bluuebunny/crossref_metadata_2025_split huggingface dataset:
SH3BP2 Cherubism Mutation Potentiates TNF-α–Induced Osteoclastogenesis via NFATc1 and TNF-α–Mediated Inflammatory Bone Loss
Authors: Mukai Tomoyuki , Ishida Shu , Ishikawa Remi , Yoshitaka Teruhito , Kittaka Mizuho , Gallant Richard , Lin Yi-Ling , Rottapel Robert , Brotto Marco , Reichenberger Ernst J , Ueki Yasuyoshi 
Published: June 2014

ABSTRACT

Cherubism (OMIM# 118400) is a genetic disorder with excessive jawbone resorption caused by mutations in SH3 domain binding protein 2 (SH3BP2), a signaling adaptor protein. Studies on the mouse model for cherubism carrying a P416R knock-in (KI) mutation have revealed that mutant SH3BP2 enhances tumor necrosis factor (TNF)-α production and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in myeloid cells. TNF-α is expressed in human cherubism lesions, which contain a large number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, and TNF-α plays a critical role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2KI/KI). The data suggest a pathophysiological relationship between mutant SH3BP2 and TNF-α–mediated bone loss by osteoclasts. Therefore, we investigated whether P416R mutant SH3BP2 is involved in TNF-α–mediated osteoclast formation and bone loss. Here, we show that bone marrow–derived M-CSF–dependent macrophages (BMMs) from the heterozygous cherubism mutant (Sh3bp2KI/+) mice are highly responsive to TNF-α and can differentiate into osteoclasts independently of RANKL in vitro by a mechanism that involves spleen tyrosine kinase (SYK) and phospholipase Cγ2 (PLCγ2) phosphorylation, leading to increased nuclear translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone loss with increased osteoclast formation in a mouse calvarial TNF-α injection model as well as in a human TNF-α transgenic mouse model (hTNFtg). SH3BP2 knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated cell formation. These findings suggest that the SH3BP2 cherubism mutation can cause jawbone destruction by promoting osteoclast formation in response to TNF-α expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF-α–induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast progenitors could be a potential strategy for the treatment of bone loss in cherubism as well as in other inflammatory bone disorders. © 2014 American Society for Bone and Mineral Research.
Detecting False Intent Amongst Small Cells of Suspects: Single Versus Repeated Interviews
Authors: Mac Giolla Erik , Granhag Pär Anders 
Published: June 2014

AbstractThe study adds to the growing research field of true and false intentions. Specifically, we examined the benefit of asking unanticipated questions when interviewing groups of suspects on repeated occasions. Participants were divided into truth tellers and liars and were further divided into groups of three. Truth tellers planned a neutral task. Liars planned a mock crime and additionally prepared a cover‐story—thematically similar to the truth tellers' task—to be used if they were apprehended. Participants were intercepted after planning their tasks. In subsequent interviews, participants were asked anticipated questions on their intentions and unanticipated questions on the planning of their intentions. Participants were interviewed once in Experiment 1 (N = 132) and three times in Experiment 2 (N = 123). Truth tellers provided longer and more detailed answers than liars and had higher levels of within‐group consistency compared with liars. This was the case for answers to both anticipated and unanticipated questions. No differences between truth tellers and liars were found for between‐statement consistency. Repeated interviews had minimal effect on statement length or within‐group consistency. The results highlight within‐group consistency as an important cue to deceit. However, a number of limitations to the unanticipated questions approach were evident. Copyright © 2014 John Wiley & Sons, Ltd.
Substantial net N mineralization during the dormant season in temperate forest soils
Authors: Schütt Marianne , Borken Werner , Stange Claus Florian , Matzner Egbert 
Published: June 2014

AbstractIn temperate forest soils, N net mineralization has been extensively investigated during the growing season, whereas N cycling during winter was barely addressed. Here, we quantified net ammonification and nitrification during the dormant season by in situ and laboratory incubations in soils of a temperate European beech and a Norway spruce forest. Further, we compared temperature dependency of N net mineralization in in situ field incubations with those from laboratory incubations at controlled temperatures. From November to April, in situ N net mineralization of the organic and upper mineral horizons amounted to 10.9 kg N (ha · 6 months)–1 in the spruce soil and to 44.3 kg N (ha · 6 months)–1 in the beech soil, representing 65% (beech) and 26% (spruce) of the annual above ground litterfall. N net mineralization was largest in the Oi/Oe horizon and lowest in the A and EA horizons. Net nitrification in the beech soil [1.5 kg N (ha · 6 months)–1] was less than in the spruce soil [5.9 kg N (ha · 6 months)–1]. In the range of soil temperatures observed in the field (0–8°C), the temperature dependency of N net mineralization was generally high for both soils and more pronounced in the laboratory incubations than in the in situ incubations. We suggest that homogenization of laboratory samples increased substrate availability and, thus, enhanced the temperature response of N net mineralization. In temperate forest soils, N net mineralization during the dormant season contributes substantially to the annual N cycling, especially in deciduous sites with large amounts of litterfall immediately before the dormant season. High Q10 values of N net mineralization at low temperatures suggest a huge effect of future increasing winter temperature on the N cycle in temperate forests.
Effect of chromatographic conditions and plasmid DNA size on the dynamic binding capacity of a monolithic support
Authors: Bicho Diana , Sousa Ângela , Sousa Fani , Queiroz João , Tomaz Cãndida 
Published: June 2014

DNA therapies are becoming recognized alternatives for the treatment and prevention of severe pathologies. Although most current trials have used plasmids <10 kbp, in the future larger plasmids would be required. The purpose of this work was to study the chromatographic behavior of nongrafted carbonyldiimidazole monolithic disks using plasmids with different sizes under hydrophobic conditions. Thereunto, the purification of several plasmids was performed. Higher size plasmids needed lower ammonium sulfate concentration, due to the greater number of interactions between the plasmids and monolith. The dynamic binding capacity experiments for the different plasmids revealed a lower capacity for bigger plasmids. It was also verified that the increase of salt concentration from 2.5 to 3 M of ammonium sulfate increased the capacity. At the highest salt concentration, a slight improvement in the capacity using lower flow rate was observed, possibly due to compaction of plasmid molecules and its better organization on the monolith channels. Finally, a low pH also had a positive effect on the capacity. So, this monolithic support proved to be appropriate to purify the supercoiled isoform of different plasmids with different sizes, providing a valuable instrument as a purification technique.
Unusual interaction of RNA polymerase with the bacteriophage Mu middle promoter Pm in the absence of its activator protein Mor
Authors: Mo Yongkai , Howe Martha M. 
Published: June 2014

AbstractThe bacteriophage Mu Mor activator protein is absolutely required for transcription from the Mu middle promoter Pm. However, when RNA polymerase (RNAP) was incubated with Pm DNA in the absence of Mor, a band at promoter position −51 was hypersensitive to DNase I cleavage, demonstrating an interaction of RNAP with the promoter DNA. The hypersensitivity was similar at four different lengths of Pm DNA assayed from −62 to +10, −62 to +46, −96 to +10, and −96 to +46. The hypersensitivity occurred equally well at 5°C, 15°C, and 30°C, indicating that it did not require open complex formation, which only occurred at 30°C. The −51 hypersensitivity at 5°C and 15°C was eliminated by the addition of heparin, consistent with the possibility that it arose by formation of unstable closed complexes of RNAP bound to Pm DNA. Generation of the hypersensitive band required the complete RNAP with its αCTDs, but neither the αCTD nor intact α were sufficient for the interaction and resulting hypersensitivity. There was no correlation between the level of hypersensitivity observed in vitro and the level of Pm activity in vivo, as assayed by the Mor‐dependent production of β‐galactosidase from a Pm‐lacZ fusion. In an “order of addition” experiment, preincubation of Pm DNA with Mor followed by addition of RNAP led to the fastest open complex formation, whereas preincubation of Pm DNA with RNAP gave the slowest. These results support the conclusion that Mor recruits RNAP to Pm rather than reposition a prebound RNAP, as occurs for C‐dependent repositioning of RNAP at the Mu late promoter Pmom.
AglB, catalyzing the oligosaccharyl transferase step of the archaeal N‐glycosylation process, is essential in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius
Authors: Meyer Benjamin H. , Albers Sonja‐Verena 
Published: June 2014

AbstractSulfolobus acidocaldarius, a thermo‐acidophilic crenarchaeon which grows optimally at 76°C and pH 3, exhibits an astonishing high number of N‐glycans linked to the surface (S‐) layer proteins. The S‐layer proteins as well as other surface‐exposed proteins are modified via N‐glycosylation, in which the oligosaccharyl transferase AglB catalyzes the final step of the transfer of the glycan tree to the nascent protein. In this study, we demonstrated that AglB is essential for the viability of S. acidocaldarius. Different deletion approaches, that is, markerless in‐frame deletion as well as a marker insertion were unsuccessful to create an aglB deletion mutant. Only the integration of a second aglB gene copy allowed the successful deletion of the original aglB.
Randomized, controlled trial of rasagiline as an add‐on to dopamine agonists in Parkinson's disease
Authors: Hauser Robert A. , Silver Dee , Choudhry Azhar , Eyal Eli , Isaacson Stuart ,   for the ANDANTE study investigators
Published: June 2014

ABSTRACTDopamine agonists (DA) are often used as first‐line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase‐B (MAO‐B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18‐week, randomized, double‐blind, placebo‐controlled trial of rasagiline 1 mg/d as an add‐on to DA therapy (ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent‐to‐treat (ITT) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7, and duration of PD was 2.1 ± 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference ± SE, −2.4 ± 0.95; 95% confidence interval [CI], −4.3, −0.5; P = 0.012). Mean improvement (LS mean ± SE) was −3.6 ± 0.68 in the rasagiline group and −1.2 ± 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated. © 2014 International Parkinson and Movement Disorder Society
Multidisciplinary Rehabilitation for Chronic Widespread Musculoskeletal Pain: Results from Daily Practice
Authors: Koele Robin , Volker Gerard , van Vree Félicie , van Gestel Marc , Köke Albère , Vliet Vlieland Theodora 
Published: June 2014

AbstractIntroductionEvidence for the efficacy of a multi‐component approach for chronic widespread musculoskeletal pain (CWP) has been reported, although the effects are overall moderate and this approach has rarely been investigated in real life.AimThe aim of the study was to describe the effects of a 15‐week multidisciplinary pain rehabilitation programme on pain, activities and participation in patients with CWP.MethodsThe current retrospective study used data which were routinely gathered on all consecutive patients with CWP referred to a rehabilitation programme over a 21‐month period. The 15‐week multidisciplinary rehabilitation programme consisted of cognitive behavioural therapy and exercise, as well as individual and group sessions with additional treatment modalities. Assessments included the Pain Disability Index (PDI), the Pain Catastrophizing Scale (PCS), the Multidimensional Pain Inventory (MPI), numerical scales for pain and fatigue, the Canadian Occupational Performance Measure (COPM), the one‐minute stair‐climb test and the RAND‐36. Paired t‐tests and Wilcoxon signed‐rank tests were carried out to analyse changes over time.ResultsA total of 165 patients were included [mean age 44.1 (standard deviation 12.9) years], 143 (87%) women). Discharge data were available for 154 patients (93%). All outcomes showed statistically significant improvements between admission and discharge (p < 0.05), with the largest effect sizes (>1.0) observed for the COPM. A longer duration of complaints was associated with less improvement in the PDI.Discussion and conclusionIn daily rehabilitation practice, a 15‐week multidisciplinary treatment programme for patients with CWP showed statistically significant improvements in pain, activities and participation over time. Future studies are needed further to substantiate the long‐term cost‐effectiveness, and to identify the patients who benefit the most. Copyright © 2014 John Wiley & Sons, Ltd.
Twitch potentiation induced by two different modalities of neuromuscular electrical stimulation: Implications for motor unit recruitment
Authors: Regina Dias Da Silva Sarah , Neyroud Daria , Maffiuletti Nicola A. , Gondin Julien , Place Nicolas 
Published: June 2014

ABSTRACTIntroduction: We tested the hypothesis that twitch potentiation would be greater following conventional (CONV) neuromuscular electrical stimulation (50‐µs pulse width and 25‐Hz frequency) compared with wide‐pulse high‐frequency (WPHF) neuromuscular electrical stimulation (1‐ms, 100‐Hz) and voluntary (VOL) contractions, because of specificities in motor unit recruitment (random in CONV vs. random and orderly in WPHF vs. orderly in VOL). Methods: A single twitch was evoked by means of tibial nerve stimulation before and 2 s after CONV, WPHF, and VOL conditioning contractions of the plantar flexors (intensity: 10% maximal voluntary contraction; duration: 10 s) in 13 young healthy subjects. Results: Peak twitch increased (P < 0.05) after CONV (+4.5 ± 4.0%) and WPHF (+3.3 ± 5.9%), with no difference between the 2 modalities, whereas no changes were observed after VOL (+0.8 ± 2.6%). Conclusions: Our results demonstrate that presumed differences in motor unit recruitment between WPHF and CONV do not seem to influence twitch potentiation results. Muscle Nerve 51: 412–418, 2015
The relationship between posttraumatic stress and posttraumatic growth among adolescent and young adult (AYA) cancer patients
Authors: Zebrack Brad , Kwak Minyoung , Salsman John , Cousino Melissa , Meeske Kathleen , Aguilar Christine , Embry Leanne , Block Rebecca , Hayes‐Lattin Brandon , Cole Steve 
Published: June 2014

ABSTRACTObjectiveTheories of posttraumatic growth suggest that some degree of distress is necessary to stimulate growth; yet, investigations of the relationship between stress and growth following trauma are mixed. This study aims to understand the relationship between posttraumatic stress symptoms and posttraumatic growth in adolescent and young adult (AYA) cancer patients.Method165 AYA patients aged 14–39 years at diagnosis completed standardized measures of posttraumatic stress and posttraumatic growth at 12 months following diagnosis. Locally weighted scatterplot smoothing and regression were used to examine linear and curvilinear relationships between posttraumatic stress and posttraumatic growth.ResultsNo significant relationships between overall posttraumatic stress severity and posttraumatic growth were observed at 12‐month follow‐up. However, curvilinear relationships between re‐experiencing (a posttraumatic stress symptom) and two of five posttraumatic growth indicators (New Possibilities, Personal Strengths) were observed.ConclusionFindings suggest that re‐experiencing is associated with some aspects of posttraumatic growth but not others. Although re‐experiencing is considered a symptom of posttraumatic stress disorder, it also may represent a cognitive process necessary to achieve personal growth for AYAs. Findings call into question the supposed psychopathological nature of re‐experiencing and suggest that re‐experiencing, as a cognitive process, may be psychologically adaptive. Opportunities to engage family, friends, cancer survivors, or health care professionals in frank discussions about fears, worries, or concerns may help AYAs re‐experience cancer in a way that enhances their understanding of what happened to them and contributes to positive adaptation to life after cancer. Copyright © 2014 John Wiley & Sons, Ltd.
Inflammation and psychosocial factors mediate exercise effects on sleep quality in breast cancer survivors: pilot randomized controlled trial
Authors: Rogers Laura Q. , Fogleman Amanda , Trammell Rita , Hopkins‐Price Patricia , Spenner Allison , Vicari Sandra , Rao Krishna , Courneya Kerry S. , Hoelzer Karen , Robbs Randall , Verhulst Steven 
Published: June 2014

AbstractObjectiveTo improve mechanistic understanding, this pilot randomized controlled trial examined mediators of an exercise intervention effects on sleep in breast cancer survivors (BCS).MethodsForty‐six postmenopausal BCS (≤Stage II, off primary treatment) were randomized to a 3‐month exercise intervention or control group. Intervention included 160 min/week of moderate intensity aerobic walking, twice weekly resistance training (resistance bands), and six discussion groups (to improve adherence). Blinded assessments at baseline and post‐intervention included sleep disturbance (PSQI and PROMIS®), objective sleep quality (accelerometer), serum cytokines, accelerometer physical activity, cardiorespiratory fitness, body composition, fatigue, and psychosocial factors. Mediation was tested using Freedman–Schatzkin difference‐in‐coefficients tests.ResultsWhen compared with control, the intervention group demonstrated a significant increase in PSQI sleep duration (i.e., fewer hours of sleep/night) (d = 0.73, p = .03). Medium to large but non‐significant standardized effect sizes were noted for PSQI daytime somnolence (d = −0.63, p = .05) and accelerometer latency (d = −0.49, p = .14). No statistically significant mediators were detected for PSQI sleep duration score or accelerometer latency. Daytime somnolence was mediated by tumor necrosis factor‐alpha (mediated 23% of intervention effect, p < .05), interleukin (IL)‐6:IL‐10 (16%, p < .01), IL‐8:IL‐10 (26%, p < .01), and fatigue (38%, p < .05). Mediating or enhancing relationships for several of the sleep outcomes were noted for accelerometer physical activity, PROMIS® fatigue, exercise social support, and/or physical activity enjoyment.ConclusionsInflammation and psychosocial factors may mediate or enhance sleep response to our exercise intervention. Further study is warranted to confirm our results and translate our findings into more effective interventions aimed at improving sleep quality in BCS. Copyright © 2014 John Wiley & Sons, Ltd.
Quality‐adjusted time without symptoms or toxicity (Q‐TWiST): patient‐reported outcome or mathematical model? A systematic review in cancer
Authors: Tate Wendy R. , Skrepnek Grant H. 
Published: June 2014

AbstractObjectiveSuccessful cancer treatment is defined as an increase in overall survival and/or progression‐free survival. Despite their importance, these metrics omit patient quality of life. Quality‐adjusted time without symptoms or toxicity (Q‐TWiST) was developed to adjust survival gained, accounting for quality of life. The purpose of this systematic review was to assess the methods reported in cancer literature to determine Q‐TWiST values and how these are currently translated to the clinic.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta‐analyses guidelines were used to conduct a systematic review of studies indexed on MEDLINE and Web of Science through April 2013. Cancer studies that measured Q‐TWiST either as a primary outcome or retrospectively and determined utility coefficients from a patient population were identified, and their methods reviewed to determine how the utility coefficient was calculated. Additionally, other relevant factors such as definitions of health states and significant findings were collected and summarized.ResultsOut of 284 studies, 11 were identified that calculated patient‐defined utility coefficients. Several methods to determine utility coefficients were reported, and multiple definitions of health state toxicity were applied. Of these studies, seven reported significant differences (p < 0.05) in quality‐adjusted survival. No studies, however, directly discussed the clinical relevance of their findings.ConclusionsCurrently, Q‐TWiST is utilized as a mathematical theory rather than a clinical tool. Standardization of terminology plus reliability and validity testing of determining both utility coefficients and time frame definitions must be performed before Q‐TWiST can become clinically useful to physicians and patients alike for making treatment decisions. Copyright © 2014 John Wiley & Sons, Ltd.
Defeat scanning worms in cyber warfare
Authors: Hsu Fu‐Hau , Chen Li‐Han , Lin Chia‐Jun 
Published: June 2014

AbstractIn this paper, we propose an automatic defense system, called Serum System, against scanning worms. The homeland security department of a country can use Serum System to protect its Internet infrastructure. When an infecting host is infecting a Serum System host, called Serum System Server (SSS), the SSS automatically replaces the shellcode inside the infecting string with its code (called serum code) and then uses the modified string (called serum string) to counterattack the infecting host and takes control of it. The serum code transforms the infecting host into a Serum System Client (SSC) that has the same functions as the SSS and is immune to the same worm. Therefore, infecting hosts attacking SSSs or SSCs will transform themselves into SSCs. We implemented Serum System on Linux and also built a mathematical model for Serum System to analyze its effectiveness and bandwidth savings. Our analyses show that with only a small number of SSSs and through chain counterattacks, Serum System can automatically and rapidly defeat related infected hosts. Compared with white worms whose spread cannot be controlled, Serum System only spreads on infected hosts. The amount of accumulative traffic saved by Serum System at time tick 450 reached 90%. Copyright © 2014 John Wiley & Sons, Ltd.