bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paired associative transcranial alternating current stimulation increases the excitability of corticospinal projections in humans
Authors: McNickle Emmet , Carson Richard G. 
Published: December 2014

Key pointsRepeatedly pairing short trains of peripheral afferent stimulation with bursts (500–1000 ms) of high frequency (≥80 Hz) transcranial alternating current stimulation (tACS) over the contralateral primary motor cortex (M1) induces reliable elevations in corticospinal excitability.The effect can be obtained using a range of tACS current intensities and frequencies, and with different forms of peripheral afferent stimulation.The generation of a temporally discrete cortical event is not a critical determinant of the increases in corticospinal excitability induced by associative stimulation protocols.AbstractMany types of non‐invasive brain stimulation alter corticospinal excitability (CSE). Paired associative stimulation (PAS) has attracted particular attention as its effects ostensibly adhere to Hebbian principles of neural plasticity. In prototypical form, a single electrical stimulus is directed to a peripheral nerve in close temporal contiguity with transcranial magnetic stimulation delivered to the contralateral primary motor cortex (M1). Repeated pairing of the two discrete stimulus events (i.e. association) over an extended period either increases or decreases the excitability of corticospinal projections from M1, contingent on the interstimulus interval. We studied a novel form of associative stimulation, consisting of brief trains of peripheral afferent stimulation paired with short bursts of high frequency (≥80 Hz) transcranial alternating current stimulation (tACS) over contralateral M1. Elevations in the excitability of corticospinal projections to the forearm were observed for a range of tACS frequency (80, 140 and 250 Hz), current (1, 2 and 3 mA) and duration (500 and 1000 ms) parameters. The effects were at least as reliable as those brought about by PAS or transcranial direct current stimulation. When paired with tACS, muscle tendon vibration also induced elevations of CSE. No such changes were brought about by the tACS or peripheral afferent stimulation alone. In demonstrating that associative effects are expressed when the timing of the peripheral and cortical events is not precisely circumscribed, these findings suggest that multiple cellular pathways may contribute to a long term potentiation‐type response. Their relative contributions will differ depending on the nature of the induction protocol that is used.
Multiple blocks of intermittent and continuous theta‐burst stimulation applied via transcranial magnetic stimulation differently affect sensory responses in rat barrel cortex
Authors: Thimm Andreas , Funke Klaus 
Published: December 2014

Key points
Theta‐burst stimulation (TBS) applied via transcranial magnetic stimulation is able to modulate human cortical excitability.
Here we investigated in a rat model how two different forms of TBS, intermittent (iTBS) and continuous (cTBS), affect sensory responses in rat barrel cortex.
We found that iTBS but less cTBS promoted late (>18 ms) sensory response components while not affecting the earliest response (8–18 ms). The effect increased with each of the five iTBS blocks applied.
cTBS somewhat reduced the early response component after the first block but had a similar effect as iTBS after four to five blocks.
We conclude that iTBS primarly modulates the activity of (inhibitory) cortical interneurons while cTBS may first reduce general neuronal excitability with a single block but reverse to iTBS‐like effects with application of several blocks.
AbstractCortical sensory processing varies with cortical state and the balance of inhibition to excitation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to modulate human cortical excitability. In a rat model, we recently showed that intermittent theta‐burst stimulation (iTBS) applied to the corpus callosum, to activate primarily supragranular cortical pyramidal cells but fewer subcortical neurons, strongly reduced the cortical expression of parvalbumin (PV), indicating reduced activity of fast‐spiking interneurons. Here, we used the well‐studied rodent barrel cortex system to test how iTBS and continuous TBS (cTBS) modulate sensory responses evoked by either single or double stimuli applied to the principal (PW) and/or adjacent whisker (AW) in urethane‐anaesthetized rats. Compared to sham stimulation, iTBS but not cTBS particularly enhanced late (>18 ms) response components of multi‐unit spiking and local field potential responses in layer 4 but not the very early response (<18 ms). Similarly, only iTBS diminished the suppression of the second response evoked by paired PW or AW–PW stimulation at 20 ms intervals. The effects increased with each of the five iTBS blocks applied. With cTBS a mild effect similar to that of iTBS was first evident after 4–5 stimulation blocks. Enhanced cortical c‐Fos and zif268 expression but reduced PV and GAD67 expression was found only after iTBS, indicating increased cortical activity due to lowered inhibition. We conclude that iTBS but less cTBS may primarily weaken a late recurrent‐type cortical inhibition mediated via a subset of PV+ interneurons, enabling stronger late response components believed to contribute to the perception of sensory events.
Anchoring protein AKAP79‐mediated PKA phosphorylation of STIM1 determines selective activation of the ARC channel, a store‐independent Orai channel
Authors: Thompson Jill L. , Shuttleworth Trevor J. 
Published: December 2014

Key points
Although both the calcium store‐dependent CRAC channels and the store‐independent ARC channels are regulated by the protein STIM1, CRAC channels are regulated by STIM1 in the endoplasmic reticulum, whilst ARC channels are regulated by the STIM1 constitutively resident in the plasma membrane.
We now demonstrate that activation of the ARC channels, but not CRAC channels, is uniquely dependent on phosphorylation of a single residue (T389) in the extensive cytosolic domain of STIM1 by protein kinase A.
We further demonstrate that the phosphorylation of the T389 residue by protein kinase A is mediated by the association of plasma membrane STIM1 with the scaffolding protein AKAP79.
Together, these findings indicate that the phosphorylation status of this single residue in STIM1 represents a key molecular determinant of the relative activities of these two co‐existing Ca2+ entry channels that are known to play critical, but distinct, roles in modulating a variety of physiologically relevant activities.
AbstractThe low‐conductance, highly calcium‐selective channels encoded by the Orai family of proteins represent a major pathway for the agonist‐induced entry of calcium associated with the generation and modulation of the key intracellular calcium signals that initiate and control a wide variety of physiologically important processes in cells. There are two distinct members of this channel family that co‐exist endogenously in many cell types: the store‐operated Ca2+ release‐activated CRAC channels and the store‐independent arachidonic acid‐regulated ARC channels. Although the activities of both channels are regulated by the stromal‐interacting molecule‐1 (STIM1) protein, two distinct pools of this protein are responsible, with the major pool of STIM1 in the endoplasmic reticulum membrane regulating CRAC channel activity, whilst the minor pool of plasma membrane STIM1 regulates ARC channel activity. We now show that a critical feature in determining this selective activation of the two channels is the phosphorylation status of a single threonine residue (T389) within the extensive (∼450 residue) cytosolic domain of STIM1. Specifically, protein kinase A (PKA)‐mediated phosphorylation of T389 of STIM1 is necessary for effective activation of the ARC channels, whilst phosphorylation of the same residue actually inhibits the ability of STIM1 to activate the CRAC channels. We further demonstrate that the PKA‐mediated phosphorylation of T389 occurs at the plasma membrane via the involvement of the anchoring protein AKAP79, which is constitutively associated with the pool of STIM1 in the plasma membrane. The novel mechanism we have described provides a means for the cell to precisely regulate the relative activities of these two channels to independently modulate the resulting intracellular calcium signals in a physiologically relevant manner.
Noradrenaline upregulates T‐type calcium channels in rat pinealocytes
Authors: Yu Haijie , Seo Jong Bae , Jung Seung‐Ryoung , Koh Duk‐Su , Hille Bertil 
Published: December 2014

Key points
The mammalian pineal gland is a neuroendocrine organ that responds to circadian and seasonal rhythms. Its major function is to secrete melatonin as a hormonal night signal in response to nocturnal delivery of noradrenaline from sympathetic neurons.
Culturing rat pinealocytes in noradrenaline for 24 h induced a low‐voltage activated transient Ca2+ current whose pharmacology and kinetics corresponded to a CaV3.1 T‐type channel.
The upregulation of the T‐type Ca2+ current is initiated by β‐adrenergic receptors, cyclic AMP and cyclic AMP‐dependent protein kinase.
Messenger RNA for CaV3.1 T‐type channels is significantly elevated by noradrenaline at 8 h and 24 h.
The noradrenaline‐induced T‐type channel mediated an increased Ca2+ entry and supported modest transient electrical responses to depolarizing stimuli, revealing the potential for circadian regulation of pinealocyte electrical excitability and Ca2+ signalling.
AbstractOur basic hypothesis is that mammalian pinealocytes have cycling electrical excitability and Ca2+ signalling that may contribute to the circadian rhythm of pineal melatonin secretion. This study asked whether the functional expression of voltage‐gated Ca2+ channels (CaV channels) in rat pinealocytes is changed by culturing them in noradrenaline (NA) as a surrogate for the night signal. Channel activity was assayed as ionic currents under patch clamp and as optical signals from a Ca2+‐sensitive dye. Channel mRNAs were assayed by quantitative polymerase chain reaction. Cultured without NA, pinealocytes showed only non‐inactivating L‐type dihydropyridine‐sensitive Ca2+ current. After 24 h in NA, additional low‐voltage activated transient Ca2+ current developed whose pharmacology and kinetics corresponded to a T‐type CaV3.1 channel. This change was initiated by β‐adrenergic receptors, cyclic AMP and protein kinase A as revealed by pharmacological experiments. mRNA for CaV3.1 T‐type channels became significantly elevated, but mRNA for another T‐type channel and for the major L‐type channel did not change. After only 8 h of NA treatment, the CaV3.1 mRNA was already elevated, but the transient Ca2+ current was not. Even a 16 h wait without NA following the 8 h NA treatment induced little additional transient current. However, these cells were somehow primed to make transient current as a second NA exposure for only 60 min sufficed to induce large T‐type currents. The NA‐induced T‐type channel mediated an increased Ca2+ entry during short depolarizations and supported modest transient electrical responses to depolarizing stimuli. Such experiments reveal the potential for circadian regulation of excitability.
Chronic activation of CB2 cannabinoid receptors in the hippocampus increases excitatory synaptic transmission
Authors: Kim Jimok , Li Yong 
Published: December 2014

Key points
The effects of cannabinoids are primarily mediated by two types of cannabinoid receptors, CB1 receptors in the nervous system and CB2 receptors in the immune system.
Recent evidence indicates that CB2 receptors are also widely expressed in the brain and involved in neuropsychiatric functions, such as schizophrenia‐like behaviours, anxiety, memory, vomiting and pain.
The cellular mechanisms by which CB2 receptors regulate neuronal functions are unknown.
We show that chronic activation of CB2 receptors in the hippocampus for 7–10 days increases excitatory synaptic transmission, whereas short‐term activation of CB2 receptors has little effect on synaptic activity.
This study reveals a novel role of CB2 receptors in the brain, which is clearly distinct from that of CB1 receptors, and thus, will help us to understand better the diverse effects of cannabinoids in the nervous system.
AbstractThe roles of CB1 cannabinoid receptors in regulating neuronal activity have been extensively characterized. Although early studies show that CB1 receptors are present in the nervous system and CB2 cannabinoid receptors are in the immune system, recent evidence indicates that CB2 receptors are also expressed in the brain. Activation or blockade of CB2 receptors in vivo induces neuropsychiatric effects, but the cellular mechanisms of CB2 receptor function are unclear. The aim of this study is to determine how activation of CB2 receptors present in the hippocampus regulates synaptic function. Here, we show that when organotypic cultures of rodent hippocampal slices were treated with a CB2 receptor agonist (JWH133 or GP1a) for 7–10 days, quantal glutamate release became more frequent and spine density was increased via extracellular signal‐regulated kinases. Chronic intraperitoneal injection of JWH133 into mice also increased excitatory synaptic transmission. These effects were blocked by a CB2 receptor antagonist (SR144528) or absent from hippocampal slices of CB2 receptor knock‐out mice. This study reveals a novel cellular function of CB2 cannabinoid receptors in the hippocampus and provides insights into how cannabinoid receptor subtypes diversify the roles of cannabinoids in the brain.
Ratiometric Imaging of Extracellular pH in Bacterial Biofilms with C-SNARF-4
Authors: Schlafer Sebastian , Garcia Javier E. , Greve Matilde , Raarup Merete K. , Nyvad Bente , Dige Irene 
Published: December 2014

ABSTRACT

pH in the extracellular matrix of bacterial biofilms is of central importance for microbial metabolism. Biofilms possess a complex three-dimensional architecture characterized by chemically different microenvironments in close proximity. For decades, pH measurements in biofilms have been limited to monitoring bulk pH with electrodes. Although pH microelectrodes with a better spatial resolution have been developed, they do not permit the monitoring of horizontal pH gradients in biofilms in real time. Quantitative fluorescence microscopy can overcome these problems, but none of the hitherto employed methods differentiated accurately between extracellular and intracellular microbial pH and visualized extracellular pH in all areas of the biofilms. Here, we developed a method to reliably monitor extracellular biofilm pH microscopically with the ratiometric pH-sensitive dye C-SNARF-4, choosing dental biofilms as an example. Fluorescent emissions of C-SNARF-4 can be used to calculate extracellular pH irrespective of the dye concentration. We showed that at pH values of <6, C-SNARF-4 stained 15 bacterial species frequently isolated from dental biofilm and visualized the entire bacterial biomass in
in vivo
-grown dental biofilms with unknown species composition. We then employed digital image analysis to remove the bacterial biomass from the microscopic images and adequately calculate extracellular pH values. As a proof of concept, we monitored the extracellular pH drop in
in vivo
-grown dental biofilms fermenting glucose. The combination of pH ratiometry with C-SNARF-4 and digital image analysis allows the accurate monitoring of extracellular pH in bacterial biofilms in three dimensions in real time and represents a significant improvement to previously employed methods of biofilm pH measurement.
Sensor Kinase PA4398 Modulates Swarming Motility and Biofilm Formation in Pseudomonas aeruginosa PA14
Authors: Strehmel Janine , Neidig Anke , Nusser Michael , Geffers Robert , Brenner-Weiss Gerald , Overhage Joerg 
Published: December 2014

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic human pathogen that is able to sense and adapt to numerous environmental stimuli by the use of transcriptional regulators, including two-component regulatory systems. In this study, we demonstrate that the sensor kinase PA4398 is involved in the regulation of swarming motility and biofilm formation in
P. aeruginosa
PA14. A PA4398
−
mutant strain was considerably impaired in swarming motility, while biofilm formation was increased by approximately 2-fold. The PA4398
−
mutant showed no changes in growth rate, rhamnolipid synthesis, or the production of the Pel exopolysaccharide but exhibited levels of the intracellular second messenger cyclic dimeric GMP (c-di-GMP) 50% higher than those in wild-type cells. The role of PA4398 in gene regulation was investigated by comparing the PA4398
−
mutant to the wild-type strain by using microarray analysis, which demonstrated that 64 genes were up- or downregulated more than 1.5-fold (
P
< 0.05) under swarming conditions. In addition, more-sensitive real-time PCR studies were performed on genes known to be involved in c-di-GMP metabolism. Among the dysregulated genes were several involved in the synthesis and degradation of c-di-GMP or in the biosynthesis, transport, or function of the iron-scavenging siderophores pyoverdine and pyochelin, in agreement with the swarming phenotype observed. By analyzing additional mutants of selected pyoverdine- and pyochelin-related genes, we were able to show that not only
pvdQ
but also
pvdR
,
fptA
,
pchA
,
pchD
, and
pchH
are essential for the normal swarming behavior of
P. aeruginosa
PA14 and may also contribute to the swarming-deficient phenotype of the PA4398
−
mutant in addition to elevated c-di-GMP levels.
Prepartum and Postpartum Rumen Fluid Microbiomes: Characterization and Correlation with Production Traits in Dairy Cows
Authors: Lima Fabio S. , Oikonomou Georgios , Lima Svetlana F. , Bicalho Marcela L. S. , Ganda Erika K. , de Oliveira Filho Jose C. , Lorenzo Gustavo , Trojacanec Plamen , Bicalho Rodrigo C. 
Published: December 2014

ABSTRACT

Microbes present in the rumen of dairy cows are essential for degradation of cellulosic and nonstructural carbohydrates of plant origin. The prepartum and postpartum diets of high-producing dairy cows are substantially different, but in what ways the rumen microbiome changes in response and how those changes may influence production traits are not well elucidated. Here, we sequenced the 16S and 18S rRNA genes using the MiSeq platform to characterize the prepartum and postpartum rumen fluid microbiomes in 115 high-producing dairy cows, including both primiparous and multiparous animals. Discriminant analysis identified differences between the microbiomes of prepartum and postpartum samples and between primiparous and multiparous cows. 18S rRNA sequencing revealed an overwhelming dominance of the protozoan class Litostomatea, with over 90% of the eukaryotic microbial population belonging to that group. Additionally, fungi were relatively more prevalent and Litostomatea relatively less prevalent in prepartum samples than in postpartum ones. The core rumen microbiome (common to all samples) consisted of 64 bacterial taxa, of which members of the genus
Prevotella
were the most prevalent. The Chao1 richness index was greater for prepartum multiparous cows than for postpartum multiparous cows. Multivariable models identified bacterial taxa associated with increased or reduced milk production, and general linear models revealed that a metagenomically based prediction of productivity is highly associated with production of actual milk and milk components. In conclusion, the structure of the rumen fluid microbiome shifts between the prepartum and first-week postpartum periods, and its profile within the context of this study could be used to accurately predict production traits.
Growth of Anaerobic Methane-Oxidizing Archaea and Sulfate-Reducing Bacteria in a High-Pressure Membrane Capsule Bioreactor
Authors: Timmers Peer H. A. , Gieteling Jarno , Widjaja-Greefkes H. C. Aura , Plugge Caroline M. , Stams Alfons J. M. , Lens Piet N. L. , Meulepas Roel J. W. 
Published: December 2014

ABSTRACT

Communities of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria (SRB) grow slowly, which limits the ability to perform physiological studies. High methane partial pressure was previously successfully applied to stimulate growth, but it is not clear how different ANME subtypes and associated SRB are affected by it. Here, we report on the growth of ANME-SRB in a membrane capsule bioreactor inoculated with Eckernförde Bay sediment that combines high-pressure incubation (10.1 MPa methane) and thorough mixing (100 rpm) with complete cell retention by a 0.2-μm-pore-size membrane. The results were compared to previously obtained data from an ambient-pressure (0.101 MPa methane) bioreactor inoculated with the same sediment. The rates of oxidation of labeled methane were not higher at 10.1 MPa, likely because measurements were done at ambient pressure. The subtype ANME-2a/b was abundant in both reactors, but subtype ANME-2c was enriched only at 10.1 MPa. SRB at 10.1 MPa mainly belonged to the SEEP-SRB2 and Eel-1 groups and the
Desulfuromonadales
and not to the typically found SEEP-SRB1 group. The increase of ANME-2a/b occurred in parallel with the increase of SEEP-SRB2, which was previously found to be associated only with ANME-2c. Our results imply that the syntrophic association is flexible and that methane pressure and sulfide concentration influence the growth of different ANME-SRB consortia. We also studied the effect of elevated methane pressure on methane production and oxidation by a mixture of methanogenic and sulfate-reducing sludge. Here, methane oxidation rates decreased and were not coupled to sulfide production, indicating trace methane oxidation during net methanogenesis and not anaerobic methane oxidation, even at a high methane partial pressure.
Atmospheric Hydrogen Scavenging: from Enzymes to Ecosystems
Authors: Greening Chris , Constant Philippe , Hards Kiel , Morales Sergio E. , Oakeshott John G. , Russell Robyn J. , Taylor Matthew C. , Berney Michael , Conrad Ralf , Cook Gregory M. 
Published: December 2014

ABSTRACT

We have known for 40 years that soils can consume the trace amounts of molecular hydrogen (H
2
) found in the Earth's atmosphere. This process is predicted to be the most significant term in the global hydrogen cycle. However, the organisms and enzymes responsible for this process were only recently identified. Pure culture experiments demonstrated that several species of
Actinobacteria
, including streptomycetes and mycobacteria, can couple the oxidation of atmospheric H
2
to the reduction of ambient O
2
. A combination of genetic, biochemical, and phenotypic studies suggest that these organisms primarily use this fuel source to sustain electron input into the respiratory chain during energy starvation. This process is mediated by a specialized enzyme, the group 5 [NiFe]-hydrogenase, which is unusual for its high affinity, oxygen insensitivity, and thermostability. Atmospheric hydrogen scavenging is a particularly dependable mode of energy generation, given both the ubiquity of the substrate and the stress tolerance of its catalyst. This minireview summarizes the recent progress in understanding how and why certain organisms scavenge atmospheric H
2
. In addition, it provides insight into the wider significance of hydrogen scavenging in global H
2
cycling and soil microbial ecology.