bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for the blockade of MATE multidrug efflux pumps
Authors: Radchenko Martha , Symersky Jindrich , Nie Rongxin , Lu Min 
Published: August 2015

AbstractMultidrug and toxic compound extrusion (MATE) transporters underpin multidrug resistance by using the H+ or Na+ electrochemical gradient to extrude different drugs across cell membranes. MATE transporters can be further parsed into the DinF, NorM and eukaryotic subfamilies based on their amino-acid sequence similarity. Here we report the 3.0 Å resolution X-ray structures of a protonation-mimetic mutant of an H+-coupled DinF transporter, as well as of an H+-coupled DinF and a Na+-coupled NorM transporters in complexes with verapamil, a small-molecule pharmaceutical that inhibits MATE-mediated multidrug extrusion. Combining structure-inspired mutational and functional studies, we confirm the biological relevance of our crystal structures, reveal the mechanistic differences among MATE transporters, and suggest how verapamil inhibits MATE-mediated multidrug efflux. Our findings offer insights into how MATE transporters extrude chemically and structurally dissimilar drugs and could inform the design of new strategies for tackling multidrug resistance.
Diacetin, a reliable cue and private communication channel in a specialized pollination system
Authors: Schäffler Irmgard , Steiner Kim E. , Haid Mark , van Berkel Sander S. , Gerlach Günter , Johnson Steven D. , Wessjohann Ludger , Dötterl Stefan 
Published: August 2015

AbstractThe interaction between floral oil secreting plants and oil-collecting bees is one of the most specialized of all pollination mutualisms. Yet, the specific stimuli used by the bees to locate their host flowers have remained elusive. This study identifies diacetin, a volatile acetylated glycerol, as a floral signal compound shared by unrelated oil plants from around the globe. Electrophysiological measurements of antennae and behavioural assays identified diacetin as the key volatile used by oil-collecting bees to locate their host flowers. Furthermore, electrophysiological measurements indicate that only oil-collecting bees are capable of detecting diacetin. The structural and obvious biosynthetic similarity between diacetin and associated floral oils make it a reliable cue for oil-collecting bees. It is easily perceived by oil bees, but can’t be detected by other potential pollinators. Therefore, diacetin represents the first demonstrated private communication channel in a pollination system.
The Bounds Of Education In The Human Brain Connectome
Authors: Marques P. , Soares J. M. , Magalhães R. , Santos N. C. , Sousa N. 
Published: August 2015

AbstractInter-individual heterogeneity is evident in aging; education level is known to contribute for this heterogeneity. Using a cross-sectional study design and network inference applied to resting-state fMRI data, we show that aging was associated with decreased functional connectivity in a large cortical network. On the other hand, education level, as measured by years of formal education, produced an opposite effect on the long-term. These results demonstrate the increased brain efficiency in individuals with higher education level that may mitigate the impact of age on brain functional connectivity.
Molecular and chemical dialogues in bacteria-protozoa interactions
Authors: Song Chunxu , Mazzola Mark , Cheng Xu , Oetjen Janina , Alexandrov Theodore , Dorrestein Pieter , Watrous Jeramie , van der Voort Menno , Raaijmakers Jos M. 
Published: August 2015

AbstractProtozoan predation of bacteria can significantly affect soil microbial community composition and ecosystem functioning. Bacteria possess diverse defense strategies to resist or evade protozoan predation. For soil-dwelling Pseudomonas species, several secondary metabolites were proposed to provide protection against different protozoan genera. By combining whole-genome transcriptome analyses with (live) imaging mass spectrometry (IMS), we observed multiple changes in the molecular and chemical dialogues between Pseudomonas fluorescens and the protist Naegleria americana. Lipopeptide (LP) biosynthesis was induced in Pseudomonas upon protozoan grazing and LP accumulation transitioned from homogeneous distributions across bacterial colonies to site-specific accumulation at the bacteria-protist interface. Also putrescine biosynthesis was upregulated in P. fluorescens upon predation. We demonstrated that putrescine induces protozoan trophozoite encystment and adversely affects cyst viability. This multifaceted study provides new insights in common and strain-specific responses in bacteria-protozoa interactions, including responses that contribute to bacterial survival in highly competitive soil and rhizosphere environments.
Estrogen deficiency heterogeneously affects tissue specific stem cells in mice
Authors: Kitajima Yuriko , Doi Hanako , Ono Yusuke , Urata Yoshishige , Goto Shinji , Kitajima Michio , Miura Kiyonori , Li Tao-Sheng , Masuzaki Hideaki 
Published: August 2015

AbstractPostmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type coloniesin vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growthin vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders.
Serum miRNA expression profile as a prognostic biomarker of stage II/III colorectal adenocarcinoma
Authors: Li Jialu , Liu Yang , Wang Cheng , Deng Ting , Liang Hongwei , Wang Yifei , Huang Dingzhi , Fan Qian , Wang Xia , Ning Tao , Liu Rui , Zhang Chen-Yu , Zen Ke , Chen Xi , Ba Yi 
Published: August 2015

AbstractWe sought to identify a serum miRNA expression profile to improve disease surveillance and to predict post-operative disease recurrence for stage II/III colorectal cancer (CRC) patients. Using the TaqMan Low-Density Array (TLDA), we performed an initial survey to analyze 749 miRNAs in the pooled serum of 20 paired pre- and post-operative CRC patients and 20 matched normal subjects. Using individual RT-qPCR verification in 175 stage II/III CRC patients, we identified that miR-145, miR-106a and miR-17-3p were significantly differentially expressed between pre- and post-operative CRC patients and between pre-operative CRC patients and normal controls (P < 0.0001). The area under the ROC curve (AUC) for the three-miRNA panel was 0.886 (95% CI 0.850–0.921) for discriminating between pre-operative CRC patients and normal subjects and 0.850 (95% CI 0.809–0.891) for discriminating between pre- and post-operative CRC patients. Furthermore, using the Kaplan-Meier method and Cox proportional hazards analysis, we found that miR-17-3p and miR-106a were powerful and independent prognostic indicators and that high levels of these miRNAs were associated with shorter disease-free survival (DFS) (P < 0.0001 for miR-17-3p and P = 0.001 for miR-106a). The present study reveals novel serum-miRNA-based biomarkers for monitoring tumor dynamics as well as for predicting disease recurrence in patients with stage II/III CRC.
Turing instabilities on Cartesian product networks
Authors: Asllani Malbor , Busiello Daniel M. , Carletti Timoteo , Fanelli Duccio , Planchon Gwendoline 
Published: August 2015

AbstractThe problem of Turing instabilities for a reaction-diffusion system defined on a complex Cartesian product network is considered. To this end we operate in the linear regime and expand the time dependent perturbation on a basis formed by the tensor product of the eigenvectors of the discrete Laplacian operators, associated to each of the individual networks that build the Cartesian product. The dispersion relation which controls the onset of the instability depends on a set of discrete wavelengths, the eigenvalues of the aforementioned Laplacians. Patterns can develop on the Cartesian network, if they are supported on at least one of its constitutive sub-graphs. Multiplex networks are also obtained under specific prescriptions. In this case, the criteria for the instability reduce to compact explicit formulae. Numerical simulations carried out for the Mimura-Murray reaction kinetics confirm the adequacy of the proposed theory.
Antibacterial and residual antimicrobial activities against Enterococcus faecalis biofilm: A comparison between EDTA, chlorhexidine, cetrimide, MTAD and QMix
Authors: Zhang Rui , Chen Min , Lu Yan , Guo Xiangjun , Qiao Feng , Wu Ligeng 
Published: August 2015

AbstractWe compared the antibacterial and residual antimicrobial activities of five root canal irrigants (17% EDTA,2% chlorhexidine,0.2% cetrimide, MTAD and QMix) in a model of Enterococcus faecalis biofilm formation. Sixty dentin blocks with 3-week E. faecalis biofilm were divided into six equal groups and flushed with irrigant for 2 min or left untreated. A blank control group was also established. Antibacterial activities of the irrigants were evaluated by counting colony forming units. To test residual antimicrobial activities, 280 dentin blocks were divided into seven equal groups and flushed with irrigant for 2 min or left untreated and then incubated with E. faecalis suspension for 48 h, or used as a blank. No bacteria were observed in the blank control group. The number of viable E. faecalis was significantly fewer in the irrigant-treated groups compared with the untreated control (P < 0.05). Among the five irrigants, QMix had the strongest antibacterial activity. Residual antimicrobial activities of CHX were significantly higher at 12 h, 24 h and 36 h compared to untreated control (P < 0.05). All five root canal irrigants were effective to some extent against E. faecalis, but QMix and CHX had the strongest and CHX the longest (up to 36 h), antimicrobial activity.
Heat shock protein 90 inhibition abrogates TLR4-mediated NF-κB activity and reduces renal ischemia-reperfusion injury
Authors: O’Neill Stephen , Humphries Duncan , Tse George , Marson Lorna P. , Dhaliwal Kevin , Hughes Jeremy , Ross James A. , Wigmore Stephen J , Harrison Ewen M. 
Published: August 2015

AbstractRenal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury. Toll-like receptor 4 (TLR4) mediates sterile inflammation following renal IRI. Heat shock protein 90 (Hsp90) inhibition is a potential strategy to reduce IRI and AT13387 is a novel Hsp90 inhibitor with low toxicity. This study assessed if pre-treatment with AT13387 could reduce renal IRI and established if the mechanism of protection involved a reduction in inflammatory signalling. Mice were pre-treated with AT13387 prior to renal IRI. 24 h later, renal function was determined by serum creatinine, kidney damage by tubular necrosis score, renal TLR4 expression by PCR and inflammation by cytokine array. In vitro, human embryonic kidney cells were co-transfected to express TLR4 and a secreted alkaline phosphatase NF-κB reporter. Cells were pre-treated with AT13387 and exposed to endotoxin-free hyaluronan to stimulate sterile TLR4-specific NF-κB inflammatory activation. Following renal IRI, AT13387 significantly reduced serum creatinine, tubular necrosis, TLR4 expression and NF-κB-dependent chemokines. In vitro, AT13387-treatment resulted in breakdown of IκB kinase, which abolished TLR4-mediated NF-κB activation by hyaluronan. AT13387 is a new agent with translational potential that reduces renal IRI. The mechanism of protection may involve breakdown of IκB kinase and repression of TLR4-mediated NF-κB inflammatory activity.
Effect of Temperature on the Aging rate of Li Ion Battery Operating above Room Temperature
Authors: Leng Feng , Tan Cher Ming , Pecht Michael 
Published: August 2015

AbstractTemperature is known to have a significant impact on the performance, safety and cycle lifetime of lithium-ion batteries (LiB). However, the comprehensive effects of temperature on the cyclic aging rate of LiB have yet to be found. We use an electrochemistry-based model (ECBE) here to measure the effects on the aging behavior of cycled LiB operating within the temperature range of 25 °C to 55 °C. The increasing degradation rate of the maximum charge storage of LiB during cycling at elevated temperature is found to relate mainly to the degradations at the electrodes and that the degradation of LCO cathode is larger than graphite anode at elevated temperature. In particular, the formation and modification of the surface films on the electrodes as well as structural/phase changes of the LCO electrode, as reported in the literatures, are found to be the main contributors to the increasing degradation rate of the maximum charge storage of LiB with temperature for the specific operating temperature range. Larger increases in the Warburg elements and cell impedance are also found with cycling at higher temperature, but they do not seriously affect the state of health (SoH) of LiB as shown in this work.
Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory
Authors: Okada Kana , Nishizawa Kayo , Kobayashi Tomoko , Sakata Shogo , Kobayashi Kazuto 
Published: August 2015

AbstractRecognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer’s disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB) and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated and it remains unclear how they contribute to it. We use a genetic cell targeting technique to selectively eliminate cholinergic cell groups and then test spatial and object recognition memory through different behavioural tasks. Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task. These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD. Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.
Role of plasma-membrane-bound sialidase NEU3 in clathrin-mediated endocytosis
Authors: Rodriguez-Walker Macarena , Vilcaes Aldo A. , Garbarino-Pico Eduardo , Daniotti José L. 
Published: August 2015

Gangliosides are sialic acid-containing glycosphingolipids mainly expressed at the outer leaflet of the plasma membrane. Sialidase NEU3 is a key enzyme in the catabolism of gangliosides with its up-regulation having been observed in human cancer cells. In the case of CME (clathrin-mediated endocytosis), although this has been widely studied, the role of NEU3 and gangliosides in this cellular process has not yet been established. In the present study, we found an increased internalization of Tf (transferrin), the archetypical cargo for CME, in cells expressing complex gangliosides with high levels of sialylation. The ectopic expression of NEU3 led to a drastic decrease in Tf endocytosis, suggesting the participation of gangliosides in this process. However, the reduction in Tf endocytosis caused by NEU3 was still observed in glycosphingolipid-depleted cells, indicating that NEU3 could operate in a way that is independent of its action on gangliosides. Additionally, internalization of α2-macroglobulin and low-density lipoprotein, other typical ligands in CME, was also decreased in NEU3-expressing cells. In contrast, internalization of cholera toxin β-subunit, which is endocytosed by both clathrin-dependent and clathrin-independent mechanisms, remained unaltered. Kinetic assays revealed that NEU3 caused a reduction in the sorting of endocytosed Tf to early and recycling endosomes, with the Tf binding at the cell surface being also reduced. NEU3-expressing cells showed an altered subcellular distribution of clathrin adaptor AP-2 (adaptor protein 2), but did not reveal any changes in the membrane distribution of clathrin, PtdIns(4,5)P2 or caveolin-1. Overall, these results suggest a specific and novel role of NEU3 in CME.
Iron Metabolism in Patients with Chronic Renal Failure
Authors: Boddy K. , Lawson D. H. , Linton A. L. , Will G. 
Published: August 2015

1. Iron metabolism has been investigated in patients suffering from chronic renal failure, using a whole body monitoring technique.
2. Absorption of labelled inorganic iron was decreased.
3. Radio-iron was lost from the body at a rate comparable to that found in normal subjects.
4. The red cell incorporation of radioactive iron was diminished.
5. The results suggest that anaemia in these patients was due to decreased erythropoiesis and not due to iron deficiency despite the evidence of markedly abnormal iron handling presented.
Protein Synthesis in the Myocardiopathy and Muscular Dystrophy of the Syrian Hamster
Authors: Lochner Amanda , Brink Anke , Brink A. J. 
Published: August 2015

1. Incorporation in vitro of l-[4,5-3H]leucine and l-[U-14C]lysine into a soluble protein fraction and into actomyosin of hearts, diaphragms and biceps femoris of an inbred strain of Syrian hamsters suffering from a hereditary myocardiopathy and muscular dystrophy was studied.
2. Incorporation of both amino acids was normal in myopathic hearts from hamsters aged 60–90 days but significantly elevated at 180–240 days of age. Their incorporation was higher in the myopathic diaphragm and biceps femoris of both age groups.
The Gastrointestinal Absorption of Atropine in Man
Authors: Beermann B. , Hellström K. , Rosén A. 
Published: August 2015

1. An aqueous solution of [3H]atropine (2 mg, 50 μCi) and polyethylene glycol (PEG, unabsorbable marker), was administered orally orby intrajejunal infusion (100 cm from the nose) to healthy subjects.
2. The ratio between the amount of radioactivity per mg PEG of intestinal aspirates and that of the test solution demonstrated that 90% of the given label is absorbed in theproximal part of the small intestine.
3. The maximum amount of label recovered in 3000 ml plasma corresponded to 3% of the given dose.
4. The cumulative excretion of label in urine and faeces during 6 days amounted to 65% and 5%, respectively.
5. A 50% yield of radioactivity in urine after an instillation of [3H]atropine into the jejunum 200 cm from the nose indicated that a substantial absorption occurs distal to this level.
6. The cumulative excretion of radioactivity in urine and faeces during 6 days after an intravenous injection of 1 mg [3H]atropine to one subject amounted to 66% and 1·5%, respectively.
7. Electrophoretic and chromatographic analyses of small intestinal aspirates showed no consistent evidence of a metabolic change of the drug.
Cardio-Respiratory Response to Treadmill Exercise in Normal Children
Authors: Anderson Sandra D. , Godfrey S. 
Published: August 2015

1. Studies have been made of the response to running on a treadmill in forty boys and girls aged 5–15 years.
2. Each child was studied at two consecutive levels of steady-state work representing about 50% and 80% of his physical working capacity. Cardiac output was measured by the Indirect (CO2) Fick method.
3. The cardiac and ventilatory responses to exercise were similar to those seen during cycling on an ergometer except that the heart rate and the respiratory exchange ratio were a little lower. Stroke volume was the same.
4. The responses of children to running and cycling are discussed and the similarity to the responses of adults is noted.
Influence of Extracellular Volume Expansion on the Composition of Proximal Tubular Fluid in Man
Authors: Fillastre J. P. , Ardaillou R. , Isaac R. 
Published: August 2015

1. Distal blockade by simultaneous administration of ethacrynic acid and chlorothiazide was performed in healthy subjects whose extracellular fluid was expanded by iso-osmotic sodium chloride or bicarbonate. The results obtained were compared with those from non-expanded subjects (Ardaillou & Fillastre, 1969).
2. By this technique urine approximates in composition to proximal tubular fluid and may be used to provide information on its composition. As in other mammals, UNa/PNa and Uosm/Posm were close to 1, whatever the experimental conditions. UCl/PCl was always higher and UHCO3/PHCO3 always less than 1.
3. Extracellular fluid expansion with sodium chloride depresses water and sodium reabsorption as shown by the increase of tubular fluid and the diminution of UInul/PInul and TNa/GFR × PNa where TNa and GFR × PNa are respectively the amounts of sodium reabsorbed and filtered per min. It also decreases bicarbonate proximal Tm. The influence on bicarbonate reabsorption is more marked in alkali-loaded than in acid-loaded subjects.
4. Extracellular fluid expansion with iso-osmotic sodium bicarbonate also depresses water, sodium and bicarbonate reabsorption. These results suggest that chloride administration is not necessary to diminish bicarbonate reabsorption and that tubular reabsorption of bicarbonate depends in part on the state of effective extracellular volume.
Respiratory and Haemodynamic Response to Carbon Dioxide Breathing in Patients with and without Bronchial Obstruction
Authors: Ježek V. , Boudík F. 
Published: August 2015

1. The effect of breathing a mixture of 5–6% carbon dioxide in air was examined in seven patients with obstructive bronchitis and in eight patients with lung disease but without bronchial obstruction.
2. Hyperventilation during CO2 breathing was less marked in patients with bronchial obstruction than in the others. Cardiac output did not change in patients with airways obstruction but rose in the control group. The increase of arterial carbon dioxide tension, hydrogen ion concentration, pulmonary arterial and pulmonary wedge pressures (P̄pa and P̄paw was comparable in both groups. The increase of P̄pa and P̄paw was proportional to the Pa,co2 but the change of cardiac output was not. The ventilatory response to CO2 breathing was correlated with the spirometric measurements, but the haemodynamic changes were not.
3. No significant changes of pulmonary vascular resistance or of the P̄pa–P̄paw pressure gradient were observed. The increase of pulmonary arterial pressure during CO2 breathing appears to be due to increased pulmonary wedge pressure.
4. The contribution of depressed myocardial function during CO2 breathing to the response of cardiac output is discussed on the basis of a negative correlation between Pa,co2 and stroke volume during CO2 breathing.