bluuebunny/crossref_metadata_2025_split huggingface dataset:
New ways to separate Graft‐versus‐Host Disease and Graft‐versus‐Tumour effects after allogeneic haematopoietic stem cell transplantation
Authors: Kotsiou Eleni , Davies Jeff K. 
Published: November 2012

SummaryA major challenge to transplant immunologists and physicians remains the separation of harmful graft‐versus‐host disease (GvHD) and beneficial graft‐versus‐tumour (GvT) effects after allogeneic haematopoietic stem cell transplantation. Recent advances in our understanding of the allogeneic immune response provide potential new opportunities to achieve this goal. Three potential new approaches that capitalize on this new knowledge are considered in depth; the manipulation of organ‐specific cytokines and other pro‐inflammatory signals, the selective manipulation of donor effector T cell migration, and the development of cell‐mediated immunosuppressive strategies using donor‐derived regulatory T cells. These new approaches could provide strategies for local control of allogeneic immune responses, a new paradigm to separate GvHD and GvT effects. Although these strategies are currently in their infancy and have challenges to successful translation to clinical practice, all have exciting potential for the future.
Deficiency in Mural Vascular Cells Coincides with Blood–Brain Barrier Disruption in Alzheimer's Disease
Authors: Sengillo Jesse D. , Winkler Ethan A. , Walker Corey T. , Sullivan John S. , Johnson Mahlon , Zlokovic Berislav V. 
Published: November 2012

AbstractNeurovascular dysfunction contributes to Alzheimer's disease (AD). Cerebrovascular abnormalities and blood–brain barrier (BBB) damage have been shown in AD. The BBB dysfunction can lead to leakage of potentially neurotoxic plasma components in brain that may contribute to neuronal injury. Pericytes are integral in maintaining the BBB integrity. Pericyte‐deficient mice develop a chronic BBB damage preceding neuronal injury. Moreover, loss of pericytes was associated with BBB breakdown in patients with amyotrophic lateral sclerosis. Here, we demonstrate a decrease in mural vascular cells in AD, and show that pericyte number and coverage in the cortex and hippocampus of AD subjects compared with neurologically intact controls are reduced by 59% and 60% (P < 0.01), and 32% and 33% (P < 0.01), respectively. An increase in extravascular immunoglobulin G (IgG) and fibrin deposition correlated with reductions in pericyte coverage in AD cases compared with controls; the Pearson's correlation coefficient r for the magnitude of BBB breakdown to IgG and fibrin vs. reduction in pericyte coverage was −0.96 (P < 0.01) and −0.81 (P < 0.01) in the cortex, respectively, and −0.86 (P < 0.01) and −0.98 (P < 0.01) in the hippocampus, respectively. Thus, deficiency in mural vascular cells may contribute to disrupted vascular barrier properties and resultant neuronal dysfunction during AD pathogenesis.
Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo
Authors: Ford SJ , Obeidy P , Lovejoy DB , Bedford M , Nichols L , Chadwick C , Tucker O , Lui GYL , Kalinowski DS , Jansson PJ , Iqbal TH , Alderson D , Richardson DR , Tselepis C 
Published: November 2012

Background and PurposeGrowing evidence implicates iron in the aetiology of gastrointestinal cancer. Furthermore, studies demonstrate that iron chelators possess potent anti‐tumour activity, although whether iron chelators show activity against oesophageal cancer is not known.Experimental ApproachThe effect of the iron chelators, deferoxamine (DFO) and deferasirox, on cellular iron metabolism, viability and proliferation was assessed in two oesophageal adenocarcinoma cell lines, OE33 and OE19, and the squamous oesophageal cell line, OE21. A murine xenograft model was employed to assess the effect of deferasirox on oesophageal tumour burden. The ability of chelators to overcome chemoresistance and to enhance the efficacy of standard chemotherapeutic agents (cisplatin, fluorouracil and epirubicin) was also assessed.Key ResultsDeferasirox and DFO effectively inhibited cellular iron acquisition and promoted intracellular iron mobilization. The resulting reduction in cellular iron levels was reflected by increased transferrin receptor 1 expression and reduced cellular viability and proliferation. Treating oesophageal tumour cell lines with an iron chelator in addition to a standard chemotherapeutic agent resulted in a reduction in cellular viability and proliferation compared with the chemotherapeutic agent alone. Both DFO and deferasirox were able to overcome cisplatin resistance. Furthermore, in human xenograft models, deferasirox was able to significantly suppress tumour growth, which was associated with decreased tumour iron levels.Conclusions and ImplicationsThe clinically established iron chelators, DFO and deferasirox, effectively deplete iron from oesophageal tumour cells, resulting in growth suppression. These data provide a platform for assessing the utility of these chelators in the treatment of oesophageal cancer patients.Linked ArticleThis article is commented on by Keeler and Brookes, pp. 1313–1315 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12093
Physical Activity and Cognitive Control: Implications for Drug Abuse
Authors: Hillman Charles H. , Drobes David J. 
Published: November 2012

AbstractThis article focuses on a growing body of research that has studied the beneficial relation between chronic participation in—and acute responses to—physical activity and brain health, cognition, and scholastic achievement. Specifically, it highlights the relevant behavioral and neuroimaging findings of this beneficial relation in children and adults, providing evidence for the influence of chronic and acute physical activity on brain structure and function that underlie cognition and scholastic achievement. In addition, the article discusses the implications for the role of physical activity on drug use, as well as its prevention and treatment, and makes recommendations for further research in this area.
What Developmental Science Can Contribute to a Transdisciplinary Understanding of Childhood Obesity: An Interpersonal and Intrapersonal Risk Model
Authors: Harrist Amanda W. , Topham Glade L. , Hubbs‐Tait Laura , Page Melanie C. , Kennedy Tay S. , Shriver Lenka H. 
Published: November 2012

AbstractMore complex models than those currently available are needed to guide research about childhood obesity. This article presents an interpersonal and intrapersonal risk model of child obesity, a transdisciplinary model of psychosocial risk factors that is based on work in developmental, family, and nutritional sciences. Two interpersonal realms of child development identified as being potentially significant for understanding the development and maintenance of overweight include the child's family and peer contexts. Child intrapersonal variables proposed as mediators between these contexts and weight outcomes include poor self‐regulation and self‐awareness, negative affect, and emotional or external eating. The article encourages developmental scientists to add their expertise to the study of childhood obesity by using models such as the one outlined here for the generation and testing of hypotheses so that future intervention efforts may be improved.
Efficacy of azithromycin in preventing lethal graft-versus-host disease
Authors: Iwamoto S , Azuma E , Kumamoto T , Hirayama M , Yoshida T , Ito M , Amano K , Ido M , Komada Y 
Published: November 2012

SummaryAcute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (BMT) is initiated by donor T lymphocytes that recognize histocompatibility antigens presented by recipient dendritic cells (DCs). Current approaches to reduce GVHD are focused on suppressing donor T lymphocyte responses to alloantigens. However, these strategies may be inadequate in the setting of allogeneic transplants (particularly histoincompatible transplants), may increase the risk of tumour relapse and are associated with high rates of opportunistic infections. We hypothesized that inhibition of recipient DCs might suppress GVHD. We recently demonstrated in vitro that azithromycin, a macrolide antibiotic, also acts as a nuclear factor (NF)-κB inhibitor of murine DCs and inhibits their maturation and functions, including allogeneic responses. We investigated whether azithromycin could prevent alloreactions in a murine histoincompatibility model. Oral administration of azithromycin to recipient mice for 5 days during major-histoincompatible BMT suppressed lethal GVHD significantly, whereas ex-vivo lymphocyte function was not affected by the drug. These data suggest that azithromycin has potential as a novel prophylactic drug for lethal GVHD.
Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice
Authors: Kärner J , Meager A , Laan M , Maslovskaja J , Pihlap M , Remm A , Juronen E , Wolff A S B , Husebye E S , Podkrajšek K T , Bratanic N , Battelino T , Willcox N , Peterson P , Kisand K 
Published: November 2012

Summary
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a recessive disorder resulting from mutations in the autoimmune regulator (AIRE). The patients' autoantibodies recognize not only multiple organ-specific targets, but also many type I interferons (IFNs) and most T helper type 17 (Th17) cell-associated cytokines, whose biological actions they neutralize in vitro. These anti-cytokine autoantibodies are highly disease-specific: otherwise, they have been found only in patients with thymomas, tumours of thymic epithelial cells that fail to express AIRE. Moreover, autoantibodies against Th17 cell-associated cytokines correlate with chronic mucocutaneous candidiasis in both syndromes. Here, we demonstrate that the immunoglobulin (Ig)Gs but not the IgAs in APECED sera are responsible for neutralizing IFN-ω, IFN-α2a, interleukin (IL)-17A and IL-22. Their dominant subclasses proved to be IgG1 and, surprisingly, IgG4 without IgE, possibly implicating regulatory T cell responses and/or epithelia in their initiation in these AIRE-deficiency states. The epitopes on IL-22 and IFN-α2a appeared mainly conformational. We also found mainly IgG1 neutralizing autoantibodies to IL-17A in aged AIRE-deficient BALB/c mice – the first report of any target shared by these human and murine AIRE-deficiency states. We conclude that autoimmunization against cytokines in AIRE deficiency is not simply a mere side effect of chronic mucosal Candida infection, but appears to be related more closely to disease initiation.
Phylogenetic analyses of Tolpis Adans. (Asteraceae) reveal patterns of adaptive radiation, multiple colonization and interspecific hybridization
Authors: Gruenstaeudl Michael , Santos‐Guerra Arnoldo , Jansen Robert K. 
Published: November 2012

AbstractThe plant genus Tolpis (Asteraceae) has been the subject of several investigations on the evolution of oceanic island plants. Its insular species were utilized in studies of artificial hybrid fertility, testing the validity of Baker’s law, the application of DNA barcodes, and the phylogenetic utility of inter‐simple sequence repeat markers. Despite this considerable interest in Tolpis, little is known about its phylogenetic history. Past investigations were unable to resolve most of the interspecific relationships, especially within the Canary Islands, where the genus is particularly diverse. Incomplete taxon sampling, the use of ambiguous outgroups and the limited utility of slowly evolving chloroplast DNA markers precluded detailed reconstructions. The present investigation presents a comprehensive molecular phylogeny of Tolpis. By utilizing highly variable nuclear DNA markers and a comprehensive taxon set, we have resolved the majority of interspecific relationships in the genus. Evaluations of competing tree topologies and ancestral area reconstructions complemented the analyses. Our results highlight the presence of three dominant mechanisms of island plant evolution—island colonization, adaptive radiation and interspecific hybridization—in Tolpis: (i) the extant distribution of the genus is the result of two independent colonization pathways, (ii) Tolpis has colonized at least one archipelago multiple times, (iii) the present insular diversity is the product of adaptive radiation, (iv) potential hybridization was detected between species now inhabiting different islands and archipelagoes, indicating sympatric historical distributions, and (v) several undescribed species await taxonomic recognition.
Neuronal responses to face‐like stimuli in the monkey pulvinar
Authors: Nguyen Minh Nui , Hori Etsuro , Matsumoto Jumpei , Tran Anh Hai , Ono Taketoshi , Nishijo Hisao 
Published: November 2012

AbstractThe pulvinar nuclei appear to function as the subcortical visual pathway that bypasses the striate cortex, rapidly processing coarse facial information. We investigated responses from monkey pulvinar neurons during a delayed non‐matching‐to‐sample task, in which monkeys were required to discriminate five categories of visual stimuli [photos of faces with different gaze directions, line drawings of faces, face‐like patterns (three dark blobs on a bright oval), eye‐like patterns and simple geometric patterns]. Of 401 neurons recorded, 165 neurons responded differentially to the visual stimuli. These visual responses were suppressed by scrambling the images. Although these neurons exhibited a broad response latency distribution, face‐like patterns elicited responses with the shortest latencies (approximately 50 ms). Multidimensional scaling analysis indicated that the pulvinar neurons could specifically encode face‐like patterns during the first 50‐ms period after stimulus onset and classify the stimuli into one of the five different categories during the next 50‐ms period. The amount of stimulus information conveyed by the pulvinar neurons and the number of stimulus‐differentiating neurons were consistently higher during the second 50‐ms period than during the first 50‐ms period. These results suggest that responsiveness to face‐like patterns during the first 50‐ms period might be attributed to ascending inputs from the superior colliculus or the retina, while responsiveness to the five different stimulus categories during the second 50‐ms period might be mediated by descending inputs from cortical regions. These findings provide neurophysiological evidence for pulvinar involvement in social cognition and, specifically, rapid coarse facial information processing.
Antisaccades as decisions: LATER model predicts latency distributions and error responses
Authors: Noorani I. , Carpenter R. H. S. 
Published: November 2012

AbstractAntisaccades are widely used in the study of voluntary behavioural control: a subject told to look in the opposite direction to a stimulus must suppress the automatic response of looking towards it, leading to delays and errors that are commonly believed to be generated by competing decision processes. However, currently we lack a precise model of the details of antisaccade behaviour, or indeed detailed quantitative data in the form of full reaction time distributions by which any such model could be evaluated. We measured subjects' antisaccade latency distributions and error rates, and found that we could account precisely for both distributions and errors with a model having three competing LATER processes racing to threshold. In an even more stringent test, we manipulated subjects' expectation of the stimulus, leading to large changes in behaviour that were nevertheless still accurately predicted. The antisaccade task is widely used in the laboratory and clinic because of the relative complexity and vulnerability of the underlying decision mechanisms: our model, grounded in detailed quantitative data, is a robust way of conceptualizing these processes.
Regulation of acetylcholinesterase activity by nitric oxide in rat neuromuscular junction via N‐methyl‐d‐aspartate receptor activation
Authors: Petrov Konstantin A. , Malomouzh Artem I. , Kovyazina Irina V. , Krejci Eric , Nikitashina Alexandra D. , Proskurina Svetlana E. , Zobov Vladimir V. , Nikolsky Evgeny E. 
Published: November 2012

AbstractAcetylcholinesterase (AChE) is an enzyme that hydrolyses the neurotransmitter acetylcholine, thereby limiting spillover and duration of action. This study demonstrates the existence of an endogenous mechanism for the regulation of synaptic AChE activity. At the rat extensor digitorum longus neuromuscular junction, activation of N‐methyl‐d‐aspartate (NMDA) receptors by combined application of glutamate and glycine led to enhancement of nitric oxide (NO) production, resulting in partial AChE inhibition. Partial AChE inhibition was measured using increases in miniature endplate current amplitude. AChE inhibition by paraoxon, inactivation of NO synthase by Nω‐nitro‐l‐arginine methyl ester, and NMDA receptor blockade by dl‐2‐amino‐5‐phosphopentanoic acid prevented the increase in miniature endplate current amplitude caused by amino acids. High‐frequency (10 Hz) motor nerve stimulation in a glycine‐containing bathing solution also resulted in an increase in the amplitude of miniature endplate currents recorded during the interstimulus intervals. Pretreatment with an NO synthase inhibitor and NMDA receptor blockade fully eliminated this effect. This suggests that endogenous glutamate, released into the synaptic cleft as a co‐mediator of acetylcholine, is capable of triggering the NMDA receptor/NO synthase‐mediated pathway that modulates synaptic AChE activity. Therefore, in addition to well‐established modes of synaptic plasticity (e.g. changes in the effectiveness of neurotransmitter release and/or the sensitivity of the postsynaptic membrane), another mechanism exists based on the prompt regulation of AChE activity.
Elevated potassium provides an ionic mechanism for deep brain stimulation in the hemiparkinsonian rat
Authors: Sutton Alexander C. , Yu Wilson , Calos Megan E. , Mueller Lauren E. , Berk Matthew , Shim Jenny , Molho Eric S. , Brotchie Jonathan M. , Carlen Peter L. , Shin Damian S. 
Published: November 2012

AbstractThe mechanism of high‐frequency stimulation used in deep brain stimulation (DBS) for Parkinson's disease (PD) has not been completely elucidated. Previously, high‐frequency stimulation of the rat entopeduncular nucleus, a basal ganglia output nucleus, elicited an increase in [K+]e to 18 mm, in vitro. In this study, we assessed whether elevated K+ can elicit DBS‐like therapeutic effects in hemiparkinsonian rats by employing the limb‐use asymmetry test and the self‐adjusting stepping test. We then identified how these effects were meditated with in‐vivo and in‐vitro electrophysiology. Forelimb akinesia improved in hemiparkinsonian rats undergoing both tests after 20 mm KCl injection into the substantia nigra pars reticulata (SNr) or the subthalamic nucleus. In the SNr, neuronal spiking activity decreased from 38.2 ± 1.2 to 14.6 ± 1.6 Hz and attenuated SNr beta‐frequency (12–30 Hz) oscillations after K+ treatment. These oscillations are commonly associated with akinesia/bradykinesia in patients with PD and animal models of PD. Pressure ejection of 20 mm KCl onto SNr neurons in vitro caused a depolarisation block and sustained quiescence of SNr activity. In conclusion, our data showed that elevated K+ injection into the hemiparkinsonian rat SNr improved forelimb akinesia, which coincided with a decrease in SNr neuronal spiking activity and desynchronised activity in SNr beta frequency, and subsequently an overall increase in ventral medial thalamic neuronal activity. Moreover, these findings also suggest that elevated K+ may provide an ionic mechanism that can contribute to the therapeutic effects of DBS for the motor treatment of advanced PD.
Exercise‐induced stress resistance is independent of exercise controllability and the medial prefrontal cortex
Authors: Greenwood Benjamin N. , Spence Katie G. , Crevling Danielle M. , Clark Peter J. , Craig Wendy C. , Fleshner Monika 
Published: November 2012

AbstractExercise increases resistance against stress‐related disorders such as anxiety and depression. Similarly, the perception of control is a powerful predictor of neurochemical and behavioral responses to stress, but whether the experience of choosing to exercise, and exerting control over that exercise, is a critical factor in producing exercise‐induced stress resistance is unknown. The current studies investigated whether the protective effects of exercise against the anxiety‐ and depression‐like consequences of stress are dependent on exercise controllability and a brain region implicated in the protective effects of controllable experiences, the medial prefrontal cortex. Adult male Fischer 344 rats remained sedentary, were forced to run on treadmills or motorised running wheels, or had voluntary access to wheels for 6 weeks. Three weeks after exercise onset, rats received sham surgery or excitotoxic lesions of the medial prefrontal cortex. Rats were exposed to home cage or uncontrollable tail shock treatment three weeks later. Shock‐elicited fear conditioning and shuttle box escape testing occurred the next day. Both forced and voluntary wheel running, but not treadmill training, prevented the exaggerated fear conditioning and interference with escape learning produced by uncontrollable stress. Lesions of the medial prefrontal cortex failed to eliminate the protective effects of forced or voluntary wheel running. These data suggest that exercise controllability and the medial prefrontal cortex are not critical factors in conferring the protective effects of exercise against the affective consequences of stressor exposure, and imply that exercise perceived as forced may still benefit affect and mental health.
Mesial temporal lobe epilepsy as a neuropsychiatric syndrome of systemic lupus erythematosus
Authors: Toyota Tomoko , Akamatsu Naoki , Tanaka Akihiro , Shouzaki Taisaku , Tsuji Sadatoshi , Saito Kazuyoshi , Tanaka Yoshiya 
Published: November 2012

SummaryIn this study, we aimed to investigate the types of seizures and epilepsy associated with systemic lupus erythematosus (SLE). We searched the medical records at a tertiary referral center to identify a cohort of epilepsy patients with SLE who were treated between January 2000 and August 2011. We analyzed the clinical and immunologic profiles of these patients, their seizure and epilepsy classifications, electroencephalography (EEG) and magnetic resonance imaging (MRI) assessments, and the treatment administered for epilepsy and SLE. As the result, 17 patients with SLE and epilepsy were identified. Seven patients had mesial temporal lobe epilepsy (MTLE), eight had epilepsy secondary to stroke, and two had generalized epilepsy. Of the seven patients with MTLE, anteriotemporal spikes were noted in all patients with EEG, and MRI findings suggesting hippocampal sclerosis were noted in four patients. Clobazam and levetiracetam were effective in treating three patients, and one patient underwent amygdalohippocampectomy. In conclusion, MTLE may be a characteristic manifestation of neuropsychiatric syndrome of systemic lupus erythematosus.