bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of a local renin–angiotensin system in the rat carotid body during chronic intermittent hypoxia
Authors: Lam Siu‐Yin , Liu Yu , Ng Kwong‐Man , Liong Emily C. , Tipoe George L. , Leung Po Sing , Fung Man‐Lung 
Published: September 2013

New Findings
What is the central question of this study?Expression of the renin–angiotensin system (RAS) may play a pathogenic role in the augmented activity of carotid body chemosensitive cells and the carotid body (CB) inflammation in chronic intermittent hypoxia (IH). The aim of this study was to examine the expression and function of the RAS components in the CB during chronic IH resembling a severe sleep‐apnoeic condition.
What is the main finding and its importance?Chronic IH induces a functional upregulation of the RAS expression in the CB. The upregulation of RAS expression could play a pathogenic role in the augmented CB excitability during IH, which is relevant to early pathogenesis in sleep‐disordered breathing.
The carotid body (CB) plays an important role in the alteration of cardiorespiratory activity in chronic intermittent hypoxia (IH) associated with sleep‐disordered breathing, which may be mediated by local expression of the renin–angiotensin system (RAS). We hypothesized a pathogenic role for IH‐induced RAS expression in the CB. The CB expression of RAS components was examined in rats exposed to IH resembling a severe sleep‐apnoeic condition for 7 days. In situ hybridization showed an elevated expression of angiotensinogen in the CB glomus cells in the hypoxic group when compared with the normoxic control group. Immunohistochemical studies and Western blot analysis revealed increases in the protein level of both angiotensinogen and angiotensin II type 1 (AT1) receptors in the hypoxic group, which were localized to the glomic clusters containing tyrosine hydroxylase. RT‐PCR studies confirmed that levels of the mRNA expression of angiotensinogen, angiotensin‐converting enzyme, AT1a and AT2 receptors were significantly increased in the CBs of the hypoxic rats. Functionally, the [Ca2+]i response to exogenous angiotensin II was enhanced in fura‐2‐loaded glomus cells dissociated from hypoxic rats when compared with those of the normoxic control animals. Pretreatment with losartan, but not PD123319, abolished the angiotensin II‐induced [Ca2+]i response, suggesting an involvement of AT1 receptors. Moreover, daily treatment of the IH group of rats with losartan attenuated the levels of oxidative stress, gp91phox expression and macrophage infiltration in the CB. Collectively, the upregulated local RAS expression could play a pathogenic role in the augmented CB activity and local inflammation via AT1 receptor activation during IH conditions in patients with sleep‐disordered breathing.
The stimulating effect of ghrelin on gastric motility and firing activity of gastric‐distension‐sensitive hippocampal neurons and its underlying regulation by the hypothalamus
Authors: Xu Luo , Gong Yanling , Wang Hongbo , Sun Xiangrong , Guo Feifei , Gao Shengli , Gu Fang 
Published: September 2013

New Findings
What is the central question of this study?Is there a direct pathway of ghrelin from the hypothalamic arcuate nucleus to the hippocampus? Is this pathway involved in the regulation of gastric motility and gastric afferent signalling?
What is the main finding and its importance?There exists a direct pathway of ghrelin from the hypothalamic arcuate nucleus to the hippocampus that is involved in the regulation of gastric motility. In the emotional hub hippocampus, ghrelin is involved in the regulation of gastric motility and gastric afferent signalling. These effects can be regulated by the hypothalamic arcuate nucleus. This supports and advances the theory of energy balance involving the regulation of the central and brain–gut peptides.
Ghrelin is an acylated peptide originally identified in the rat stomach as the endogenous ligand for growth hormone secretagogue receptor (GHSR) that promotes gastric motility. Our aims were to explore the effects of ghrelin on gastric‐distension‐sensitive neurons in the hippocampus and the potential for ghrelin to regulate gastric motility through the arcuate nucleus (Arc). Single‐unit discharges in the hippocampus were recorded extracellularly, and gastric motility in conscious rats was monitored. The expression of GHSR‐1a in the hippocampus was determined by PCR, Western blot and fluo‐immunohistochemistry staining. Retrograde tracing and fluo‐immunohistochemistry staining were used to determine ghrelin neuron projection. Ghrelin–Fluoro‐Gold double‐labelled neurons and GHSR‐1a expression were observed in the Arc and hippocampus, respectively. There were gastric‐distension‐sensitive neurons in the hippocampus that could be excited by ghrelin or by electrical stimulation of the Arc. The excitatory effects could be blocked completely or partly by pretreatment with the ghrelin receptor antagonist [d‐Lys‐3]‐GHRP‐6. Gastric motility was significantly promoted by the administration of ghrelin into the hippocampus in a dose‐dependent manner that could be completely abolished by [d‐Lys‐3]‐GHRP‐6. Electrical stimulation of the Arc could promote gastric motility as well. Nevertheless, these effects could be mitigated by pretreatment with [d‐Lys‐3]‐GHRP‐6. Electrical lesioning of the hippocampus diminished the excitatory effects on gastric motility that were induced by electrical stimulation the Arc. Our findings suggest that ghrelin plays an important role in promoting gastric motility via the hippocampus. The Arc may be involved in regulation of the influence of the hippocampus on gastric motility.
The influence of gap junction network complexity on pulmonary artery smooth muscle reactivity in normoxic and chronically hypoxic conditions
Authors: Gosak Marko , Guibert Christelle , Billaud Marie , Roux Etienne , Marhl Marko 
Published: September 2013

New Findings
What is the central question of this study?Experimental results on intrapulmonary arteries indicate that the relationship between gap junctional intercellular communication and its functional involvement in tissue reactivity is very complex, both in normoxic and in chronically hypoxic conditions. The relationship between the gap junction network and vasoreactivity is poorly known and needs to be explored, including theoretical modelling approaches.
What is the main finding and its importance?Our results indicate that the role of gap junctions and their contribution to intrapulmonary artery reactivity depends crucially on the topology of the gap junctional communication network. In normoxia, myocytes are connected in a complex network, whereas chronic hypoxia is related to loss of the network complexity, leading to hypersensitivity.
Experiments on intrapulmonary arteries (IPAs) isolated from rats maintained in normoxia and chronic hypobaric hypoxia showed that in normoxia, the IPA contractile sensitivity to KCl was not modified by gap junction inhibition. In contrast, chronic hypoxia induced an endothelium‐independent hypersensitivity, which was suppressed by gap junction inhibition. For the theoretical analysis of these results, we developed a model of interconnected myocytes. Given that smooth muscle cells in IPAs are known to communicate via gap junctions, we regard the cytoarchitecture of the IPA as a spatial network, in which nodes represent individual smooth muscle cells and the links signify intercellular communication. A single‐cell model that drives the dynamics of individual nodes includes the major elements of voltage‐dependent Ca2+ signalling. In addition, interindividual variability of SMCs is introduced by distributing the reversal potentials for K+. Cell‐to‐cell connection consists of passive Ca2+ diffusion and electrical coupling, and connection between cells is determined by the topology of the intercellular network. Model predictions indicate that the experimental results can be explained by topological modifications and not by changes in the number of gap junctions. According to the model, in normoxia the myocytes are connected in a complex network, whereas chronic hypoxia is related to loss of complexity, leading to hypersensitivity. Our results thus indicate that chronic hypoxia entails gap junction network rearrangements, leading to disturbances in the intercellular communication pathways.
The cardiovascular actions of fractalkine/CX3CL1 in the hypothalamic paraventricular nucleus are attenuated in rats with heart failure
Authors: Ruchaya P. J. , Antunes V. R. , Paton J. F. R. , Murphy D. , Yao S. T. 
Published: September 2013

New Findings
What is the central question of this study?The chemokine fractalkine (FKN) and its cognate receptor, CX3CR1, are expressed in the brain, but their distribution and function within the paraventricular nucleus of the hypothalamus (PVN) have not been previously investigated.
What is the main finding and its importance?We show that both FKN and CX3CR1 receptor mRNA and protein are expressed in the PVN and that FKN elicits hypotension and tachycardia when exogeneously applied by microinjection, an effect that is attenuated in rats with heart failure. These findings are important because they demonstrate that FKN and its cognate receptor are expressed and play a role in controlling cardiovascular function within the PVN.
The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the regulation of sympathetic nerve activity, which is significantly elevated in chronic heart failure (CHF). Fractalkine (FKN) and its cognate receptor, CX3CR1, are constitutively expressed in the central nervous system, but their role and physiological significance are not well known. The aims of the present study were to determine whether FKN plays a cardiovascular role within the PVN and to investigate how the actions of FKN might be altered in CHF. We show that both FKN and CX3CR1 are expressed on neurons in the PVN of rats, suggesting that they may have a physiological function in this brain nucleus. Unilateral microinjection of FKN directly into the PVN of anaesthetized rats elicited a significant dose‐related decrease in blood pressure (1.0 nmol, −5 ± 3 mmHg; 2.5 nmol, −13 ± 2 mmHg; 5.0 nmol, −22 ± 3 mmHg; and 7.5 nmol, −32 ± 3 mmHg) and a concomitant increase in heart rate (1.0 nmol, 6 ± 3 beats min−1; 2.5 nmol, 11 ± 3 beats min−1; 5 nmol, 18 ± 4 beats min−1; and 7.5 nmol, 27 ± 5 beats min−1) compared with control saline microinjections. In order to determine whether FKN signalling is altered in rats with CHF, we first performed quantitative RT‐PCR and Western blot analysis and followed these experiments with functional studies in rats with CHF and sham‐operated control rats. We found a significant increase in CX3CR1 mRNA and protein expression, as determined by quantitative RT‐PCR and Western blot analysis, respectively, in the PVN of rats with CHF compared with sham‐operated control rats. We also found that the blood pressure effects of FKN (2.5 nmol in 50 nl) were significantly attenuated in rats with CHF (change in mean arterial pressure, −6 ± 3 mmHg) compared with sham‐operated control rats (change in mean arterial pressure, −16 ± 6 mmHg). These data suggest that FKN and its receptor, CX3CR1, modulate cardiovascular function at the level of the PVN and that the actions of FKN within this nucleus are altered in heart failure.
Exercise reveals impairments in left ventricular systolic function in patients with metabolic syndrome
Authors: Fournier Sara B. , Reger Brian L. , Donley David A. , Bonner Daniel E. , Warden Bradford E. , Gharib Wissam , Failinger Conard F. , Olfert Melissa D. , Frisbee Jefferson C. , Olfert I. Mark , Chantler Paul D. 
Published: September 2013

New Findings
What is the central question of this study?Metabolic syndrome (MetS) is associated with a threefold increase in risk of cardiovascular disease mortality, which may be mediated, in part, by impaired left ventricular systolic function. The severity of left ventricular and arterial dysfunction during dynamic exercise in individuals with MetS without diabetes and/or overt cardiovascular disease has not previously been explored.
What is the main finding and its importance?Cardiovascular function was characterized at rest and during peak exercise using echocardiography and gas exchange. During exercise, individuals with MetS displayed impaired left ventricular contractility, a blunted arterial–ventricular coupling reserve and limited aerobic capacity. These findings provide insight into the pathophysiological changes that may occur to predispose individuals with MetS to an increased risk of cardiovascular disease.
Metabolic syndrome (MetS) is the manifestation of a cluster of cardiovascular risk factors and is associated with a threefold increase in the risk of cardiovascular morbidity and mortality, which is suggested to be mediated, in part, by resting left ventricular (LV) systolic dysfunction. However, to what extent resting LV systolic function is impaired in MetS is controversial, and there are no data indicating whether LV systolic function is impaired during exercise. Accordingly, the objective of this study was to examine comprehensively the LV and arterial responses to exercise in individuals with MetS without diabetes and/or overt cardiovascular disease in comparison to a healthy control population. Cardiovascular function was characterized using Doppler echocardiography and gas exchange in individuals with MetS (n= 27) versus healthy control subjects (n= 20) at rest and during peak exercise. At rest, individuals with MetS displayed normal LV systolic function but reduced LV diastolic function compared with healthy control subjects. During peak exercise, individuals with MetS had impaired contractility, pump performance and vasodilator reserve capacity versus control subjects. A blunted contractile reserve response resulted in diminished arterial–ventricular coupling reserve and limited aerobic capacity in individuals with MetS versus control subjects. These findings are of clinical importance, because they provide insight into the pathophysiological changes in MetS that may predispose this population of individuals to an increased risk of cardiovascular morbidity and mortality.
Aspergillus fumigatus SidJ Mediates Intracellular Siderophore Hydrolysis
Authors: Gründlinger Mario , Gsaller Fabio , Schrettl Markus , Lindner Herbert , Haas Hubertus 
Published: September 2013

ABSTRACT

Siderophore-mediated iron handling is crucial for the virulence of
Aspergillus fumigatus
. Here we identified a new component of its siderophore metabolism, termed SidJ, which is encoded by AFUA_3G03390. The encoding gene is localized in a siderophore biosynthetic gene cluster that is conserved in a variety of fungi. During iron starvation, SidJ deficiency resulted in decreased growth and increased intracellular accumulation of hydrolysis products of the siderophore fusarinine C. The implied role in siderophore hydrolysis is consistent with a putative esterase domain in SidJ, which now represents the first functionally characterized member of the DUF1749 (
d
omain of
u
nknown
f
unction) protein family, with members found exclusively in fungi and plants.
Bacterial Contribution to Dissolved Organic Matter in Eutrophic Lake Kasumigaura, Japan
Authors: Kawasaki Nobuyuki , Komatsu Kazuhiro , Kohzu Ayato , Tomioka Noriko , Shinohara Ryuichiro , Satou Takayuki , Watanabe Fumiko Nara , Tada Yuya , Hamasaki Koji , Kushairi M. R. M. , Imai Akio 
Published: September 2013

ABSTRACTIncubation experiments using filtered waters from Lake Kasumigaura were conducted to examine bacterial contribution to a dissolved organic carbon (DOC) pool. Bacterial abundance, bacterial production, concentrations of DOC, total dissolved amino acids (TDAA), and total dissolved neutral sugars (TDNS) were monitored during the experiments. Bacterial production during the first few days was very high (20 to 35 μg C liter−1day−1), accounting for 40 to 70% of primary production. The total bacterial production accounted for 34 to 55% of the DOC loss during the experiment, indicating high bacterial activities in Lake Kasumigaura. The DOC degradation was only 12 to 15%, whereas the degradation of TDAA and TDNS ranged from 30 to 50%, suggesting the preferential usage of TDAA and TDNS. The contribution of bacterially derived carbon to a DOC pool in Lake Kasumigaura was estimated usingd-amino acids as bacterial biomarkers and accounted for 30 to 50% of the lake DOC. These values were much higher than those estimated for the open ocean (20 to 30%). The ratio of bacterially derived carbon to bulk carbon increased slightly with time, suggesting that the bacterially derived carbon is more resistant to microbial degradation than bulk carbon. This is the first study to estimate the bacterial contribution to a DOC pool in freshwater environments. These results indicate that bacteria play even more important roles in carbon cycles in freshwater environments than in open oceans and also suggests that recent increases in recalcitrant DOC in various lakes could be attributed to bacterially derived carbon. The potential differences in bacterial contributions to dissolved organic matter (DOM) between freshwater and marine environments are discussed.
Analysis of Genes for Succinoyl Trehalose Lipid Production and Increasing Production in Rhodococcus sp. Strain SD-74
Authors: Inaba Tomohiro , Tokumoto Yuta , Miyazaki Yusuke , Inoue Naoyuki , Maseda Hideaki , Nakajima-Kambe Toshiaki , Uchiyama Hiroo , Nomura Nobuhiko 
Published: September 2013

ABSTRACT

Succinoyl trehalose lipids (STLs) are promising glycolipid biosurfactants produced from
n
-alkanes that are secreted by
Rhodococcus
species bacteria. These compounds not only exhibit unique interfacial properties but also demonstrate versatile biochemical actions. In this study, three novel types of genes involved in the biosynthesis of STLs, including a putative acyl coenzyme A (acyl-CoA) transferase (
tlsA
), fructose-bisphosphate aldolase (
fda
), and alkane monooxygenase (
alkB
), were identified. The predicted functions of these genes indicate that alkane metabolism, sugar synthesis, and the addition of acyl groups are important for the biosynthesis of STLs. Based on these results, we propose a biosynthesis pathway for STLs from alkanes in
Rhodococcus
sp. strain SD-74. By overexpressing
tlsA
, we achieved a 2-fold increase in the production of STLs. This study advances our understanding of bacterial glycolipid production in
Rhodococcus
species.
Role of Filamentous Phage SW1 in Regulating the Lateral Flagella of Shewanella piezotolerans Strain WP3 at Low Temperatures
Authors: Jian Huahua , Xiao Xiang , Wang Fengping 
Published: September 2013

ABSTRACT

Low-temperature ecosystems represent the largest biosphere on Earth, and yet our understanding of the roles of bacteriophages in these systems is limited. Here, the influence of the cold-active filamentous phage SW1 on the phenotype and gene transcription of its host,
Shewanella piezotolerans
WP3 (WP3), was investigated by construction of a phage-free strain (WP3ΔSW1), which was compared with the wild-type strain. The expression of 49 genes, including 16 lateral flagellar genes, was found to be significantly influenced by SW1 at 4°C, as demonstrated by comparative whole-genome microarray analysis. WP3ΔSW1 was shown to have a higher production of lateral flagella than WP3 and enhanced swarming motility when cultivated on solid agar plates. Besides, SW1 has a remarkable impact on the expression of a variety of host genes in liquid culture, particularly the genes related to the membrane and to the production of lateral flagella. These results suggest that the deep-sea bacterium WP3 might balance the high-energy demands of phage maintenance and swarming motility at low temperatures. The phage SW1 is shown to have a significant influence on the swarming ability of the host and thus may play an important role in adjusting the fitness of the cells in the deep-sea environment.
Single-Cell Measurements of Enzyme Levels as a Predictive Tool for Cellular Fates during Organic Acid Production
Authors: Zdraljevic Stefan , Wagner Drew , Cheng Kevin , Ruohonen Laura , Jäntti Jussi , Penttilä Merja , Resnekov Orna , Pesce C. Gustavo 
Published: September 2013

ABSTRACT

Organic acids derived from engineered microbes can replace fossil-derived chemicals in many applications. Fungal hosts are preferred for organic acid production because they tolerate lignocellulosic hydrolysates and low pH, allowing economic production and recovery of the free acid. However, cell death caused by cytosolic acidification constrains productivity. Cytosolic acidification affects cells asynchronously, suggesting that there is an underlying cell-to-cell heterogeneity in acid productivity and/or in resistance to toxicity. We used fluorescence microscopy to investigate the relationship between enzyme concentration, cytosolic pH, and viability at the single-cell level in
Saccharomyces cerevisiae
engineered to synthesize xylonic acid. We found that cultures producing xylonic acid accumulate cells with cytosolic pH below 5 (referred to here as “acidified”). Using live-cell time courses, we found that the probability of acidification was related to the initial levels of xylose dehydrogenase and sharply increased from 0.2 to 0.8 with just a 60% increase in enzyme abundance (Hill coefficient, >6). This “switch-like” relationship likely results from an enzyme level threshold above which the produced acid overwhelms the cell's pH buffering capacity. Consistent with this hypothesis, we showed that expression of xylose dehydrogenase from a chromosomal locus yields ∼20 times fewer acidified cells and ∼2-fold more xylonic acid relative to expression of the enzyme from a plasmid with variable copy number. These results suggest that strategies that further reduce cell-to-cell heterogeneity in enzyme levels could result in additional gains in xylonic acid productivity. Our results demonstrate a generalizable approach that takes advantage of the cell-to-cell variation of a clonal population to uncover causal relationships in the toxicity of engineered pathways.
Prevalence of Viral Photosynthetic and Capsid Protein Genes from Cyanophages in Two Large and Deep Perialpine Lakes
Authors: Zhong Xu , Jacquet Stéphan 
Published: September 2013

ABSTRACT

Cyanophages are important components of aquatic ecosystems, but their genetic diversity has been little investigated in freshwaters. A yearlong survey was conducted in surface waters of the two largest natural perialpine lakes in France (Lake Annecy and Lake Bourget) to investigate part of this cyanophage diversity through the analysis of both structural (e.g.,
g20
) and functional (e.g.,
psbA
) genes. We found that these cyanophage signature genes were prevalent throughout the year but that the community compositions of
g20
cyanomyoviruses were significantly different between the two lakes. In contrast,
psbA
-containing cyanophages seemed to be more similar between the two ecosystems. We also found that a large proportion of
g20
sequences grouped with cyanomyophage isolates.
psbA
sequences, belonging to phages of
Synechococcus
spp., were characterized by distinct triplet motifs (with a novel viral triplet motif, EFE). Thus, our results show that cyanophages (i) are a diverse viral community in alpine lakes and (ii) are clearly distinct from some other freshwater and marine environments, suggesting the influence of unique biogeographic factors.