bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid aggregation of lysozyme: The synergy study of red wine polyphenols
Authors: Gazova Zuzana , Siposova Katarina , Kurin Elena , Mučaji Pavel , Nagy Milan 
Published: February 2013

AbstractThe amyloidoses are diseases associated with nonnative folding of proteins and characterized by the presence of protein amyloid aggregates. The ability of quercetin, resveratrol, caffeic acid, and their equimolar mixtures to affect amyloid aggregation of hen egg white lysozyme in vitro was detected by Thioflavin T fluorescence assay. The anti‐amyloid activities of tested polyphenols were evaluated by the median depolymerization concentrations DC50 and median inhibition concentrations IC50. Single substances are more efficient (by at least one order) in the depolymerization of amyloid aggregates assay than in the inhibition of the amyloid formation with IC50 in 10−4 to 10−5M range. Analyzed mixture samples showed synergic or antagonistic effects in both assays. DC50 values ranged from 10−5 to 10−8M and IC50 from 10−5 to 10−9M, respectively. We observed that certain mixtures of studied polyphenols can synergistically inhibit production of amyloids aggregates and are also effective in depolymerization of the aggregates. Synergic or antagonistic effects of studied mixtures were correlated with protein–small ligand docking studies and AFM results. Differences in these activities could be explained by binding of each polyphenol to a different amino acid sequence within the protein. Our results indicate that synergic/antagonistic anti‐amyloid effects of studied mixtures depend on the selective binding of polyphenols to the known amyloidogenic sequences in the lysozyme chain. Our findings of the effective reduction of amyloid aggregation of lysozyme by polyphenol mixtures in vitro are of the utter physiological relevance considering the bioavailability and low toxicity of tested phenols. Proteins 2013; © 2012 Wiley Periodicals, Inc.
Shockwaves Induce Osteogenic Differentiation of Human Mesenchymal Stem Cells Through ATP Release and Activation of P2X7 Receptors
Authors: Sun Dahui , Junger Wolfgang G. , Yuan Changji , Zhang Wenyan , Bao Yi , Qin Daming , Wang Chengxue , Tan Lei , Qi Baochang , Zhu Dong , Zhang Xizheng , Yu Tiecheng 
Published: February 2013

Abstract
Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5′-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave-induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (∼7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c-fos and c-jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation.
Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula
Authors: Lee Woo Yong , Park Kyu Joo , Cho Yong Beom , Yoon Sang Nam , Song Kee Ho , Kim Do Sun , Jung Sang Hun , Kim Mihyung , Yoo Hee-Won , Kim Inok , Ha Hunjoo , Yu Chang Sik 
Published: February 2013

Abstract
Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence.
Matrix Remodeling Maintains Embryonic Stem Cell Self-Renewal by Activating Stat3
Authors: Przybyla Laralynne M. , Theunissen Thorold W. , Jaenisch Rudolf , Voldman Joel 
Published: February 2013

AbstractWhile a variety of natural and synthetic matrices have been used to influence embryonic stem cell (ESC) self-renewal or differentiation, and ESCs also deposit a rich matrix of their own, the mechanisms behind how extracellular matrix affects cell fate are largely unexplored. The ESC matrix is continuously remodeled by matrix metalloproteinases (MMPs), a process that we find is enhanced by the presence of mouse embryonic fibroblast feeders in a paracrine manner. Matrix remodeling by MMPs aids in the self-renewal of ESCs, as inhibition of MMPs inhibits the ability of ESCs to self-renew. We also find that addition of the interstitial collagenase MMP1 is sufficient to maintain long-term leukemia inhibitory factor (LIF)-independent mouse ESC (mESC) self-renewal in a dose-dependent manner. This remarkable ability is due to the presence of endogenously produced self-renewal-inducing signals, including the LIF-family ligand ciliary neurotrophic factor, that are normally trapped within the ECM and become exposed upon MMP-induced matrix remodeling to signal through JAK and Stat3. These results uncover a new role for feeder cells in maintaining self-renewal and show that mESCs normally produce sufficient levels of autocrine-acting pro-self-renewal ligands.
Developing melanoma therapeutics: overview and update
Authors: Korman John B. , Fisher David E. 
Published: February 2013

AbstractMelanoma is a common, often deadly malignancy, historically associated with limited treatment options for advanced disease. In recent years, systems‐based research has resulted in significant clinical advancements. Strategic inhibition of mutated oncoproteins and targeting of immune checkpoints have emerged as very promising approaches. Vemurafenib, which received US Food and Drug Administration (FDA) approval in 2011, selectively inhibits BRAFV600E, a hyperactivated mutant signaling kinase in the mitogen‐activated protein kinase (MAPK) pathway. Another recently FDA‐approved drug, ipilimumab, blocks the cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) pathway from inhibiting T cell activation. Despite this apparent progress, compelling challenges remain for both researchers and clinicians. Responses to therapy remain unacceptably incomplete and, in most cases, resistance mechanisms quickly develop that lead to relapse and subsequent patient mortality. Combining therapeutic modalities may increase the percentage of responding patients as well as the magnitude and durability of response. Notably, combined therapies involving selective BRAF inhibitors (SBIs) and other inhibitors of MAPK‐dependent or MAPK‐independent resistance pathways appear particularly promising. Preclinical and clinical studies are needed to comprehensively evaluate the optimal combinations of therapies, to identify melanoma subtypes that will be most responsive, and to determine optimal dosing, timing, and route of delivery. WIREs Syst Biol Med 2013, 5:257–271. doi: 10.1002/wsbm.1210This article is categorized under:

Translational, Genomic, and Systems Medicine > Therapeutic Methods
Lower urinary tract development and disease
Authors: Rasouly Hila Milo , Lu Weining 
Published: February 2013

AbstractCongenital anomalies of the lower urinary tract (CALUT) are a family of birth defects of the ureter, the bladder, and the urethra. CALUT includes ureteral anomaliesc such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder‐exstrophy‐epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUVs). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease, and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, the bladder, and the urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, the bladder and the urethra and associated gene mutations are also presented. As we are entering the postgenomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence‐based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. WIREs Syst Biol Med 2013, 5:307–342. doi: 10.1002/wsbm.1212This article is categorized under:

Developmental Biology > Developmental Processes in Health and Disease
Translational, Genomic, and Systems Medicine > Translational Medicine
Cloning of a novel feruloyl esterase gene from rumen microbial metagenome and enzyme characterization in synergism with endoxylanases
Authors: Wong Dominic W S , Chan Victor J , Liao Hans , Zidwick Mary J 
Published: February 2013

AbstractA feruloyl esterase (FAE) gene was isolated from a rumen microbial metagenome, cloned into E. coli, and expressed in active form. The enzyme (RuFae2) was identified as a type C feruloyl esterase. The RuFae2 alone released ferulic acid from rice bran, wheat bran, wheat-insoluble arabinoxylan, corn fiber, switchgrass, and corn bran in the order of decreasing activity. Using a saturating amount of RuFae2 for 100 mg substrate, a maximum of 18.7 and 80.0 μg FA was released from 100 mg corn fiber and wheat-insoluble arabinoxylan, respectively. Addition of GH10 endoxylanase (EX) synergistically increased the release of FA with the highest level of 6.7-fold for wheat bran. The synergistic effect of adding GH11 EX was significantly smaller with all the substrates tested. The difference in the effect of the two EXs was further analyzed by comparing the rate in the release of FA with increasing EX concentration using wheat-insoluble arabinoxylan as the substrate.
Craniocervical decompression in patients with mucopolysaccharidosis VI: development of a scoring system to determine indication and outcome of surgery
Authors: Lampe Christina , Lampe Christian , Schwarz Manfred , Müller‐Forell Wibke , Harmatz Paul , Mengel Eugen 
Published: February 2013

AbstractObjectiveTo analyse diagnostic value of somato‐sensory evoked potentials (SEP), magnetic resonance imaging (MRI), and clinical neurological examination in the decision for decompression surgery in mucopolysaccharidosis (MPS) VI patients with craniocervical cord compression (CCJ).MethodsWe retrospectively analysed neurological examination, SEP of the median nerve and MRI outcomes from 31 MPS VI patients. Individual scores for each test (based on severity of findings) and a sum of scores of all three procedures (CCJ score) were evaluated for their potential to measure the need for and improvement after surgery. Differences between rapidly and slowly progressive patients were also evaluated.ResultsFourteen patients (45 %) aged 4–34 years underwent decompression surgery. Median age at first operation was lower in rapidly than in slowly progressive patients (12 vs. 24 years; P = 0.008). Neurological and SEP findings but not MRI results differed significantly between non‐operated and operated patients (P < 0.001, P = 0.003 and P = 0.08, respectively). A significant relationship was found between MRI and clinical neurological examination (P < 0.001) and between SEP and clinical neurological examination (P = 0.01) but not between MRI and SEP (P = 0.06). The CCJ score discriminated between operated and non‐operated patients (4–9 points vs. 0–3 points; P < 0.001) and decreased in 61.5 % of patients after surgery.ConclusionsCCJ is common in rapidly and slowly progressive MPS VI patients. The CCJ score is an objective and transparent tool for assessing pathology of the CCJ, the need for surgery, and improvement after surgery.
Hypertrichosis in presymptomatic mitochondrial disease
Authors: Baertling Fabian , Mayatepek Ertan , Distelmaier Felix 
Published: February 2013

AbstractLeigh syndrome is a neurometabolic disorder commonly associated with disturbed oxidative phosphorylation, which leads to bilateral symmetric necrotizing lesions in the central nervous system. Neurological symptoms may be accompanied by cutaneous abnormalities. Here, we present images of distinct hypertrichosis in an otherwise asymptomatic one‐year‐old patient with pathogenic SURF1 gene mutations. We conclude that, if Leigh syndrome is suspected, the presence of characteristic hypertrichosis should prompt SURF1 mutation analysis.
Disclosure of amyloid imaging results to research participants: Has the time come?
Authors: Lingler Jennifer H. , Klunk William E. 
Published: February 2013

AbstractAmyloid imaging is becoming an increasingly popular tool in clinical research on Alzheimer's disease. In early studies, questions of whether to disclose amyloid imaging results were largely mooted by the immature state of the science. Lack of clarity as to what constituted a positive scan and what a positive scan meant from a prognostic or diagnostic perspective required investigators to advise research participants that, because their scans could not be meaningfully interpreted in a clinical sense, individual research scan results would not be disclosed. With a focus on the most widely used research tracer, Pittsburgh Compound B (PiB), we consider how advances in amyloid imaging are raising new questions about the appropriateness of withholding research results from study participants. We conclude that, although it remains advisable to withhold amyloid scan results from cognitively normal participants, it is no longer reasonable to uphold policies that unilaterally advise research participants with documented cognitive impairment that their PiB scans are uninterpretable. We outline circumstances that we believe compel investigators to provide research participants with the option of receiving their PiB scan results in a carefully managed fashion. Our findings can potentially be generalized to research involving all validated amyloid tracers.
“Functional Pain,” Functional Outcomes, and Quality of Life After Hyaluronic Acid Intra‐articular Injection for Knee Osteoarthritis
Authors: Vincent Heather K. , Montero Cindy , Conrad Bryan P. , Horodyski MaryBeth , Connelly Jacob , Martenson Matthew , Seay Amanda N. , Vincent Kevin R. 
Published: February 2013

ObjectiveTo compare the effect of hyaluronic acid (HA) intra‐articular knee injections on pain and functional outcomes in persons with knee osteoarthritis (OA) over 6 months, and to determine whether or not changes in functional pain are related to improvements in quality of life.DesignA prospective cohort study.SettingA research laboratory in an academic medical center.ParticipantsPatients with knee OA (N = 53) who were receiving medical care for OA.InterventionsIntra‐articular knee injections of HA (3 injections, each separated by 1 week) and a comparative noninjection group.Main Outcome MeasurementsFunctional pain and outcomes assessments during chair rise, stair climbing, and a 6‐minute walking test (by using 0‐10 point numerical pain ratings during each test); gait parameters; Medical Outcomes Short Form‐36 (SF‐36) scores and subscores; the Western Ontario McMaster University Osteoarthritis Index (WOMAC).ResultsSix months after HA, the completion times for the chair rise and stair climb tasks, and the distance covered during the 6‐minute walk were not different between the groups. However, functional pain ratings during stair climbing decreased in the HA‐treated group (P = .05). Six‐month changes in gait velocity, cadence, stride length, step length, and the percentage of the gait cycle spent in single support were all higher after HA injection at month 6 (all P < .05). Significant group‐by‐time interactions existed for total WOMAC scores. SF‐36 Vitality subscores improved by 13%, and Role Physical scores were higher in patients treated with HA injection compared with participants in the noninjection group (P < .05). Regression analyses revealed that changes in the functional pain measures did not correspond with SF‐36 scores.ConclusionsHA is associated with lower functional pain severity, with minimal impact on functional test scores. We interpreted this finding to represent an increase in the quality of the movement and functional activity. The change in functional pain did not correspond to changes in SF‐36 quality‐of‐life scores.
Sinusoidal input-based visual control for nonholonomic vehicles
Authors: Aranda M. , López-Nicolás G. , Sagüés C. 
Published: February 2013

SUMMARYThis paper proposes a new visual control approach based on sinusoidal inputs to be used on a nonholonomic robot. We present several contributions: In our method, developed considering a unicycle kinematic model, sinusoids are used in such a way that the generated vehicle trajectories are feasible, smooth and versatile. Our technique improves previous sinusoidal-based control works in terms of efficiency and flexibility. As further contributions, we present analytical expressions for the evolution of the robot's state, and propose a new state-feedback control law based on these expressions. All the information used in the control scheme is obtained from omnidirectional vision by means of the one-dimensional trifocal tensor. Stability analysis of the proposed approach is presented, and its performance is illustrated through experiments.
Tip-contact force control of a single-link flexible arm using feedback and parallel compensation approach
Authors: Liu Liang-Yih , Lin Hsiung-Cheng 
Published: February 2013

SUMMARYIn this paper, the force control of a constrained one-link flexible arm is investigated using a feedback parallel compensation algorithm based on a linear distributed parameter model with internal damping of Kelvin–Voigt type. Generally, the non-collocation of the joint torque input and the tip contact force output comes along with the non-minimum phase in nature. To overcome this inherent limitation, a new input induced by the measurement of root-bending moment and its derivative, and a virtual contact force output generated by a parallel compensator are defined. Therefore, the transfer function from the new input to the virtual contact force output is proved not only strictly minimum phase but also in a stable condition. A PD controller then improves the performance of the overall closed-loop system. Furthermore, the perfect asymptotic tracking of a desired contact force trajectory with internal stability can be achieved accurately. The exact solutions of the infinite-dimensional system are obtained using the infinite product formulation. The proposed system promises stability robustness to parameter uncertainties, also free of spillover problems. Numerical simulations are provided to verify the effectiveness of the proposed approach.
Pertussis resurgence: waning immunity and pathogen adaptation – two sides of the same coin
Authors: MOOI F. R. , VAN DER MAAS N. A. T. , De MELKER H. E. 
Published: February 2013

SUMMARYPertussis or whooping cough has persisted and resurged in the face of vaccination and has become one of the most prevalent vaccine-preventable diseases in Western countries. The high circulation rate ofBordetella pertussisposes a threat to infants that have not been (completely) vaccinated and for whom pertussis is a severe, life-threatening, disease. The increase in pertussis is mainly found in age groups in which immunity has waned and this has resulted in the perception that waning immunity is the main or exclusive cause for the resurgence of pertussis. However, significant changes inB. pertussispopulations have been observed after the introduction of vaccinations, suggesting a role for pathogen adaptation in the persistence and resurgence of pertussis. These changes include antigenic divergence with vaccine strains and increased production of pertussis toxin. Antigenic divergence will affect both memory recall and the efficacy of antibodies, while higher levels of pertussis toxin may increase suppression of the innate and acquired immune system. We propose these adaptations ofB. pertussishave decreased the period in which pertussis vaccines are effective and thus enhanced the waning of immunity. We plead for a more integrated approach to the pertussis problem which includes the characteristics of the vaccines, theB. pertussispopulations and the interaction between the two.
Filling in the gaps: Linking theory and practice through telecollaboration in teacher education
Authors: Dooly Melinda , Sadler Randall 
Published: February 2013

AbstractThis article discusses a two-year telecollaborative project in teacher education that took an integrated approach to teaching about and through technological resources in order to introduce student-teachers to innovative methods for communicative-based language learning through computer-mediated communication (CMC). Via ‘technological immersion’, student-teachers in two groups in Spain and the US were required to work together online to give peer feedback and evaluation of several activities, including teaching sequences. They also co-created podcasts, along with accompanying educational activities. Some of the tools used were Moodle, Skype, emails, wikis, Second Life and podcasting. The article analyzes and discusses multimodal data collected during the collaboration. Results indicate that the online collaboration enhanced teacher development through opportunities unavailable in more traditional teacher education classrooms and enabled student-teachers to better make connections between theory and practice.