bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of sensory afferents activation and visceral pain by a brominated algal diterpene
Authors: Chatter R. , Cenac N. , Roussis V. , Kharrat R. , Vergnolle N. 
Published: June 2012

AbstractBackground  In the search of new therapeutic options for the treatment of pain, isolation, and testing of secondary metabolites from plant extracts has raised significant attention. We have investigated the effects of the brominated diterpene O1115‐ cyclo‐14‐bromo‐14,15‐dihydrorogiol‐3,11‐diol (that we have named VLC5), extracted from the Mediterranean red algae Laurencia glandulifera.Methods  The pure extract was tested on primary afferent calcium signals induced by high concentration of KCl, transcient receptor potential vanilloid (TRPV)1 (capsaicin) or TRPV4 agonists, histamine, or protease‐activated receptor‐2 (PAR2) agonist. It was also tested in mice in a model of mustard oil‐induced colonic hypersensitivity.Key Results  VLC5 was inhibited PAR2 agonist or histamine‐induced calcium mobilization in mouse primary afferents, but did not modify calcium signals induced by high concentrations of KCl, TRPV1 or TRPV4 agonists. The effect of VLC5 on histamine‐induced calcium signal in primary afferent was inhibited by pertussis toxin pretreatment and was dependent on the activation of mu‐ or kappa‐opioid receptor agonists, as it was inhibited by selective antagonists of those two receptors, but not by selective antagonist of the delta‐opioid receptor. Intraperitoneal treatment of mice with VLC5 (10 mg kg−1) significantly reduced visceral pain behaviors induced by the intracolonic administration of mustard oil, in an opioid receptor‐dependent manner.Conclusions & Inferences  We have demonstrated significant analgesic properties for the algal metabolite VLC5, which is able to signal directly to primary afferents, through a mechanism dependent on the activation of opioid receptors. This identifies a new natural compound capable of activating peripheral opioidergic systems, exerting analgesic properties.
Imatinib mesylate alleviates diarrhea in a mouse model of intestinal allergy
Authors: Vaali K. , Lappalainen J. , Lin A. H. , Mäyränpää M. I. , Kovanen P. T , Berstad A. , Eklund K. K. 
Published: June 2012

AbstractBackground  When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice develop allergen‐induced diarrhea. As mast cells play important roles in diarrhea, we studied whether allergic diarrhea could be alleviated with imatinib mesylate.Methods  Balb/c mice were sensitized and challenged with ovalbumin and treated orally with imatinib. Cytokine mRNA expressions were determined with quantitative RT‐PCR and numbers of small intestinal mast cells determined by staining for chloroacetate esterase and mucosal mast cell protease‐1. Immunofluorescence staining was used to assess the intestinal CCL1 expression.Key Results  Ovalbumin‐sensitized and challenged Balb/c mice developed diarrhea, which was associated with increased number of mast cells and expression of interleukin (IL)‐4 and ‐13, and chemokines CCL1 and CCL17 in the small intestine. Treatment with imatinib reduced the incidence of diarrhea, inhibited the development of mastocytosis and jejunal mRNA expression of IL‐13, CCL1, CCL17 and CCL22. Mast cell‐deficient W/W‐V mice, and surprisingly, also their mast cell‐competent control (+/+) littermates failed to develop diarrhea as a response to ovalbumin. This strain‐dependent difference was associated with the inability of +/+ and W/W‐V mice to increase the number of intestinal mast cells and expression of IL‐4, IL‐13, CCL1 and CCL17 after ovalbumin challenge.Conclusions & Inferences  Development of allergic diarrhea is associated with the ability of mice to develop intestinal mastocytosis. Imatinib inhibited the development of intestinal mastocytosis, reduced the incidence of diarrhea, and reduced the expression of IL‐13, CCL1, and CCL17. Targeting intestinal mast cells could be a feasible approach to treat allergic diarrhea.
Breeding Strategies for Adaptation of Pearl Millet and Sorghum to Climate Variability and Change in West Africa
Authors: Haussmann B. I. G. , Fred Rattunde H. , Weltzien‐Rattunde E. , Traoré P. S. C. , vom Brocke K. , Parzies H. K. 
Published: June 2012

AbstractSemi‐arid and subhumid West Africa is characterized by high inter‐annual rainfall variability, with variable onset of the rainy season, somewhat more predictable endings, and drought or excess water occurrence at any time during the growing season. Climate change is predicted to increase this variability. This article summarizes options for plant breeders to enhance the adaptation of pearl millet (Pennisetum glaucum [L.] R. Br.) and sorghum (Sorghum bicolor [L.] Moench) to climate variability in West Africa. Developing variety types with high degrees of heterozygosity and genetic heterogeneity for adaptation traits helps achieving better individual and population buffering capacity. Traits that potentially enhance adaptive phenotypic plasticity or yield stability in variable climates include photoperiod‐sensitive flowering, plastic tillering, flooding tolerance, seedling heat tolerance and phosphorus efficiency. Farmer‐participatory dynamic gene pool management using broad‐based populations and diverse selection environments is useful to develop new diverse germplasm adapted to specific production constraints including climate variability. For sustainable productivity increase, improved cultivars should respond to farmer‐adoptable soil fertility management and water harvesting techniques. Larger‐scale, on‐farm participatory testing will enable assessments of varietal performance under evolving climatic variability, provide perspective on needs and opportunities and enhance adoption. Strengthening seed systems will be required to achieve sustainable impacts.
The early contribution of cerebrovascular factors to the pathogenesis of Alzheimer’s disease
Authors: Pimentel‐Coelho Pedro M. , Rivest Serge 
Published: June 2012

AbstractAlzheimer’s disease (AD) and cerebrovascular disorders are the leading causes of dementia in our ageing population. Given that the progression of neuropathological changes in the brains of AD patients initiates several years, and even decades, before the diagnosis of dementia, a great effort has been made to identify potentially modifiable factors that contribute to the pathogenesis of sporadic late‐onset AD. Among these factors, cerebrovascular disease and microvascular alterations seem to bilaterally interact with the underlying AD pathology, affecting the progression of cognitive deficits. In addition, cerebrovascular dysfunction has emerged as an early event in AD, encompassing changes in virtually all cell types of the neurovascular unit, including bone marrow‐derived cells, astrocytes, pericytes, vascular smooth muscle cells and endothelial cells. In this review, we discuss recent studies implicating cerebrovascular factors in the pathogenesis of AD. We also discuss how the impairment of mechanisms of brain regeneration, such as neurogenesis and angiogenesis, might be related to the vascular dysfunction. Finally, we briefly discuss several therapeutic options targeting the vascular system, which might represent an interesting strategy for preventing or delaying the onset of dementia in AD.
Neonatal seizures: controversies and challenges in translating new therapies from the lab to the isolette
Authors: Chapman Kevin E. , Raol Yogendra H. , Brooks‐Kayal Amy 
Published: June 2012

AbstractNeonatal seizures have unique properties that have proved challenging for both clinicians and basic science researchers. Clinical therapies aimed at neonatal seizures have proven only partially effective and new therapies are slow to develop. This article will discuss neonatal seizures within the framework of the barriers that exist to the development of new therapies, and the challenges inherent in bringing new therapies from the bench to the bedside. With the European Union and USA creating national collaborative project infrastructure, improved collaborative resources should advance clinical research on urgently needed new therapies for this disorder.
Extrusion of misfolded and aggregated proteins – a protective strategy of aging neurons?
Authors: Doehner Jana , Genoud Christel , Imhof Claudine , Krstic Dimitrije , Knuesel Irene 
Published: June 2012

AbstractCellular senescence is the consequence of repetitive exposures to oxidative stress, perturbed energy homeostasis, accumulation of damaged proteins and lesions in their nucleic acids. Whereas mitotic cells are equipped with efficient cell replacement strategies; postmitotic neurons have ‐ with a few exceptions ‐ no mechanism to substitute dysfunctional cells within a complex neuronal network. Here we propose a potential strategy by which aging neurons contend against abnormal accumulation of damaged/misfolded proteins. The suggested mechanism involves the formation of ‘budding‐like’ extrusions and their subsequent clearance by glia. This hypothesis emerged from our previous investigations of the aged hippocampus revealing layer‐specific accumulations of Reelin, a glycoprotein with fundamental roles during brain development and adult synaptic plasticity. We showed that Reelin deposits constitute a conserved neuropathological feature of aging, which is significantly accelerated in adult wild‐type mice prenatally exposed to a viral‐like infection. Here, we employed two‐ and three‐dimensional immunoelectron microscopy to elucidate their morphological properties, localization and origin in immune challenged vs. control mice. In controls, Reelin‐positive deposits were dispersed in the neuropil, some being engulfed by glia. In immune challenged mice, however, significantly more Reelin‐immunoreactive deposits were associated with neuritic swellings containing mitochondria, vacuoles and cellular debris, pointing to their intracellular origin and suggesting that ‘budding‐like’ neuronal extrusions of misfolded proteins and glial clearance may represent a protective strategy to counteract aging‐associated impairments in proteosomal/lysosomal degradation. Neurons exposed to chronic neuroinflammation with increased levels of misfolded/damaged proteins, however, may fail to combat intraneuronal protein accumulations, a process probably underlying neuronal dysfunction and degeneration during aging.
Cholinergic responses in GABAergic and non‐GABAergic neurons in the intermediate gray layer of mouse superior colliculus
Authors: Sooksawate Thongchai , Yanagawa Yuchio , Isa Tadashi 
Published: June 2012

AbstractNeurons in the intermediate gray layer (SGI) of the mammalian superior colliculus (SC) receive dense cholinergic innervations from the brainstem parabrachial region. Such cholinergic inputs may influence execution of orienting behaviors. To obtain deeper insights into how the cholinergic inputs modulate the SC local circuits, we analysed the cholinergic responses in identified γ‐aminobutyric acid (GABA)ergic and non‐GABAergic neurons using SC slices obtained from GAD67‐GFP knock‐in mice. The responses of SGI neurons to cholinergic agonists were various combinations of fast inward currents mediated mainly via α4β2 and partly by α7 nicotinic receptors (nIN), slow inward currents caused by activation of M1 plus M3 muscarinic receptors (mIN), and slow outward currents caused by activation of M2 muscarinic receptors (mOUT). The most common cholinergic responses in non‐GABAergic neurons was nIN + mIN + mOUT (38/68), followed by nIN + mIN (16/68), nIN + mOUT (11/68), nIN only (2/68), and no response (1/68). On the other hand, the major response pattern in GABAergic neurons was either nIN only (26/54) or nIN + mIN (21/54), followed by nIN + mOUT (4/54), mOUT only (2/54), and no response (1/54). Thus, major effects of cholinergic inputs to both SGI GABAergic and non‐GABAergic neurons are excitatory, but the response patterns in these two types of SGI neurons are different. Thus, actions of the cholinergic inputs to non‐GABAergic and GABAergic SGI neurons are not simple push–pull mechanisms, like excitation vs inhibition, but might cooperate to balance the level of excitation and inhibition for setting the state of the response property of the local circuit.
Medical literature searches: a comparison of PubMed and Google Scholar
Authors: Nourbakhsh Eva , Nugent Rebecca , Wang Helen , Cevik Cihan , Nugent Kenneth 
Published: June 2012

AbstractBackgroundMedical literature searches provide critical information for clinicians. However, the best strategy for identifying relevant high‐quality literature is unknown.ObjectivesWe compared search results using PubMed and Google Scholar on four clinical questions and analysed these results with respect to article relevance and quality.MethodsAbstracts from the first 20 citations for each search were classified into three relevance categories. We used the weighted kappa statistic to analyse reviewer agreement and nonparametric rank tests to compare the number of citations for each article and the corresponding journals' impact factors.ResultsReviewers ranked 67.6% of PubMed articles and 80% of Google Scholar articles as at least possibly relevant (P = 0.116) with high agreement (all kappa P‐values < 0.01). Google Scholar articles had a higher median number of citations (34 vs. 1.5, P < 0.0001) and came from higher impact factor journals (5.17 vs. 3.55, P = 0.036).Conclusions
PubMed searches and Google Scholar searches often identify different articles. In this study, Google Scholar articles were more likely to be classified as relevant, had higher numbers of citations and were published in higher impact factor journals. The identification of frequently cited articles using Google Scholar for searches probably has value for initial literature searches.
Cyanobacterial diversity and activity in modern conical microbialites
Authors: Bosak T. , Liang B. , Wu T.‐D. , Templer S. P. , Evans A. , Vali H. , Guerquin‐Kern J.‐L. , Klepac‐Ceraj V. , Sim M. S. , Mui J. 
Published: June 2012

AbstractModern conical microbialites are similar to some ancient conical stromatolites, but growth, behavior and diversity of cyanobacteria in modern conical microbialites remain poorly characterized. Here, we analyze the diversity of cyanobacterial 16S rRNA gene sequences in conical microbialites from 14 ponds fed by four thermal sources in Yellowstone National Park and compare cyanobacterial activity in the tips of cones and in the surrounding topographic lows (mats), respectively, by high‐resolution mapping of labeled carbon. Cones and adjacent mats contain similar 16S rRNA gene sequences from genetically distinct clusters of filamentous, non‐heterocystous cyanobacteria from Subsection III and unicellular cyanobacteria from Subsection I. These sequences vary among different ponds and between two sampling years, suggesting that coniform mats through time and space contain a number of cyanobacteria capable of vertical aggregation, filamentous cyanobacteria incapable of initiating cone formation and unicellular cyanobacteria. Unicellular cyanobacteria are more diverse in topographic lows, where some of these organisms respond to nutrient pulses more rapidly than thin filamentous cyanobacteria. The densest active cyanobacteria are found below the upper 50 μm of the cone tip, whereas cyanobacterial cells in mats are less dense, and are more commonly degraded or encrusted by silica. These spatial differences in cellular activity and density within macroscopic coniform mats imply a strong role for diffusion limitation in the development and the persistence of the conical shape. Similar mechanisms may have controlled the growth, morphology and persistence of small coniform stromatolites in shallow, quiet environments throughout geologic history.
Health‐related quality of life and ambulation in children with myelomeningocele in a Swedish population
Authors: Bartonek Åsa , Saraste Helena , Danielsson Aina 
Published: June 2012

AbstractAim:  The aim was to study health‐related quality of life (HRQL) in Swedish children with myelomeningocele (MMC) with respect to ambulatory function.Methods:  A physical examination of the lower limbs was performed, and occurrence of orthopaedic deformities and shunted hydrocephalus was documented. A questionnaire on general health‐related quality of life Child Health Questionnaire‐50 Parent Form (CHQ‐PF50) was answered by the parents of 62 children, mean age 12.5 (3.1) years.Results:  The non‐ambulatory children had significantly more frequent spasticity in the lower limbs, more often joint contractures as well as hip dislocation or spine deformity compared with ambulating patients. Thirty‐two per cent of the ambulators managed without wheelchair use. All non‐ambulators were wheelchair users, of which 60% used both a manual and a powered wheelchair. The children with MMC perceived significantly lower HRQL of all subscales of CHQ compared with the healthy control group. Physical function was significantly higher in ambulatory patients, PF = 57.1 compared with 22.2 for non‐ambulatory patients.Conclusion:  A Swedish population of children with MMC perceived lower HRQL compared with healthy children, but similar HRQL irrespective of ambulatory function except for the physical domain was reported.
Erythroid differentiation‐associated gene interacts with NPM1 (nucleophosmin/B23) and increases its protein stability, resisting cell apoptosis
Authors: Zhang Mei‐Jiang , Ding Ya‐Li , Xu Cheng‐Wang , Yang Yang , Lian Wen‐Xi , Zhan Yi‐Qun , Li Wei , Xu Wang‐Xiang , Yu Miao , Ge Chang‐Hui , Ning Hong‐Mei , Li Chang‐Yan , Yang Xiao‐Ming 
Published: June 2012

Erythroid differentiation‐associated gene (EDAG) is a haematopoietic tissue‐specific transcription regulator that plays a key role in maintaining the homeostasis of haematopoietic lineage commitment. In acute myeloid leukaemia (AML) patients, the high expression level of EDAG is associated with poor prognosis. NPM1 (nucleophosmin/B23), a ubiquitous nucleolar phosphoprotein, comprises a multifunctional protein that is involved in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, cell growth and transformation. Various studies have implicated NPM1 overexpression in promoting tumour cell proliferation, blocking the differentiation of leukaemia cells and resisting apoptosis. In the present study, using co‐immunoprecipitation, we characterized EDAG as a physiological binding partner of NPM1; The N‐terminal (amino acids 1–124) region of EDAG interacts with the N‐terminal (amino acids 118–187) of NPM1. Under cycloheximide treatment, the stability of NPM1 protein was enhanced by EDAG overexpression, whereas knockdown of EDAG by lentivirus‐mediated small interfering RNA resulted in an increased degradation rate of NPM1 in K562 cells. During 4β‐phorbol l2‐myristate 13‐acetate‐induced K562 megakaryocytic differentiation, overexpression of EDAG prevented the down‐regulation of NPM1 proteins, whereas knockdown of EDAG accelerated the down‐regulation of NPM1. EDAG deletion mutant lacking the binding domain with NPM1 lost the ability to stabilize NPM1 protein. Furthermore, knockdown of EDAG in K562 cells led to increased cell apoptosis induced by imatinib, and re‐expression of NPM1 attenuated the increased apoptosis. These results suggest that EDAG enhances the protein stability of NPM1 via binding to NPM1, which plays a critical role in the anti‐apoptosis of leukaemia cells.Structured digital abstract
NPM1 physically interacts with EDAG by anti bait coimmunoprecipitation (View interaction)
EDAG physically interacts with HSPA1A, UBTF, SP100, NPM1, HNRPA3, MCM3 ,UBE1, FBL, ZnF20, ZnF25 and MNDA by anti bait coimmunoprecipitation (View interaction)
EDAG physically interacts with NPM1 by anti tag coimmunoprecipitation (View Interaction: 1, 2, 3)
EDAG and NPM1 colocalize by fluorescence microscopy (View Interaction: 1, 2)
Abdominal Aortic Calcification is an Independent Predictor of Cardiovascular Events in Peritoneal Dialysis Patients
Authors: Martino Francesca , Di Loreto Pierluigi , Giacomini Dario , Kaushik Manish , Rodighiero Maria Pia , Crepaldi Carlo , Ronco Claudio 
Published: June 2012

AbstractAbdominal aortic calcification (AAC) is reported as a predictor for cardiovascular events in general population and in hemodialysis patients. At present, there are no AAC data in peritoneal dialysis. The purpose of this study was to evaluate the prognostic role of AAC score on cardiovascular events in peritoneal dialysis patients. Seventy‐four peritoneal dialysis patients were enrolled. AAC was measured on baseline lateral abdomen radiographs by the semi‐quantitative method as described by Kauppila. The other cardiovascular risk factors were obtained from patient history and blood examination. The Kaplan–Meier method was used to evaluate freedom from cardiovascular events, and differences were assessed with the log‐rank statistic. Multivariate Cox regression models addressed time to cardiovascular events. The median period of follow‐up was 30.5 months (IQR 19.4–32.7). During follow‐up, there were 29 cardiovascular events (39.2%). In univariable analysis, patient's age (HR = 1.050; P = 0.001), urine output (HR = 0.999; P = 0.02), and AAC stratified by tertiles (overall P‐value < 0.001) were significantly associated with cardiovascular events. In multivariable regression analysis, AAC score stratified by tertiles was the only independent predictor for cardiovascular events (overall P‐value <0.001). To our knowledge, we have shown for the first time that AAC score is an independent predictor of cardiovascular events in peritoneal dialysis patients. Risk stratification by assessment of AAC score may provide important information for the management of cardiovascular disease in peritoneal dialysis patients without any additional expense, because these patients have several abdominal X‐ray scans to evaluate the catheter position.
CHANGES IN ACID AND HEAT RESISTANCE OF SALMONELLA NEWPORT AND SALMONELLA SAINTPAUL STORED IN MANGO AND PINEAPPLE JUICES
Authors: YANG YISHAN , TEO JIA HAN , BANG WOO‐SUK , YUK HYUN‐GYUN 
Published: June 2012

ABSTRACTThe aim of this study was to investigate survival of Salmonella Newport and Salmonella Saintpaul in simulated gastric fluid (SGF) at pH 1.9 or at 56C after storage in mango or pineapple juice at 4 or 24C for 24 h. In SGF, only Salmonella Saintpaul adapted to mango juice at 4C significantly (P < 0.05) enhanced its acid resistance with D value of 3.88 min, whereas both serovars stored in mango juice at 24C had significantly lower D values with 0.88 and 0.72 min, respectively. The D56C values of both serovars adapted to juices significantly decreased compared with nonadapted cells, except for Salmonella Newport stored in pineapple juice at 24C. Overall, two Salmonella serovars tested in this study did not show the enhanced acid or heat resistance after storage in these two tropical fruit juices, indicating that introduction of Salmonella Newport and Salmonella Saintpaul to mango and pineapple juices is unlikely to enhance their survival during gastric transit or thermal processing.PRACTICAL APPLICATIONSSalmonella spp., one of the leading causative agents of gastroenteritis, are a major public health concern in the world. It has been reported that Salmonella spp. can survive in unpasteurized orange juice or apple cider and become more resistant to subsequent exposure to acid or heat conditions. However, there is limited information in the literature on the effect of survival of Salmonella spp. in tropical fruit juices on their acid and heat resistance. This research was conducted to investigate the survivability of Salmonella Newport and Salmonella Saintpaul in simulated gastric fluid at pH 1.9 or at 56C after adaptation in mango or pineapple juice. The results of this study would enrich our understanding on the stress response of Salmonella spp. in these juices, as well as provide guidance to developing intervention technology to eliminate Salmonella Newport and Salmonella Saintpaul in mango and pineapple juices.