bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal components of cholinergic terminal to dopaminergic terminal transmission in dorsal striatum slices of mice
Authors: Wang Li , Zhang Xiaoyu , Xu Huadong , Zhou Li , Jiao Ruiying , Liu Wei , Zhu Feipeng , Kang Xinjiang , Liu Bin , Teng Sasa , Wu Qihui , Li Mingli , Dou Haiqiang , Zuo Panli , Wang Changhe , Wang Shirong , Zhou Zhuan 
Published: June 2014

Key points
The timing of synaptic transmission is critical to synaptic plasticity in the striatum.
However, the timing of striatal dopamine (DA) release induced by cholinergic interneurons (ChIs) in the striatum is unclear.
In this study, we focused on the temporal components of DA release and replenishment triggered by different pathways.
We show that stimulation of ChIs induces DA release with a total delay of 20.6 ms, including 2.8 ms for action potential firing of ChIs, 7.0 ms for cholinergic transmission between acetylcholine terminals and DA terminals, and 10.8 ms for downstream DA release. The delay of DA release via this ChI pathway is 1.9 times that via the nigrostriatal pathways.
We describe the time course of recovery of DA release via the two pathways and that of vesicle replenishment in DA terminals.
Our work provides an example of unravelling the temporal building blocks during fundamental synaptic terminal–terminal transmission.
AbstractStriatal dopamine (DA) is critically involved in major brain functions such as motor control and deficits such as Parkinson's disease. DA is released following stimulation by two pathways: the nigrostriatal pathway and the cholinergic interneuron (ChI) pathway. The timing of synaptic transmission is critical in striatal circuits, because millisecond latency changes can reverse synaptic plasticity from long‐term potentiation to long‐term depression in a DA‐dependent manner. Here, we determined the temporal components of ChI‐driven DA release in striatal slices from optogenetic ChAT‐ChR2‐EYFP mice. After a light stimulus at room temperature, ChIs fired an action potential with a delay of 2.8 ms. The subsequent DA release mediated by nicotinic acetylcholine (ACh) receptors had a total latency of 17.8 ms, comprising 7.0 ms for cholinergic transmission and 10.8 ms for the downstream terminal DA release. Similar latencies of DA release were also found in striatal slices from wild‐type mice. The latency of ChI‐driven DA release was regulated by inhibiting the presynaptic vesicular ACh release. Moreover, we describe the time course of recovery of DA release via the two pathways and that of vesicle replenishment in DA terminals. Our work provides an example of unravelling the temporal building blocks during fundamental synaptic terminal–terminal transmission in motor regulation.
Airway turbulence and changes in upper airway hydraulic diameter can be estimated from the intensity of high frequency inspiratory sounds in sleeping adults
Authors: Rembold Christopher M. , Suratt Paul M. 
Published: June 2014

Key points
Adults and children with obstructive sleep disordered breathing make loud high frequency inspiratory sounds (HFIS, defined as inspiratory sounds >2 kHz) while sleeping.
In an in vitro model, the intensity of high frequency sounds was found to be an estimate of airflow turbulence as reflected by the Reynold's number (Re).
Hydraulic diameter (D) of the in vitro model could be calculated using Re determined by sound intensity, the pressure gradient, the Swamee–Jain formula and the Darcy formula.
In four adult humans, D was calculated from measured HFIS intensity and the pressure gradient across the upper airway (estimated with oesophageal pressure, Pes).
At apnoea termination when the airway opens, we observed (1) an increase in HFIS intensity suggesting an increase in turbulence (higher Re), and (2) a larger calculated D.
This method allows dynamic estimation of changes in relative upper airway D in sleeping humans with narrowed upper airways.
AbstractObstructive sleep disordered breathing can cause death and significant morbidity in adults and children. We previously found that children with smaller upper airways (measured by magnetic resonance imaging while awake) generated loud high frequency inspiratory sounds (HFIS, defined as inspiratory sounds > 2 kHz) while they slept. The purpose of this study was (1) to determine what characteristics of airflow predicted HFIS intensity, and (b) to determine if we could calculate changes in hydraulic diameter (D) in both an in vitro model and in the upper airways of sleeping humans. In an in vitro model, high frequency sound intensity was an estimate of airflow turbulence as reflected by the Reynold's number (Re). D of the in vitro model was calculated using Re, the pressure gradient, Swamee–Jain formula and Darcy formula. D was proportional to but smaller than the actual diameters (r2 = 0.94). In humans, we measured HFIS intensity and the pressure gradient across the upper airway (estimated with oesophageal pressure, Pes) during polysomnography in four adult volunteers and applied the same formulae to calculate D. At apnoea termination when the airway opens, we observed (1) an increase in HFIS intensity suggesting an increase in turbulence (higher Re), and (2) a larger calculated D. This method allows dynamic estimation of changes in relative upper airway hydraulic diameter (D) in sleeping humans with narrowed upper airways.
Central command dysfunction in rats with heart failure is mediated by brain oxidative stress and normalized by exercise training
Authors: Koba Satoshi , Hisatome Ichiro , Watanabe Tatsuo 
Published: June 2014

Key points
In heart failure, sympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, is exaggerated.
Mechanisms underlying central command dysfunction in heart failure were unexplored, and effects of exercise training on central command dysfunction in heart failure were not determined.
Data presented here suggest that oxidative stress in the medulla in heart failure mediates central command dysfunction, and that exercise training in heart failure is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.
The present study contributes to our understanding of brain mechanisms underlying abnormal autonomic adjustments to exercise in heart failure.
AbstractSympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, has been shown to become exaggerated in chronic heart failure (CHF). The present study tested the hypotheses that oxidative stress in the medulla in CHF plays a role in exaggerating central command‐elicited sympathoexcitation, and that exercise training in CHF suppresses central command‐elicited sympathoexcitation through its antioxidant effects in the medulla. In decerebrate rats, central command was activated by electrically stimulating the mesencephalic locomotor region (MLR) after neuromuscular blockade. The MLR stimulation at a current intensity greater than locomotion threshold in rats with CHF after myocardial infarction (MI) evoked larger (P < 0.05) increases in renal sympathetic nerve activity and arterial pressure than in sham‐operated healthy rats (Sham) and rats with CHF that had completed longterm (8–12 weeks) exercise training (MI + TR). In the Sham and MI + TR rats, bilateral microinjection of a superoxide dismutase (SOD) mimetic Tempol into the rostral ventrolateral medulla (RVLM) had no effects on MLR stimulation‐elicited responses. By contrast, in MI rats, Tempol treatment significantly reduced MLR stimulation‐elicited responses. In a subset of MI rats, treatment with Tiron, another SOD mimetic, within the RVLM also reduced responses. Superoxide generation in the RVLM, as evaluated by dihydroethidium staining, was enhanced in MI rats compared with that in Sham and MI + TR rats. Collectively, these results support the study hypotheses. We suggest that oxidative stress in the medulla in CHF mediates central command dysfunction, and that exercise training in CHF is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.
Regulation of hypoxia‐inducible factor‐α isoforms and redox state by carotid body neural activity in rats
Authors: Peng Ying‐Jie , Yuan Guoxiang , Khan Shakil , Nanduri Jayasri , Makarenko Vladislav V. , Reddy Vaddi Damodara , Vasavda Chirag , Kumar Ganesh K. , Semenza Gregg L. , Prabhakar Nanduri R. 
Published: June 2014

Key points
Rats exposed to chronic intermittent hypoxia (CIH) exhibited imbalanced expression of hypoxia‐inducible factor (HIF)‐α isoforms and oxidative stress in brainstem regions associated with the carotid body (CB) chemoreflex, and in the adrenal medulla, an end organ of the sympathetic nervous system.
Selective ablation of the CB abolished the effects of CIH on HIF‐α isoform expression and oxidative stress.
In the adrenal medulla, chemoreflex‐mediated sympathetic activation regulates HIF‐α isoform expression via muscarinic acetylcholine receptor‐mediated Ca2+ influx and the resultant activation of the mammalian target of rapamycin pathway and calpain proteases.
Thus, CB neural activity regulates HIF‐α isoform expressions and redox state in the central and peripheral nervous system associated with the chemoreflex pathway under the setting of CIH.
AbstractPrevious studies reported that chronic intermittent hypoxia (CIH) results in an imbalanced expression of hypoxia‐inducible factor‐α (HIF‐α) isoforms and oxidative stress in rodents, which may be due either to the direct effect of CIH or indirectly via hitherto uncharacterized mechanism(s). As neural activity is a potent regulator of gene transcription, we hypothesized that carotid body (CB) neural activity contributes to CIH‐induced HIF‐α isoform expression and oxidative stress in the chemoreflex pathway. Experiments were performed on adult rats exposed to CIH for 10 days. Rats exposed to CIH exhibited: increased HIF‐1α and decreased HIF‐2α expression; increased NADPH oxidase 2 and decreased superoxide dismutase 2 expression; and oxidative stress in the nucleus tractus solitarius and rostral ventrolateral medulla as well as in the adrenal medulla (AM), a major end organ of the sympathetic nervous system. Selective ablation of the CB abolished these effects. In the AM, sympathetic activation by the CB chemoreflex mediates CIH‐induced HIF‐α isoform imbalance via muscarinic acetylcholine receptor‐mediated Ca2+ influx, and the resultant activation of mammalian target of rapamycin pathway and calpain proteases. Rats exposed to CIH presented with hypertension, elevated sympathetic activity and increased circulating catecholamines. Selective ablation of either the CB (afferent pathway) or sympathetic innervation to the AM (efferent pathway) abolished these effects. These observations uncover CB neural activity‐dependent regulation of HIF‐α isoforms and the redox state by CIH in the central and peripheral nervous systems associated with the chemoreflex.
Regulation of serum phosphate
Authors: Lederer Eleanor 
Published: June 2014

AbstractThe regulation of serum phosphate, an acknowledged risk factor for chronic kidney disease and cardiovascular mortality, is poorly understood. The discovery of fibroblast growth factor 23 (FGF23) as a key regulator of renal phosphate handling and activation of vitamin D has revolutionized our comprehension of phosphate homeostasis. Through as yet undetermined mechanisms, circulating and dietary phosphate appear to have a direct effect on FGF23 release by bone cells that, in turn, causes renal phosphate excretion and decreases intestinal phosphate absorption through a decrease in vitamin D production. Thus, the two major phosphaturic hormones, PTH and FGF23, have opposing effects on vitamin D production, placing vitamin D at the nexus of phosphate homeostasis. While our understanding of phosphate homeostasis has advanced, the factors determining regulation of serum phosphate level remain enigmatic. Diet, time of day, season, gender, age and genetics have all been identified as significant contributors to serum phosphate level. The effects of these factors on serum phosphate have major implications for what is understood as ‘normal’ and for studies of phosphate homeostasis and metabolism. Moreover, other hormonal mediators such as dopamine, insulin‐like growth factor, and angiotensin II also affect renal handling of phosphate. How the major hormone effects on phosphate handling are regulated and how the effect of these other factors are integrated to yield the measurable serum phosphate are only now beginning to be studied.
Knockdown of mineralocorticoid or angiotensin II type 1 receptor gene expression in the paraventricular nucleus prevents angiotensin II hypertension in rats
Authors: Chen Aidong , Huang Bing S. , Wang Hong‐Wei , Ahmad Monir , Leenen Frans H. H. 
Published: June 2014

Key points
Chronic subcutaneous infusion of Ang II causes a progressive increase in blood pressure (BP) associated with significant increases in angiotensin type 1 receptor (AT1R) and mineralocorticoid receptor (MR) expression in hypothalamic nuclei.
Intra‐paraventricular nucleus (PVN) infusion of AAV‐ AT1aR‐siRNA or of AAV‐MR‐siRNA markedly knockdown AT1a‐R or MR expression in the PVN but not in the subfornical organ; or supraoptic nucleus, and prevent most of the increase in BP.
These findings indicate that increased MR and AT1R activation in the PVN play a critical role in Ang II‐induced hypertension in rats on regular salt intake.
AbstractCirculating Ang II activates an aldosterone‐mineralocorticoid receptor (MR) – angiotensin II (Ang II) – angiotensin type 1 receptor (AT1R) pathway in the hypothalamus. To obtain insights into the actual neuronal projections involved, adeno‐associated virus carrying small interfering RNA against either AT1aR (AAV‐AT1aR‐siRNA) or MR (AAV‐MR‐siRNA) were infused into the paraventricular nucleus (PVN) in Wistar rats. Intra‐PVN infusion of AAV‐AT1aR‐siRNA or AAV‐MR‐siRNA decreased AT1R or MR expression in the PVN but not in the subfornical organ (SFO) or supraoptic nucleus (SON). Subcutaneous infusion of Ang II at 500 ng kg−1 min−1 for 2 weeks increased mean arterial pressure by 60–70 mmHg, and increased AT1R and MR expression in the SFO, SON and PVN. Intra‐PVN AT1aR‐siRNA prevented the Ang II‐induced increase in AT1R but not MR expression in the PVN, and MR‐siRNA prevented MR but not AT1R expression in the PVN. The increases in AT1R and MR expression in both the SFO and the SON were not changed by the two AAV‐siRNAs. Specific knockdown of AT1R or MR in the PVN by AAV‐siRNA each prevented most of the Ang II‐induced hypertension. Prevention of the subcutaneous Ang II‐induced increase in MR but not the increase in AT1R by knockdown of MR and vice versa suggests an independent regulation of MR and AT1R expression in the PVN. Both AT1R and MR activation in the PVN play a critical role in Ang II‐induced hypertension in rats.
Blood pressure is maintained during dehydration by hypothalamic paraventricular nucleus‐driven tonic sympathetic nerve activity
Authors: Holbein Walter W. , Bardgett Megan E. , Toney Glenn M. 
Published: June 2014

Key points
At normal resting mean arterial pressure (MAP), sympathetic nerve activity (SNA) mostly consists of respiratory and cardiac rhythmic bursts of action potentials.
In animal models of sympathetic hyperactivity, elevated SNA and MAP become reliant on activity of neurones in the hypothalamic paraventricular nucleus (PVN).
Dehydrated (DH) rats (48 h water deprived) were used as a model of sympathetic hyperactivity. As expected, acute PVN inhibition reduced MAP and integrated splanchnic SNA (sSNA) in DH rats, but had no effect in euhydrated controls. Unexpectedly, the fall of sSNA in DH rats was due to a reduction of irregular, tonic activity as neither respiratory nor cardiac rhythmic bursting was significantly affected.
We conclude that MAP is largely maintained during dehydration by PVN‐driven tonic SNA and speculate that a normally quiescent tonic component of SNA might also be recruited in chronic diseases (hypertension, heart failure, obesity) where PVN activation drives sympathetic hyperactivity.
AbstractResting sympathetic nerve activity (SNA) consists primarily of respiratory and cardiac rhythmic bursts of action potentials. During homeostatic challenges such as dehydration, the hypothalamic paraventricular nucleus (PVN) is activated and drives SNA in support of arterial pressure (AP). Given that PVN neurones project to brainstem cardio‐respiratory regions that generate bursting patterns of SNA, we sought to determine the contribution of PVN to support of rhythmic bursting of SNA during dehydration and to elucidate which bursts dominantly contribute to maintenance of AP. Euhydrated (EH) and dehydrated (DH) (48 h water deprived) rats were anaesthetized, bilaterally vagotomized and underwent acute PVN inhibition by bilateral injection of the GABA‐A receptor agonist muscimol (0.1 nmol in 50 nl). Consistent with previous studies, muscimol had no effect in EH rats (n = 6), but reduced mean AP (MAP; P < 0.001) and integrated splanchnic SNA (sSNA; P < 0.001) in DH rats (n = 6). Arterial pulse pressure was unaffected in both groups. Muscimol reduced burst frequency of phrenic nerve activity (P < 0.05) equally in both groups without affecting the burst amplitude–duration integral (i.e. area under the curve). PVN inhibition did not affect the amplitude of the inspiratory peak, expiratory trough or expiratory peak of sSNA in either group, but reduced cardiac rhythmic sSNA in DH rats only (P < 0.001). The latter was largely reversed by inflating an aortic cuff to restore MAP (n = 5), suggesting that the muscimol‐induced reduction of cardiac rhythmic sSNA in DH rats was an indirect effect of reducing MAP and thus arterial baroreceptor input. We conclude that MAP is largely maintained in anaesthetized DH rats by a PVN‐driven component of sSNA that is neither respiratory nor cardiac rhythmic.
Synaptic mechanisms underlying cholinergic control of thalamic reticular nucleus neurons
Authors: Beierlein Michael 
Published: June 2014

AbstractNeuronal networks of the thalamus are the target of extensive cholinergic projections from the basal forebrain and the brainstem. Activation of these afferents can regulate neuronal excitability, transmitter release, and firing patterns in thalamic networks, thereby altering the flow of sensory information during distinct behavioural states. However, cholinergic regulation in the thalamus has been primarily examined by using receptor agonist and antagonist, which has precluded a detailed understanding of the spatiotemporal dynamics that govern cholinergic signalling under physiological conditions. This review summarizes recent studies on cholinergic synaptic transmission in the thalamic reticular nucleus (TRN), a brain structure intimately involved in the control of sensory processing and the generation of rhythmic activity in the thalamocortical system. This work has shown that acetylcholine (ACh) released from individual axons can rapidly and reliably activate both pre‐ and postsynaptic cholinergic receptors, thereby controlling TRN neuronal activity with high spatiotemporal precision.
Ostreid Herpesvirus 1 Infection among Pacific Oyster (Crassostrea gigas) Spat: Relevance of Water Temperature to Virus Replication and Circulation Prior to the Onset of Mortality
Authors: Renault Tristan , Bouquet Anne Lise , Maurice Julien-Thomas , Lupo Coralie , Blachier Philippe 
Published: June 2014

ABSTRACT

A number of bivalve species worldwide, including the Pacific oyster,
Crassostrea gigas
, have been affected by mass mortality events associated with herpesviruses, resulting in significant losses. A particular herpesvirus was purified from naturally infected larval Pacific oysters, and its genome was completely sequenced. This virus has been classified as
Ostreid herpesvirus 1
(OsHV-1) within the family
Malacoherpesviridae
. Since 2008, mass mortality outbreaks among
C. gigas
in Europe have been related to the detection of a variant of OsHV-1 called μVar. Additional data are necessary to better describe mortality events in relation to environmental-parameter fluctuations and OsHV-1 detection. For this purpose, a single batch of Pacific oyster spat was deployed in 4 different locations in the Marennes-Oleron area (France): an oyster pond (“claire”), a shellfish nursery, and two locations in the field. Mortality rates were recorded based on regular observation, and samples were collected to search for and quantify OsHV-1 DNA by real-time PCR. Although similar massive mortality rates were reported at the 4 sites, mortality was detected earlier in the pond and in the nursery than at both field sites. This difference may be related to earlier increases in water temperature. Mass mortality was observed among oysters a few days after increases in the number of PCR-positive oysters and viral-DNA amounts were recorded. An initial increment in the number of PCR-positive oysters was reported at both field sites during the survey in the absence of significant mortality. During this period, the water temperature was below 16°C.
Improved Production of a Heterologous Amylase in Saccharomyces cerevisiae by Inverse Metabolic Engineering
Authors: Liu Zihe , Liu Lifang , Österlund Tobias , Hou Jin , Huang Mingtao , Fagerberg Linn , Petranovic Dina , Uhlén Mathias , Nielsen Jens 
Published: June 2014

ABSTRACT

The increasing demand for industrial enzymes and biopharmaceutical proteins relies on robust production hosts with high protein yield and productivity. Being one of the best-studied model organisms and capable of performing posttranslational modifications, the yeast
Saccharomyces cerevisiae
is widely used as a cell factory for recombinant protein production. However, many recombinant proteins are produced at only 1% (or less) of the theoretical capacity due to the complexity of the secretory pathway, which has not been fully exploited. In this study, we applied the concept of inverse metabolic engineering to identify novel targets for improving protein secretion. Screening that combined UV-random mutagenesis and selection for growth on starch was performed to find mutant strains producing heterologous amylase 5-fold above the level produced by the reference strain. Genomic mutations that could be associated with higher amylase secretion were identified through whole-genome sequencing. Several single-point mutations, including an S196I point mutation in the
VTA1
gene coding for a protein involved in vacuolar sorting, were evaluated by introducing these to the starting strain. By applying this modification alone, the amylase secretion could be improved by 35%. As a complement to the identification of genomic variants, transcriptome analysis was also performed in order to understand on a global level the transcriptional changes associated with the improved amylase production caused by UV mutagenesis.