bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of serine 21 modulates the proliferation inhibitory more than the differentiation inducing effects of C/EBPα in K562 cells
Authors: Fragliasso Valentina , Chiodo Yuri , Ferrari‐Amorotti Giovanna , Soliera Angela Rachele , Manzotti Gloria , Cattelani Sara , Candini Olivia , Grisendi Giulia , Vergalli Jenny , Mariani Samanta Antonella , Guerzoni Clara , Calabretta Bruno 
Published: December 2011

AbstractThe CCAAT/enhancer binding protein α (C/EBPα) is a transcription factor required for differentiation of myeloid progenitors. In acute myeloid leukemia (AML) cells expressing the constitutively active FLT3‐ITD receptor tyrosine kinase, MAP kinase‐dependent phosphorylation of serine 21 (S21) inhibits the ability of C/EBPα to induce granulocytic differentiation. To assess whether this post‐translational modification also modulates the activity of C/EBPα in BCR/ABL‐expressing cells, we tested the biological effects of wild‐type and mutant C/EBPα mimicking phosphorylated or non‐phosphorylatable serine 21 (S21D and S21A, respectively) in K562 cells ectopically expressing tamoxifen‐regulated C/EBPα‐ER chimeric proteins. We show here that S21D C/EBPα‐ER induced terminal granulocytic differentiation of K562 cells almost as well as wild‐type C/EBPα‐ER, while S21A C/EBPα‐ER was less efficient. Furthermore, wild‐type C/EBPα suppressed the proliferation and colony formation of K562 cells vigorously, while S21D and S21A C/EBPα mutants had more modest anti‐proliferative effects. Both mutants were less effective than wild‐type C/EBPα in suppressing endogenous E2F‐dependent transactivation and bound less E2F‐2 and/or E2F‐3 proteins in anti‐C/EBPα immunoprecipitates. Together, these findings suggest that mutation of S21 more than its phosphorylation inhibits the anti‐proliferative effects of C/EBPα due to reduced interaction with or impaired regulation of the activity of E2F proteins. By contrast, phosphorylation of serine 21 appears to have a modest role in modulating the differentiation‐inducing effects of C/EBPα in K562 cells. J. Cell. Biochem. 113: 1704–1713, 2012. © 2011 Wiley Periodicals, Inc.
A novel DNA intercalator, 8‐methoxy pyrimido[4′,5′:4,5]thieno (2,3‐b)quinoline‐4(3H)‐one induces apoptosis in cancer cells, inhibits the tumor progression and enhances lifespan in mice with tumor
Authors: Sharma Sheetal , Panjamurthy Kuppusamy , Choudhary Bibha , Srivastava Mrinal , Shahabuddin MS , Giri Ranjit , Advirao Gopal M. , Raghavan Sathees C. 
Published: December 2011

AbstractPolycyclic aromatic molecules such as ellipticine intercalate into double‐stranded DNA and interfere with physiological functions. In the present study, we evaluate the chemotherapeutic potential of MPTQ on animal models and its mode of action. In order to test the antitumor activity, monohydrochloride of MPTQ was orally administered in mice bearing tumor. Results showed a significant inhibition of tumor growth compared to that of untreated controls. More importantly, mean lifespan of tumor bearing animals treated with MPTQ was significantly higher as compared to that of untreated tumor bearing mice suggesting that the treatment affected viability of cancerous cells, but not of normal cells. Consistent with this, we find that administration of MPTQ to normal mice did not cause any major side effects as observed upon hematological and serum profiling. We also found that MPTQ induces cytotoxicity in cancer cell lines, by activating apoptosis both by intrinsic and extrinsic pathways. Thus, MPTQ could be used as a potential cancer therapeutic agent. © 2011 Wiley Periodicals, Inc.
Inherent correction of motion‐induced phase errors in multishot spiral diffusion‐weighted imaging
Authors: Truong Trong‐Kha , Chen Nan‐kuei , Song Allen W. 
Published: December 2011

AbstractMultishot spiral imaging is a promising alternative to echo‐planar imaging for high‐resolution diffusion‐weighted imaging and diffusion tensor imaging. However, subject motion in the presence of diffusion‐weighting gradients causes phase inconsistencies among different shots, resulting in signal loss and aliasing artifacts in the reconstructed images. Such artifacts can be reduced using a variable‐density spiral trajectory or a navigator echo, however at the cost of a longer scan time. Here, a novel iterative phase correction method is proposed to inherently correct for the motion‐induced phase errors without requiring any additional scan time. In this initial study, numerical simulations and in vivo experiments are performed to demonstrate that the proposed method can effectively and efficiently correct for spatially linear phase errors caused by rigid‐body motion in multishot spiral diffusion‐weighted imaging of the human brain. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Efficient spectral editing at 7 T: GABA detection with MEGA‐sLASER
Authors: Andreychenko Anna , Boer Vincent O. , Arteaga de Castro Catalina S. , Luijten Peter R. , Klomp Dennis W. J. 
Published: December 2011

AbstractAt high field (7 T) spectral editing of γ‐aminobutyric acid with MEGA‐point‐resolved spectroscopy is inefficient due to the large chemical shift displacement error. In this article, a new pulse sequence is designed which has minimal chemical shift displacement error to perform an efficient spectral editing of the γ‐aminobutyric acid 3.0 ppm resonance at 7 T. The sequence consists of the conventional MEGA editing pulses and a semi‐localized by adiabatic selective refocusing sequence. Phantom and in vivo measurements demonstrated an efficient detection of γ‐aminobutyric acid. Using ECG triggering, excellent in vivo performance of the MEGA‐semi‐localized by adiabatic selective refocusing (MEGA‐sLASER) provided well‐resolved γ‐aminobutyric acid signals in 27 mL volumes in the human brain at an echo time of 74 ms within a relatively short acquisition time (5 min). Furthermore, the high efficiency of the MEGA‐sLASER was demonstrated by acquiring small volumes (8 mL) at an echo time of 74 ms, as well as long echo time measurements (222 ms in 27 mL volume). Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome
Authors: Brašić James Robert , Bibat Genila , Kumar Anil , Zhou Yun , Hilton John , Yablonski Marybeth E. , Dogan Ahmet Semih , Guevara Maria Rita , Stephane Massoud , Johnston Michael , Wong Dean Foster , Naidu Sakkubai 
Published: December 2011

AbstractRett syndrome (RTT) is a neurodevelopmental disability characterized by mutations in the X‐linked methyl‐CpG‐binding protein 2 located at the Xq28 region. The severity is modified in part by X chromosomal inactivation resulting in wide clinical variability. We hypothesized that the ability to perform the activities of daily living (ADL) is correlated with the density of vesicular acetylcholine transporters in the striata of women with RTT. The density of the vesicular acetylcholine transporters in the living human brain can be estimated by single‐photon emission‐computed tomography (SPECT) after the administration of (−)‐5‐[123I]iodobenzovesamicol ([123I]IBVM). Twenty‐four hours following the intravenous injection of ∼333 MBq (9 mCi) [123I]IBVM, four women with RTT and nine healthy adult volunteer control participants underwent SPECT brain scans for 60 min. The Vesicular Acetylcholine Transporter Binding Site Index (Kuhl et al., 1994), a measurement of the density of vesicular acetylcholine transporters, was estimated in the striatum and the reference structure, the cerebellum. The women with RTT were assessed for certain ADL. Although the striatal Vesicular Acetylcholine Transporter Binding Site Index was not significantly lower in RTT (5.2 ± 0.9) than in healthy adults (5.7 ± 1.6), RTT striatal Vesicular Acetylcholine Transporter Binding Site Indices and ADL scores were linearly associated (ADL = 0.89*(Vesicular Acetylcholine Transporter Binding Site Index) + 4.5; R2 = 0.93; P < 0.01), suggesting a correlation between the ability to perform ADL and the density of vesicular acetylcholine transporters in the striata of women with RTT. [123I]IBVM is a promising tool to characterize the pathophysiological mechanisms of RTT and other neurodevelopmental disabilities. Synapse, 2012. © 2011 Wiley Periodicals, Inc.
Immunology in the clinic review series; focus on type 1 diabetes and viruses: how viral infections modulate beta cell function
Authors: Grieco F A , Sebastiani G , Spagnuolo I , Patti A , Dotta F 
Published: December 2011

Summary
OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES
Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy.
Type 1 diabetes mellitus (T1DM) is a multi-factorial immune-mediated disease characterized by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically susceptible individuals. Epidemiological evidence has also documented the constant rise in the incidence of T1DM worldwide, with viral infections representing one of the candidate environmental risk factors identified by several independent studies. In fact, epidemiological data showed that T1DM incidence increases after epidemics due to enteroviruses and that enteroviral RNA can be detected in the blood of &gt;50% of T1DM patients at the time of disease onset. Furthermore, both in-vitro and ex-vivo studies have shown that viruses can infect pancreatic beta cells with consequent effects ranging from functional damage to cell death.
Heritability estimates for racing performance in Japanese Thoroughbred racehorses using linear and non‐linear model analyses
Authors: Tozaki T. , Miyake T. , Kakoi H. , Gawahara H. , Hirota K. , Nakano Y. , Kurosawa M. 
Published: December 2011

SummaryThis study evaluated the differences between linear and non‐linear modelled heritability estimates of racing performance based on lifetime earnings (LE) and lifetime ranking (LR) in Japanese Thoroughbred racehorses. The heritability estimate (h2 = 0.25) obtained from a non‐linear model based on formal Japan Racing Association ranking was much higher than that obtained from a linear model based on the original trait phenotype (h2 = 0.11). The linear models showed slightly higher heritability estimates under the trait categorizations than under the original phenotypes, while the non‐linear categorical trait models showed much higher heritability estimates than the linear models, especially for binary trait categorizations (h2 = 0.34) with non‐winning and winning horses. The binary trait categorizations were consistent with the case and control classifications in the previous genome‐wide association study (GWAS), which identified possible sequence variants on ECA18 that affect racing performance in Japanese Thoroughbred racehorses. Those findings suggested that the different heritability estimates obtained from several trait categorizations would reflect the possible presence of susceptibility gene segregations in the analyzed population, indicating that heritability estimates from non‐linear models are useful for the selection of case and control populations in GWAS.
Work of breathing and respiratory drive in obesity
Authors: LIN CHING‐KAI , LIN CHING‐CHI 
Published: December 2011

ABSTRACTObesity, particularly severe central obesity, affects respiratory physiology both at rest and during exercise. Reductions in expiratory reserve volume, functional residual capacity, respiratory system compliance and impaired respiratory system mechanics produce a restrictive ventilatory defect. Low functional residual capacity and reductions in expiratory reserve volume increase the risk of expiratory flow limitation and airway closure during quiet breathing. Consequently, obesity may cause expiratory flow limitation and the development of intrinsic positive end expiratory pressure, especially in the supine position. This increases the work of breathing by imposing a threshold load on the respiratory muscles leading to dyspnoea. Marked reductions in expiratory reserve volume may lead to ventilation distribution abnormalities, with closure of airways in the dependent zones of the lungs, inducing ventilation perfusion mismatch and gas exchange abnormalities. Obesity may also impair upper airway mechanical function and neuromuscular strength, and increase oxygen consumption, which in turn, increase the work of breathing and impair ventilatory drive. The combination of ventilatory impairment, excess CO2 production and reduced ventilatory drive predisposes obese individuals to obesity hypoventilation syndrome.
Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity
Authors: Conte A. , Giannantoni A. , Proietti S. , Giovannozzi S. , Fabbrini G. , Rossi A. , Porena M. , Berardelli A. 
Published: December 2011

Background:  Although botulinum toxin (BoNT/A) injected into the detrusor muscle improves overactive bladder symptoms in patients with neurogenic detrusor overactivity, how it does so remains unclear. In this study, we investigated whether BoNT/A improves detrusor overactivity by modulating bladder afferent activity.Methods:  To do so, during urodynamic assessment, we tested the soleus muscle Hoffmann (H) reflex during bladder filling before and after intradetrusor BoNT/A in patients with Parkinson’s disease (PD) and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conventional therapy. Healthy subjects underwent H reflex studies during urodynamic assessment and acted as controls.Results:  Our findings show that BoNT/A injected into the detrusor muscle effectively reduces clinical overactive bladder symptoms in patients with PD and SCI. In healthy subjects and patients with PD, bladder filling [at maximum cystometric capacity, (MCC)] significantly decreased the H reflex size, whereas in patients with SCI, it slightly facilitated the H reflex size. At MCC, in patients with PD, BoNT/A significantly reduced the expected H reflex inhibition, whereas in those with SCI, BoNT/A turned the H reflex facilitation at maximum bladder filling into a slight inhibition.Conclusions:  These findings show that BoNT/A injected into the detrusor muscle in patients with PD and SCI modulates bladder afferent activity. Modulation of bladder afferents possibly explains why BoNT/A improves detrusor overactivity.
Physical Training Improves Motor Performance in People with Dementia: A Randomized Controlled Trial
Authors: Hauer Klaus , Schwenk Michael , Zieschang Tania , Essig Marco , Becker Clemens , Oster Peter 
Published: December 2011

ObjectivesTo determine whether a specific, standardized training regimen can improve muscle strength and physical functioning in people with dementia.DesignDouble‐blinded, randomized, controlled trial with 3‐month intervention and 3‐month follow‐up period in 2006 to 2009.SettingOutpatient geriatric rehabilitation.ParticipantsIndividuals with confirmed mild to moderate dementia, no severe somatic or psychological disease, and ability to walk 10 m. Most participants were still living independently with or without supportive care.InterventionSupervised, progressive resistance and functional group training for 3 months specifically developed for people with dementia (intervention, n = 62) compared with a low‐intensity motor placebo activity (control, n = 60).MeasurementsPrimary outcome measures were one‐repetition maximum in a leg press device for maximal strength and duration of the five‐chair‐stand test for functional performance. Secondary outcome measures were assessed for a number of established parameters for maximal strength, physical function, and physical activity.ResultsTraining significantly improved both primary outcomes (percentage change from baseline: maximal strength, intervention group (IG): +51.5 ± 41.5 kg vs control group (CG): –1.0 ± 28.9 kg, P < .001; functional performance, IG: –25.9 ± 15.1 seconds vs CG: +11.3 ± 60.4 seconds, P < .001). Secondary analysis confirmed effects for all strength and functional parameters. Training gains were partly sustained during follow‐up. Low baseline performance on motor tasks but not cognitive impairment predicted positive training response. Physical activity increased significantly during the intervention (P < .001).ConclusionThe intensive, dementia‐adjusted training was feasible and substantially improved motor performance in frail, older people with dementia and may represent a model for structured rehabilitation or outpatient training.
Maximum Occlusal Force and Physical Performance in the Oldest Old: The Tokyo Oldest Old Survey on Total Health
Authors: Iinuma Toshimitsu , Arai Yasumichi , Fukumoto Motoko , Takayama Michiyo , Abe Yukiko , Asakura Keiko , Nishiwaki Yuji , Takebayashi Toru , Iwase Takashi , Komiyama Kazuo , Gionhaku Nobuhito , Hirose Nobuyoshi 
Published: December 2011

ObjectivesTo elucidate the independent relationship between masticatory and physical performance in community‐living oldest old people (mean age ± standard deviation 87.8 ± 2.2, range 85–102).DesignCross‐sectional analysis.SettingUniversity research center or home‐based examination.ParticipantsFour hundred eighty‐nine community‐living individuals (219 men, 270 women) aged 85 and older.MeasurementsMaximum occlusal force (MOF) was measured using an occlusal force measuring device. Sociodemographic and functional factors, oral health, comorbidities, blood chemistry, lower extremity performance, and handgrip strength were assessed. Blood chemistry analyses included serum albumin, C‐reactive protein, interleukin (IL)‐6, and total and free testosterone.ResultsMOF was significantly associated with age, body mass index, and cognitive impairment in men but not in women. Comorbidities and blood chemistry were not associated with MOF except for a significant association with IL‐6 concentration in women. In a multivariate model adjusted for various confounders, lower MOF was associated with greater risk for poor performance on the timed up and go (TUG) test in men and women (men: odds ratio (OR)=2.34, 95% confidence interval (CI)=1.02–5.38; women: OR=2.44, 95% CI=1.12–5.33). MOF was similarly associated with performance in chair standing, one‐leg standing, and handgrip strength only in men. These associations remained after adjustment for number of natural teeth.ConclusionMOF was strongly and independently associated with all measures of physical performance in men and with the TUG test in women after adjustment for various confounders, suggesting that age‐related declines in masticatory and skeletal muscle functions share common mechanistic pathways in older age, particularly in men.
Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature
Authors: Krishnamoorthy Naveen , Viswanathan Seethalakshmi , Rekhi Bharat , Jambhekar Nirmala A. 
Published: December 2011

Cutaneous angiosarcoma or lymphangiosarcoma represents an uncommon aggressive tumor known to arise on a background of chronic lymphedema secondary to various etiologies, principally following surgery or irradiation. There have been rarely reported cases of angiosarcoma following infective conditions that eventuate with lymphatic stasis. We report a case of angiosarcoma arising after 33 years within a background of filariasis. Awareness of this association can lead to early diagnosis and appropriate treatment of this potentially fatal malignant tumor.Krishnamoorthy N, Viswanathan S, Rekhi B, Jambhekar NA. Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature.
Major and Trace Element Characteristics of Apatites in Granitoids from Central Kazakhstan: Implications for Petrogenesis and Mineralization
Authors: CAO Mingjian , LI Guangming , QIN Kezhang , SEITMURATOVA Eleonora Yusupovha , LIU Yongsheng 
Published: December 2011

AbstractThis paper presents abundances of major and trace elements of apatites in granitic rocks associated with different types of ore deposits in Central Kazakhstan on the basis of electron probe microanalysis and laser ablation inductively coupled plasma mass spectrometry. Our results demonstrate that the concentrations and ratios of elements in apatites from different granitoid rocks show distinct features, and are sensitive to magma evolution, petrogenetic and metallogenetic processes. Apatites in the rocks associated with Mo‐W deposits have high content of F and MnO, low content of Cl, which may be indicative of sedimentary sources, while apatites from a Pb‐Zn deposit show relatively high content of Cl and low F content, which possibly suggest a high water content. In these apatites, Sr contents decrease, while Mn and Y contents increase with magma evolution. This relationship reflects that these elements in apatites are related with the degree of magmatic differentiation. Four types of REE patterns in apatites are identified. Type 1 character of highest (La/Yb)N in apatites of Aktogai porphyry Cu‐Mo deposit, Sayak‐I skarn Cu deposit and Akzhal skarn Pb‐Zn depposit is likely produced by the crystallization of heavy REE‐enriched minerals. Type 2 character of upward‐convex light REE in apatite of Aktogai porphyries likely results from La‐enriched mineral crystallization. Type 3 feature of Nd depletion in apatites of East Kounrad and Zhanet deposits both from Mo‐W deposits primarily inherits the character of host‐rock. Type 4 apatites of Aktogai deposit and Akshatau W‐Mo deposit with wide range of REE contents may suggest that apatites crystallize under a wide temperature range. Three types of apatite with distinct redox states are identified based on Eu anomaly. The Aktogai apatite with slight negative Eu anomaly displays the most oxidized state of the magma, and the apatites of other samples at Aktogai, East Kounrad and Akzhal with moderate negative Eu anomaly show moderate oxidizing condition of these rocks, while the remaining apatites with strong En anomaly indicate a moderate reductive state of these rocks.
In Vitro
Characterization of the Activity of PF-05095808, a Novel Biological Agent for Hepatitis C Virus Therapy
Authors: Lavender Helen , Brady Kevin , Burden Frances , Delpuech-Adams Oona , Denise Hubert , Palmer Amy , Perkins Hannah , Savic Boris , Scott Sarah , Smith-Burchnell Caroline , Troke Phil , Wright J. Fraser , Suhy David , Corbau Romu 
Published: December 2011

ABSTRACT

PF-05095808 is a novel biological agent for chronic hepatitis C virus (HCV) therapy. It comprises a recombinant adeno-associated virus (AAV) DNA vector packaged into an AAV serotype 8 capsid. The vector directs expression of three short hairpin RNAs (shRNAs) targeted to conserved regions of the HCV genome. These shRNAs are processed by the host cell into the small interfering RNAs which mediate sequence-specific cleavage of target regions. For small-molecule inhibitors the key screens needed to assess
in vitro
activity are well defined; we developed new assays to assess this RNA interference agent and so to understand its therapeutic potential. Following administration of PF-05095808 or corresponding synthetic shRNAs, sequence-specific antiviral activity was observed in HCV replicon and infectious virus systems. To quantify the numbers of shRNA molecules required for antiviral activity
in vitro
and potentially also
in vivo
, a universal quantitative PCR (qPCR) assay was developed. The number of shRNA molecules needed to drive antiviral activity proved to be independent of the vector delivery system used for PF-05095808 administration. The emergence of resistant variants at the target site of one shRNA was characterized. A novel RNA cleavage assay was developed to confirm the spectrum of activity of PF-05095808 against common HCV clinical isolates. In summary, our data both support antiviral activity consistent with an RNA interference mechanism and demonstrate the potential of PF-05095808 as a therapeutic agent for chronic HCV infection.