bluuebunny/crossref_metadata_2025 huggingface dataset:
CCAAT/enhancer binding protein α (C/EBPα)-induced transdifferentiation of pre-B cells into macrophages involves no overt retrodifferentiation
Authors: Di Tullio Alessandro , Manh Thien Phong Vu , Schubert Alexis , Castellano Giancarlo , Månsson Robert , Graf Thomas
Published: October 2011

Earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor CCAAT/enhancer binding protein α at very high frequencies. Using this system, we performed a systematic analysis of whether during transdifferentiation the cells transiently reactivate progenitor-restricted genes or even retrodifferentiate. A transcriptome analysis of transdifferentiating cells showed that most genes are up- or down-regulated continuously, acquiring a macrophage phenotype within 5 d. In addition, we observed the transient reactivation of a subset of immature myeloid markers, as well as low levels of the progenitor markers
Kit
and FMS-like tyrosine kinase 3 and a few lineage-inappropriate genes. Importantly, however, we were unable to observe the reexpression of cell-surface marker combinations that characterize hematopoietic stem and progenitor cells, including c-Kit and FMS-like tyrosine kinase 3, even when CAAT/enhancer binding protein α was activated in pre-B cells under culture conditions that favor growth of hematopoietic stem and progenitor cells or when the transcription factor was activated in a time-limited fashion. Together, our findings are consistent with the notion that the conversion from pre-B cells to macrophages is mostly direct and does not involve overt retrodifferentiation.
Place‐related identity, texts, and transcultural meanings
Authors: Wyse Dominic , Nikolajeva Maria , Charlton Emma , Hodges Gabrielle Cliff , Pointon Pam , Taylor Liz
Published: October 2011

The spatial turn has been marked by increasing interest in conceptions of space and place in diverse areas of research. However, the important links between place and identity have received less attention, particularly in educational research. This paper reports an 18‐month research project that aimed to develop a theory of place‐related identity through the textual transactions of reading and writing. The research was an in‐depth qualitative study in two phases: the first phase involved the development of an interdisciplinary theory of place‐related identity, which was ‘tested’ in a second empirical phase. Two contrasting primary school classes were the site for the research that included the development of a unit of work, inspired by the book My place, as a vehicle for exploring place‐related identity. The data were interviews, classroom observations and outcomes from pupils’ work. The construct of transcultural meanings, established from the analytic categories of localising identity, othering identity and identity as belonging, was identified as a defining phenomenon of place‐related identity. The conclusions offer reflections on the development of our initial theory as a result of the empirical work, and the implications for practice and future research.
Beware Greeks bearing steam engines: a response to the Kastelle and Steen proposition
Authors: Scally Kevin
Published: October 2011

Kevin Scally has particular interests in the global regime of intellectual property monopolies and their consequences for business, particularly entrepreneurial, small business and startups. His research explores themes and provides data that support and guide policy makers in the areas of innovation and entrepreneurship. The focus of his research is on small business, university technology transfer and individual entrepreneurs.
Ideas are not innovations?
Authors: Rainford John
Published: October 2011

John Rainford is a lecturer and speaker on managing creativity and implementing change for competitive advantage through innovation, entrepreneurship and leadership development. He has developed a process called ‘game changer’ that challenges old strategies and delivers new, better and more innovative ones.
XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes
Authors: Saribasak Huseyin , Maul Robert W. , Cao Zheng , McClure Rhonda L. , Yang William , McNeill Daniel R. , Wilson David M. , Gearhart Patricia J.
Published: October 2011

Activation-induced deaminase (AID) deaminates cytosine to uracil in immunoglobulin genes. Uracils in DNA can be recognized by uracil DNA glycosylase and abasic endonuclease to produce single-strand breaks. The breaks are repaired either faithfully by DNA base excision repair (BER) or mutagenically to produce somatic hypermutation (SHM) and class switch recombination (CSR). To unravel the interplay between repair and mutagenesis, we decreased the level of x-ray cross-complementing 1 (XRCC1), a scaffold protein involved in BER. Mice heterozygous for XRCC1 showed a significant increase in the frequencies of SHM in Igh variable regions in Peyer’s patch cells, and of double-strand breaks in the switch regions during CSR. Although the frequency of CSR was normal in Xrcc1+/− splenic B cells, the length of microhomology at the switch junctions decreased, suggesting that XRCC1 also participates in alternative nonhomologous end joining. Furthermore, Xrcc1+/− B cells had reduced Igh/c-myc translocations during CSR, supporting a role for XRCC1 in microhomology-mediated joining. Our results imply that AID-induced single-strand breaks in Igh variable and switch regions become substrates simultaneously for BER and mutagenesis pathways.
Welfare Impacts of Alternative Biofuel and Energy Policies
Authors: Cui Jingbo , Lapan Harvey , Moschini GianCarlo , Cooper Joseph
Published: October 2011

An open‐economy equilibrium model is derived to investigate the effects of energy policy on the U.S. economy, with emphasis on corn‐based ethanol. A second best policy of a fuel tax and ethanol subsidy is found to approximate fairly closely the welfare gains associated with the first best policy of an optimal carbon tax and tariffs on traded goods. The largest economic gains to the U.S. economy from these energy policies arise from their impact on U.S. terms of trade, particularly in the oil market. Conditional on the current fuel tax, an optimal ethanol mandate is superior to an optimal ethanol subsidy.
Improving the detection of transmembrane β-barrel chains with N-to-1 extreme learning machines
Authors: Savojardo Castrense , Fariselli Piero , Casadio Rita
Published: October 2011

Motivation: Transmembrane β-barrels (TMBBs) are extremely important proteins that play key roles in several cell functions. They cross the lipid bilayer with β-barrel structures. TMBBs are presently found in the outer membranes of Gram-negative bacteria and of mitochondria and chloroplasts. Loop exposure outside the bacterial cell membranes makes TMBBs important targets for vaccine or drug therapies. In genomes, they are not highly represented and are difficult to identify with experimental approaches. Several computational methods have been developed to discriminate TMBBs from other types of proteins. However, the best performing approaches have a high fraction of false positive predictions.

Results: In this article, we introduce a new machine learning approach for TMBB detection based on N-to-1 Extreme Learning Machines that significantly outperforms previous methods achieving a Matthews correlation coefficient of 0.82, a probability of correct prediction of 0.92 and a sensitivity of 0.73.

Availability: The method and the cross-validation sets are available at the web page http://betaware.biocomp.unibo.it/BetAware.

Contact:  piero.fariselli@unibo.it
MDpocket: open-source cavity detection and characterization on molecular dynamics trajectories
Authors: Schmidtke Peter , Bidon-Chanal Axel , Luque F. Javier , Barril Xavier
Published: October 2011

Motivation: A variety of pocket detection algorithms are now freely or commercially available to the scientific community for the analysis of static protein structures. However, since proteins are dynamic entities, enhancing the capabilities of these programs for the straightforward detection and characterization of cavities taking into account protein conformational ensembles should be valuable for capturing the plasticity of pockets, and therefore allow gaining insight into structure–function relationships.

Results: This article describes a new method, called MDpocket, providing a fast, free and open-source tool for tracking small molecule binding sites and gas migration pathways on molecular dynamics (MDs) trajectories or other conformational ensembles. MDpocket is based on the fpocket cavity detection algorithm and a valuable contribution to existing analysis tools. The capabilities of MDpocket are illustrated for three relevant cases: (i) the detection of transient subpockets using an ensemble of crystal structures of HSP90; (ii) the detection of known xenon binding sites and migration pathways in myoglobin; and (iii) the identification of suitable pockets for molecular docking in P38 Map kinase.

Availability: MDpocket is free and open-source software and can be downloaded at http://fpocket.sourceforge.net.

Contact:  pschmidtke@ub.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Shoulder Pain in Amyotrophic Lateral Sclerosis
Authors: Ho Doreen T , Ruthazer Robin , Russell James A
Published: October 2011

Objective:

To determine the frequency of shoulder pain in our amyotrophic lateral sclerosis (ALS) population and to explore potential associations with demographic and clinical features.

Methods:

We retrospectively reviewed the medical records of 193 patients with ALS patients seen at the Lahey Clinic between 2005 and 2009. Patients were categorized by the predominance of upper and lower motor neuron signs and the body regions initially involved. The frequency of shoulder pain was identified in each of these subgroups.

Results:

Forty-five (23%) of the 193 patients reported shoulder pain at some time during the course of their illness. Age, gender, manual labor, prior shoulder problems, ALS phenotype, and initial region of involvement were not correlated with shoulder pain. Patients with shoulder pain were more likely to develop proximal arm weakness during their illness and to report pain elsewhere.

Conclusions:

Despite the limitations posed by this retrospective study, it underscores the prevalence of shoulder pain in patients with ALS. Further studies to identify risk factors, mechanisms of, and treatments for shoulder pain in patients with ALS may benefit this population.
A Novel Biodegradable Septal Defect Occluder the “Chinese Lantern” Design, Proof of Concept
Authors: Wu Wei , Yip James , Tang Yong-Dan , Khoo Vincent , Kong Jen Fong , Duong-Hong Duc , Boey Freddy , Venkatraman Subbu S.
Published: October 2011

Objective

Atrial septal defect (ASD) is a general term used to describe an opening in the atrial septum that divides the two atria; unless the hole is occluded, it can give rise to serious complications. Given the need for percutaneous deployment for ASD or patent foramen ovale (PFO) occluders, all currently available devices are made of metals (specifically nitinol) and synthetic fabric. However, their permanent presence in the human body is not desirable due to the risks of long-term allergy, toxicity, and complications such as thrombus formation, device arm fracture, and nickel allergy. Once the hole is covered by a newly regenerated tissue, the device is no longer needed; thus it is ideal if the device is fully absorbed by the body when healing is completed.

Methods

The “Chinese Lantern” device is made of fully biodegradable polymers featured with a unique pull-fold mechanism. The device was inserted across the ASD/PFO model created on Yorkshire swines through a short sheath by hybrid open surgery. X-ray imaging, echocardiography, and postmortem histopathology were obtained during the 1-month follow-up study period.

Results

X-ray imaging showed that the devices were in satisfactory position and stable. Echocardiography showed that there is no shunting from the right atrium to the left atrium, indicating excellent sealing. The in vitro degradation study and postmortem explantation study confirmed that the devices have good integrity during the 1-month trial. Furthermore, the devices appeared to be completely endothelialized after 1 month.

Conclusions

This work proves the feasibility of interventional closure of ASD or PFO with an innovative biodegradable device, which we call the “Chinese Lantern” for its symbolic design.
Insertion of the Impella 5.0 Left Ventricular Assist Device via Right Anterior Mini-Thoracotomy a Novel Practical Approach
Authors: Choi Daniel C. , Anderson Mark B. , Batsides George P.
Published: October 2011

The Impella 5.0 microaxial pump is a miniaturized left ventricular assist device commonly used for circulatory support in acute cardiogenic shock. The catheter-based pump is designed to be inserted either into a peripheral artery or directly into the ascending aorta. We report the first case in which the Impella 5.0 device was placed directly into the ascending aorta via a small right anterior thoracotomy in a patient following acute myocardial infarction complicated by cardiogenic shock.
Tissue Temperature Feedback Control of Power the Key to Successful Ablation
Authors: Swanson David K. , Smith Wendel J. , Ibrahim Tamer , Wechsler Andrew S.
Published: October 2011

Multiple ablation technologies are used to treat atrial fibrillation during cardiac operations. All such ablation technologies use locally induced temperature extremes (>50°C or −20°C) to kill tissue and create a lesion pattern in the atria which blocks activation pathways that initiate and sustain atrial fibrillation. The technologies used to heat tissue have included radiofrequency (RF), microwave, high-intensity focused ultrasound, and infrared laser. RF accounts for more than 95% of the heating-based ablation technology used by cardiac surgeons. Energy delivery with RF is easier to control than with some other technologies, the heating produced by the energy source is well understood, and manufacturing costs are not excessive. Whichever heating technology is used, control of energy delivery is required to ensure both safe and effective heating of the targeted tissue. All targeted tissue needs to be heated above 50°C to achieve cell death. However, the targeted tissue should not be heated above 100°C, as this can cause perforation due to a steam pop. In addition, adjacent noncardiac tissues must not be damaged during the ablation procedure. The best method to achieve this control uses direct measurement of tissue temperature, because the tissue temperature defines both the safe and effective limits for the ablative process.
Image-Guided Transapical Aortic Valve Implantation Sensorless Tracking of Stenotic Valve Landmarks in Live Fluoroscopic Images
Authors: Merk Denis R. , Karar Mohamed Esmail , Chalopin Claire , Holzhey David , Falk Volkmar , Mohr Friedrich W. , Burgert Oliver
Published: October 2011

Objective

Aortic valve stenosis is one of the most frequently acquired valvular heart diseases, accounting for almost 70% of valvular cardiac surgery. Transapical transcatheter aortic valve implantation has recently become a suitable minimally invasive technique for high-risk and elderly patients with severe aortic stenosis. In this article, we aim to automatically define a target area of valve implantation, namely, the area between the coronary ostia and the lowest points of two aortic valve cusps. Therefore, we present a new image-based tracking method of these aortic landmarks to assist in the placement of aortic valve prosthesis under live 2D fluoroscopy guidance.

Methods

We propose a rigid intensity-based image registration technique for tracking valve landmarks in 2D fluoroscopic image sequences, based on a real-time alignment of a contrast image including the initialized manual valve landmarks to each image of sequence. The contrast image is automatically detected to visualize aortic valve features when the aortic root is filled with a contrast agent.

Results

Our registration-based tracking method has been retrospectively applied to 10 fluoroscopic image sequences from routine transapical aortic valve implantation procedures. Most of all tested fluoroscopic images showed a successful tracking of valve landmarks, especially for the images without contrast agent injections.

Conclusions

A new intraoperative image-based method has been developed for tracking aortic valve landmarks in live 2D fluoroscopic images to assist transapical aortic valve implantations and to increase the overall safety of surgery as well.
Early Experience with Robotic-Assisted Lung Resection
Authors: Fortes Daniel L. , Tomaszek Sandra C. , Wigle Dennis A.
Published: October 2011

Objective

Robotic-assisted surgery is not widely accepted for general thoracic surgical procedures, and the technical advantages, cost effectiveness, and patient benefit are in question. Few reports have been published to date regarding clinical experience with this technology. We describe our first consecutive case experience with robotic-assisted lung resection.

Methods

A total of 23 robotic-assisted lung resections were performed from December 1, 2008, to September 30, 2010. Patients were selected on the basis of being candidates for a minimally invasive approach to their lung resection, including criteria such as known or suspected early-stage nonsmall-cell lung cancer, no prior thoracotomy, no neoadjuvant therapy, and a body mass index (BMI) less than 40 kg/cm2. Data on patient characteristics and perioperative results were collected retrospectively.

Results

Overall 90-day mortality was 0%. The total postoperative complication rate was 39%. Conversion of the robotic-assisted procedure to a video-assisted procedure was necessary in four patients (17%), and to a thoracotomy in one patient (4%). We assessed operative time, chest tube duration, and length of hospital stay. Comparison to published outcomes from the Society of Thoracic Surgeons database demonstrated comparable outcomes to standard approaches.

Conclusions

Robotic-assisted lung resection is safe and feasible, with comparable short-term outcomes to published results from video-assisted or open approaches.
Role of Gastroesophageal Reflux in Children With Unexplained Chronic Cough
Authors: Borrelli Osvaldo , Marabotto Caterina , Mancini Valentina , Aloi Marina , Macrì Francesco , Falconieri Paola , Lindley Keith J. , Cucchiara Salvatore
Published: October 2011

Objective:

The relation between respiratory symptoms and gastroesophageal reflux (GER) is a matter of contention and debate, with limited data in children to substantiate or refute cause and effect. Moreover, there are few data on the relation between nonacid reflux and chronic cough in childhood. We aimed to describe the type and physical characteristics of reflux episodes in children with unexplained chronic cough.

Patients and Methods:

Forty‐five children with chronic cough underwent 24‐hour multichannel intraluminal impedance‐pH monitoring (MII‐pH monitoring). Symptom association probability (SAP) characterized the reflux‐cough association. Twenty children with erosive reflux disease (ERD) served as controls.

Results:

Twenty‐four children had cough‐related reflux (CRR), with 19 having no gastrointestinal symptoms. Twenty‐one had cough‐unrelated reflux (CUR). CRR and ERD had increased acid (AR), weakly acidic (WAc), and weakly alkaline (WAlk) reflux. Esophageal acid exposure time and acid clearance time were higher in ERD than in CRR and CUR. In the CRR group, of 158 cough episodes related to reflux episodes, 66% involved AR, 18% WAc, and 16% WAlk. Seventeen children had positive SAP, 7 for AR, 5 for both AR and WAc, 4 for both WAc and WAlk, and 1 for WAlk.

Conclusions:

In children with unexplained chronic cough, asymptomatic acid and nonacid GER is a potential etiologic factor. The increased acid exposure time and delayed acid clearance characteristic of ERD are absent in cough‐related GER. MII‐pH monitoring increases the likelihood of demonstrating a temporal association between the cough and all types of reflux.
Siglec‐F Inhibition Reduces Esophageal Eosinophilia and Angiogenesis in a Mouse Model of Eosinophilic Esophagitis
Authors: Rubinstein Eitan , Cho Jae Youn , Rosenthal Peter , Chao James , Miller Marina , Pham Alexa , Aceves Seema S. , Varki Ajit , Broide David H.
Published: October 2011

Objectives:

Eosinophilic esophagitis (EoE) is a disorder characterized histologically by tissue eosinophilia. Sialic acid–binding immunoglobulin‐like lectin (Siglec‐F) is a receptor highly expressed on mouse eosinophils and mediates eosinophilic apoptosis. We investigated whether administration of an anti‐Siglec‐F Ab would reduce esophageal eosinophilic inflammation and remodeling in a mouse model of egg ovalbumin (OVA)–induced EoE.

Subjects and Methods:

Three groups of mice were studied (no OVA, OVA + anti‐Siglec‐F Ab, and OVA + isotype control Ab). Mice were sensitized intraperitoneally and then challenged chronically with intraesophageal OVA. Levels of esophageal eosinophils and features of remodeling (angiogenesis, vascular endothelial growth factor expression, deposition of fibronectin, basal zone hyperplasia, and fibrosis) were quantitated by immunohistochemistry and image analysis.

Results:

Administration of an anti‐Siglec‐F Ab to OVA‐challenged mice significantly reduced levels of esophageal eosinophils, down to levels noted in non‐OVA‐challenged mice. The anti‐Siglec‐F Ab also reduced features of OVA‐induced remodeling, including angiogenesis, basal zone hyperplasia, and fibronectin deposition. The reduced angiogenesis in anti‐Siglec‐F Ab‐treated mice was associated with reduced numbers of vascular endothelial growth factor–positive cells in the esophagus. The anti‐Siglec‐F antibody did not significantly reduce esophageal fibrosis as assessed by trichrome staining.

Conclusions:

Administration of an anti‐Siglec‐F antibody significantly decreased the number of eosinophils in the esophagus in a mouse model of OVA‐induced EoE. The reduction in eosinophilic inflammation was associated with a significant decrease in levels of angiogenesis, deposition of fibronectin, and basal zone hyperplasia. Studies in this pre‐clinical model of EoE suggest that Siglec‐F (and its human paralog Siglec‐8) may be novel therapeutic targets to reduce eosinophilic inflammation in EoE.
Manifestations and Evolution of Wilson Disease in Pediatric Patients Carrying ATP7B Mutation L708P
Authors: Peña‐Quintana Luis , García‐Luzardo María R. , García‐Villarreal Luis , Arias‐Santos María D. , Garay‐Sánchez Paloma , Santana Alfredo , González‐Santana Daniel , Ramos‐Varela Juan C. , Rial‐González Ramiro , Tugores Antonio
Published: October 2011

Objectives:

The aim of the study was to characterize a group of 11 pediatric patients, ages 3 to 13 years, affected by Wilson disease (WD) in the island of Gran Canaria, Spain.

Patients and Methods:

Genetic, biochemical, and pathological features, together with their response to treatment and clinical evolution, have been analyzed for this group of patients.

Results:

Genetically, the group was rather homogeneous, with an extremely high prevalence of the L708P mutation (4 homozygotes and 5 heterozygotes). Despite being initially screened because of asymptomatic hypertransaminemia, all of the patients presented with some degree of liver damage that was never accompanied by any neurological manifestation. Hepatic damage was most severe in a compound heterozygote with a novel mutation, G1266W, affecting a motif in the ATP7B polypeptide that is greatly conserved in similar proteins among metazoans. Ceruloplasmin and copper serum levels, together with the determination of hepatic copper content, were found to be of great diagnostic value, whereas urine copper measurements were found to be much less conclusive. All of the patients responded well to treatment with D‐penicillamine with no documented adverse reactions.

Conclusions:

The patients in Gran Canaria constitute, overall, one of the largest groups of patients with WD with a high incidence of a single mutation, allowing us to define the early clinical symptoms and the evolution of the disease in patients carrying the ATP7B L708P mutant allele, and the study of WD in a genetically homogeneous background.
Widening Spectrum of Liver Angiosarcoma in Children
Authors: Ackermann Oanez , Fabre Monique , Franchi Stephanie , Pariente Daniele , Debray Dominique , Jacquemin Emmanuel , Gauthier Frederic , Bernard Olivier
Published: October 2011

Objectives:

Liver hemangiomas are vascular tumors, which occur in the first months of life and carry risks of initial complications, but are considered to be benign histologically and to regress with time. Histologic studies suggest that a subtype, type 2 hemangioendothelioma, is akin to angiosarcoma and may have a severe long‐term prognosis. We report 5 girls with type 2 hemangioendothelioma of the liver.

Methods and Results:

Three children initially presented with classical infantile multinodular hemangioma, including cardiac and pulmonary complications and regression of tumors at age 1½ to 2½ years. All 3 experienced tumor relapse at ages 2½ to 3, leading to death at ages 2½ to 5. Tumor histology showed type 2 hemangioendothelioma. The other 2 children presented with liver tumors at ages 2 and 3 years. In 1, initial biopsy of a single tumor showed benign type 1 hemangioendothelioma, but surgical resection was followed by relapse in the remaining liver, lung metastases, and death. Whole tumor histology showed both type 1 and 2 lesions. In the other child, tumor biopsy showed type 2 lesions. She underwent liver transplantation and is alive without tumor recurrence 3 years later.

Conclusions:

Careful follow‐up is necessary to detect late recurrence in infants with multinodular liver hemangiomas. Vascular liver tumors occurring after infancy are likely to be malignant. The high risk of relapse in the remaining liver suggests that if no metastases are detected, liver transplantation is preferable to surgical tumor resection in both situations.
Toll‐like Receptor mRNA Expression in Liver Tissue From Patients With Biliary Atresia
Authors: Saito Takeshi , Hishiki Tomoro , Terui Keita , Mitsunaga Tetsuya , Terui Elena , Nakata Mitsuyuki , Yoshida Hideo
Published: October 2011

Background and Aim:

Inappropriate host immunological reactions against unknown ligands via the Toll‐like receptor (TLR) cascades may trigger progressive inflammatory biliary destruction that manifests as biliary atresia (BA) in newborns or infants. The aim of the study was to clarify the role of the innate immune system in the development of BA.

Patients and Methods:

Liver tissue was obtained from 49 patients with pediatric hepatobiliary diseases: 19 with BA, 21 with choledochal cysts, and 9 with other hepatobiliary diseases. BA samples obtained during the initial portoenterostomy and reoperation or liver transplantation (LT) were classified as early and late BA groups, respectively. Of the early BA group, those requiring LT were designated as the LT group, and the others were designated as the non‐LT group. The mRNA expression levels of TLRs 2, 3, 4, 7, and 8 were determined by real‐time quantitative reverse transcription‐polymerase chain reaction and were compared between groups. The correlation between TLR mRNA expression level and age at sampling was examined for each TLR in the patients with BA.

Results:

TLR8 mRNA, encoding the receptor for single‐stranded RNA, was significantly higher in the early BA group, compared with non‐BA groups (P = 0.008). Within the BA group, mRNA levels of TLRs 2 and 8 were significantly higher in the early group than in the late group (P = 0.02 and 0.006, respectively), despite there being no significant correlation between TLR mRNA expression and age at sampling, except for TLR7 (r = 0.77, P = 0.001). Compared with the non‐LT group, the LT group demonstrated significantly higher mRNA expression of TLRs 3 and 7 (P = 0.02 and 0.01, respectively).

Conclusions:

Innate immune responses may contribute to the initiation and progression of BA. Severe inflammation characteristic of BA around the time of the first operation may abate postoperatively, but determination of selected TLR mRNA expression levels in the liver at the time of Kasai portoenterostomy may assist in predicting the prognosis of patients with BA.
Bovine Lactoferrin Can Be Taken Up by the Human Intestinal Lactoferrin Receptor and Exert Bioactivities
Authors: Lönnerdal Bo , Jiang Rulan , Du Xiaou
Published: October 2011

Objective:

Human lactoferrin (hLF), a major protein in human milk, has been shown to exert multiple biological activities. To achieve some of the benefits of breast‐fed infants, we investigated the feasibility of adding commercially available bovine LF (CbLF) to infant formula.

Subjects and Methods:

An intestinal enterocyte model (Caco‐2 cells) was used to compare the ability of bovine LF (bLF) purified by our laboratory and CbLF with hLF to resist digestion, bind to the receptor, and exert bioactivities, including cellular proliferation, differentiation, interleukin 18 secretion, and transforming growth factor‐β1 expression.

Results:

bLf and CbLF, which are partially iron (Fe)‐saturated, can bind additional Fe, partially resist digestion either dissolved in phosphate buffered saline or in the presence of infant formula at conditions similar to those of the infant gastrointestinal tract, and bind to Caco‐2 cells in a manner similar to hLF. bLF and CbLF, as well as bound Fe, also are internalized by Caco‐2 cells, as demonstrated by 125I and 59Fe labeling, albeit to somewhat less of an extent than hLF. CbLF promoted cell proliferation and differentiation to an extent similar to that of bLF and hLF, but these effects were not seen when the LF samples were saturated with Fe (holo‐LF). Native forms of hLF and bLF significantly increased expression of transforming growth factor‐β1, and holo‐forms of LFs stimulated interleukin 18 secretion significantly, with the highest results for CbLF.

Conclusions:

CbLF is biologically active and is likely to exert several of the bioactivities of hLF if added to infant formula.
Nutritional Strategy for Adolescents Undergoing Bariatric Surgery
Authors: Fullmer Michell A. , Abrams Stephanie H. , Hrovat Kathleen , Mooney Lori , Scheimann Ann O. , Hillman Jennifer B. , Suskind David L.
Published: October 2011

Surgical options for the treatment of adolescent obesity have been gaining popularity. Adolescent patients present a particular challenge to clinicians, secondary to age‐related issues, revolving around both mental and physical growth. These age‐related issues require a unique approach to nutritional intervention for adolescents undergoing bariatric surgery as opposed to standardized approaches for adults. Despite the increasing numbers of adolescents undergoing obesity surgery, evidence‐based nutritional guidelines have yet to be published. The goal of this document is to provide the clinician with recommendations on how to assess, educate, nourish, and monitor the adolescent who has undergone obesity surgery. A multidisciplinary panel composed of 3 pediatric gastroenterologists, 1 psychologist, and 3 registered dietitians from the Nutrition Committee for the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition and National Association of Children's Hospitals and Related Institutions, with experience in nutrition and adolescent weight loss surgery, reviewed the medical literature for evidence‐based practice for nutritional strategies for patients undergoing bariatric surgery. In addition to this group, an adolescent medicine physician was consulted for matters related to reproductive health. The present article presents a consensus of recommendations based on a review of the literature. In areas for which there was a lack of evidence to support the recommendations, best‐practice guidelines were used. The present article provides the clinician with an overview of the nutritional concerns for adolescent patients undergoing obesity surgery. These guidelines address the preoperative educational pathway, the postoperative diet progression, recognition of disordered eating, guidelines for female reproductive issues, and assistance for the adolescent in a school/college environment.
Caregiver Evaluation and Satisfaction With Autologous Bowel Reconstruction in Children With Short Bowel Syndrome
Authors: Edge Harriet , Hurrell Ruth , Bianchi Adrian , Carlson Gordon , Zaidi Taqi , Gozzini Sara , Khalil Basem A. , Morabito Antonino
Published: October 2011

Background and Aims:

Short bowel syndrome (SBS) describes the malabsorptive state seen following extensive bowel resection. Management aims to optimise nutritional intake, promote intestinal adaptation, and prevent the development of complications. Surgical options such as autologous gastrointestinal reconstruction (AGIR) attempt to restore enteral autonomy to the patient. Although the literature focuses on the objective measurements of success following AGIR techniques, subjective assessment of its effect on the quality of life (QoL) should also be sought. Because children with SBS are reliant on caregivers, caregivers' satisfaction with surgery and their perception of the effect of AGIR on their daily lives should be assessed. This is the first report of caregiver satisfaction following AGIR in children.

Methods:

All children with SBS who had AGIR between January 1999 and June 2010 were identified. A questionnaire was developed. Caregivers were asked to complete the questionnaire to rate their satisfaction with surgery and the pre‐ and postoperative daily care, medical needs, and subjective interpretation of QoL for their child. Data were analysed using SPSS version 18, using the Friedman nonparametric test and 2‐way analysis of variance by rank. Statistical significance was set at ≤0.05.

Results:

Thirty‐two children were identified. Seven assessments were done outside our centre (5 outside the UK) and were not included in the study. One patient moved to another city and was not contacted. Two children died. Twenty patients were contactable and were included in the present study. Parents were satisfied with the AGIR and saw improvements in their child's physical condition, bowel habit, and subjective interpretation of QoL postoperatively. Parents perceived significant improvements in the ease of caring and in aspects of their relationship with their child, including the quality of time spent, their enjoyment, and the level of their frustration with them.

Conclusions:

The present study found that AGIR improved the physical well‐being of the child and gave the impression of improvements on specific QoL aspects for both the child and the parents.
OsYSL6 Is Involved in the Detoxification of Excess Manganese in Rice
Authors: Sasaki Akimasa , Yamaji Naoki , Xia Jixing , Ma Jian Feng
Published: October 2011

Yellow Stripe-Like (YSL) proteins belong to the oligopeptide transporter family and have been implicated in metal transport and homeostasis in different plant species. Here, we functionally characterized a rice (Oryza sativa) YSL member, OsYSL6. Knockout of OsYSL6 resulted in decreased growth of both roots and shoots only in the high-manganese (Mn) condition. There was no difference in the concentration of total Mn and other essential metals between the wild-type rice and the knockout line, but the knockout line showed a higher Mn concentration in the leaf apoplastic solution and a lower Mn concentration in the symplastic solution than wild-type rice. OsYSL6 was constitutively expressed in both the shoots and roots, and the expression level was not affected by either deficiency or toxicity of various metals. Furthermore, the expression level increased with leaf age. Analysis with OsYSL6 promoter-green fluorescent protein transgenic rice revealed that OsYSL6 was expressed in all cells of both the roots and shoots. Heterogolous expression of OsYSL6 in yeast showed transport activity for the Mn-nicotianamine complex but not for the Mn-mugineic acid complex. Taken together, our results suggest that OsYSL6 is a Mn-nicotianamine transporter that is required for the detoxification of excess Mn in rice.
CD147‐targeting siRNA inhibits cell‐matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase
Authors: NISHIBABA Rie , HIGASHI Yuko , SU Juan , FURUKAWA Tatsuhiko , KAWAI Kazuhiro , KANEKURA Takuro
Published: October 2011

CD147/basigin, highly expressed on the surface of malignant tumor cells including malignant melanoma (MM) cells, plays a critical role in the invasiveness and metastasis of MM. Metastasis is an orchestrated process comprised of multiple steps including adhesion and invasion. Integrin, a major adhesion molecule, co‐localizes with CD147/basigin on the cell surface. Using the human MM cell line A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin is involved in adhesion in association with integrin. CD147/basigin was knocked‐down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell adhesion was evaluated by adhesion assay on matrix‐coated plates. The localization of integrin was inspected under a confocal microscope and the expression and phosphorylation of focal adhesion kinase (FAK), a downstream kinase of integrin, were examined by western blot analysis. Silencing of CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397. Integrin identified on the surface of parental cells was distributed in a speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in morphological changes from a round to a polygonal shape with pseudopodial protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their adhesiveness to collagen I and IV. Our results suggest that CD147/basigin regulates the adhesion of MM cells to extracellular matrices and of integrin β1 signaling via the phosphorylation of FAK.
Next‐generation sequencing and syntenic integration of flow‐sorted arms of wheat chromosome 4A exposes the chromosome structure and gene content
Authors: Hernandez Pilar , Martis Mihaela , Dorado Gabriel , Pfeifer Matthias , Gálvez Sergio , Schaaf Sebastian , Jouve Nicolás , Šimková Hana , Valárik Miroslav , Doležel Jaroslav , Mayer Klaus F.X.
Published: October 2011

Wheat is the third most important crop for human nutrition in the world. The availability of high‐resolution genetic and physical maps and ultimately a complete genome sequence holds great promise for breeding improved varieties to cope with increasing food demand under the conditions of changing global climate. However, the large size of the bread wheat (Triticum aestivum) genome (approximately 17 Gb/1C) and the triplication of genic sequence resulting from its hexaploid status have impeded genome sequencing of this important crop species. Here we describe the use of mitotic chromosome flow sorting to separately purify and then shotgun‐sequence a pair of telocentric chromosomes that together form chromosome 4A (856 Mb/1C) of wheat. The isolation of this much reduced template and the consequent avoidance of the problem of sequence duplication, in conjunction with synteny‐based comparisons with other grass genomes, have facilitated construction of an ordered gene map of chromosome 4A, embracing ≥85% of its total gene content, and have enabled precise localization of the various translocation and inversion breakpoints on chromosome 4A that differentiate it from its progenitor chromosome in the A genome diploid donor. The gene map of chromosome 4A, together with the emerging sequences of homoeologous wheat chromosome groups 4, 5 and 7, represent unique resources that will allow us to obtain new insights into the evolutionary dynamics between homoeologous chromosomes and syntenic chromosomal regions.
Health risks of using mothballs in Greater Accra, Ghana
Authors: Soghoian S. , Nyadedzor C. , Ed Nignpense B. , Clarke E. E. K. , Hoffman R. S.
Published: October 2011

Objective  Internal use of ‘camphor’ is a potential public health concern in Accra. We sought to identify the toxins being sold as mothballs in Greater Accra and use this information to help educate both clinicians and the public.

Methods  Mothballs are commonly sold by street and marketplace vendors in unmarked cling film‐wrapped packs. Fifteen small packs of mothballs were purchased from random vendors in three major markets and six roadside stands in Greater Accra. All samples were subjected to the float test; one sample was confirmed by gas chromatography/mass spectroscopy.

Results  All samples sank in tap water but floated in a saturated salt solution, consistent with naphthalene. The analysed sample was identified as naphthalene.

Conclusion  Naphthalene was most likely the primary ingredient in all the mothballs purchased for the study. Naphthalene is poorly soluble in water, and ‘camphor water’ is unlikely to cause harm. However, ideas about the efficacy of ‘camphor’ as a purification tool may lead to therapeutic misuse by analogy. A high prevalence of G6PD in the Ghanaian population may increase the risk of toxic haematologic effects from ingestion of mothballs. Mothballs known in Greater Accra as ‘camphor’ are likely to be predominantly naphthalene. A public awareness campaign about the health risks of mothball ingestion is planned.
Beyond cue reactivity: blunted brain responses to pleasant stimuli predict long‐term smoking abstinence
Authors: Versace Francesco , Lam Cho Y. , Engelmann Jeffrey M. , Robinson Jason D. , Minnix Jennifer A. , Brown Victoria L. , Cinciripini Paul M.
Published: October 2011

Identifying addicts with higher risk of relapse would provide the opportunity to implement individualized interventions and increase cessation success rates. Unfortunately, the ability to predict the long‐term success of drug cessation treatments continues to elude researchers. We tested whether brain responses to emotional and cigarette‐related pictures were predictive of the ability to abstain from smoking. Smokers interested in quitting (n = 180) participated in a smoking cessation clinical trial. Before the initiation of any treatment, we recorded event‐related potentials (ERPs) evoked by emotional (both pleasant and unpleasant), neutral, and cigarette‐related images. Cluster analysis was used to assign smokers to two groups based on the amplitude of the late positive potential (LPP) to the experimental stimuli. While both groups showed enhanced responses to cigarette‐related cues, one group (n = 81) also showed blunted brain responses to intrinsically pleasant stimuli. Smokers in the latter group were significantly less likely to be abstinent at 10, 12 and 24 weeks after their quit date. In conclusion, using ERPs, a direct measure of brain activity, we found that smokers with blunted brain responses to intrinsically pleasant stimuli had lower rates of long‐term smoking abstinence. This response offers a new biomarker for identifying smokers at higher risk of relapse and for testing the efficacy of new interventions aimed at normalizing brain reward systems' responses to intrinsically pleasant stimuli.
Poor impulse control predicts inelastic demand for nicotine but not alcohol in rats
Authors: Diergaarde Leontien , van Mourik Yvar , Pattij Tommy , Schoffelmeer Anton N. M. , De Vries Taco J.
Published: October 2011

Tobacco and alcohol dependence are characterized by continued use despite deleterious health, social and occupational consequences, implying that addicted individuals pay a high price for their use. In behavioral economic terms, such persistent consumption despite increased costs can be conceptualized as inelastic demand. Recent animal studies demonstrated that high‐impulsive individuals are more willing to work for nicotine or cocaine infusions than their low‐impulsive counterparts, indicating that this trait might be causally related to inelastic drug demand. By employing progressive ratio schedules of reinforcement combined with a behavioral economics approach of analysis, we determined whether trait impulsivity is associated with an insensitivity of nicotine or alcohol consumption to price increments. Rats were trained on a delayed discounting task, measuring impulsive choice. Hereafter, high‐ and low‐impulsive rats were selected and trained to nose poke for intravenous nicotine or oral alcohol. Upon stable self‐administration on a continuous reinforcement schedule, the price (i.e. response requirement) was increased. Demand curves, depicting the relationship between price and consumption, were produced using Hursh's exponential demand equation. Similar to human observations, nicotine and alcohol consumption in rats fitted this equation, thereby demonstrating the validity of our model. Moreover, high‐impulsive rats displayed inelastic nicotine demand, as their nicotine consumption was less sensitive to price increments as compared with that in low‐impulsive rats. Impulsive choice was not related to differences in alcohol demand elasticity. Our model seems well suited for studying nicotine and alcohol demand in rats and, as such, might contribute to our understanding of tobacco and alcohol dependence.
Involvement of hippocampal phosphatidylethanolamine‐binding protein in morphine dependence and withdrawal
Authors: Wei Qiu‐Hua , Wu Ning , Bian Jia‐Ming , Chen Ying , Su Rui‐Bin , Li Jin
Published: October 2011

Drug addiction is thought to result from an intractable and aberrant learning and memory in response to drug‐related stimulation, and cholinergic neurotransmission plays an important role in this process. Phosphatidylethanolamine‐binding protein (PEBP) is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP), an 11 amino acid peptide that enhances the production of choline acetyltransferase (ChAT) and assists in the development of cholinergic projections from the medial septal nuclei to the hippocampus. However, whether PEBP is involved in drug addiction remains unclear. In the present study, PEBP expression in the hippocampus, as detected by proteomics analysis, was found to be dramatically up‐regulated after rats received chronic morphine treatment. Western blotting analysis revealed a specific up‐regulation of PEBP expression in the hippocampus but not in any other brain regions assessed. A down‐regulation of hippocampal PEBP levels induced by antisense oligodeoxynucleotides resulted in aggravated morphine dependence. Together, these findings indicate that PEBP is involved in morphine dependence. Moreover, the time course of PEBP expression changes and ChAT activity was investigated during chronic morphine treatment and withdrawal. The results showed that the hippocampal PEBP levels were up‐regulated during chronic morphine treatment and returned to the baseline 3 days after withdrawal, after which PEBP levels were persistently up‐regulated for 28 days after withdrawal. The changes in hippocampal ChAT activity followed a pattern that was similar to that of the PEBP levels. Taken together, these results suggest that hippocampal PEBP is involved in morphine dependence and withdrawal, perhaps through modulating cholinergic transmission in the hippocampus.