bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing AM404 for the treatment of oral infections by Porphyromonas gingivalis
Authors: Gerits Evelien , Spincemaille Pieter , De Cremer Kaat , De Brucker Katrijn , Beullens Serge , Thevissen Karin , Cammue Bruno P.A. , Vandamme Katleen , Fauvart Maarten , Verstraeten Natalie , Michiels Jan 
Published: April 2017

AbstractPorphyromonas gingivalis is a major pathogen involved in oral diseases such as periodontitis and peri‐implantitis. Management of these diseases typically includes mechanical debridement of the colonized surfaces followed by application of antiseptics or antibiotics. Disadvantages associated with the use of antiseptics and the growing worldwide problem of antibiotic resistance have necessitated the search for alternative agents. In this study, the antibacterial and antibiofilm properties of AM404, an active metabolite of paracetamol, were tested against P. gingivalis and other bacterial pathogens. The activity of AM404 was tested against 10 bacteria, including both oral and nonoral human pathogens. The minimal inhibitory concentration (MIC) of AM404 was determined by measuring optical density (OD) values. The minimum biofilm inhibitory concentration (MBIC) was detected by crystal violet staining. The activity of structural analogs of AM404 was tested by MIC determinations. The effect of AM404 on P. gingivalis biofilms formed on titanium disks as a model for dental implants was evaluated by colony forming unit counting. Potential cytotoxicity of AM404 towards HEK‐293 (human embryonic kidney cells), HepG2 (human hepatoma cells), IEC‐6 (rat intestinal cells), and Panc‐1 cells (pancreatic cancer cells) was assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays. To get more insight in the mode of action of AM404, we used the fluorescent dyes N‐phenyl‐1‐napthylamine and SYTOX green to investigate outer and inner membrane damage of P. gingivalis induced by AM404, respectively. Of all tested pathogens, AM404 only inhibited growth and biofilm formation of P. gingivalis. Moreover, it showed potent activity against P. gingivalis biofilms formed on titanium surfaces. A structure–activity analysis demonstrated that the unsaturated carbon chain is essential for its antibacterial activity. Importantly, AM404 was not toxic towards the tested mammalian cells up to concentrations approaching 4× the MIC. Membrane damage assays using fluorescent probes N‐phenyl‐1‐napthylamine and SYTOX green revealed that membrane permeabilization presumably is the primary antibacterial mode of action of AM404. Collectively, our results suggest that AM404 has the potential to be used for the development of new drugs specifically targeting P. gingivalis‐related infections.
Estrogen signaling is necessary for exercise‐mediated enhancement of motoneuron participation in axon regeneration after peripheral nerve injury in mice
Authors: Acosta Melina C. , Copley Patricia A. , Harrell Jamie R. , Wilhelm Jennifer C. 
Published: April 2017

ABSTRACTThousands of people each year suffer from peripheral nerve injury. Treatment options are limited, and recovery is often incomplete. Treadmill exercise can enhance nerve regeneration; however, this appears to occur in a sex‐dependent manner. Females respond best to short duration, high speed interval training; whereas, males respond best to slower, continuous training. Previous studies have shown a role for testosterone in this process, but the role of estrogen is unknown. To evaluate the role of estrogen signaling in treadmill exercise, we blocked estrogen receptor (ER) signaling during treadmill exercise in males and female wild type mice. The right common fibular (CF) branch of the sciatic nerve was cut and repaired with fibrin glue that contained the ER antagonist ICI 182,780. Estradiol‐filled or blank Silastic capsules were implanted subcutaneously at the time of nerve transection. Starting three days post‐transection, exercised mice received treadmill training using the paradigm appropriate to their sex 5 days a week for 2 weeks. Fourteen days after the initial nerve transection, motoneurons whose axons had regenerated at least 1.5 mm distal to the original cut sites were labeled with a retrograde tracer. Regeneration was quantified by counting the number of fluorescent labeled motoneurons in the lumbar region of the spinal cord. Both treadmill training and estradiol administration increased the number of motoneurons participating in axon regeneration, but these effects were blocked by ER antagonist treatment. Estrogen signaling is important for the enhancing effects of treadmill exercise on motoneuron participation after peripheral nerve cut. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1133–1143, 2017
Different categories of biodiversity explain productivity variation after fertilization in a Tibetan alpine meadow community
Authors: Zhou Xiaolong , Guo Zhi , Zhang Pengfei , Li Honglin , Chu Chengjin , Li Xilai , Du Guozhen 
Published: April 2017

AbstractThe relationship between productivity and biodiversity has long been an important issue in ecological research. However, in recent decades, most ecologists have primarily focused on species diversity while paying little attention to functional diversity and phylogenetic diversity (PD), especially in alpine meadow communities following fertilization. In this study, a fertilization experiment involving the addition of nitrogen, phosphorus, and a mixture of both was implemented in an alpine meadow on the Tibetan Plateau. Species diversity, functional diversity, andPDwere measured, and the responses of these parameters to the variation in productivity were analyzed. We found that the productivity of alpine plant communities was colimited by N and P, with N being the principal and P being the secondary limiting nutrient. Our results supported the prediction of both the mass ratio hypothesis and niche complementarity hypothesis in fertilized communities, but these hypotheses were not mutually exclusive. The combination of different aspects of biodiversity not only provides a crucial tool to explain the variation in productivity and to understand the underlying mechanisms but also plays an important role in predicting the variation in productivity of alpine meadow communities, which are sensitive to nutrient enrichment in the context of global change.
Epidemiology and one‐year outcomes in patients with chronic heart failure and preserved, mid‐range and reduced ejection fraction: an analysis of the ESC Heart Failure Long‐Term Registry
Authors: Chioncel Ovidiu , Lainscak Mitja , Seferovic Petar M. , Anker Stefan D. , Crespo‐Leiro Maria G. , Harjola Veli‐Pekka , Parissis John , Laroche Cecile , Piepoli Massimo Francesco , Fonseca Candida , Mebazaa Alexandre , Lund Lars , Ambrosio Giuseppe A. , Coats Andrew J. , Ferrari Roberto , Ruschitzka Frank , Maggioni Aldo P. , Filippatos Gerasimos 
Published: April 2017

AbstractAimsThe objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure (HF) patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group.Methods and resultsThe European Society of Cardiology Heart Failure Long‐Term Registry is a prospective, observational study collecting epidemiological information and 1‐year follow‐up data in 9134 HF patients. Patients were classified according to baseline LVEF into HF with reduced EF [EF <40% (HFrEF)], mid‐range EF [EF 40–50% (HFmrEF)] and preserved EF [EF >50% (HFpEF)]. In comparison with HFpEF subjects, patients with HFrEF were younger (64 years vs. 69 years), more commonly male (78% vs. 52%), more likely to have an ischaemic aetiology (49% vs. 24%) and left bundle branch block (24% vs. 9%), but less likely to have hypertension (56% vs. 67%) or atrial fibrillation (18% vs. 32%). The HFmrEF group resembled the HFrEF group in some features, including age, gender and ischaemic aetiology, but had less left ventricular and atrial dilation. Mortality at 1 year differed significantly between HFrEF and HFpEF (8.8% vs. 6.3%); HFmrEF patients experienced intermediate rates (7.6%). Age, New York Heart Association (NYHA) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups. Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF. A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients. Atrial fibrillation predicted mortality in HFpEF patients.ConclusionsHeart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography, clinical presentation, aetiology and outcomes at 1 year. Differences in predictors for mortality might improve risk stratification and management goals.
Recovered heart failure with reduced ejection fraction and outcomes: a prospective study
Authors: Lupón Josep , Díez‐López Carles , de Antonio Marta , Domingo Mar , Zamora Elisabet , Moliner Pedro , González Beatriz , Santesmases Javier , Troya Maria I. , Bayés‐Genís Antoni 
Published: April 2017

AbstractAimsSignificant recovery of left ventricular ejection fraction (LVEF) occurs in a proportion of patients with heart failure (HF) and reduced ejection fraction (HFrEF). We analysed outcomes, including mortality [all‐cause, cardiovascular (CV), HF‐related, and sudden death], and HF‐related hospitalizations in this HF‐recovered group. The primary endpoint was a composite of CV death or HF hospitalization.Methods and resultsLVEF was assessed at baseline and at 1 year in 1057 consecutive HF patients. Patients were classified into three groups: (i) HF‐recovered: LVEF <45% at baseline and ≥45% at 1 year (n = 233); (ii) HF with preserved EF (HFpEF): LVEF ≥45% throughout follow‐up (n = 117); and (iii) HFrEF: LVEF <45% throughout follow‐up (n = 707). Mean follow‐up was 5.6 ± 3.1 years. HF‐recovered patients differed from HFrEF and HFpEF groups in demographic and clinical characteristics. The mean LVEF increase was 21.1 ± 10 points in HF‐recovered patients. Using the HF‐recovered group as a reference, the risks for the primary composite endpoint (n = 376), with non‐CV death as competing risk, for HFpEF and HFrEF groups were: hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.60–3.39], P < 0.001 and HR 1.99 (95% CI 1.50–2.65), P < 0.001, respectively. All‐cause (n = 429), CV (n = 245), HF‐related (n = 127), and sudden death (n = 60) were significantly lower in HF‐recovered subjects relative to HFrEF (all P < 0.01). HF‐recovered patients also experienced less recurrent HF hospitalizations (P < 0.001).ConclusionOne in four treated patients with HFrEF showed recovery of systolic function. HF‐recovered patients had significantly improved mortality and morbidity relative to HFpEF and HFrEF subjects. Further research is needed to identify optimal medications and device indications for HF‐recovered patients.
High Power Output Microbial Fuel Cell using Nitrogen and Iron Co‐Doped Carbon Nanospheres as Oxygen‐Reduction Catalyst
Authors: Shi Xinxin , Zhang Jiaona , Huang Tinglin 
Published: April 2017

AbstractMicrobial fuel cells (MFCs), widely recognized as a promising technology, naturally combine the functions of green energy generation and wastewater treatment. Developing effective catalysts for the cathodic oxygen reduction reaction (ORR) to improve the power outputs of MFCs has aroused extensive research interests. To achieve a high‐performance MFC, low‐cost nitrogen and trace iron co‐doped porous carbon nanospheres (NFe/CNS) were synthesized in this work by using a facile method. The MFC using NFe/CNS as an ORR catalyst showed a maximum power density of 866.5±7 mW m−2, which is 24 % higher than that of a MFC using Pt/C as a catalyst. Moreover, compared with Pt/C, NFe/CNS demonstrated a stronger tolerance against acetate (a typical anodic fuel in MFCs) crossover and durability in the MFC neutral electrolyte. Benefiting from the outstanding catalytic properties of NFe/CNS, the normalized energy recovery of the MFC with NFe/CNS was two times higher than that of the MFC with Pt/C. These results demonstrated that NFe/CNS could be expected to be a practical and breakthrough catalyst for MFCs.
Von alten Knochen und neuen Beinen
Authors: Fröbisch Nadia B. 
Published: April 2017

AbstractWie Amphibien entstanden und sich entwickelten — auf diese alte Frage lässt sich durch die Verknüpfung evolutionsgeschichtlicher und paläontologischer Befunde neu blicken: Salamander sind dabei ein reizvolles Forschungsobjekt. Sie zeigen eine ganz außergewöhnliche Entwicklung ihrer Extremitäten bis hin zur Regeneration ganzer Gliedmaßen.
Systemic iron homeostasis and erythropoiesis
Authors: Papanikolaou George , Pantopoulos Kostas 
Published: April 2017

AbstractIron is an essential nutrient that is potentially toxic due to its redox reactivity. Insufficient iron supply to erythroid cells, the major iron consumers in the body, leads to various forms of anemia. On the other hand, iron overload (hemochromatosis) is associated with tissue damage and diseases of liver, pancreas, and heart. Physiological iron balance is tightly controlled at the cellular and systemic level by iron regulatory proteins (IRP1, IRP2) and the iron regulatory hormone hepcidin, respectively. Underlying mechanisms often intersect to achieve optimal iron utilization, to control immune responses, and to prevent iron toxicity. This review focuses on systemic iron homeostasis in the context of erythropoiesis, a highly iron‐demanding process. We discuss the function and regulation of hepcidin by various stimuli, and highlight hepcidin‐dependent and ‐independent mechanisms that link iron utilization with maturation of erythroid progenitor cells. © 2017 IUBMB Life, 69(6):399–413, 2017
Recent strategies in cartilage repair: A systemic review of the scaffold development and tissue engineering
Authors: Rai Vikrant , Dilisio Matthew F. , Dietz Nicholas E. , Agrawal Devendra K. 
Published: April 2017

AbstractOsteoarthritis results in irreparable loss of articular cartilage. Due to its avascular nature and low mitotic activity, cartilage has little intrinsic capacity for repair. Cartilage loss leads to pain, physical disability, movement restriction, and morbidity. Various treatment strategies have been proposed for cartilage regeneration, but the optimum treatment is yet to be defined. Tissue engineering with engineered constructs aimed towards developing a suitable substrate may help in cartilage regeneration by providing the mechanical, biological and chemical support to the cells. The use of scaffold as a substrate to support the progenitor cells or autologous chondrocytes has given promising results. Leakage of cells, poor cell survival, poor cell differentiation, inadequate integration into the host tissue, incorrect distribution of cells, and dedifferentiation of the normal cartilage are the common problems in tissue engineering. Current research is focused on improving mechanical and biochemical properties of scaffold to make it more efficient. The aim of this review is to provide a critical discussion on existing challenges, scaffold type and properties, and an update on ongoing recent developments in the architecture and composition of scaffold to enhance the proliferation and viability of mesenchymal stem cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2343–2354, 2017.
Anti‐Tumorigenic Potential of a Novel Orlistat‐AICAR Combination in Prostate Cancer Cells
Authors: Wright Clayton , Iyer Anand Krishnan V. , Kaushik Vivek , Azad Neelam 
Published: April 2017

ABSTRACTProstate cancer (PCa) is one of the leading causes of cancer‐related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various FASN inhibitors such as the anti‐obesity drug, Orlistat. However, pharmacological limitations have impeded the progress in cancer treatments expected thus far with FASN inhibition. In this study, we investigated a novel therapeutic combination to enhance the toxic potential of Orlistat in three different PCa cell‐lines (DU145, PC3, and LNCaP). We show that Orlistat and 5‐Aminoimidazole‐4‐carboxamide ribonucleotide (AICAR) (AMP‐activated protein kinase [AMPK] activator) co‐treatment induces significant downregulation of two key fatty acid synthesis regulatory proteins (FASN, Sterol regulatory element‐binding protein 1 [SREBP‐1c]) as compared to control and Orlistat alone. Orlistat and AICAR co‐treatment induced a significant decrease in cell viability and proliferation, and a significant increase in apoptosis in all three PCa cell‐lines. Apoptosis induction was preceded by a marked increase in reactive oxygen species (ROS) production followed by G0/G1 cell cycle arrest and activation of pro‐apoptotic caspases. We also observed a significant decrease in migration potential and VEGF expression in Orlistat and AICAR co‐treated samples in all three PCa cell‐lines. Compound C (AMPK inhibitor) negatively affected some of the enhanced anti‐cancer effects observed with Orlistat treatment. We conclude that AICAR co‐treatment potentiates the anti‐proliferative effects of Orlistat at a low dose (100 µM), and this combination has the potential to be a viable and effective therapeutic option in PCa treatment. J. Cell. Biochem. 118: 3834–3845, 2017. © 2017 Wiley Periodicals, Inc.
Parent‐Metabolite Pharmacokinetic Modeling and Pharmacodynamics of Veliparib (ABT‐888), a PARP Inhibitor, in Patients With BRCA 1/2–Mutated Cancer or PARP‐Sensitive Tumor Types
Authors: Niu Jing , Scheuerell Christie , Mehrotra Shailly , Karan Sharon , Puhalla Shannon , Kiesel Brian F. , Ji Jiuping , Chu Edward , Gopalakrishnan Mathangi , Ivaturi Vijay , Gobburu Jogarao , Beumer Jan H. 
Published: April 2017

AbstractVeliparib (ABT‐888) is a novel oral poly‐ADP‐ribose polymerase (PARP) inhibitor that is being developed for the treatment of hematologic malignancies and solid tumors. Although the pharmacokinetics of veliparib have been studied in combination with cytotoxic agents, limited information exists regarding the pharmacokinetics (PK) of chronically dosed single‐agent veliparib in patients with either BRCA 1/2–mutated cancer or PARP‐sensitive tumors. The objectives of the current analysis were to characterize the population pharmacokinetics of veliparib and its primary, active metabolite, M8, and to evaluate the relationship between veliparib and M8 concentrations and poly‐ADP‐ribose (PAR) level observed in peripheral blood mononuclear cells (PBMCs). Seventy‐one subjects contributed with veliparib plasma concentrations, M8 plasma concentrations, and PAR levels in PBMCs. Veliparib and M8 concentrations were modeled simultaneously using a population PK approach. A 2‐compartment model with delayed first‐order absorption and the elimination parameterized as renal (CLR/F) and nonrenal clearance (CLNR/F) adequately described veliparib pharmacokinetics. The pharmacokinetics of the M8 metabolite was described with a 2‐compartment model. Creatinine clearance(CLCR) and lean body mass (LBM) were identified as significant predictors of veliparib CLR/F and central volume of distribution, respectively. For a typical subject (LBM, 48 kg; CLCR, 95 mL/min), total clearance (CLR/F + CLNR/F), and central and peripheral volume of distribution for veliparib were estimated as 17.3 L/h, 98.7 L, and 48.3 L, respectively. At least 50% inhibition of PAR levels in PBMCs was observed at dose levels ranging from 50 to 500 mg.
Red mud as secondary source for critical raw materials – extraction study
Authors: Ujaczki Éva , Zimmermann Yannick S , Gasser Christoph A , Molnár Mónika , Feigl Viktória , Lenz Markus 
Published: April 2017

ABSTRACTBACKGROUNDRed mud is a by‐product of alumina extraction from bauxite by the Bayer process produced in the billion tons scale worldwide. Red muds, or more generally bauxite residues, are regarded as waste, but may potentially be valuable sources of critical raw materials (CRM). In the present study both conventional extracting agents (mineral acids) and small molecular weight complexing agents (organic acids) were evaluated regarding their efficiency to extract CRM such as rare earth elements (REEs) from red mud. On a molar base, highest extraction efficiencies for REEs were achieved using HCl compared with the other acids investigated. Consequently, an experimental design approach was used to determine optimal conditions for CRM extraction using HCl. Instead of maximizing the extraction of a number of selected metals, the maximum economic potential as the sum of all metals (total metal extracted × economic value of the respective metal) was chosen as the application relevant response variable. Four explanatory variables (i.e. HCl concentration, contact time, temperature and slurry concentration) were used.RESULTSOptimal conditions maximizing the economic potential were predicted for 5.98 mol L−1 HCl, 21 h contact time, 50°C, and 56.7 g L−1 slurry concentration. Indeed, experimentally determined economic potential corresponded well (71% of predicted) with the predictions, allowing a maximum recovery of 297.6 US $ t−1.CONCLUSIONThough the studied red muds were relatively low in CRM concentrations, the systematic approach developed here allows straightforward transfer to other red muds, harnessing the potential of the latter as important secondary source for CRM. © 2017 Society of Chemical Industry
Collagen V haploinsufficiency in a murine model of classic Ehlers–Danlos syndrome is associated with deficient structural and mechanical healing in tendons
Authors: Johnston Jessica M. , Connizzo Brianne K. , Shetye Snehal S. , Robinson Kelsey A. , Huegel Julianne , Rodriguez Ashley B. , Sun Mei , Adams Sheila M. , Birk David E. , Soslowsky Louis J. 
Published: April 2017

ABSTRACTClassic Ehlers–Danlos syndrome (EDS) patients suffer from connective tissue hyperelasticity, joint instability, skin hyperextensibility, tissue fragility, and poor wound healing due to heterozygous mutations in COL5a1 or COL5a2 genes. This study investigated the roles of collagen V in establishing structure and function in uninjured patellar tendons as well as in the injury response using a Col5a1+/− mouse, a model for classic EDS. These analyses were done comparing tendons from a classic EDS model (Col5a1+/−) with wild‐type controls. Tendons were subjected to mechanical testing, histological, and fibril analysis before injury as well as 3 and 6 weeks after injury. We found that Col5a1+/− tendons demonstrated diminished recovery of mechanical competency after injury as compared to normal wild‐type tendons, which recovered their pre‐injury values by 6 weeks post injury. Additionally, the Col5a1+/−tendons demonstrated altered fibril morphology and diameter distributions compared to the wild‐type tendons. This study indicates that collagen V plays an important role in regulating collagen fibrillogenesis and the associated recovery of mechanical integrity in tendons after injury. In addition, the dysregulation with decreased collagen V expression in EDS is associated with a diminished injury response. The results presented herein have the potential to direct future targeted therapeutics for classic EDS patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2707–2715, 2017.