bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of CD154/IL4 proliferation by the T follicular helper (Tfh) cytokine, IL21 and increased numbers of circulating cells resembling Tfh cells in chronic lymphocytic leukaemia
Authors: Ahearne Matthew J. , Willimott Shaun , Piñon Lucia , Kennedy D. Benjamin , Miall Fiona , Dyer Martin J. S. , Wagner Simon D. 
Published: May 2013

SummaryChronic lymphocytic leukaemia (CLL) cells encounter T‐cells and proliferate in response to T‐cell signals in the lymph node microenvironment. In this report we determined interleukin 21 (IL21) function in CLL and showed that IL21 and interleukin 4 (IL4) act co‐operatively to promote leukaemic cell proliferation without apoptosis or differentiation We further show that IL21 increased side population (SP) cells, which are associated with resistance to chemotherapy and increased self‐renewal capacity in CLL. IL21 and IL4 are the major cytokines produced by the recently described CD4+ T follicular helper (Tfh) cell subset. Determination of Tfh cells in peripheral blood showed that patients had significantly increased numbers as compared to normal subjects although no association was found between Tfh numbers and IGHV gene mutational status or clinical stage. Our data suggests that the Tfh cytokines, IL4 and IL21, contribute to driving leukaemic cell proliferation in the lymph node microenvironment, and may contribute to the specific production of cells resistant to conventional chemotherapy. We suggest that increased circulating Tfh cells is a component of T‐cell dysregulation in CLL. Our findings have implications for the therapeutic use of IL21.
Thermal Buffering of Microhabitats is a Critical Factor Mediating Warming Vulnerability of Frogs in the Philippine Biodiversity Hotspot
Authors: Scheffers Brett R. , Brunner Rebecca M. , Ramirez Sara D. , Shoo Luke P. , Diesmos Arvin , Williams Stephen E. 
Published: May 2013

AbstractSpecies may circumvent the impacts of climate warming if the habitats they use reduce ambient temperature. In this study, we identified which frog species from a tropical montane rain forest in the Philippines may be vulnerable to climate warming. To do so, we selected five anuran species that utilize four breeding habitats and identified the sensitivity and exposure of tadpoles and direct‐developer eggs to heat by measuring their critical thermal maximums (CTmax) and the habitat‐specific temperatures they experience. Our study species included two direct‐developer frogs—one species that lays its eggs on exposed leaves, and another that lays its eggs in ferns—and three species that produce aquatic free‐swimming tadpoles—two stream breeders, and one phytotelm (tree hole) breeder. We compared thermal tolerances derived from microclimates of breeding habitats with tolerances derived from macroclimate (i.e., non‐buffered air temperature taken from the rain forest canopy). We also examined whether differences in CTmax existed across life‐history stages (egg, metamorph/young‐of‐year, and adult) for the two direct‐developer frog species. Habitats buffered ambient temperature and expanded thermal tolerances of all frog species. We found that direct‐developers, however, are more vulnerable to increased temperatures than aquatic breeders—indicated by their high sensitivity to temperature, and exposure to high temperatures. Direct‐developer eggs were more sensitive to warming than both metamorph and adult life‐history stages. Thermally buffered microhabitats may represent the only protection against current and impending climate warming. Our data highlight the importance of considering sensitivity and exposure in unison when deciphering warming vulnerability of frogs.
Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study
Authors: Price J D , Linder G , Li W P , Zimmermann B , Rother K I , Malek R , Alattar M , Tarbell K V 
Published: May 2013

SummarySitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.
Fine specificity of anti-citrullinated peptide antibodies discloses a heterogeneous antibody population in rheumatoid arthritis
Authors: Goules J D , Goules A V , Tzioufas A G 
Published: May 2013

Summary
Anti-citrullinated peptide antibodies (ACPA) are highly specific for rheumatoid arthritis (RA). However, the predominant B cell epitopes have not yet been defined. The aim of this study was to examine the reactivity of ACPA against different peptides derived from citrullinated proteins and to investigate whether or not these antibodies constitute a homogeneous population. For this purpose, sera from patients with RA (n = 141), systemic lupus erythematosus (SLE) (n = 60), Sjögren's syndrome (SS) (n = 54) and healthy controls (n = 100) were tested for their reactivity against six citrullinated peptides derived from peptidyl arginine deiminase (PAD), vimentin (vim), alpha-enolase (enol), fibrin, type II collagen (col-II) and filaggrin, respectively. A non-citrullinated control peptide derived from PAD was used as control (ctrlPAD621–40). Antibody reactivity against each individual peptide was evaluated by enzyme-linked immunosorbent assay (ELISA). Specificity and cross-reactivity of ACPA were tested by using two prototype sera with homologous and cross-inhibition assays. Specificity of ACPA from two prototype sera was confirmed by purification of anti-peptide antibodies and homologous-inhibition experiments. We found that sera from patients with RA reacted diversely with the six citrullinated peptides. More specifically, PAD211–30 displayed 29·08% sensitivity, vim60–75 29·08%, enol5–21 37·59%, fibrin617–31 31·21%, col-II358–75 29·97% and filaggrin306–24 28·37%, while control ctrlPAD621–40 showed no reactivity. All reactive peptides were found to be highly specific for RA. A notable cross-reaction (&gt;70%) was found mainly between filaggrin and the majority of anti-citrullinated peptide antibodies. We concluded that ACPA in RA constitute a heterogeneous population with limited cross-reactivity and without a predominant epitope.
Melanocyte-specific CD8+ T cells are associated with epidermal depigmentation in a novel mouse model of vitiligo
Authors: You S , Cho Y-H , Byun J-S , Shin E-C 
Published: May 2013

Summary
In the present study, we established a novel murine model of vitiligo by sequential prime/boost immunizations into the hind footpad and tail dermis with tyrosinase-related protein 2 (TRP2)-180 (SVYDFFVWL) peptide, lipopolysaccharides and cytosine–phosphate–guanosine (CpG) oligodeoxynucleotides. Immunized mice developed epidermal depigmentation in the tail skin without hair depigmentation, thereby differentiating this approach from established models of vitiligo. Following intradermal tail immunization, activated CD8+ interferon (IFN)-γ+ T cells were recruited locally to the tail skin. In-vivo cytotoxicity assays demonstrated specific lysis of TRP2-180-presenting cells in immunized mice. Furthermore, the extent of skin depigmentation correlated with the frequency of TRP2-180-specific splenic CD8+ T cells, as determined by IFN-γ and tumour necrosis factor (TNF)-α production, and cytotoxic degranulation evidenced by CD107a staining. These findings suggest a correlation between the presence of TRP2-180-specific CD8+ effector T cells and the development of depigmented skin lesions in our vitiligo model. This new model of vitiligo, characterized by skin depigmentation without hair depigmentation, is more similar to human disease than previous murine models. Therefore, this model is well suited to future studies on the pathogenesis of vitiligo and the development of novel therapeutics for vitiligo.
Impaired quality of life in growth hormone–deficient adults is independent of the altered skeletal muscle oxidative metabolism found in conditions with peripheral fatigue
Authors: Sinha Akash , Hollingsworth Kieren G. , Ball Steve , Cheetham Tim 
Published: May 2013

SummaryContextGrowth hormone–deficient (GHD) adults often report impaired quality of life (QoL) – with fatigue, a key element. This deficit can improve following GH replacement. The basis of this response is unclear. Perturbations in skeletal muscle metabolism have been demonstrated in several conditions in which fatigue is a prominent symptom. We wished to define the role of skeletal muscle metabolism in the impaired QoL observed in patients with GHD.ObjectiveTo compare in vivo skeletal muscle mitochondrial oxidative phosphorylation using phosphorus‐31 magnetic resonance spectroscopy in matched untreated GHD adults, treated GHD adults and healthy volunteers.DesignTwenty‐two untreated GHD adults, 23 treated GHD adults and 20 healthy volunteers were recruited at a regional centre. All patients underwent assessment of muscle mitochondrial function (τ1/2PCr) and proton handling using spectroscopy. Fasting biochemical analyses and anthropometric measurement were obtained. All patients completed the QoL‐AGHDA and physical activity assessment (IPAQ) questionnaires.ResultsUntreated and treated GHD adults complained of significantly increased fatigue and an impaired QoL (P = 0·002) when compared to healthy controls. There was no difference in maximal mitochondrial function (P = 0·53) nor pH recovery (P = 0·38) of skeletal muscle between the three groups. Untreated GHD patients had significantly lower IGF‐1 than both treated GHD and healthy volunteers (P < 0·001), but there was no association between τ1/2PCr and serum IGF‐1 (r = −0·13, P = 0·32).ConclusionsThe impaired QoL seen in GHD adults is not associated with the skeletal muscle spectroscopic ‘footprint’ of altered mitochondrial oxidative function, anaerobic glycolysis or proton clearance that are a feature of several conditions in which fatigue is a prominent feature. These data suggest that the pathophysiology of fatigue and impaired QoL in GHD may have a significant central rather than peripheral (skeletal muscle) component.
Comparison of two low‐dose calcium infusion schedules for localization of insulinomas by selective pancreatic arterial injection with hepatic venous sampling for insulin
Authors: Braatvedt G. , Jennison E. , Holdaway I. M. 
Published: May 2013

SummaryObjectiveLocalization of small insulinomas may be difficult. Selective pancreatic arterial injection of calcium with hepatic venous insulin measurement (SACST) has been used for this purpose, but can rarely cause hypoglycaemia. Two low‐dose concentrations of calcium, 0·25 and 0·1 of the usual concentration used for the test, have been compared for sensitivity of localization and safety.DesignSelective pancreatic arterial injection of calcium with hepatic venous insulin measurement was performed at calcium concentrations of 0·0025 (Protocol A) and 0·00625 (Protocol B) mEq calcium per kg. The standard concentration is 0·025 mEq/kg.PatientsTwenty one successive patients with biochemical evidence of insulinoma were studied.ResultsUsing surgical localization as the gold standard, Protocol A had a sensitivity of 91% and Protocol B 75% for correct localization. The false‐positive localization rate was 16%. No hypoglycaemia was observed. These results compare favourably with published data using the standard calcium concentration. Selective pancreatic arterial injection of calcium with hepatic venous insulin measurement was superior to localization by noninvasive imaging; in seven cases, SACST was correct when conventional imaging was negative (five) or false positive (two).ConclusionLow concentrations of calcium are effective and safe when performing SACST for localization of insulinoma.
Calorie Restriction is a Major Determinant of the Short‐Term Metabolic Effects of Gastric Bypass Surgery in Obese Type 2 Diabetic Patients
Authors: Lips Mirjam A. , de Groot Gerrit H. , van Klinken Jan B. , Aarts Edo , Berends Frits J. , Janssen Ignace M. , Van Ramshorst Bert , Van Wagensveld Bart A. , Swank Dingeman J. , Van Dielen Francois , Willems van Dijk Ko , Pijl Hanno 
Published: May 2013

SummaryObjectiveRoux‐en‐Y gastric bypass (RYGB) and restrictive weight loss interventions, such as gastric banding (GB) and very‐low‐calorie diets (VLCD) directly impact glucose metabolism, possibly by calorie restriction and/or altered secretion of gut hormones. We aimed to establish the direct endocrine and metabolic effects of RYGB compared to restrictive interventions in obese glucose‐tolerant (NGT) subjects and subjects with type 2 diabetes (T2DM).DesignControlled, nonrandomized observational trial.Patients and measurementsFour groups of obese females received a mixed meal at baseline and 3 weeks after intervention; NGT‐GB (n = 11), NGT‐RYGB (n = 16), T2DM‐RYGB (n = 15) and T2DM‐VLCD (n = 12). Normal weight controls (n = 12) were studied once.ResultsAt baseline, all obese subjects were hyperinsulinemic. T2DM was associated with hyperglycaemia and decreased GLP‐1 levels. RYGB and VLCD reduced glucose levels to a similar extent in T2DM, insulin levels decreased only after VLCD. Comparison of restrictive intervention vs RYGB showed a more pronounced decrease in glucose and insulin AUC after restriction. In NGT and T2DM subjects, RYGB increased GLP‐1 and PYY levels and decreased ghrelin levels, whereas VLCD and GB only increased GIP levels.ConclusionsThese data indicate that deterioration of glucose metabolism in T2DM is associated with a decline of GLP‐1 levels. Calorie restriction facilitates glucose metabolism and blunts hyperinsulinemia in obese (diabetic) humans. Additional duodenal exclusion through RYGB induces gut hormone release and hyperinsulinemia but does not improve postprandial glucose levels any further. Our data thus strongly suggest that calorie restriction underlies the short‐term metabolic benefits of RYGB in obese T2DM patients.
Analysis and Visualization of Maps Between Shapes
Authors: Ovsjanikov M. , Ben‐Chen M. , Chazal F. , Guibas L. 
Published: May 2013

AbstractIn this paper we propose a method for analysing and visualizing individual maps between shapes, or collections of such maps. Our method is based on isolating and highlighting areas where the maps induce significant distortion of a given measure in a multi‐scale way. Unlike the majority of prior work, which focuses on discovering maps in the context of shape matching, our main focus is on evaluating, analysing and visualizing a given map, and the distortion(s) it introduces, in an efficient and intuitive way. We are motivated primarily by the fact that most existing metrics for map evaluation are quadratic and expensive to compute in practice, and that current map visualization techniques are suitable primarily for global map understanding, and typically do not highlight areas where the map fails to meet certain quality criteria in a multi‐scale way. We propose to address these challenges in a unified way by considering the functional representation of a map, and performing spectral analysis on this representation. In particular, we propose a simple multi‐scale method for map evaluation and visualization, which provides detailed multi‐scale information about the distortion induced by a map, which can be used alongside existing global visualization techniques.
Customizable LoD for Procedural Architecture
Authors: Besuievsky Gonzalo , Patow Gustavo 
Published: May 2013

AbstractThis paper presents a new semantic and procedural level‐of‐detail (LoD) method applicable to any rule‐based procedural building definition. This new LoD system allows the customizable and flexible selection of the architectural assets to simplify, doing it in an efficient and artist‐transparent way. The method, based on an extension of traditional grammars, uses LoD‐oriented commands. A graph‐rewriting process introduces these new commands in the artist‐provided rule set, which allows to select different simplification criteria (distance, screen‐size projection, semantic selection or any arbitrary method) through a scripting interface, according to user needs. This way we define a flexible, customizable and efficient procedural LoD system, which generates buildings directly with the correct LoD for a given set of viewing and semantic conditions.
Motion Synthesis for Sports Using Unobtrusive Lightweight Body‐Worn and Environment Sensing
Authors: Kelly P. , Conaire C. Ó , O'Connor N. E. , Hodgins J. 
Published: May 2013

AbstractThe ability to accurately achieve performance capture of athlete motion during competitive play in near real‐time promises to revolutionize not only broadcast sports graphics visualization and commentary, but also potentially performance analysis, sports medicine, fantasy sports and wagering. In this paper, we present a highly portable, non‐intrusive approach for synthesizing human athlete motion in competitive game‐play with lightweight instrumentation of both the athlete and field of play. Our data‐driven puppetry technique relies on a pre‐captured database of short segments of motion capture data to construct a motion graph augmented with interpolated motions and speed variations. An athlete's performed motion is synthesized by finding a related action sequence through the motion graph using a sparse set of measurements from the performance, acquired from both worn inertial and global location sensors. We demonstrate the efficacy of our approach in a challenging application scenario, with a high‐performance tennis athlete wearing one or more lightweight body‐worn accelerometers and a single overhead camera providing the athlete's global position and orientation data. However, the approach is flexible in both the number and variety of input sensor data used. The technique can also be adopted for searching a motion graph efficiently in linear time in alternative applications.
Real‐time thermographic analysis of low‐density bone during implant placement: a randomized parallel‐group clinical study comparing lateral condensation with bone drilling surgical technique
Authors: Marković Aleksa , Mišić Tijana , Mančić Dragan , Jovanović Igor , Šćepanović Miodrag , Jezdić Zoran 
Published: May 2013

AbstractObjectivesTo compare the effect of two surgical techniques, lateral condensation and bone drilling, on changes in temperature of the adjacent low‐density bone during implant placement into posterior maxilla and to investigate the influence of the host factors – age, gender, region of implantation, bone density, and thickness of the cortical bone at the recipient sites.Material and methodsLocal bone temperature was measured thermographically during implant placement into posterior maxilla following lateral bone condensing (test group) or bone drilling (controls). The main study outcomes were baseline bone temperature prior to implantation and maximum bone temperature recorded during implantation. Early implant success was evaluated after 6 months of healing.ResultsA total of 40 implants were randomly allocated to test and control groups and placed into maxillary premolar and/or molar region of 18 participants of both genders and average age of 51.74 years. All recorded bone temperatures were below the threshold for thermal necrosis. Although both groups showed significant increase in bone temperature during implant placement procedure (P ≤ 0.0005), it was significantly higher for bone condensing compared with drilling (P ≤ 0.0005; 3.79 ± 1.54°C; 1.91 ± 0.70°C respectively). No host factor was singled out as a significant predictor of bone temperature changes, although trend of higher increase was observed in young patients, regardless of gender, during implant placement procedure into maxillary first premolar region with bone density type 3 and cortical layer thicker than 1 mm. Early implant success rate after 6 months follow‐up was 100%.ConclusionAlthough both surgical techniques, bone condensing and bone drilling, can be considered safe regarding their thermal effect on the bone of posterior maxilla, bone drilling is associated with fewer local bone heating during implantation. Host factors do not affect the bone thermal changes significantly.
Octodon degus: A Model for the Cognitive Impairment Associated with Alzheimer's Disease
Authors: Tarragon Ernesto , Lopez Dolores , Estrada Cristina , Ana Gonzalez‐Cuello , Schenker Esther , Pifferi Fabien , Bordet Regis , Richardson Jill C. , Herrero Maria Trinidad 
Published: May 2013

SummaryOctodon degus (O. degus) is a diurnal rodent that spontaneously develops several physiopathological conditions, analogous in many cases to those experienced by humans. In light of this, O. degus has recently been identified as a very valuable animal model for research in several medical fields, especially those concerned with neurodegenerative diseases in which risk is associated with aging. Octodon degus spontaneously develops β‐amyloid deposits analogous to those observed in some cases of Alzheimer's disease (AD). Moreover, these deposits are thought to be the key feature for AD diagnosis, and one of the suggested causes of cell loss and cognitive deficit. This review aims to bring together information to support O. degus as a valuable model for the study of AD.
Impacts of Rodenticide and Insecticide Toxicants from Marijuana Cultivation Sites on Fisher Survival Rates in the Sierra National Forest, California
Authors: Thompson Craig , Sweitzer Richard , Gabriel Mourad , Purcell Kathryn , Barrett Reginald , Poppenga Robert 
Published: May 2013

AbstractSecondary exposure of wildlife to pesticides has been well documented, yet exposure is typically associated with agricultural or wildland‐urban interface areas. Wildlife in undeveloped areas is generally presumed free from risk. In 2009, a male fisher was found dead in the Sierra National Forest and subsequent necropsy revealed that the animal died of acute rodenticide poisoning. Follow‐up testing revealed that 85% of fisher carcasses recovered by two research projects in the previous three years tested positive for rodenticides. Concern arose that exposure could predispose an animal to mortality from other causes, and that the underlying role of toxicants would escape notice. Further investigation indicated that the most likely source was the numerous illegal marijuana cultivation sites currently found on public lands throughout the western United States. To determine whether the presence of cultivation sites predisposed fishers to mortality from other sources, we related survival rates to the presence and number of cultivation sites found within that animal's home range over the past 10 years. Likelihood of exposure was related to the presence of cultivation sites, and female fisher survival was influenced by the number of cultivation sites within its home range. We discuss the conservation implications of this unexpected relationship.