss of utrophin is increased Ca2+ entry.
The results suggest utrophin organizes local membrane microdomains containing MS channels. Disruption of these domains causes changes in membrane composition, which favour channel open states and subunit aggregation. Utrophin‐replacement therapies may act by correcting MS channel gating, and specific MS channel inhibitors have the potential to prevent disease progression.
AbstractDystrophin is a large, submembrane cytoskeletal protein, absence of which causes Duchenne muscular dystrophy. Utrophin is a dystrophin homologue found in both muscle and brain whose physiological function is unknown. Recordings of single‐channel activity were made from membrane patches on skeletal muscle from mdx, mdx/utrn+/– heterozygotes and mdx/utrn–/– double knockout mice to investigate the role of these cytoskeletal proteins in mechanosensitive (MS) channel gating. We find complex, gene dose‐dependent effects of utrophin depletion in dystrophin‐deficient mdx muscle: (1) increased MS channel open probability, (2) a shift of MS channel gating to larger pressures, (3) appearance of modal gating of MS channels and small conductance channels and (4) expression of large conductance MS channels. We suggest a physical model in which utrophin acts as a scaffolding protein that stabilizes lipid microdomains and clusters MS channel subunits. Depletion of utrophin disrupts domain composition in a manner that favours open channel area expansion, as well as allowing diffusion and aggregation of additional MS channel subunits.
Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells resolved by high‐density diamond ultra‐microelectrode arrays
Authors: Gosso Sara , Turturici Marco , Franchino Claudio , Colombo Elisabetta , Pasquarelli Alberto , Carbone Emilio , Carabelli Valentina 
Published: May 2014

Key points
A planar nanocrystalline diamond array with nine ultra‐microelectrodes (9‐Ch NCD‐UMEA) has been designed for high spatial resolution of amperometric recordings in single chromaffin cells.
The 9‐Ch NCD‐UMEA operates in voltammetric and amperometric mode to reveal low doses of adrenaline, dopamine and serotonin. The lowest detectable concentration of adrenaline is ∼5 μm.
Using mouse and bovine chromaffin cells, single quantal exocytotic events are recorded from nine microareas of 12–27 μm2. We found an excellent correspondence with recordings from the cell apex using carbon fibre electrodes.
In the bovine, secretion is heterogeneous. There are areas of high and medium activity covering 54% of the cell surface and areas of low and no activity covering the remainder. The ‘non‐active zones’ (silent) cover 24% of the cell surface and persist for minutes as the ‘active zones’.
The 9‐Ch NCD‐UMEA brings new insights into the spatial mapping of secretory sites in chromaffin cells.
AbstractHere we describe the ability of a high‐density diamond microelectrode array targeted to resolve multi‐site detection of fast exocytotic events from single cells. The array consists of nine boron‐doped nanocrystalline diamond ultra‐microelectrodes (9‐Ch NCD‐UMEA) radially distributed within a circular area of the dimensions of a single cell. The device can be operated in voltammetric or chronoamperometric configuration. Sensitivity to catecholamines, tested by dose–response calibrations, set the lowest detectable concentration of adrenaline to ∼5 μm. Catecholamine release from bovine or mouse chromaffin cells could be triggered by electrical stimulation or external KCl‐enriched solutions. Spikes detected from the cell apex using carbon fibre microelectrodes showed an excellent correspondence with events measured at the bottom of the cell by the 9‐Ch NCD‐UMEA, confirming the ability of the array to resolve single quantal secretory events. Subcellular localization of exocytosis was provided by assigning each quantal event to one of the nine channels based on its location. The resulting mapping highlights the heterogeneous distribution of secretory activity in cell microdomains of 12–27 μm2. In bovine chromaffin cells, secretion was highly heterogeneous with zones of high and medium activity in 54% of the cell surface and zones of low or no activity in the remainder. The ‘non‐active’ (‘silent’) zones covered 24% of the total and persisted for 6–8 min, indicating stable location. The 9‐Ch NCD‐UMEA therefore appears suitable for investigating the microdomain organization of neurosecretion with high spatial resolution.
Direct excitation of parvalbumin‐positive interneurons by M1 muscarinic acetylcholine receptors: roles in cellular excitability, inhibitory transmission and cognition
Authors: Yi Feng , Ball Jackson , Stoll Kurt E. , Satpute Vaishali C. , Mitchell Samantha M. , Pauli Jordan L. , Holloway Benjamin B. , Johnston April D. , Nathanson Neil M. , Deisseroth Karl , Gerber David J. , Tonegawa Susumu , Lawrence J. Josh 
Published: May 2014

Key points
Parvalbumin‐containing (PV) neurons from mouse CA1 hippocampus (HC) and prefrontal cortex exhibit a fast spiking phenotype in vitro. Within CA1, HC PV cells are mainly comprised of basket and bistratified cell types.
Direct activation of muscarinic acetylcholine receptors (mAChRs) enhances excitability more in CA1 HC than in prefrontal cortex PV cells.
mAChR‐induced excitation of CA1 PV cells occurs through direct activation of M1 mAChRs.
Transgenetic deletion of M1 mAChRs from PV cells diminishes M1 mAChR expression and cholinergic excitation of CA1 PV cells.
mAChR‐induced excitation exclusively in PV cells enhances GABAergic transmission in CA1 pyramidal cells.
In vivo activation of M1 mAChRs in PV cells is important in recognition and working memory but not spatial memory.
AbstractParvalbumin‐containing (PV) neurons, a major class of GABAergic interneurons, are essential circuit elements of learning networks. As levels of acetylcholine rise during active learning tasks, PV neurons become increasingly engaged in network dynamics. Conversely, impairment of either cholinergic or PV interneuron function induces learning deficits. Here, we examined PV interneurons in hippocampus (HC) and prefrontal cortex (PFC) and their modulation by muscarinic acetylcholine receptors (mAChRs). HC PV cells, visualized by crossing PV‐CRE mice with Rosa26YFP mice, were anatomically identified as basket cells and PV bistratified cells in the stratum pyramidale; in stratum oriens, HC PV cells were electrophysiologically distinct from somatostatin‐containing cells. With glutamatergic transmission pharmacologically blocked, mAChR activation enhanced PV cell excitability in both CA1 HC and PFC; however, CA1 HC PV cells exhibited a stronger postsynaptic depolarization than PFC PV cells. To delete M1 mAChRs genetically from PV interneurons, we created PV‐M1 knockout mice by crossing PV‐CRE and floxed M1 mice. The elimination of M1 mAChRs from PV cells diminished M1 mAChR immunoreactivity and muscarinic excitation of HC PV cells. Selective cholinergic activation of HC PV interneurons using Designer Receptors Exclusively Activated by Designer Drugs technology enhanced the frequency and amplitude of inhibitory synaptic currents in CA1 pyramidal cells. Finally, relative to wild‐type controls, PV‐M1 knockout mice exhibited impaired novel object recognition and, to a lesser extent, impaired spatial working memory, but reference memory remained intact. Therefore, the direct activation of M1 mAChRs on PV cells contributes to some forms of learning and memory.