bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene flow among wild and domesticated almond species: insights from chloroplast and nuclear markers
Authors: Delplancke Malou , Alvarez Nadir , Espíndola Anahí , Joly Hélène , Benoit Laure , Brouck Elise , Arrigo Nils 
Published: December 2011

AbstractHybridization has played a central role in the evolutionary history of domesticated plants. Notably, several breeding programs relying on gene introgression from the wild compartment have been performed in fruit tree species within the genus Prunus but few studies investigated spontaneous gene flow among wild and domesticated Prunus species. Consequently, a comprehensive understanding of genetic relationships and levels of gene flow between domesticated and wild Prunus species is needed. Combining nuclear and chloroplastic microsatellites, we investigated the gene flow and hybridization among two key almond tree species, the cultivated Prunus dulcis and one of the most widespread wild relative Prunus orientalis in the Fertile Crescent. We detected high genetic diversity levels in both species along with substantial and symmetric gene flow between the domesticated P. dulcis and the wild P. orientalis. These results were discussed in light of the cultivated species diversity, by outlining the frequent spontaneous genetic contributions of wild species to the domesticated compartment. In addition, crop‐to‐wild gene flow suggests that ad hoc transgene containment strategies would be required if genetically modified cultivars were introduced in the northwestern Mediterranean.
Changing organisms in rapidly changing anthropogenic landscapes: the significance of the ‘Umwelt’‐concept and functional habitat for animal conservation
Authors: Van Dyck Hans 
Published: December 2011

AbstractThere is a growing recognition for the significance of evolutionary thinking in ecology and conservation biology. However, ecology and conservation studies often work with species‐specific, fixed traits that ignore intraspecific variation. The way the habitat of a species is considered is an example of typological thinking biased by human perception. Structural habitat units (e.g., land cover types) as perceived by humans may not represent functional habitat units for other organisms. Human activity may also interfere with the environmental information used by organisms. Therefore, the Umwelt‐concept from ethology needs to be integrated in the way we think about habitat and habitat selection. It states that different organisms live in different perceptual worlds dealing with specific subsamples of the environment as a result of their evolutionary and developmental history. The resource‐based habitat concept is a functional habitat model based on resource distributions (consumables and conditions) and individual movements. This behavioural approach takes into account aspects that relate to the perceptual world of organisms. This approach may offer new opportunities for conservation and may help avoid failures with habitat restoration. Perceptual ability may be subject to adaptive change, but it may also constrain organisms from showing adaptive behaviours in rapidly changing environments.
Impact of a single one‐to‐one education session on glycemic control in patients with diabetes
Authors: BANERJEE Moulinath , MACDOUGALL Michelle , LAKHDAR Abdul F. 
Published: December 2011

AbstractBackground:  Education is one of the pivotal aspects of diabetes care. The impact of education has been found to be efficacious in the short term, but tends to lose efficacy in the long term. The hypothesis tested here was that one‐to‐one education would confer knowledge that would be reflected in metabolic improvement in this group of participants with diabetes.Methods:  Thirty‐nine patients with type 2 diabetes mellitus and poor diabetes control attended a one‐to‐one diabetic and dietetic education session with a diabetic specialist nurse and a diabetes specialist dieticican. Glycemic control was assessed by measuring serum glycosolated hemoglobin (HbA1c) measurements before the session and at 6 and 12 months afterwards.Results:  The HbA1c levels fell significantly in the whole group to 8.0 ± 0.5% (P < 0.05) at 6 months and to 8.3 ± 0.7% (P < 0.05) at the final visit from a baseline of 9.2 ± 0.5%. Compared to female patients, male patients had a similar drop in HbA1c at 6 months of 1.1%, which persisted until the final visit, when the drop was –1.3% vs 0.3% (P < 0.05).Conclusions:  A single episode of one‐to‐one diabetic and dietetic education to subjects with poor diabetic control is effective in improving short‐ and long‐term diabetic control for up to 1 year. Male patients were found to have a better response than female patients.
Role and therapeutic potential of PI3K‐mTOR signaling in de novo resistance to BRAF inhibition
Authors: Deng W. , Vashisht Gopal Y. N. , Scott A. , Chen G. , Woodman S. E. , Davies M. A. 
Published: December 2011

SummaryBRAF inhibition is highly active in BRAF‐mutant melanoma, but the degree and duration of responses is quite variable. Improved understanding of the mechanisms of de novo resistance may lead to rational therapeutic strategies with improved efficacy. Proteomic analysis of BRAF‐mutant, PTEN‐wild‐type human melanoma cell lines treated with PLX4720 demonstrated that sensitive and de novo resistant lines exhibit similar RAS‐RAF‐MEK‐ERK pathway inhibition, but the resistant cells exhibited durable activation of S6 and P70S6K. Treatment with the mTOR inhibitor rapamycin blocked activation of P70S6K and S6, but it also increased activation of AKT and failed to induce cell death. Combined treatment with rapamycin and PX‐866, a PI3K inhibitor, blocked the activation of S6 and AKT and resulted in marked cell death when combined with PLX4720. The results support the rationale for combined targeting of BRAF and the PI3K‐AKT pathways and illustrate how target selection will be critical to such strategies.
The prevalence of cataract in a population with and without type 2 diabetes mellitus
Authors: Olafsdottir Eydis , Andersson Dan K. G. , Stefánsson Einar 
Published: December 2011

Abstract.Purpose:  To evaluate the prevalence and risk factors of lens opacities in a geographically defined population of subjects with type 2 diabetes mellitus compared with a control population.Methods:  Subjects in the community of Laxå with a diagnosis of type 2 diabetes mellitus (n = 275) and a control group (n = 256) participated in the study. Lens opacities were graded with Lens Opacities Classification System II in all participants. Lens Opacities Classification System score ≥2 was considered as significant lens opacity. Anthropometric and blood chemistry data were collected for all participants in connection with the eye examination. For the diabetic population, yearly updated information on glucose control, blood pressure and body mass index was available through medical records from diabetes diagnosis until the time of the eye examination.Results:  The prevalence of significant cortical, posterior subcapsular and nuclear cataract was 65.5%, 42.5% and 48.0%, respectively, in the type 2 diabetes population in Laxå. In logistic regression analyses, all types of lens opacities were strongly associated with age (p < 0.0001). Cortical lens opacity was also associated with a diagnosis of diabetes (p < 0.0001), posterior subcapsular lens opacity with HbA1c (p < 0.0001) and nuclear lens opacity with female gender and higher heart rate (both p = 0.0004). In the diabetic population, all types of cataract were likewise strongly associated with age (p < 0.0001), posterior subcapsular cataract with HbA1c (p = 0.0032), nuclear cataract with female gender (p = 0.0002) and higher heart rate (p = 0.0008).Conclusions:  Our study shows that cortical cataract is associated with diabetes mellitus, not necessarily defined by glucose control, whereas posterior subcapsular cataract is associated with glucose levels. Nuclear cataract is not associated with diabetes mellitus, but is more frequent in women and is also associated with higher heart rate.
Modeling spatial and dynamic variation in growth, yield, and yield stability of the bioenergy cropsMiscanthus × giganteusandPanicum virgatumacross the conterminousUnitedStates
Authors: Miguez Fernando E. , Maughan Matthew , Bollero Germán A. , Long Stephen P. 
Published: December 2011

AbstractC4perennial grasses are being considered as environmentally and economically sustainable high yielding bioenergy feedstocks. Temporal and spatial variation in yield across the conterminiousUnitedStates is uncertain due to the limited number of field trials. Here, we use a semi‐mechanistic dynamic crop growth and production model to explore the potential ofMiscanthus × giganteus(Greef et.Deu.) andPanicum virgatumL. across the conterminousUnitedStates. By running the model for 32 years (1979–2010), we were able to estimate dry biomass production and stability. The maximum rainfed simulated end‐of‐growth‐season harvestable biomass forM. × giganteuswas ca. 40 Mg ha−1and ca. 20 Mg ha−1forP. virgatum. In addition, regions of the southeasternUnitedStates were identified as promising due to their high potential production and stability and their relative advantage when compared with county‐level maize biomass production. Regional and temporal variation was most strongly influenced by precipitation and soil water holding capacity.Miscanthus × giganteuswas on average 2.2 times more productive thanP. virgatumfor locations where yields were ≥10 Mg ha−1. The predictive ability of the model forP. virgatumwas tested with 30 previously published studies covering the eastern half of theUnitedStates and resulted in an index of agreement of 0.71 and a mean bias of only −0.62 Mg ha−1showing that, on average, the model tended to only slightly overestimate productivity. This study provides with potential production and variability which can be used for regional assessment of the suitability of dedicated bioenergy crops.
Occurrence of clinical depression during combination therapy with pegylated interferon alpha or natural human interferon beta plus ribavirin
Authors: Nomura Hideyuki , Miyagi Yuugou , Tanimoto Hironori , Yamashita Nobuyuki , Oohashi Seiji , Nishiura Saburo 
Published: December 2011

Aim:  The onset of depression symptoms during pegylated interferon α plus ribavirin (PEG‐IFN/RBV) combination therapy has led to treatment discontinuation in some cases. In the present study, we conducted a questionnaire survey during treatment to determine whether natural human interferon β plus ribavirin (IFNβ/RBV) therapy is associated with a lower incidence of depression symptom onset compared with PEG‐IFN/RBV therapy.Methods:  Seventy‐seven patients with chronic hepatitis C received PEG‐IFN/RBV (PR) or IFNβ/RBV (FR) therapy. A questionnaire survey was administered at the start of treatment, and at 4 and 12 weeks, using the Beck Depression Inventory II (BDI‐II) and the Pittsburgh Sleep Quality Index (PSQI).Results:  BDI‐II scores in the PR group increased at 4 and 12 weeks, but remained unchanged in the FR group. At 12 weeks, the mean BDI‐II score and incidence of abnormalities with a BDI‐II score of ≥14 were significantly lower in the FR group than in the PR group. BDI‐II scores during IFNβ/RBV therapy in 11 patients currently using antidepressants remained unchanged up to 12 weeks. None of these 11 patients required addition or dose increases of antidepressants, and there was no evidence of worsened depression symptoms. Nine PR patients had BDI‐II scores of ≥14 and PSQI scores of ≥11 at 12 weeks.Conclusions:  IFNβ/RBV therapy was associated with a lower incidence of depression symptom onset during treatment. In patients already diagnosed with depression, there was no evidence that IFNβ/RBV therapy caused any worsening of symptoms, indicating that IFNβ/RBV therapy is safe for patients with depression.
Histone deacetylase inhibitors as suppressors of bone destruction in inflammatory diseases
Authors: Cantley Melissa D , Bartold Peter M , Fairlie David P , Rainsford K D , Haynes David R 
Published: December 2011

Abstract

Objectives
Despite progress in developing many new anti-inflammatory treatments in the last decade, there has been little progress in finding treatments for bone loss associated with inflammatory diseases, such as rheumatoid arthritis and periodontitis. For instance, treatment of rheumatic diseases with anti-tumour necrosis factor-alpha agents has been largely successful in reducing inflammation, but there have been varying reports regarding its effectiveness at inhibiting bone loss. In addition, there is often a delay in finding the appropriate anti-inflammatory therapy for individual patients, and some therapies, such as disease modifying drugs, take time to have an effect. In order to protect the bone, adjunct therapies targeting bone resorption are being developed. This review focuses on new treatments based on using histone deacetylase inhibitors (HDACi) to suppress bone loss in these chronic inflammatory diseases.

Key findings
A number of selected HDACi have been shown to suppress bone resorption by osteoclasts in vitro and in animal models of chronic inflammatory diseases. Recent reports indicate that these small molecules, which can be administered orally, could protect the bone and might be used in combination with current anti-inflammatory treatments.

Summary
HDACi do have potential to suppress bone destruction in chronic inflammatory diseases including periodontitis and rheumatoid arthritis.
Liposomal topotecan formulation with a low polyethylene glycol grafting density: pharmacokinetics and antitumour activity
Authors: Li Chunlei , Wang Caixia , Yang Hanyu , Zhao Xi , Wei Na , Cui Jingxia 
Published: December 2011

Abstract

Objectives
PEGylated liposomes could evade recognition by the reticulo-endothelial system and prolong the circulation time of vesicles, resulting in enhanced targeting efficiency and antitumour effect. Typically, vesicles are modified with distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol (PEG) at a high PEG grafting density. However, long circulation time and slow drug release rate might induce severe hand-foot syndrome in clinical practice. In this study, a liposomal topotecan formulation with a low PEG grafting density was prepared and its pharmacokinetics, acute toxicity and antitumour effect were investigated.

Methods
Topotecan was loaded into liposomes using an ammonium sulfate gradient. The resulting formulation was injected to healthy Wistar rats at different dose levels to investigate whether its clearance followed linear kinetics. Biodistribution was performed in Lewis lung cancer-bearing mice. The acute toxicity was evaluated in healthy mice and beagle dogs. To compare the antitumour effects of different formulations and dose schedule, RM-1 prostate, Lewis lung, H446 and L1210 cancer models were used.

Key findings
Topotecan could be encapsulated into low DSPE-PEG liposomes with ∼100% loading efficiency. The clearance of the liposomal formulation followed linear kinetics at a dose level ranging from 0.5 to 4 mg/kg despite the fact that the vesicles were coated at a low PEG density. Compared with free topotecan the liposomal formulation preferentially accumulated into tumour zones instead of normal tissues. Both formulations could rapidly accumulate into liver and tumour, but the liposomal formulation was cleared from tissues at a slow rate relative to the conventional formulation. In rats and beagle dogs, liposomal formulations could not induce skin toxicity. In all the tumour models, smaller split doses were more therapeutically active than larger doses when the overall dose intensity was equivalent.

Conclusions
This has been the first report that plasma kinetics of a liposomal formulation with a low PEG density followed linear kinetics. Moreover, due to its short circulation half-life, the formulation did not induce skin toxicity. Our data revealed that the dose schedule of liposomal drugs should be adjusted in accordance with the biophysical and biological properties of the formulations to achieve the optimal therapeutic efficacy.
Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes
Authors: Jantan Ibrahim , Bukhari Syed Nasir Abbas , Lajis Nordin Haji , Abas Faridah , Wai Lam Kok , Jasamai Malina 
Published: December 2011

Abstract

Objectives
A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro.

Methods
The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol-based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique.

Key findings
Compounds 6, 17, 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7, 17, 18, 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration.

Conclusions
The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.
Preclinical Activity of the Rational Combination of Selumetinib (AZD6244) in Combination with Vorinostat in KRAS-Mutant Colorectal Cancer Models
Authors: Morelli M. Pia , Tentler John J. , Kulikowski Gillian N. , Tan Aik-Choon , Bradshaw-Pierce Erica L. , Pitts Todd M. , Brown Amy M. , Nallapareddy Sujatha , Arcaroli John J. , Serkova Natalie J. , Hidalgo Manuel , Ciardiello Fortunato , Eckhardt S. Gail 
Published: December 2011

Abstract
Purpose: Despite the availability of several active combination regimens for advanced colorectal cancer (CRC), the 5-year survival rate remains poor at less than 10%, supporting the development of novel therapeutic approaches. In this study, we focused on the preclinical assessment of a rationally based combination against KRAS-mutated CRC by testing the combination of the MEK inhibitor, selumetinib, and vorinostat, a histone deacetylase (HDAC) inhibitor.
Experimental Design: Transcriptional profiling and gene set enrichment analysis (baseline and posttreatment) of CRC cell lines provided the rationale for the combination. The activity of selumetinib and vorinostat against the KRAS-mutant SW620 and SW480 CRC cell lines was studied in vitro and in vivo. The effects of this combination on tumor phenotype were assessed using monolayer and 3-dimensional cultures, flow cytometry, apoptosis, and cell migration. In vivo, tumor growth inhibition, 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET), and proton nuclear magnetic resonance were carried out to evaluate the growth inhibitory and metabolic responses, respectively, in CRC xenografts.
Results: In vitro, treatment with selumetinib and vorinostat resulted in a synergistic inhibition of proliferation and spheroid formation in both CRC cell lines. This inhibition was associated with an increase in apoptosis, cell-cycle arrest in G1, and reduced cellular migration and VEGF-A secretion. In vivo, the combination resulted in additive tumor growth inhibition. The metabolic response to selumetinib and vorinostat consisted of significant inhibition of membrane phospholipids; no significant changes in glucose uptake or metabolism were observed in any of the treatment groups.
Conclusion: These data indicate that the rationally based combination of the mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, selumetinib, with the HDAC inhibitor vorinostat results in synergistic antiproliferative activity against KRAS-mutant CRC cell lines in vitro. In vivo, the combination showed additive effects that were associated with metabolic changes in phospholipid turnover, but not on FDG-PET, indicating that the former is a more sensitive endpoint of the combination effects. Clin Cancer Res; 18(4); 1051–62. ©2011 AACR.
Effect of Suture Properties on Stability of Middle Cerebral Artery Occlusion Evaluated by Synchrotron Radiation Angiography
Authors: Guan Yongjing , Wang Yongting , Yuan Falei , Lu Haiyan , Ren Yuqi , Xiao Tiqiao , Chen Kemin , Greenberg David A. , Jin Kunlin , Yang Guo-Yuan 
Published: December 2011

Background and Purpose—
The intraluminal suture technique for producing middle cerebral artery occlusion in rodents is the most commonly used method for modeling focal cerebral ischemia associated with clinical ischemic stroke. Synchrotron radiation angiography may provide a novel solution to directly monitor the success of middle cerebral artery occlusion.

Methods—
Twenty adult Sprague-Dawley rats for middle cerebral artery occlusion models were prepared randomly with different suture head silicone coating. In vivo imaging was performed at beam line BL13W1, Shanghai Synchrotron Radiation Facility, Shanghai, China.

Results—
Silicone-coated suture was superior to uncoated suture for producing consistent brain infarction. Additionally, silicone coating length was an important variable controlling the extent of the ischemic lesion: infarcts affected predominantly the caudate–putamen with large variability (<2 mm), both the cortex and caudate–putamen (2–3.3 mm), and most of the hemisphere, including the hypothalamus (>3.3 mm).

Conclusions—
Synchrotron radiation angiography provides a useful tool to observe hemodynamic changes after middle cerebral artery occlusion, and the physical properties of suture are critical to the success of the middle cerebral artery occlusion model.
Sequential State and Observation Noise Covariance Estimation Using Combined Ensemble Kalman and Particle Filters
Authors: Frei Marco , Künsch Hans R. 
Published: December 2011

AbstractThe authors consider the joint state and parameter estimation problem for dynamical models where the system evolution is known and where the observations are linear with additive Gaussian noise whose covariance matrix depends on unknown parameters. The form of this dependence is general, both diagonal and off-diagonal elements of the covariance matrix may depend on the unknown parameters. In this situation, the ensemble Kalman filter (EnKF) cannot be applied directly to update state and parameters simultaneously. Two novel approximate Monte Carlo methods are proposed for this purpose, which are both based on the assumption that parameters and state are approximately independent after the propagation step. The first method begins with a particle filter update of the parameters followed by an EnKF update of the state. The second method first makes an EnKF update of the state based on an approximate likelihood that does not depend on the parameters, followed by a particle filter update of the parameters with weights proportional to the ratio of the correct to the approximate likelihood. To counteract sample depletion, the authors introduce algorithmic refinements like balanced sampling, kernel resampling, and increasing the number of samples for the parameters while keeping the size of the state ensemble fixed. The performance and flexibility of these methods is demonstrated in simulations with a linear Gaussian model and with the Lorenz-96 model. Provided the EnKF with all parameters known is reasonably well calibrated, then this is also true for the state estimates in the new algorithms, and the estimated posterior distributions of the parameters are consistent with the truth.