bluuebunny/crossref_metadata_2025_split huggingface dataset:
The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells
Authors: Hitakomate Ekarat , Hood Fiona E , Sanderson Helen S , Clarke Paul R 
Published: July 2010

Abstract

Background
Regulator of chromosome condensation 1 (RCC1) is the guanine nucleotide exchange factor for Ran GTPase. Localised generation of Ran-GTP by RCC1 on chromatin is critical for nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Both the N-terminal tail of RCC1 and its association with Ran are important for its interaction with chromatin in cells. In vitro, the association of Ran with RCC1 induces a conformational change in the N-terminal tail that promotes its interaction with DNA.

Results
We have investigated the mechanism of the dynamic interaction of the α isoform of human RCC1 (RCC1α) with chromatin in live cells using fluorescence recovery after photobleaching (FRAP) of green fluorescent protein (GFP) fusions. We show that the N-terminal tail stabilises the interaction of RCC1α with chromatin and this function can be partially replaced by another lysine-rich nuclear localisation signal. Removal of the tail prevents the interaction of RCC1α with chromatin from being stabilised by RanT24N, a mutant that binds stably to RCC1α. The interaction of RCC1α with chromatin is destabilised by mutation of lysine 4 (K4Q), which abolishes α-N-terminal methylation, and this interaction is no longer stabilised by RanT24N. However, α-N-terminal methylation of RCC1α is not regulated by the binding of RanT24N. Conversely, the association of Ran with precipitated RCC1α does not require the N-terminal tail of RCC1α or its methylation. The mobility of RCC1α on chromatin is increased by mutation of aspartate 182 (D182A), which inhibits guanine-nucleotide exchange activity, but RCC1αD182A can still bind nucleotide-free Ran and its interaction with chromatin is stabilised by RanT24N.

Conclusions
These results show that the stabilisation of the dynamic interaction of RCC1α with chromatin by Ran in live cells requires the N-terminal tail of RCC1α. α-N-methylation is not regulated by formation of the binary complex with Ran, but it promotes chromatin binding through the tail. This work supports a model in which the association of RCC1α with chromatin is promoted by a conformational change in the α-N-terminal methylated tail that is induced allosterically in the binary complex with Ran.
Genomic patterns of nucleotide diversity in divergent populations of U.S. weedy rice
Authors: Reagon Michael , Thurber Carrie S , Gross Briana L , Olsen Kenneth M , Jia Yulin , Caicedo Ana L 
Published: July 2010

AbstractBackgroundWeedy rice (red rice), a conspecific weed of cultivated rice (Oryza sativaL.), is a significant problem throughout the world and an emerging threat in regions where it was previously absent. Despite belonging to the same species complex as domesticated rice and its wild relatives, the evolutionary origins of weedy rice remain unclear. We use genome-wide patterns of single nucleotide polymorphism (SNP) variation in a broad geographic sample of weedy, domesticated, and wildOryzasamples to infer the origin and demographic processes influencing U.S. weedy rice evolution.ResultsWe find greater population structure than has been previously reported for U.S. weedy rice, and that the multiple, genetically divergent populations have separate origins. The two main U.S. weedy rice populations share genetic backgrounds with cultivatedO. sativavarietal groups not grown commercially in the U.S., suggesting weed origins from domesticated ancestors. Hybridization between weedy groups and between weedy rice and local crops has also led to the evolution of distinct U.S. weedy rice populations. Demographic simulations indicate differences among the main weedy groups in the impact of bottlenecks on their establishment in the U.S., and in the timing of divergence from their cultivated relatives.ConclusionsUnlike prior research, we did not find unambiguous evidence for U.S. weedy rice originating via hybridization between cultivated and wildOryzaspecies. Our results demonstrate the potential for weedy life-histories to evolve directly from within domesticated lineages. The diverse origins of U.S. weedy rice populations demonstrate the multiplicity of evolutionary forces that can influence the emergence of weeds from a single species complex.
Impact of Body Mass Index on the relationship of epicardial adipose tissue to metabolic syndrome and coronary artery disease in an Asian population
Authors: Park Jin-Sun , Ahn Sung-Gyun , Hwang Jung-Won , Lim Hong-Seok , Choi Byoung-Joo , Choi So-Yeon , Yoon Myeong-Ho , Hwang Gyo-Seung , Tahk Seung-Jea , Shin Joon-Han 
Published: July 2010

Abstract

Background
In a previous study, we demonstrated that the thickness of epicardial adipose tissue (EAT), measured by echocardiography, was increased in patients with metabolic syndrome (MS) and coronary artery disease (CAD). Several studies on obese patients, however, failed to demonstrate any relationship between EAT and CAD. We hypothesized that body mass index (BMI) affected the link between EAT and MS and CAD.

Methods
We consecutively enrolled 643 patients (302 males, 341 females; 59 ± 11 years), who underwent echocardiography and coronary angiography. The EAT thickness was measured on the free wall of the right ventricle at the end of diastole. All patients were divided into two groups: high BMI group, ≥27 kg/m2 (n = 165), and non-high BMI group, < 27 kg/m2 (n = 478).

Results
The median and mean EAT thickness of 643 patients were 3.0 mm and 3.1 ± 2.4 mm, respectively. In the non-high BMI group, the median EAT thickness was significantly increased in patients with MS compared to those without MS (3.5 vs. 1.9 mm, p < 0.001). In the high BMI group, however, there was no significant difference in the median EAT thickness between patients with and without MS (3.0 vs. 2.5 mm, p = 0.813). A receiver operating characteristic (ROC) curve analysis predicting MS revealed that the area under the curve (AUC) of the non-high BMI group was significantly larger than that of the high BMI group (0.659 vs. 0.506, p = 0.007). When compared to patients without CAD, patients with CAD in both the non-high and high BMI groups had a significantly higher median EAT thickness (3.5 vs. 1.5 mm, p < 0.001 and 4.0 vs. 2.5 mm, p = 0.001, respectively). However, an ROC curve analysis predicting CAD revealed that the AUC of the non-high BMI group tended to be larger than that of the high BMI group (0.735 vs. 0.657, p = 0.055).

Conclusions
While EAT thickness was significantly increased in patients with MS and CAD, the power of EAT thickness to predict MS and CAD was stronger in patients with BMI < 27 kg/m2. These findings showed that the measurement of EAT thickness by echocardiography might be especially useful in an Asian population with a non-high BMI, less than 27 kg/m2.
Production of biohydrogen by recombinant expression of [NiFe]-hydrogenase 1 in Escherichia coli
Authors: Kim Jaoon YH , Jo Byung Hoon , Cha Hyung Joon 
Published: July 2010

Abstract

Background
Hydrogenases catalyze reversible reaction between hydrogen (H2) and proton. Inactivation of hydrogenase by exposure to oxygen is a critical limitation in biohydrogen production since strict anaerobic conditions are required. While [FeFe]-hydrogenases are irreversibly inactivated by oxygen, it was known that [NiFe]-hydrogenases are generally more tolerant to oxygen. The physiological function of [NiFe]-hydrogenase 1 is still ambiguous. We herein investigated the H2 production potential of [NiFe]-hydrogenase 1 of Escherichia coli in vivo and in vitro. The hya A and hya B genes corresponding to the small and large subunits of [NiFe]-hydrogenase 1 core enzyme, respectively, were expressed in BL21, an E. coli strain without H2 producing ability.

Results
Recombinant BL21 expressing [NiFe]-hydrogenase 1 actively produced H2 (12.5 mL H2/(h·L) in 400 mL glucose minimal medium under micro-aerobic condition, whereas the wild type BL21 did not produce H2 even when formate was added as substrate for formate hydrogenlyase (FHL) pathway. The majority of recombinant protein was produced as an insoluble form, with translocation of a small fraction to the membrane. However, the membrane fraction displayed high activity (~65% of total cell fraction), based on unit protein mass. Supplement of nickel and iron to media showed these metals contribute essentially to the function of [NiFe]-hydrogenase 1 as components of catalytic site. In addition, purified E. coli [NiFe]-hydrogenase 1 using his6-tag displayed oxygen-tolerant activity of ~12 nmol H2/(min·mg protein) under a normal aeration environment, compared to [FeFe]-hydrogenase, which remains inactive under this condition.

Conclusions
This is the first report on physiological function of E. coli [NiFe]-hydrogenase 1 for H2 production. We found that [NiFe]-hydrogenase 1 has H2 production ability even under the existence of oxygen. This oxygen-tolerant property is a significant advantage because it is not necessary to protect the H2 production process from oxygen. Therefore, we propose that [NiFe]-hydrogenase can be successfully applied as an efficient biohydrogen production tool under micro-aerobic conditions.
The active commuting route environment scale (ACRES): development and evaluation
Authors: Wahlgren Lina , Stigell Erik , Schantz Peter 
Published: July 2010

Abstract

Background
Route environments can be a potentially important factor in influencing people's behaviours in relation to active commuting. To better understand these possible relationships, assessments of route environments are needed. We therefore developed a scale; the Active Commuting Route Environment Scale (ACRES), for the assessment of bicyclists' and pedestrians' perceptions of their commuting route environments. Here we will report on the development and the results of validity and reliability assessments thereof.

Methods
Active commuters (n = 54) were recruited when they bicycled in Stockholm, Sweden. Traffic planning and environmental experts from the Municipality of Stockholm were assembled to form an expert panel (n = 24). The active commuters responded to the scale on two occasions, and the expert panel responded to it once. To test criterion-related validity, differences in ratings of the inner urban and suburban environments of Greater Stockholm were compared between the experts and the commuters. Furthermore, four items were compared with existing objective measures. Test-retest reproducibility was assessed with three types of analysis: order effect, typical error and intraclass correlation.

Results
There was a concordance in sizes and directions of differences in ratings of inner urban and suburban environments between the experts and the commuters. Furthermore, both groups' ratings were in line with existing objectively measured differences between the two environmental settings. Order effects between test and retest were observed in 6 of 36 items. The typical errors ranged from 0.93 to 2.54, and the intraclass correlation coefficients ranged from 'moderate' (0.42) to 'almost perfect' (0.87).

Conclusions
The ACRES was characterized by considerable criterion-related validity and reasonable test-retest reproducibility.
Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R
Authors: Li Ge , Park Hyeon U , Liang Dong , Zhao Richard Y 
Published: July 2010

Abstract

Background
Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive.

Results
To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV.

Conclusions
These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.
Thermal Nociceptive Properties of Trigeminal Afferent Neurons in Rats
Authors: Cuellar Jason M , Manering Neil A , Klukinov Mikhail , Nemenov Michael I , Yeomans David C 
Published: July 2010

Background: Although nociceptive afferents innervating the body have been heavily studied form many years, much less attention has been paid to trigeminal afferent biology. In particular, very little is known concerning trigeminal nociceptor responses to heat, and almost nothing in the rat. This study uses a highly controlled and reproducible diode laser stimulator to investigate the activation of trigeminal afferents to noxious skin heating. Results: The results of this experiment demonstrate that trigeminal thermonociceptors are distinct from themonociceptors innervating the limbs. Trigeminal nociceptors have considerably slower action potential conduction velocities and lower temperature thresholds than somatic afferent neurons. On the other hand, nociceptors innervating both tissue areas separate into those that respond to short pulse, high rate skin heating and those that respond to long pulse, low rate skin heating. Conclusions: This paper provides the first description in the literature of the in vivo properties of thermonociceptors in rats. These finding of two separate populations aligns with the separation between C and A-delta thermonociceptors innervating the paw, but have significant differences in terms of temperature threshold and average conduction velocities. An understanding of the temperature response properties of afferent neurons innervating the paw skin have been critical in many mechanistic discoveries, some leading to new pain therapies. A clear understanding of trigeminal nociceptors may be similarly useful in the investigation of trigeminal pain mechanisms and potential therapies.
Acute lead intoxication in a female battery worker: Diagnosis and management
Authors: Dounias George , Rachiotis George , Hadjichristodoulou Christos 
Published: July 2010

Abstract
Lead is a significant occupational and environmental hazard. Battery industry is one of the settings related to lead intoxication. Published information on the use of oral chelating agents for the treatment of anaemia in the context of acute lead intoxication is limited. The patient was a 33 year immigrant female worker in a battery manufacture for 3 months. She complained for malaise that has been developed over the past two weeks. Pallor of skin and conjunctiva was the only sign found in physical examination. The blood test on admission revealed normochromic anaemia. Endoscopic investigation of the gastrointestinal system was negative for bleeding. The bone marrow biopsy was unrevealing.
At baseline no attention has been paid to patient's occupational history. Afterwards the patient's occupational history has been re-evaluated and she has been screened for lead intoxication. The increased levels of the lead related biomarkers of exposure and effect confirmed the diagnosis. The patient received an oral chelating agent and an improvement in clinical picture, and levels of haematological and lead related biochemical parameters have been recorded. No side effect and no rebound effect were observed. This case report emphasizes the importance of the occupational history in the context of the differential diagnosis. Moreover, this report indicates that lead remains a significant occupational hazard especially in the small scale battery industry
Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis factor-alpha in synovial tissue of rheumatoid arthritis
Authors: Kawabata Tomoko , Nishida Keiichiro , Takasugi Koji , Ogawa Hiroko , Sada Kenei , Kadota Yasutaka , Inagaki Junko , Hirohata Satoshi , Ninomiya Yoshifumi , Makino Hirofumi 
Published: July 2010

Abstract
Introduction
The purpose of this study was to investigate the profile of histone deacetylase (HDAC) expression in the synovial tissue of rheumatoid arthritis (RA) compared with that of normal control and osteoarthritis (OA), and to examine whether there is a link between HDAC activity and synovial inflammation.

Methods
HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of total synovial tissue surgically obtained from normal, OA and RA joints. The level of cytoplasmic tumor necrosis factor a (TNFα) fraction was measured by ELISA. Total RNA of synovial tissue was used for RT-PCR of HDAC1-8. In synovial fibroblasts from RA (RASFs), the effects of TNFα on nuclear HDAC activity and class I HDACs (1, 2, 3, 8) mRNA expressions were examined by quantitative real-time PCR. The protein expression and distribution of class I HDACs were examined by Western blotting.

Results
Nuclear HDAC activity was significantly higher in RA than in OA and normal controls and correlated with the amount of cytoplasmic TNFα. The mRNA expression of HDAC1 in RA synovial tissue was higher than in OA and normal controls, and showed positive correlation with TNFα mRNA expression. The protein level of nuclear HDAC1 was higher in RA synovial tissue compared with OA synovial tissue. Stimulation with TNFα significantly increased the nuclear HDAC activity and HDAC1 mRNA expression at 24 hours and HDAC1 protein expression at 48 hours in RASFs.

Conclusions
Our results showed nuclear HDAC activity and expression of HDAC1 were significantly higher in RA than in OA synovial tissues, and they were upregulated by TNFα stimulation in RASFs. These data might provide important clues for the development of specific small molecule HDAC inhibitors.
Pediatric Phase I Trial and Pharmacokinetic Study of Vorinostat: A Children's Oncology Group Phase I Consortium Report
Authors: Fouladi Maryam , Park Julie R. , Stewart Clinton F. , Gilbertson Richard J. , Schaiquevich Paula , Sun Junfeng , Reid Joel M. , Ames Matthew M. , Speights Roseanne , Ingle Ashish M. , Zwiebel James , Blaney Susan M. , Adamson Peter C. 
Published: July 2010

Purpose The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of vorinostat administered as a single agent and in combination 13-cis retinoic acid (13cRA) in children with refractory solid tumors; to evaluate the tolerability of the solid tumor MTD in children with refractory leukemias; and to characterize the pharmacokinetics of a vorinostat suspension in children. Patients and Methods Vorinostat was administered orally daily starting at 180 mg/m2/d with escalations planned in 30% increments. Pharmacokinetic studies were performed with the initial dose. Acetyl-histone (H3) accumulation was assessed by Western blotting of peripheral blood mononuclear cells (PBMC). Results Sixty-four patients were enrolled on this multipart trial. In patients with solid tumors, the MTD was 230 mg/m2/d with dose-limiting neutropenia, thrombocytopenia, and hypokalemia at 300 mg/m2/d. DLTs observed with the combination of 13cRA and vorinostat included thrombocytopenia, neutropenia, anorexia, and hypertriglyceridemia, resulting in a MTD of vorinostat 180 mg/m2/d 4 times per week and 13cRA 80 mg/m2/dose twice per day, days 1 through 14 every 28 days. Wide interpatient variability was noted in vorinostat disposition, with area under the concentration-time curves at 230 mg/m2/d for the capsule (range, 1,415 to 9,291 ng/mL × hr) and oral suspension (range, 1,186 to 4,780 ng/mL × hr). Significant accumulation of acetylated H3 histone in PBMC was observed after administration of vorinostat, particularly at higher doses. One patient with neuroblastoma experienced a complete response to the combination. Conclusion In children with recurrent solid tumors, vorinostat is well-tolerated at 230 mg/m2/d, with a modest dose reduction being required when combining vorinostat with 13cRA. Drug disposition is similar to that observed in adults.
Phase II, Open-Label Study of Pazopanib or Lapatinib Monotherapy Compared With Pazopanib Plus Lapatinib Combination Therapy in Patients With Advanced and Recurrent Cervical Cancer
Authors: Monk Bradley J. , Mas Lopez Luis , Zarba Juan J. , Oaknin Ana , Tarpin Carole , Termrungruanglert Wichai , Alber Jacquelyn A. , Ding Jie , Stutts Melissa W. , Pandite Lini N. 
Published: July 2010

PurposePazopanib and lapatinib are tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit or epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/neu), respectively. In cervical cancer, EGFR and HER2/neu overexpression and high microvascular density correlate with survival.Patients and MethodsPatients with measurable stage IVB persistent/recurrent cervical carcinoma not amenable to curative therapy and at least one prior regimen in the metastatic setting were randomly assigned in a ratio of 1:1:1 to pazopanib at 800 mg once daily, lapatinib at 1,500 mg once daily, or lapatinib plus pazopanib combination therapy (lapatinib at 1,000 mg plus pazopanib at 400 mg once daily or lapatinib at 1,500 mg plus pazopanib at 800 mg once daily). Therapy continued until progression or withdrawal because of adverse events (AEs). Primary end point was progression-free survival (PFS), and secondary end points were overall survival (OS), response rate (RR), and safety. The futility boundary was crossed at the planned interim analysis for combination therapy compared with lapatinib therapy, and the combination was discontinued.ResultsOf 230 patients enrolled, 152 were randomly assigned to the monotherapy arms: pazopanib (n = 74) or lapatinib (n = 78). Most patients (62%) had recurrent cancer. Pazopanib improved PFS (hazard ratio [HR], 0.66; 90% CI, 0.48 to 0.91; P = .013) and OS (HR, 0.67; 90% CI, 0.46 to 0.99; P = .045). Median OS was 50.7 weeks and 39.1 weeks and RRs were 9% and 5% for pazopanib and lapatinib, respectively. The only grade 3 AE > 10% was diarrhea (11% pazopanib and 13% lapatinib). Grade 4 AEs were 9% (lapatinib) and 12% (pazopanib).ConclusionThis study confirms the activity of antiangiogenesis agents in advanced and recurrent cervical cancer and demonstrates the benefit of pazopanib based on the prolonged PFS and favorable toxicity profile.