bluuebunny/crossref_metadata_2025_split huggingface dataset:
Less is more: minimal expression of myoendothelial gap junctions optimizes cell–cell communication in virtual arterioles
Authors: Hald Bjørn Olav , Jacobsen Jens Christian Brings , Sandow Shaun L. , Holstein‐Rathlou Niels‐Henrik , Welsh Donald G. 
Published: June 2014

Key points
Electrical signalling in blood vessels is important in acute and long‐term flow regulation.
As myoendothelial gap junctions (MEGJs) provide electrical contacts between endothelial cells and smooth muscle cells (SMCs), a high MEGJ expression is thought to be important for intercellular communication despite observations of heterogeneous MEGJ expression.
Using a computational approach, we find that a minimal but sufficient number of heterogeneously distributed MEGJs optimize electrical cell–cell communication.
Tailoring SMC–SMC coupling to the MEGJ distribution and permeability ensures a smooth electrical response while retaining the ability to display local responses.
As heterogeneous MEGJ distributions allow for different conduction profiles along the SMC and endothelial cell layers, it is possible to observe an apparently non‐decaying conduction profile in the SMC layer of a vessel with passive electrical properties.
These findings expand our understanding of how heterogeneity in MEGJ distribution affects local and global flow.
AbstractDysfunctional electrical signalling within the arteriolar wall is a major cause of cardiovascular disease. The endothelial cell layer constitutes the primary electrical pathway, co‐ordinating contraction of the overlying smooth muscle cell (SMC) layer. As myoendothelial gap junctions (MEGJs) provide direct contact between the cell layers, proper vasomotor responses are thought to depend on a high, uniform MEGJ density. However, MEGJs are observed to be expressed heterogeneously within and among vascular beds. This discrepancy is addressed in the present study. As no direct measures of MEGJ conductance exist, we employed a computational modelling approach to vary the number, conductance and distribution of MEGJs. Our simulations demonstrate that a minimal number of randomly distributed MEGJs augment arteriolar cell–cell communication by increasing conduction efficiency and ensuring appropriate membrane potential responses in SMCs. We show that electrical coupling between SMCs must be tailored to the particular MEGJ distribution. Finally, observation of non‐decaying mechanical conduction in arterioles without regeneration has been a long‐standing controversy in the microvascular field. As heterogeneous MEGJ distributions provide for different conduction profiles along the cell layers, we demonstrate that a non‐decaying conduction profile is possible in the SMC layer of a vessel with passive electrical properties. These intriguing findings redefine the concept of efficient electrical communication in the microcirculation, illustrating how heterogeneous properties, ubiquitous in biological systems, may have a profound impact on system behaviour and how acute local and global flow control is explained from the biophysical foundations.
Nutrient‐induced changes in the phenotype and function of the enteric nervous system
Authors: Neunlist Michel , Schemann Michael 
Published: June 2014

AbstractThe enteric nervous system (ENS) integrates numerous sensory signals in order to control and maintain normal gut functions. Nutrients are one of the prominent factors which determine the chemical milieu in the lumen and, after absorption, also within the gut wall. This review summarizes current knowledge on the impact of key nutrients on ENS functions and phenotype, covering their acute and long‐term effects. Enteric neurones contain the molecular machinery to respond specifically to nutrients. These transporters and receptors are not expressed exclusively in the ENS but are also present in other cells such as enteroendocrine cells (EECs) and extrinsic sensory nerves, signalling satiety or hunger. Glucose, amino acids and fatty acids all activate enteric neurones, as suggested by enhanced c‐Fos expression or spike discharge. These excitatory effects are the result of a direct neuronal activation but also involve the activation of EECs which, upon activation by luminal nutrients, release mediators such as ghrelin, cholecystokinin or serotonin. The presence or absence of nutrients in the intestinal lumen induces long‐term changes in neurotransmitter expression, excitability, neuronal survival and ultimately impact upon gut motility, secretion or intestinal permeability. Together with EECs and vagal nerves, the ENS must be recognized as an important player initiating concerted responses to nutrients. It remains to be studied how, for instance, nutrient‐induced changes in the ENS may influence additional gut functions such as intestinal barrier repair, intestinal epithelial stem cell proliferation/differentiation and also the signalling of extrinsic nerves to brain regions which control food intake.
Cardiorenal syndrome: acute kidney injury secondary to cardiovascular disease and role of protein‐bound uraemic toxins
Authors: Lekawanvijit Suree , Krum Henry 
Published: June 2014

AbstractCardiovascular disease (CVD) and kidney disease are closely interrelated. Disease of one organ can induce dysfunction of the other, ultimately leading to failure of both. Clinical awareness of synergistic adverse clinical outcomes in patients with coexisting CVD and kidney disease or ‘cardiorenal syndrome (CRS)’ has existed. Renal dysfunction, even mild, is a strong independent predictor for poor prognosis in CVD patients. Developing therapeutic interventions targeting acute kidney injury (AKI) has been limited due mainly to lack of effective tools to accurately detect AKI in a timely manner. Neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1 have been recently demonstrated to be potential candidate biomarkers in patients undergoing cardiac surgery. However, further validation of AKI biomarkers is needed in other CVD settings, especially acute decompensated heart failure and acute myocardial infarction where AKI commonly occurs. The other concern with regard to understanding the pathogenesis of renal complications in CVD is that mechanistically oriented studies have been relatively rare. Pre‐clininal studies have shown that activation of renal inflammation–fibrosis processes, probably triggered by haemodynamic derangement, underlies CVD‐associated renal dysfunction. On the other hand, it is postulated that there still are missing links in the heart–kidney connection in CRS patients who have significant renal dysfunction. At present, non‐dialysable protein‐bound uraemic toxins (PBUTs) appear to be the main focus in this regard. Evidence of the causal role of PBUTs in CRS has been increasingly demonstrated, mainly focusing on indoxyl sulfate (IS) and p‐cresyl sulfate (pCS). Both IS and pCS are derived from colonic microbiotic metabolism of dietary amino acids, and hence the colon has become a target of treatment in addition to efforts to improve dialysis techniques for better removal of PBUTs. Novel therapy targeting the site of toxin production has led to new prospects in early intervention for predialysis patients with chronic kidney disease.
Developmental changes in Ca2+ channel subtypes regulating endocytosis at the calyx of Held
Authors: Midorikawa Mitsuharu , Okamoto Yuji , Sakaba Takeshi 
Published: June 2014

Key points
We examined the roles of each Ca2+ channel subtype in the time course of endocytosis at the calyx of Held terminal by a capacitance measurement technique.
At the calyx of Held terminal, endocytosis is mediated by two kinetically distinct components, a fast mode and a slow mode of endocytosis, in animals at postnatal days 8–11.
R‐Type Ca2+ channels are more tightly coupled to the slow mode of endocytosis than P/Q‐ and N‐type, demonstrating the differential contribution from different Ca2+ channels to endocytosis.
The fast mode of endocytosis, which was observed only following strong stimulation, was mainly mediated by P/Q‐type Ca2+ channels.
In animals at postnatal days 14–17, when fast endocytosis becomes less prominent, slow endocytosis was regulated by Ca2+ influx through P/Q‐type Ca2+ channels, indicating developmental changes in the functional coupling between Ca2+ channel subtypes and endocytosis.
AbstractAt the mammalian central synapse, Ca2+ influx through Ca2+ channels triggers neurotransmitter release by exocytosis of synaptic vesicles, which fuse with the presynaptic membrane and are subsequently retrieved by endocytosis. At the calyx of Held terminal, P/Q‐type Ca2+ channels mainly mediate exocytosis, while N‐ and R‐type channels have a minor role in young terminals (postnatal days 8–11). The role of each Ca2+ channel subtype in endocytosis remains to be elucidated; therefore, we examined the role of each type of Ca2+ channel in endocytosis, by using whole‐cell patch‐clamp recordings in conjunction with capacitance measurement techniques. We found that at the young calyx terminal, when R‐type Ca2+ channels were blocked, the slow mode of endocytosis was further slowed, while blocking of either P/Q‐ or N‐type Ca2+ channels had no major effect. In more mature terminals (postnatal days 14–17), the slow mode of endocytosis was mainly triggered by P/Q‐type Ca2+ channels, suggesting developmental changes in the regulation of the slow mode of endocytosis by different Ca2+ channel subtypes. In contrast, a fast mode of endocytosis was observed after strong stimulation in young terminals that was mediated mainly by P/Q‐type, but not R‐ or N‐type Ca2+ channels. These results suggest that different types of Ca2+ channels regulate the two different modes of endocytosis. The results may also suggest that exo‐ and endocytosis are regulated independently at different sites in young animals but are more tightly coupled in older animals, allowing more efficient synaptic vesicle cycling adapted for fast signalling.
Depression biased non‐Hebbian spike‐timing‐dependent synaptic plasticity in the rat subiculum
Authors: Pandey Anurag , Sikdar Sujit Kumar 
Published: June 2014

Key points
Spike‐timing‐dependent plasticity (STDP) is the induction of synaptic plasticity by coincident activity of pre‐ and postsynaptic neurons.
In most of the excitatory synapses, an EPSP immediately followed by a back‐propagating action potential (bAP) enhances the synaptic efficacy, whereas the reverse weakens it.
Contrary to the above observation, we demonstrate that, at the proximal excitatory synapses on the subicular pyramidal neurons, an EPSP immediately followed by a burst of bAPs weakens the synaptic strength, whereas the reverse strengthens the synapse in both bursting and regular firing neurons.
This reverse STDP rule may have strong implications in synaptic integration and information outflow from the hippocampus.
Interestingly, the mechanisms associated with synaptic depression using the same induction protocol were different in the two neuronal subtypes, being postsynaptic in the bursting neurons requiring NMDA receptor activity, but presynaptic in the regular firing neurons involving L‐type calcium channels.
AbstractThe subiculum is a structure that forms a bridge between the hippocampus and the entorhinal cortex (EC), and plays a major role in the memory consolidation process. Here, we demonstrate spike‐timing‐dependent plasticity (STDP) at the proximal excitatory inputs on the subicular pyramidal neurons of juvenile rat. Causal (positive) pairing of a single EPSP with a single back‐propagating action potential (bAP) after a time interval of 10 ms (+10 ms) failed to induce plasticity. However, increasing the number of bAPs in a burst to three, at two different frequencies of 50 Hz (bAP burst) and 150 Hz, induced long‐term depression (LTD) after a time interval of +10 ms in both the regular‐firing (RF), and the weak burst firing (WBF) neurons. The LTD amplitude decreased with increasing time interval between the EPSP and the bAP burst. Reversing the order of the pairing of the EPSP and the bAP burst induced LTP at a time interval of −10 ms. This finding is in contrast with reports at other synapses, wherein pre‐ before postsynaptic (causal) pairing induced LTP and vice versa. Our results reaffirm the earlier observations that the relative timing of the pre‐ and postsynaptic activities can lead to multiple types of plasticity profiles. The induction of timing‐dependent LTD (t‐LTD) was dependent on postsynaptic calcium change via NMDA receptors in the WBF neurons, while it was independent of postsynaptic calcium change, but required active L‐type calcium channels in the RF neurons. Thus the mechanism of synaptic plasticity may vary within a hippocampal subfield depending on the postsynaptic neuron involved. This study also reports a novel mechanism of LTD induction, where L‐type calcium channels are involved in a presynaptically induced synaptic plasticity. The findings may have strong implications in the memory consolidation process owing to the central role of the subiculum and LTD in this process.
The multifaceted subunit interfaces of ionotropic glutamate receptors
Authors: Green Tim , Nayeem Naushaba 
Published: June 2014

AbstractThe past fifteen years has seen a revolution in our understanding of ionotropic glutamate receptor (iGluR) structure, starting with the first view of the ligand binding domain (LBD) published in 1998, and in many ways culminating in the publication of the full‐length structure of GluA2 in 2009. These reports have revealed not only the central role played by subunit interfaces in iGluR function, but also myriad binding sites within interfaces for endogenous and exogenous factors. Changes in the conformation of inter‐subunit interfaces are central to transmission of ligand gating into pore opening (itself a rearrangement of interfaces), and subsequent closure through desensitization. With the exception of the agonist binding site, which is located entirely within individual subunits, almost all modulatory factors affecting iGluRs appear to bind to sites in subunit interfaces. This review seeks to summarize what we currently understand about the diverse roles interfaces play in iGluR function, and to highlight questions for future research.
Mechanisms of Antiviral Action of Plant Antimicrobials against Murine Norovirus
Authors: Gilling Damian H. , Kitajima Masaaki , Torrey Jason R. , Bright Kelly R. 
Published: June 2014

ABSTRACT

Numerous plant compounds have antibacterial or antiviral properties; however, limited research has been conducted with nonenveloped viruses. The efficacies of allspice oil, lemongrass oil, and citral were evaluated against the nonenveloped murine norovirus (MNV), a human norovirus surrogate. The antiviral mechanisms of action were also examined using an RNase I protection assay, a host cell binding assay, and transmission electron microscopy. All three antimicrobials produced significant reductions (
P
≤ 0.05) in viral infectivity within 6 h of exposure (0.90 log
10
to 1.88 log
10
). After 24 h, the reductions were 2.74, 3.00, and 3.41 log
10
for lemongrass oil, citral, and allspice oil, respectively. The antiviral effect of allspice oil was both time and concentration dependent; the effects of lemongrass oil and citral were time dependent. Based on the RNase I assay, allspice oil appeared to act directly upon the viral capsid and RNA. The capsids enlarged from ≤35 nm to up to 75 nm following treatment. MNV adsorption to host cells was not significantly affected. Alternatively, the capsid remained intact following exposure to lemongrass oil and citral, which appeared to coat the capsid, causing nonspecific and nonproductive binding to host cells that did not lead to successful infection. Such contrasting effects between allspice oil and both lemongrass oil and citral suggest that though different plant compounds may yield similar reductions in virus infectivity, the mechanisms of inactivation may be highly varied and specific to the antimicrobial. This study demonstrates the antiviral properties of allspice oil, lemongrass oil, and citral against MNV and thus indicates their potential as natural food and surface sanitizers to control noroviruses.
Genomic Heterogeneity and Ecological Speciation within One Subspecies of Bacillus subtilis
Authors: Kopac Sarah , Wang Zhang , Wiedenbeck Jane , Sherry Jessica , Wu Martin , Cohan Frederick M. 
Published: June 2014

ABSTRACTClosely related bacterial genomes usually differ in gene content, suggesting that nearly every strain in nature may be ecologically unique. We have tested this hypothesis by sequencing the genomes of extremely close relatives within a recognized taxon and analyzing the genomes for evidence of ecological distinctness. We compared the genomes of four Death Valley isolates plus the laboratory strain W23, all previously classified asBacillus subtilissubsp.spizizeniiand hypothesized through multilocus analysis to be members of the same ecotype (an ecologically homogeneous population), named putative ecotype 15 (PE15). These strains showed a history of positive selection on amino acid sequences in 38 genes. Each of the strains was under a different regimen of positive selection, suggesting that each strain is ecologically unique and represents a distinct ecological speciation event. The rate of speciation appears to be much faster than can be resolved with multilocus sequencing. Each PE15 strain contained unique genes known to confer a function for bacteria. Remarkably, no unique gene conferred a metabolic system or subsystem function that was not already present in all the PE15 strains sampled. Thus, the origin of ecotypes within this clade shows no evidence of qualitative divergence in the set of resources utilized. Ecotype formation within this clade is consistent with the nanoniche model of bacterial speciation, in which ecotypes use the same set of resources but in different proportions, and genetic cohesion extends beyond a single ecotype to the set of ecotypes utilizing the same resources.
Carriage of Staphylococcus aureus by Free-Living Wild Animals in Spain
Authors: Porrero M. Concepción , Mentaberre Gregorio , Sánchez Sergio , Fernández-Llario Pedro , Casas-Díaz Encarna , Mateos Ana , Vidal Dolors , Lavín Santiago , Fernández-Garayzábal José-Francisco , Domínguez Lucas 
Published: June 2014

ABSTRACT

The presence of methicillin-susceptible
Staphylococcus aureus
(MSSA) was analyzed in different free-living wild animals to assess the genetic diversity and predominant genotypes on each animal species. Samples were taken from the skin and/or nares, and isolates were characterized by
spa
typing, multilocus sequence typing (MLST) and antimicrobial susceptibility testing. The proportion of MSSA carriers were 5.00, 22.93, 19.78, and 17.67% in Eurasian griffon vulture, Iberian ibex, red deer, and wild boar, respectively (
P
= 0.057). A higher proportion of isolates (
P
= 0.000) were recovered from nasal samples (78.51%) than skin samples (21.49%), but the 9.26% of red deer and 18.25% of wild boar would have been undetected if only nasal samples had been tested. Sixty-three different
spa
types were identified, including 25 new
spa
types. The most common were t528 (43.59%) in Iberian ibex, t548 and t11212 (15.79% and 14.04%) in red deer, and t3750 (36.11%) in wild boar. By MLST, 27 STs were detected, of which 12 had not been described previously. The most frequent were ST581 for Iberian ibex (48.72%), ST425 for red deer (29.82%), and ST2328 for wild boar (42.36%). Isolates from Eurasian griffon vulture belong to ST133. Host specificity has been observed for the most frequent
spa
types and STs (
P
= 0.000). The highest resistance percentage was found against benzylpenicillin (average, 22.2%), although most of the
S. aureus
isolates were susceptible to all antimicrobial tested. Basically, MSSA isolates were different from those MRSA isolates previously detected in the same animal species.
Applied Usage of Yeast Spores as Chitosan Beads
Authors: Zhang Haini , Tachikawa Hiroyuki , Gao Xiao-Dong , Nakanishi Hideki 
Published: June 2014

ABSTRACTIn this study, we present a nonhazardous biological method of producing chitosan beads using the budding yeastSaccharomyces cerevisiae. Yeast cells cultured under conditions of nutritional starvation cease vegetative growth and instead form spores. The spore wall has a multilaminar structure with the chitosan layer as the second outermost layer. Thus, removal of the outermost dityrosine layer by disruption of theDIT1gene, which is required for dityrosine synthesis, leads to exposure of the chitosan layer at the spore surface. In this way, spores can be made to resemble chitosan beads. Chitosan has adsorptive features and can be used to remove heavy metals and negatively charged molecules from solution. Consistent with this practical application, we find that spores are capable of adsorbing heavy metals such as Cu2+, Cr3+, and Cd2+, and removal of the dityrosine layer further improves the adsorption. Removal of the chitosan layer decreases the adsorption, indicating that chitosan works as an adsorbent in the spores. Besides heavy metals, spores can also adsorb a negatively charged cholesterol derivative, taurocholic acid. Furthermore, chitosan is amenable to chemical modifications, and, consistent with this property,dit1Δspores can serve as a carrier for immobilization of enzymes. Given that yeast spores are a natural product, our results demonstrate that they, and especiallydit1Δmutants, can be used as chitosan beads and used for multiple purposes.
Lactulose and Lactobacillus plantarum, a Potential Complementary Synbiotic To Control Postweaning Colibacillosis in Piglets
Authors: Guerra-Ordaz A. A. , González-Ortiz G. , La Ragione R. M. , Woodward M. J. , Collins J. W. , Pérez J. F. , Martín-Orúe S. M. 
Published: June 2014

ABSTRACT

The potential of a prebiotic oligosaccharide lactulose, a probiotic strain of
Lactobacillus plantarum
, or their synbiotic combination to control postweaning colibacillosis in pigs was evaluated using an enterotoxigenic
Escherichia coli
(ETEC) K88 oral challenge. Seventy-two weanlings were fed four diets: a control diet (CTR), that diet supplemented with
L. plantarum
(2 × 10
10
CFU · day
−1
) (LPN), that diet supplemented with 10 g · kg
−1
lactulose (LAC), or a combination of the two treatments (SYN). After 7 days, the pigs were orally challenged. Six pigs per treatment were euthanized on days 6 and 10 postchallenge (PC). Inclusion of lactulose improved the average daily gain (ADG) (
P
< 0.05) and increased lactobacilli (
P
< 0.05) and the percentage of butyric acid (
P
< 0.02) in the colon. An increase in the ileum villous height (
P
< 0.05) and a reduction of the pig major acute-phase protein (Pig-MAP) in serum (
P
< 0.01) were observed also. The inclusion of the probiotic increased numbers of
L. plantarum
bacteria in the ileum and colon (
P
< 0.05) and in the total lactobacilli in the colon and showed a trend to reduce diarrhea (
P
= 0.09). The concentrations of ammonia in ileal and colonic digesta were decreased (
P
< 0.05), and the villous height (
P
< 0.01) and number of ileal goblet cells (
P
< 0.05) increased, at day 10 PC. A decrease in plasmatic tumor necrosis factor alpha (TNF-α) (
P
< 0.01) was also seen. The positive effects of the two additives were combined in the SYN treatment, resulting in a complementary synbiotic with potential to be used to control postweaning colibacillosis.