bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracranial Self-stimulation of the Paraventricular Nucleus of the Hypothalamus
Authors: Ewan Eric E. , Martin Thomas J. 
Published: March 2012

Background
Neuropathic pain attenuates opioid facilitation of rewarding electrical stimulation of limbic dopaminergic pathways originating from the ventral tegmental area. Whether neuropathic pain alters opioid effects of other brain-reward systems is unknown.

Methods
Control and spinal nerve-ligated (SNL) rats had electrodes implanted into the paraventricular nucleus (PVN) of the hypothalamus or medial forebrain bundle. Control and SNL rats were trained to lever-press for intracranial self-stimulation (ICSS), and modulation by morphine or cocaine was assessed.

Results
Control and SNL rats lever-pressed for stimulation of the PVN and medial forebrain bundle. Morphine produced greater reductions in the frequency at which rats emitted 50% of maximal responding for PVN ICSS (maximal effect 24.67 ± 4.60 [mean ± SEM] and 24.11 ± 5.96 in SNL [n = 6] and control [n = 8] rats, respectively, compared with medial forebrain bundle ICSS (12.38 ± 6.77 [n = 8] and 12.69 ± 1.55 [n = 7]). In contrast, cocaine was less efficacious in potentiating PVN ICSS (maximal effect 11.76 ± 2.86 and 12.38 ± 4.01 in SNL [n = 12] and control [n = 8] rats, respectively) compared with medial forebrain bundle ICSS (30.58 ± 3.40 [n = 9] and 27.55 ± 4.51 [n = 7]).

Conclusions
PVN ICSS is facilitated to a greater extent by morphine than cocaine, and the effects of each drug on this behavior are unaltered after spinal nerve ligation. These effects contrast those observed with direct stimulation of limbic dopamine pathways, suggesting that the PVN may have a greater role in the reinforcing effects of opioids than classic limbic regions, particularly in the presence of chronic pain.
Multiple Domains in MtENOD8 Protein Including the Signal Peptide Target It to The Symbiosome
Authors: Meckfessel Matthew H. , Blancaflor Elison B. , Plunkett Michael , Dong Qunfeng , Dickstein Rebecca 
Published: March 2012

Abstract
Symbiotic nitrogen fixation occurs in nodules, specialized organs on the roots of legumes. Within nodules, host plant cells are infected with rhizobia that are encapsulated by a plant-derived membrane forming a novel organelle, the symbiosome. In Medicago truncatula, the symbiosome consists of the symbiosome membrane, a single rhizobium, and the soluble space between them, called the symbiosome space. The symbiosome space is enriched with plant-derived proteins, including the M. truncatula EARLY NODULIN8 (MtENOD8) protein. Here, we present evidence from green fluorescent protein (GFP) fusion experiments that the MtENOD8 protein contains at least three symbiosome targeting domains, including its N-terminal signal peptide (SP). When ectopically expressed in nonnodulated root tissue, the MtENOD8 SP delivers GFP to the vacuole. During the course of nodulation, there is a nodule-specific redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates and subsequently to symbiosomes, with redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates preceding intracellular rhizobial infection. Experiments with M. truncatula mutants having defects in rhizobial infection and symbiosome development demonstrated that the MtNIP/LATD gene is required for redirection of the MtENOD8-SP-GFP from the vacuoles to punctate intermediates in nodules. Our evidence shows that MtENOD8 has evolved redundant targeting sequences for symbiosome targeting and that intracellular localization of ectopically expressed MtENOD8-SP-GFP is useful as a marker for monitoring the extent of development in mutant nodules.
The Arabidopsis MicroRNA396-GRF1/GRF3 Regulatory Module Acts as a Developmental Regulator in the Reprogramming of Root Cells during Cyst Nematode Infection
Authors: Hewezi Tarek , Maier Tom R. , Nettleton Dan , Baum Thomas J. 
Published: March 2012

Abstract
The syncytium is a unique plant root organ whose differentiation is induced by plant-parasitic cyst nematodes to create a source of nourishment. Syncytium formation involves the redifferentiation and fusion of hundreds of root cells. The underlying regulatory networks that control this unique change of plant cell fate are not understood. Here, we report that a strong down-regulation of Arabidopsis (Arabidopsis thaliana) microRNA396 (miR396) in cells giving rise to the syncytium coincides with the initiation of the syncytial induction/formation phase and that specific miR396 up-regulation in the developed syncytium marks the beginning of the maintenance phase, when no new cells are incorporated into the syncytium. In addition, our results show that miR396 in fact has a role in the transition from one phase to the other. Expression modulations of miR396 and its Growth-Regulating Factor (GRF) target genes resulted in reduced syncytium size and arrested nematode development. Furthermore, genome-wide expression profiling revealed that the miR396-GRF regulatory system can alter the expression of 44% of the more than 7,000 genes reported to change expression in the Arabidopsis syncytium. Thus, miR396 represents a key regulator for the reprogramming of root cells. As such, this regulatory unit represents a powerful molecular target for the parasitic animal to modulate plant cells and force them into novel developmental pathways.
Statistical quality indicators for electron-density maps
Authors: Tickle Ian J. 
Published: March 2012

The commonly used validation metrics for the local agreement of a structure model with the observed electron density, namely the real-space R (RSR) and the real-space correlation coefficient (RSCC), are reviewed. It is argued that the primary goal of all validation techniques is to verify the accuracy of the model, since precision is an inherent property of the crystal and the data. It is demonstrated that the principal weakness of both of the above metrics is their inability to distinguish the accuracy of the model from its precision. Furthermore, neither of these metrics in their usual implementation indicate the statistical significance of the result. The statistical properties of electron-density maps are reviewed and an improved alternative likelihood-based metric is suggested. This leads naturally to a χ2 significance test of the difference density using the real-space difference density Z score (RSZD). This is a metric purely of the local model accuracy, as required for effective model validation and structure optimization by practising crystallographers prior to submission of a structure model to the PDB. A new real-space observed density Z score (RSZO) is also proposed; this is a metric purely of the model precision, as a substitute for other precision metrics such as the B factor.
Expression of TREM‐1 in hepatic stellate cells and prognostic value in hepatitis B‐related hepatocellular carcinoma
Authors: Liao Rui , Sun Tai‐Wei , Yi Yong , Wu Han , Li Yi‐Wei , Wang Jia‐Xing , Zhou Jian , Shi Ying‐Hong , Cheng Yun‐Feng , Qiu Shuang‐Jian , Fan Jia 
Published: March 2012

Hepatocellular carcinoma (HCC) is a typical inflammation‐related malignancy characterized by high postoperative recurrence and metastasis. Although several inflammatory cells and inflammatory signatures have been linked to poor prognosis, the inflammation‐associated molecular mechanisms of HCC development and progression are largely unknown. Here we show that triggering receptor expressed in myeloid cells (TREM)‐1, a transmembrane receptor expressing in myeloid cells, was also expressed in tumor‐activated hepatic stellate cells (HSCs) and associated with the aggressive behavior of HCC cells. Enzyme‐linked immunosorbent assay was used to measure the expression levels of soluble TREM‐1 (sTREM‐1) in activated hepatic stellate cells supernatant and 92 preoperative and postoperative plasmas of patients with malignancy and/or benign liver tumor/disease, respectively. Expression levels of TREM‐1 were assessed by immunohistochemistry in tissue microarray from 240 patients with HCC. As a result, increased secretion of sTREM‐1 from activated HSCs was observed after co‐culture with HCC cell lines (P < 0.001), and conditioned medium collected from activated HSCs/cancer associated myofibroblasts (CAMFs) with or without agonist/inhibitor of TREM‐1 significantly changed the migratory ability of HCC cells. The levels of sTREM‐1 were significantly higher in patients with HCC than those with benign liver tumors (P < 0.005). Peritumoral density of TREM‐1 was shown to be an independent prognosis predictor according to univariate (P < 0.001 for both overall survival and time to recurrence) and multivariate analysis (P = 0.008 for overall survival; P = 0.005 for time to recurrence). Thus, these observations suggest that TREM‐1 is related to the aggressive tumor behavior and has potential value as a prognostic factor for HCC. (Cancer Sci 2012; 103: 984–992)
Clinical evaluation of a new tracheal impedance cardiography method
Authors: van der Kleij S. C. J. , Koolen B. B. , Newhall D. A. , Gerritse B. M. , Rosseel P. M. J. , Rijpstra T. A. , Geisler F. E. A. , van der Meer N. J. M. 
Published: March 2012

SummaryNon‐invasive cardiac output measurement by means of impedance cardiography has been evaluated before, and agreement with other methods has been variable. We decided to study a newly developed tracheal impedance device, that is claimed to be more accurate and reliable. This incorporates new software and mathematical formulae, that are designed to reduce signal noise from diathermy, leading to improved accuracy. In 25 cardiothoracic surgery patients, simultaneous measurements were performed using both pulmonary artery thermodilution and the tracheal impedance device, at five peri‐operative time points: before skin incision; after weaning from cardiopulmonary bypass; after sternal closure; and 30 min and 2 h after arrival in the intensive care unit. Mean cardiac output, bias and 95% limits of agreement were 5.3, 0.03 and −2.8 to 2.8 l.min−1, respectively. Tracheal impedance showed good correlation with measurement trends using thermodilution in 88% of measurements, with a mean (95% limit of agreement) angular bias of −9.0° (−83.3 to 65.3°). However, the wide limits of agreement and high percentage error of 53% that were apparent in this study mean that, in its present guise, tracheal impedance is not an acceptable alternative to thermodilution in cardiac surgical patients.
Genome‐wide association study uncovers four QTL predisposing to supernumerary teats in cattle
Authors: Pausch Hubert , Jung Simone , Edel Christian , Emmerling Reiner , Krogmeier Dieter , Götz Kay‐Uwe , Fries Ruedi 
Published: March 2012

SummarySupernumerary teats (hyperthelia, SNTs) are a common abnormality of the bovine udder with a medium to high heritability and a postulated oligogenic or polygenic inheritance pattern. SNTs not only negatively affect machine milking ability but also act as a reservoir for bacteria. A genome‐wide association study was carried out to identify genes involved in the development of SNTs in the dual‐purpose Fleckvieh breed. A total of 2467 progeny‐tested bulls were genotyped at 43 698 single nucleotide polymorphisms, and daughter yield deviations (DYDs) for ‘udder clearness' (UC) were used as high‐heritability phenotypes. Massive structuring of the study population was accounted for by principal components analysis‐based and mixed model‐based approaches. Four loci on BTA5, BTA6, BTA11 and BTA17 were significantly associated with the UC DYD. Three associated regions contain genes of the highly conserved Wnt signalling pathway. The four QTL together account for 10.7% of the variance of the UC DYD, whereas the major fraction of the DYD variance is attributable to chromosomes with no identified QTL. Our results support both an oligogenic and a polygenic inheritance pattern of SNTs in cattle. The identified candidate genes permit insights into the genetic architecture of teat malformations in cattle and provide clues to unravel the molecular mechanisms of mammary gland alterations in cattle and other species.
Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double‐blind, placebo‐controlled study
Authors: McHenry Claire M. , Bell Patrick M. , Hunter Steven J. , Thompson Christopher J. , Courtney C. H. , Ennis Cieran N. , Sheridan Brian , McCance David R. , Mullan Karen R. , Atkinson A. Brew 
Published: March 2012

SummaryObjectiveAddition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism.DesignRandomized, double‐blind, placebo‐controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks.PatientsFourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled.MeasurementsInsulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment.ResultsSerum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 μm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone‐binding globulin (SHBG) or IGF‐1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 μmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged.ConclusionThere were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.
Patients’ views of patient‐centred care: a phenomenological case study in one surgical unit
Authors: Marshall Amy , Kitson Alison , Zeitz Kathryn 
Published: March 2012

AbstractAims.  To report a study of patients’ views of patient‐centred care. The study aimed to explore patients’ understanding and conceptualization of patient‐centred care and link it to existing literature on the topic.Background.  Patient‐centred care currently lacks a widely accepted definition, with much of the literature based on definitions formulated by health professionals and researchers.Design.  Qualitative research study grounded in phenomenology.Methods.  Interpersonal interviews were conducted with ten participants who were patients in a surgical ward in a large metropolitan hospital in South Australia in 2010.Results/findings.  Participants were unfamiliar with the concept of patient‐centred care, but despite this, were able to describe what the term meant to them and what they wanted from their care. Patients equated the type and quality of care they received with the staff that provided it and themes of connectedness, involvement and attentiveness were prevalent in their descriptions of what they wanted from their care.Conclusion.  Ensuring that patients have a voice in the definition and conceptualization of patient‐centred care is essential and further and regular consultation with patients about their needs and priorities will ensure an integrated approach to patient‐centred care.
Energy density and its variation in space limit species richness of boreal forest birds
Authors: Elo Merja , Roberge Jean‐Michel , Rajasärkkä Ari , Mönkkönen Mikko 
Published: March 2012

AbstractAim  An area’s ability to support species may be dependent not only on the total amount of available energy it contains but also on energy density (i.e. available energy per unit area). Acknowledging these two aspects of energy availability may increase mechanistic understanding of how increased energy availability results in increased species richness. We studied the relationship between energy density, its variation in space and boreal forest bird species richness and investigated two possible mechanisms: (1) metabolic constraints of organisms, and (2) increased resource availability for specialists.Location  Protected areas in Finland’s boreal forest.Methods  We tested whether bird species richness was best determined by total energy availability in an area or by energy density and its variation within the area, before and after including bird abundance in the models. We evaluated two main explanatory variables: tree growth reflecting the rate of energy production and tree volume as a measure of biomass. In addition, we modelled individual species’ responses to energy density and its variation, and evaluated the prediction of the metabolic constraints hypothesis that small species are limited by energy density whereas large species are limited by total energy availability in the area.Results  Energy density and its variation were good predictors of species richness: together with abundance they explained 84% of variation in species richness (compared with 74% for abundance alone). Pure metabolic constraints were unlikely to explain this relationship. Instead, the mechanism probably involved increased habitat heterogeneity benefiting specialist species. Total energy availability was also an important factor determining species richness but its effect was indirect via abundance.Main conclusions  Our results corroborate the importance of energy availability as a driver of species richness in forest bird communities, and they indicate that energy density and its variation in the landscape strongly influence species richness even after accounting for abundance.
Stress ulcer prophylaxis in non‐critically ill patients: a prospective evaluation of current practice in a general surgery department
Authors: Bez Coraline , Perrottet Nancy , Zingg Tobias , Leung Ki En‐Ling , Demartines Nicolas , Pannatier André 
Published: March 2012

AbstractRationale, aims and objectives  There is little evidence regarding the benefit of stress ulcer prophylaxis (SUP) outside a critical care setting. Overprescription of SUP is not devoid of risks. This prospective study aimed to evaluate the use of proton pump inhibitors (PPIs) for SUP in a general surgery department.Method  Data collection was performed prospectively during an 8‐week period on patients hospitalized in a general surgery department (58 beds) by pharmacists. Patients with a PPI prescription for the treatment of ulcers, gastro‐oesophageal reflux disease, oesophagitis or epigastric pain were excluded. Patients admitted twice during the study period were not reincluded. The American Society of Health‐System Pharmacists guidelines on SUP were used to assess the appropriateness of de novo PPI prescriptions.Results  Among 255 patients in the study, 138 (54%) received a prophylaxis with PPI, of which 86 (62%) were de novo PPI prescriptions. A total of 129 patients (94%) received esomeprazole (according to the hospital drug policy). The most frequent dosage was at 40 mg once daily. Use of PPI for SUP was evaluated in 67 patients. A total of 53 patients (79%) had no risk factors for SUP. Twelve and two patients had one or two risk factors, respectively. At discharge, PPI prophylaxis was continued in 33% of patients with a de novo PPI prescription.Conclusions  This study highlights the overuse of PPIs in non‐intensive care unit patients and the inappropriate continuation of PPI prescriptions at discharge. Treatment recommendations for SUP are needed to restrict PPI use for justified indications.
Variable abnormal physiological motility in the proximal upper gastrointestinal tract in gastroparesis
Authors: Lee A. , Wilding G. , Kuo B. 
Published: March 2012

AbstractBackground  Traditional testing for gastroparesis with gastric emptying scintigraphy (GES) likely misses a subset of patients because of the heterogeneous nature of the disease. The primary aim of this study is to determine the prevalence of simultaneously measured transit and pressure abnormalities in patients with gastroparesis. The secondary aim is to assess diagnostic gain realized by measuring antroduodenal pressure and gastric transit with wireless motility capsule (WMC) compared to gastric transit measured by GES. Identification of abnormalities beyond gastric transit delay in gastroparesis may yield novel targets for pharmacological therapies.Methods  Forty‐three subjects with symptoms of gastroparesis and previous abnormal GES within 2 years were enrolled in the study. Subjects underwent simultaneous GES and WMC to assess gastric transit. Gastric and small bowel pressure profiles were measured by WMC to determine the contribution of pressure to diagnostic gain realized with WMC.Key Results  Fifty‐one percent of subjects had abnormal GES while 70% of subjects had either abnormal gastric emptying time (GET) or antroduodenal pressure. Gastric emptying time was abnormal in 60% of subjects while gastric or small bowel pressure was abnormal in 47% of subjects. The overall diagnostic gain of WMC compared to GES was 19% (P = 0.04). Seven percent of subjects had abnormal small bowel pressure profiles when both GES and GET were normal.Conclusions & Inferences  (i) Gastroparesis is a heterogeneous disorder and testing only solid food emptying by scintigraphy may miss a significant amount of pathology. (ii) Measuring complementary aspects of gastric and small bowel function simultaneously results in greater detection of physiologic abnormalities that may underlie patient symptoms.
The gastro‐esophageal reflux barrier: biophysical analysis on 3D models of anatomy from magnetic resonance imaging
Authors: Roy S. , Fox M. R. , Curcic J. , Schwizer W. , Pal A. 
Published: March 2012

AbstractBackground  The function and structure of the gastro‐esophageal junction (GEJ) determine its efficacy as a reflux barrier. This study presents a novel methodology for the quantitative assessment of GEJ and proximal gastric morphology from magnetic resonance (MR) imaging. Based on this data we propose a new conceptualization of the hypothesis that a flap valve mechanism contributes to reflux protection.Methods  3D models of the GEJ and proximal stomach were reconstructed from MR images in 12 healthy volunteers during respiration and on eating a test meal to maximum satiation. A rotating plane analysis measured the gastro‐esophageal insertion angle and span of contact. An ellipsoid fit provided quantitative assessment of gastric shape and orientation relative to a fixed anatomical reference point. Position of the esophageal insertion on the ‘gastric ellipse’ was noted. An ellipsoid‐cylinder model was designed to analyze the relationships among parameters describing the GEJ morphology.Key Results  The insertion angle became more acute on expiration, but did not change with meal ingestion. In contrast the span of contact did not vary with respiration, but increased with gastric filling. Changes in gastric morphology with distension further augmented the span of gastro‐esophageal contact in almost 70% of the studies.Conclusions & Inferences  Novel MR imaging and biophysical analysis of the GEJ and proximal stomach provide a quantitative description of structures contributing to the reflux barrier. Changes in these parameters during respiration and on eating support the hypothesis that structural components of a functional ‘flap valve’ like mechanism contribute to reflux protection.