bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive Decoupling of Metabolic Genes in Cancer
Authors: Reznik Ed , Sander Chris 
Published: September 2014

AbstractTumorigenesis involves, among other factors, the alteration of metabolic gene expression to support malignant, unrestrained proliferation. Here, we examine how the altered metabolism of cancer cells is reflected in changes in co-expression patterns of metabolic genes between normal and tumor tissues. Our emphasis on changes in the interactions of pairs of genes, rather than on the expression levels of individual genes, exposes changes in the activity of metabolic pathways which do not necessarily show clear patterns of over- or under-expression. We report the existence of key metabolic genes which act as hubs of differential co-expression, showing significantly different co-regulation patterns between normal and tumor states. Notably, we find that the extent of differential co-expression of a gene is only weakly correlated with its differential expression, suggesting that the two measures probe different features of metabolism. By leveraging our findings against existing pathway knowledge, we extract networks of functionally connected differentially co-expressed genes and the transcription factors which regulate them. Doing so, we identify a previously unreported network of dysregulated metabolic genes in clear cell renal cell carcinoma transcriptionally controlled by the transcription factor HNF4A. While HNF4A shows no significant differential expression, the co-expression HNF4A and several of its regulated target genes in normal tissue is completely abrogated in tumor tissue. Finally, we aggregate the results of differential co-expression analysis across seven distinct cancer types to identify pairs of metabolic genes which may be recurrently dysregulated. Among our results is a cluster of four genes, all located in the mitochondrial electron transport chain, which show significant loss of co-expression in tumor tissue, pointing to potential mitochondrial dysfunction in these tumor types.
Mitochondrial Alternative Oxidase Maintains Respiration and Preserves Photosynthetic Capacity during Moderate Drought in Nicotiana tabacum
Authors: Dahal Keshav , Wang Jia , Martyn Greg D. , Rahimy Farkhunda , Vanlerberghe Greg C. 
Published: September 2014

Abstract
The mitochondrial electron transport chain includes an alternative oxidase (AOX) that is hypothesized to aid photosynthetic metabolism, perhaps by acting as an additional electron sink for photogenerated reductant or by dampening the generation of reactive oxygen species. Gas exchange, chlorophyll fluorescence, photosystem I (PSI) absorbance, and biochemical and protein analyses were used to compare respiration and photosynthesis of Nicotiana tabacum ‘Petit Havana SR1’ wild-type plants with that of transgenic AOX knockdown (RNA interference) and overexpression lines, under both well-watered and moderate drought-stressed conditions. During drought, AOX knockdown lines displayed a lower rate of respiration in the light than the wild type, as confirmed by two independent methods. Furthermore, CO2 and light response curves indicated a nonstomatal limitation of photosynthesis in the knockdowns during drought, relative to the wild type. Also relative to the wild type, the knockdowns under drought maintained PSI and PSII in a more reduced redox state, showed greater regulated nonphotochemical energy quenching by PSII, and displayed a higher relative rate of cyclic electron transport around PSI. The origin of these differences may lie in the chloroplast ATP synthase amount, which declined dramatically in the knockdowns in response to drought. None of these effects were seen in plants overexpressing AOX. The results show that AOX is necessary to maintain mitochondrial respiration during moderate drought. In its absence, respiration rate slows and the lack of this electron sink feeds back on the photosynthetic apparatus, resulting in a loss of chloroplast ATP synthase that then limits photosynthetic capacity.
Seismic attenuation and velocity dispersion in fractured rocks: The role played by fracture contact areas
Authors: Rubino J. Germán , Müller Tobias M. , Milani Marco , Holliger Klaus 
Published: September 2014

ABSTRACTThe presence of fractures in fluid‐saturated porous rocks is usually associated with strong seismic P‐wave attenuation and velocity dispersion. This energy dissipation can be caused by oscillatory wave‐induced fluid pressure diffusion between the fractures and the host rock, an intrinsic attenuation mechanism generally referred to as wave‐induced fluid flow. Geological observations suggest that fracture surfaces are highly irregular at the millimetre and sub‐millimetre scale, which finds its expression in geometrical and mechanical complexities of the contact area between the fracture faces. It is well known that contact areas strongly affect the overall mechanical fracture properties. However, existing models for seismic attenuation and velocity dispersion in fractured rocks neglect this complexity. In this work, we explore the effects of fracture contact areas on seismic P‐wave attenuation and velocity dispersion using oscillatory relaxation simulations based on quasi‐static poroelastic equations. We verify that the geometrical and mechanical details of fracture contact areas have a strong impact on seismic signatures. In addition, our numerical approach allows us to quantify the vertical solid displacement jump across fractures, the key quantity in the linear slip theory. We find that the displacement jump is strongly affected by the geometrical details of the fracture contact area and, due to the oscillatory fluid pressure diffusion process, is complex‐valued and frequency‐dependent. By using laboratory measurements of stress‐induced changes in the fracture contact area, we relate seismic attenuation and dispersion to the effective stress. The corresponding results do indeed indicate that seismic attenuation and phase velocity may constitute useful attributes to constrain the effective stress. Alternatively, knowledge of the effective stress may help to identify the regions in which wave induced fluid flow is expected to be the dominant attenuation mechanism.
The 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors
Authors: Pandit J. J. , Andrade J. , Bogod D. G. , Hitchman J. M. , Jonker W. R. , Lucas N. , Mackay J. H. , Nimmo A. F. , O'Connor K. , O'Sullivan E. P. , Paul R. G. , Palmer J. H. MacG. , Plaat F. , Radcliffe J. J. , Sury M. R. J. , Torevell H. E. , Wang M. , Hainsworth J. , Cook T. M. ,   the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland
Published: September 2014

SummaryWe present the main findings of the 5th National Audit Project on accidental awareness during general anaesthesia. Incidences were estimated using reports of accidental awareness as the numerator, and a parallel national anaesthetic activity survey to provide denominator data. The incidence of certain/probable and possible accidental awareness cases was ~1:19 600 anaesthetics (95% CI 1:16 700–23 450). However, there was considerable variation across subtypes of techniques or subspecialties. The incidence with neuromuscular blockade was ~1:8200 (1:7030–9700), and without it was ~1:135 900 (1:78 600–299 000). The cases of accidental awareness during general anaesthesia reported to 5th National Audit Project were overwhelmingly cases of unintended awareness during neuromuscular blockade. The incidence of accidental awareness during caesarean section was ~1:670 (1:380–1300). Two thirds (82, 66%) of cases of accidental awareness experiences arose in the dynamic phases of anaesthesia, namely induction of and emergence from anaesthesia. During induction of anaesthesia, contributory factors included: use of thiopental; rapid sequence induction; obesity; difficult airway management; neuromuscular blockade; and interruptions of anaesthetic delivery during movement from anaesthetic room to theatre. During emergence from anaesthesia, residual paralysis was perceived by patients as accidental awareness, and commonly related to a failure to ensure full return of motor capacity. One third (43, 33%) of accidental awareness events arose during the maintenance phase of anaesthesia, most due to problems at induction or towards the end of anaesthesia. Factors increasing the risk of accidental awareness included: female sex; age (younger adults, but not children); obesity; anaesthetist seniority (junior trainees); previous awareness; out‐of‐hours operating; emergencies; type of surgery (obstetric, cardiac, thoracic); and use of neuromuscular blockade. The following factors were not risk factors for accidental awareness: ASA physical status; race; and use or omission of nitrous oxide. We recommend that an anaesthetic checklist, to be an integral part of the World Health Organization Safer Surgery checklist, is introduced as an aid to preventing accidental awareness. This paper is a shortened version describing the main findings from 5th National Audit Project – the full report can be found at http://www.nationalauditprojects.org.uk/NAP5_home#pt.
The 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: patient experiences, human factors, sedation, consent and medicolegal issues
Authors: Cook T. M. , Andrade J. , Bogod D. G. , Hitchman J. M. , Jonker W. R. , Lucas N. , Mackay J. H. , Nimmo A. F. , O'Connor K. , O'Sullivan E. P. , Paul R. G. , Palmer J. H. MacG. , Plaat F. , Radcliffe J. J. , Sury M. R. J. , Torevell H. E. , Wang M. , Hainsworth J. , Pandit J. J. ,   the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland
Published: September 2014

SummaryThe 5th National Audit Project of the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland into accidental awareness during general anaesthesia yielded data related to psychological aspects from the patient, and the anaesthetist, perspectives; patients’ experiences ranged from isolated auditory or tactile sensations to complete awareness. A striking finding was that 75% of experiences were for < 5 min, yet 51% of patients (95% CI 43–60%) experienced distress and 41% (95% CI 33–50%) suffered longer‐term adverse effect. Distress and longer‐term harm occurred across the full range of experiences but were particularly likely when the patient experienced paralysis (with or without pain). The patient's interpretation of what is happening at the time of the awareness seemed central to later impact; explanation and reassurance during suspected accidental awareness during general anaesthesia or at the time of report seemed beneficial. Quality of care before the event was judged good in 26%, poor in 39% and mixed in 31%. Three quarters of cases of accidental awareness during general anaesthesia (75%) were judged preventable. In 12% of cases of accidental awareness during general anaesthesia, care was judged good and the episode not preventable. The contributory and human factors in the genesis of the majority of cases of accidental awareness during general anaesthesia included medication, patient and education/training. The findings have implications for national guidance, institutional organisation and individual practice. The incidence of ‘accidental awareness’ during sedation (~1:15 000) was similar to that during general anaesthesia (~1:19 000). The project raises significant issues about information giving and consent for both sedation and anaesthesia. We propose a novel approach to describing sedation from the patient's perspective which could be used in communication and consent. Eight (6%) of the patients had resorted to legal action (12, 11%, to formal complaint) at the time of reporting. The 5th National Audit Project methodology provides a standardised template that might usefully inform the investigation of claims or serious incidents related to accidental awareness during general anaesthesia.
PTFE Grafts Versus Tunneled Cuffed Catheters for Hemodialysis: Which Is the Second Choice When Arteriovenous Fistula Is Not Feasible?
Authors: Donati Gabriele , Cianciolo Giuseppe , Mauro Raffaella , Rucci Paola , Scrivo Anna , Marchetti Antonio , Giampalma Emanuela , Golfieri Rita , Panicali Laura , Iorio Mario , Stella Andrea , La Manna Gaetano , Stefoni Sergio 
Published: September 2014

AbstractVascular access‐related complications are still one of the leading causes of morbidity in hemodialysis patients. The aim of this study was to compare polytetrafluoroethylene (PTFE) grafts versus tunneled cuffed permanent catheters (TCCs) in terms of vascular access and patients' survival. An observational study was carried out with a 2‐year follow‐up. Eighty‐seven chronic hemodialysis patients were enrolled: 31 with a PTFE graft as vascular access for hemodialysis versus 56 with a TCC. Patients' mean age was 63.8 ± 14.6 (grafts) versus 73.5 ± 11.3 years (TCCs), P = 0.001. Significantly more patients with TCC had atrial fibrillation than patients with grafts (30.3% versus 6.5%, P = 0.01). In an unadjusted Kaplan–Meier analysis, median TCC survival at 24 months was 5.4 months longer than that of PTFE grafts but not significantly (log‐rank test = 1.3, P = ns). In a Cox regression analysis adjusted for age, gender, number of previous vascular accesses, diabetes, atrial fibrillation, smoking, and any complication, this lack of significant difference in survival of the vascular access between TCC and PTFE groups was confirmed and diabetes proved to be an independent risk factor for the survival of both vascular accesses considered (P = 0.02). In an unadjusted Kaplan–Meier analysis, a higher mortality was found in the TCC group than in the PTFE group at 24 months (log‐rank test = 10.07, P < 0.01). The adjusted Cox regression analysis showed that patients with TCC had a 3.2 times higher risk of death than patients with PTFE grafts. When an arteriovenous fistula (AVF) is not possible, PTFE grafts can be considered the vascular access of second choice, whereas TCCs can be used when an AVF or PTFE graft are not feasible or as a bridge to AVF or PTFE graft creation.
Activation of the brain melanocortin system is required for leptin‐induced modulation of chemorespiratory function
Authors: Bassi M. , Nakamura N. B. , Furuya W. I. , Colombari D. S. A. , Menani J. V. , do Carmo J. M. , da Silva A. A. , Hall J. E. , Colombari E. 
Published: September 2014

AbstractMelanocortin receptors (MC3/4R) mediate most of the metabolic and cardiovascular actions of leptin.AimHere, we tested if MC4R also contributes to leptin's effects on respiratory function.MethodsAfter control measurements, male Holtzman rats received daily microinjections of leptin, SHU9119 (MC3/4R antagonist) or SHU9119 combined with leptin infused into the brain lateral ventricle for 7 days. On the 6th day of treatment, tidal volume (VT), respiratory frequency (fR) and pulmonary ventilation (VE) were measured by whole‐body plethysmography during normocapnia or hypercapnia (7% CO2). Baseline mean arterial pressure (MAP), heart rate (HR) and metabolic rate were also measured. VE, VT and fR were also measured in mice with leptin receptor deletion in the entire central nervous system (LepR/Nestin‐cre) or only in proopiomelanocortin neurones (LepR/POMC‐cre) and in MC4R knockout (MC4R−/−) and wild‐type mice.ResultsLeptin (5 μg day−1) reduced body weight (~17%) and increased ventilatory response to hypercapnia, whereas SHU9119 (0.6 nmol day−1) increased body weight (~18%) and reduced ventilatory responses compared with control‐PBS group (Lep: 2119 ± 90 mL min−1 kg−1 and SHU9119: 997 ± 67 mL min−1 kg−1, vs. PBS: 1379 ± 91 mL min−1 kg−1). MAP increased after leptin treatment (130 ± 2 mmHg) compared to PBS (106 ± 3 mmHg) or SHU9119 alone (109 ± 3 mmHg). SHU9119 prevented the effects of leptin on body weight, MAP (102 ± 3 mmHg) and ventilatory response to hypercapnia (1391 ± 137 mL min−1 kg−1). The ventilatory response to hypercapnia was attenuated in the LepR/Nestin‐cre, LepR/POMC‐cre and MC4R−/− mice.ConclusionThese results suggest that central MC4R mediate the effects of leptin on respiratory response to hypercapnia.
Intravenous Lipid Emulsion Given to Volunteers does not Affect Symptoms of Lidocaine Brain Toxicity
Authors: Heinonen Juho A. , Litonius Erik , Salmi Tapani , Haasio Juhani , Tarkkila Pekka , Backman Janne T. , Rosenberg Per H. 
Published: September 2014

AbstractIntravenous lipid emulsion has been suggested as treatment for local anaesthetic toxicity, but the exact mechanism of action is still uncertain. Controlled studies on the effect of lipid emulsion on toxic doses of local anaesthetics have not been performed in man. In randomized, subject‐blinded and two‐phase cross‐over fashion, eight healthy volunteers were given a 1.5 ml/kg bolus of 20% Intralipid® (200 mg/ml) or Ringer's acetate solution intravenously, followed by a rapid injection of lidocaine 1.0 mg/kg. Then, the same solution as in the bolus was infused at a rate of 0.25 ml/kg/min. for 30 min. Electroencephalography (EEG) was recorded, and 5 min. after lidocaine injection, the volunteers were asked to report subjective symptoms. Total and un‐entrapped lidocaine plasma concentrations were measured from venous blood samples. EEG band power changes (delta, alpha and beta) after the lidocaine bolus were similar during lipid and during Ringer infusion. There were no differences between infusions in the subjective symptoms of central nervous system toxicity. Lidocaine was only minimally entrapped in the plasma by lipid emulsion, but the mean un‐entrapped lidocaine area under concentration–time curve from 0 to 30 min. was clearly smaller during lipid than Ringer infusion (16.4 versus 21.3 mg × min/l, p = 0.044). Intravenous lipid emulsion did not influence subjective toxicity symptoms nor affect the EEG changes caused by lidocaine.
Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti‐inflammatory agent
Authors: Borrelli Francesca , Romano Barbara , Petrosino Stefania , Pagano Ester , Capasso Raffaele , Coppola Diana , Battista Giovanni , Orlando Pierangelo , Di Marzo Vincenzo , Izzo Angelo A 
Published: September 2014

Background and PurposePalmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type‐1 (TRPV1) ion channels, peroxisome proliferator‐activated receptor alpha (PPAR α) and orphan G protein‐coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis.Experimental ApproachColitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT‐PCR.Key ResultsDNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down‐regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1, CB2 and PPARα. Exogenous PEA (i.p. and/or p.o., 1 mg·kg−1) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti‐inflammatory effect of PEA was attenuated or abolished by CB2 receptor, GPR55 or PPARα antagonists and further increased by the TRPV1 antagonist capsazepine.Conclusions and ImplicationsPEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPARα, and modulated by TRPV1 channels.
The Many Meanings of the Only Christ
Authors: Trelstad Marit 
Published: September 2014

AbstractThe intertwining of reflection about Christ and personal experience of Jesus has been at the heart of the matter from the start of the Reformation. Luther's Christology unites the transcendent and the intimate; it is Christ alone, Solus Christus, who mediates God's presence and promise to the world. This becomes one of the “solas” of the Reformation and the one to which this volume of Dialog is dedicated. This introduction considers the variety of ways theology has described the primary experience of Christ; we will consider how Christ has been theologically presented in terms of love, liberation, creativity, co‐sufferer, and holy presence. In addition, within the last century, one can see Christologies taking on universal or particular forms. The universal approach sees Christ in, with and under all the world, whereas the more “particular” forms connect to the singularity of Christ or Jesus as the sole locus of revelation of God in history or today. This introduction also explores the contemporary debate about the meaning of the cross and atonement in relation to the understanding of Christ as savior.
Christ as Chrism, Christ Given Away
Authors: Mercedes Anna 
Published: September 2014

AbstractThis article develops the concept of Christ not as static body but as chrism for bodies. Christ as chrism travels in the matrix of relationality, on a vector toward the benefit of others. Conceptualizing christ as chrism potentially avoids both exclusionary and colonizing tendencies in Christian polity, and frames a Christian ethics that, while vulnerable and risky, marks the sanctity of the one giving Christ away.
Synergistic metabolic benefits of an exenatide analogue and cholecystokinin in diet‐induced obese and leptin‐deficient rodents
Authors: Trevaskis J. L. , Sun C. , Athanacio J. , D'Souza L. , Samant M. , Tatarkiewicz K. , Griffin P. S. , Wittmer C. , Wang Y. , Teng C.‐H. , Forood B. , Parkes D. G. , Roth J. D. 
Published: September 2014

AimTo test the impact of cholecystokinin (CCK) plus either amylin or a glucagon‐like peptide‐1 receptor (GLP‐1R) agonist on metabolic variables in diet‐induced obese (DIO) rodents.MethodsA stabilized acetylated version of CCK‐8 (Ac‐Y*‐CCK‐8), selective CCK1 receptor (CCK1R) or CCK2 receptor (CCK2R) agonists, amylin or the GLP‐1R agonist and exenatide analogue AC3174 were administered in select combinations via continuous subcutaneous infusion to DIO rats for 14 days, or Lepob/Lepob mice for 28 days, and metabolic variables were assessed.ResultsCombined administration of Ac‐Y*‐CCK‐8 with either amylin or AC3174 induced greater than additive weight loss in DIO rats, with the overall magnitude of effect being greater with AC3174 + Ac‐Y*‐CCK‐8 treatment. Co‐infusion of AC3174 with a specific CCK1R agonist, but not a CCK2R agonist, recapitulated the weight loss mediated by AC3174 + Ac‐Y*‐CCK‐8 in DIO rats, suggesting that synergy is mediated by CCK1R activation. In a 4 × 4 full‐factorial response surface methodology study in DIO rats, a synergistic interaction between AC3174 and the CCK1R‐selective agonist on body weight and food intake was noted. Co‐administration of AC3174 and the CCK1R‐selective agonist to obese diabetic Lepob/Lepob mice elicited a significantly greater reduction in percentage of glycated haemoglobin and food intake relative to the sum effects of monotherapy groups.ConclusionsThe anti‐obesity and antidiabetic potential of combined GLP‐1R and CCK1R agonism is an approach that warrants further investigation.