bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular evolution of rbcL in three gymnosperm families: identifying adaptive and coevolutionary patterns
Authors: Sen Lin , Fares Mario A , Liang Bo , Gao Lei , Wang Bo , Wang Ting , Su Ying-Juan 
Published: June 2011

Abstract

Background
The chloroplast-localized ribulose-1, 5-biphosphate carboxylase/oxygenase (Rubisco), the primary enzyme responsible for autotrophy, is instrumental in the continual adaptation of plants to variations in the concentrations of CO2. The large subunit (LSU) of Rubisco is encoded by the chloroplast rbcL gene. Although adaptive processes have been previously identified at this gene, characterizing the relationships between the mutational dynamics at the protein level may yield clues on the biological meaning of such adaptive processes. The role of such coevolutionary dynamics in the continual fine-tuning of RbcL remains obscure.

Results
We used the timescale and phylogenetic analyses to investigate and search for processes of adaptive evolution in rbcL gene in three gymnosperm families, namely Podocarpaceae, Taxaceae and Cephalotaxaceae. To understand the relationships between regions identified as having evolved under adaptive evolution, we performed coevolutionary analyses using the software CAPS. Importantly, adaptive processes were identified at amino acid sites located on the contact regions among the Rubisco subunits and on the interface between Rubisco and its activase. Adaptive amino acid replacements at these regions may have optimized the holoenzyme activity. This hypothesis was pinpointed by evidence originated from our analysis of coevolution that supported the correlated evolution between Rubisco and its activase. Interestingly, the correlated adaptive processes between both these proteins have paralleled the geological variation history of the concentration of atmospheric CO2.

Conclusions
The gene rbcL has experienced bursts of adaptations in response to the changing concentration of CO2 in the atmosphere. These adaptations have emerged as a result of a continuous dynamic of mutations, many of which may have involved innovation of functional Rubisco features. Analysis of the protein structure and the functional implications of such mutations put forward the conclusion that this evolutionary scenario has been possible through a complex interplay between adaptive mutations, often structurally destabilizing, and compensatory mutations. Our results unearth patterns of evolution that have likely optimized the Rubisco activity and uncover mutational dynamics useful in the molecular engineering of enzymatic activities.

Reviewers
This article was reviewed by Prof. Christian Blouin (nominated by Dr W Ford Doolittle), Dr Endre Barta (nominated by Dr Sandor Pongor), and Dr Nicolas Galtier.
Low early ototoxicity rates for pediatric medulloblastoma patients treated with proton radiotherapy
Authors: Moeller Benjamin J , Chintagumpala Murali , Philip Jimmy J , Grosshans David R , McAleer Mary F , Woo Shiao Y , Gidley Paul W , Vats Tribhawan S , Mahajan Anita 
Published: June 2011

Abstract

Background
Hearing loss is common following chemoradiotherapy for children with medulloblastoma. Compared to photons, proton radiotherapy reduces radiation dose to the cochlea for these patients. Here we examine whether this dosimetric advantage leads to a clinical benefit in audiometric outcomes.

Methods
From 2006-2009, 23 children treated with proton radiotherapy for medulloblastoma were enrolled on a prospective observational study, through which they underwent pre- and 1 year post-radiotherapy pure-tone audiometric testing. Ears with moderate to severe hearing loss prior to therapy were censored, leaving 35 ears in 19 patients available for analysis.

Results
The predicted mean cochlear radiation dose was 30 60Co-Gy Equivalents (range 19-43), and the mean cumulative cisplatin dose was 303 mg/m2 (range 298-330). Hearing sensitivity significantly declined following radiotherapy across all frequencies analyzed (P < 0.05). There was partial sparing of mean post-radiation hearing thresholds at low-to-midrange frequencies and, consequently, the rate of high-grade (grade 3 or 4) ototoxicity at 1 year was favorable (5%). Ototoxicity did not correlate with predicted dose to the auditory apparatus for proton-treated patients, potentially reflecting a lower-limit threshold for radiation effect on the cochlea.

Conclusions
Rates of high-grade early post-radiation ototoxicity following proton radiotherapy for pediatric medulloblastoma are low. Preservation of hearing in the audible speech range, as observed here, may improve both quality of life and cognitive functioning for these patients.
Thrombospondin 1 in hypoxia-conditioned media blocks the growth of human microvascular endothelial cells and is increased in systemic sclerosis tissues
Authors: Morgan-Rowe Luke , Nikitorowicz Joanna , Shiwen Xu , Leask Andrew , Tsui Janice , Abraham David , Stratton Richard 
Published: June 2011

Abstract

Background
Systemic sclerosis (SSc) is a chronic inflammatory autoimmune disease characterised by vascular dysfunction and damage, excess collagen deposition and subsequent organ manifestations. Vasculopathy is an early feature of the disease which leads to a chronic hypoxic environment in the tissues. Paradoxically, there is a lack of angiogenesis. We hypothesised that this may in part be due to a nonphysiological, overriding upregulation in antiangiogenic factors produced by the hypoxic tissues. We considered thrombospondin 1 (TSP-1) as a candidate antiangiogenic factor.

Results
Conditioned media from human microvascular endothelial cells cultured in both normoxic and hypoxic environments were able to block endothelial cell proliferation, with the latter environment having a more profound effect. Filtration to remove > 100-kDa proteins or heparin-binding proteins from the conditioned media eliminated their antiproliferative effect. TSP-1 was expressed in high concentrations in the hypoxic media, as was vascular endothelial growth factor (VEGF). Depletion of TSP-1 from the media by immunoprecipitation reduced the antiproliferative effect. We then show that, in a dose-dependent fashion, recombinant TSP-1 blocks the proliferation of endothelial cells. Immunohistochemistry of skin biopsy material revealed that TSP-1 expression was significantly higher throughout the skin of patients with SSc compared with healthy controls.

Conclusions
Despite the environment of chronic tissue hypoxia in SSc, there is a paradoxical absence of angiogenesis. This is thought to be due in part to aberrant expression of antiangiogenic factors, including TSP-1. We have demonstrated that TSP-1 is released in high concentrations by hypoxic endothelial cells. The conditioned media from these cells is able to block proliferation and induce apoptosis in microvascular endothelial cells, an effect that is reduced when TSP-1 is immunoprecipitated out. Further, we have shown that recombinant TSP-1 is able to block proliferation and induce apoptosis at concentrations consistent with those found in the plasma of patients with SSc and that its effect occurs in the presence of elevated VEGF levels. Taken together, these data are consistent with a model wherein injured microvascular cells in SSc fail to repair because of dysregulated induction of TSP-1 in the hypoxic tissues.
Standard of Practice and Flynn Effect Testimony in Death Penalty Cases
Authors: Gresham Frank M. , Reschly Daniel J. 
Published: June 2011

AbstractThe Flynn Effect is a well-established psychometric fact documenting substantial increases in measured intelligence test performance over time. Flynn's (1984) review of the literature established that Americans gain approximately 0.3 points per year or 3 points per decade in measured intelligence. The accurate assessment and interpretation of intellectual functioning becomes critical in death penalty cases that seek to determine whether an individual meets the criteria for intellectual disability and thereby is ineligible for execution under Atkins v. Virginia (2002). We reviewed the literature on the Flynn Effect and demonstrated how failure to adjust intelligence test scores based on this phenomenon invalidates test scores and may be in violation of the Standards for Educational and Psychological Testing as well as the “Ethical Principles for Psychologists and Code of Conduct.” Application of the Flynn Effect and score adjustments for obsolete norms clearly is supported by science and should be implemented by practicing psychologists.
Sowing the Seeds of the Autism Field: Leo Kanner (1943)
Authors: Blacher Jan , Christensen Lisa 
Published: June 2011

Abstract
More than 65 years after Leo Kanner published his seminal article, research on autism continues to be an area of increasing interest. Although much progress has been made, this field is still in its infancy, and many avenues of research are just beginning to be pursued. Despite the time that has passed, the syndrome Kanner identified and his comments about the children he observed continue to have meaning today, and although some of his suggestions about the etiology and presentation of autism were grounded in the thinking of his day, many of his observations were quite prescient. In this paper we explore Kanner's contributions to the field of autism, discuss how the field has changed, and suggest ways that research on autism spectrum disorders can continue to move forward.
MicroRNAs as Regulators of Signal Transduction in Urological Tumors
Authors: Fendler Annika , Stephan Carsten , Yousef George M , Jung Klaus 
Published: June 2011

BACKGROUNDMicroRNAs (miRNAs) are short noncoding RNAs that have been shown to play pivotal roles in carcinogenesis. In the past decade, miRNAs have been the focus of much research in oncology, and there are great expectations for their utility as cancer biomarkers and therapeutic targets.CONTENTIn this review we examine how miRNAs can regulate signal transduction pathways in urological tumors. We performed in silico target prediction using TargetScan 5.1 to identify the signal transduction targets of miRNA, and we summarize the experimental evidence detailing miRNA regulation of pathways analyzed herein.SUMMARYmiRNAs, which have been shown to be dysregulated in bladder, prostate, and renal cell cancer, are predicted to target key proteins in signal transduction. Because androgen receptor signaling is a major regulator of prostate cancer growth, its regulation by miRNAs has been well described. In addition, members of the phosphatidylinositol 3-kinase/Akt (RAC-alpha serine/threonine-protein kinase) signaling pathway have been shown to be susceptible to miRNA regulation. In contrast, there are very few studies on the impact of miRNA regulation on signaling by VHL (von Hippel-Lindau tumor suppressor) and vascular endothelial growth factor in renal cell carcinoma or by fibroblast growth factor receptor 3 and p53 in bladder cancer. Many miRNAs are predicted to target important signaling pathways in urological tumors and are dysregulated in their respective cancer types; a systematic overview of miRNA regulation of signal transduction in urological tumors is pending. The identification of these regulatory networks might lead to novel targeted cancer therapies. In general, the targeting of miRNAs is a valuable approach to cancer therapy, as has been shown recently for various types of cancer.
Subjective outcome evaluation of the Project P.A.T.H.S.: findings based on different datasets
Authors: Shek Daniel T.L. , Ma Cecilia M.S. , Tang Christina Y.P. 
Published: June 2011

Abstract
A total of 216 schools participated in the Project P.A.T.H.S. in the 2008/2009 school year. After completion of the Tier 1 Program, subjective outcome evaluation data were collected from 3274 program implementers. Based on the consolidated data with schools as units, results showed that participants had positive perceptions of the program, implementers and benefits of the program. More than four-fifths of the implementers regarded the program as helpful to the program participants. Multiple regression analysis revealed that perceived qualities of the program and the program implementers predicted perceived effectiveness of the program. Grade differences were not significant, except in the perception of the program for the Secondary 1 and Secondary 3 programs. The present study provides additional support for the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. in Hong Kong.
Influence of family structure on sexual behavior of Turkish female adolescents
Authors: Tasci Yasemin , Demir Berfu , Kocak Muberra , Ercan Fedi , Karadag Burak , Göktolga Umit 
Published: June 2011

Abstract

Background: The aim of this study was to evaluate the link between romantic relationship and/or sexual activity of adolescents, and family structure.

Methods: Medical records of 1087 adolescent girls were evaluated for age, statute (student, working, out-of-school), incidence of romantic relationship and sexual activity, and family structures.

Results: Teenager students had significantly less romantic relationships and experience of sexual intercourse than other groups. Parent-adolescent communication was negatively correlated with absence of romantic relationship and sexual intercourse.

Conclusion: Adolescents who have left school and are working constitute a population having higher romantic relationships and sexual intercourse experiences compared with the student adolescents. Good relationships with parents were associated with less risky sexual behavior. Close relationships with school delay the onset of sexual activity.
Choosing the Best Second-Line Tyrosine Kinase Inhibitor in Imatinib-Resistant Chronic Myeloid Leukemia Patients Harboring Bcr-Abl Kinase Domain Mutations: How Reliable Is the IC50?
Authors: Soverini Simona , Rosti Gianantonio , Iacobucci Ilaria , Baccarani Michele , Martinelli Giovanni 
Published: June 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Explain the IC50 of a tyrosine kinase inhibitor and the kind of information this parameter provides about its efficacy.List the multiple factors that may be responsible for resistance to a target therapeutic agent.Describe the clinical relevance of Bcr-Abl mutations in chronic myeloid leukemia patients.
This article is available for continuing medical education credit at CME.TheOncologist.com
Development of drug resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients is often accompanied by selection of point mutations in the kinase domain (KD) of the Bcr-Abl oncoprotein, where imatinib binds. Several second-generation tyrosine kinase inhibitors (TKIs) have been designed rationally so as to enhance potency and retain the ability to bind mutated forms of Bcr-Abl. Since the preclinical phase of their development, most of these inhibitors have been tested in in vitro studies to assess their half maximal inhibitory concentration (IC50) for unmutated and mutated Bcr-Abl—that is, the drug concentration required to inhibit the cell proliferation or the phosphorylation processes driven by either the unmutated or the mutated forms of the kinase. A number of such studies have been published, and now that two inhibitors—dasatinib and nilotinib—are available for the treatment of imatinib-resistant cases, it is tempting for clinicians to reason on the IC50 values to guess, case by case, which one will work best in patients harboring specific Bcr-Abl KD mutations. Here, we discuss the pros and cons of using this approach in TKI selection.
Effect of Nurse Case Management Compared With Usual Care on Controlling Cardiovascular Risk Factors in Patients With Diabetes
Authors: Ishani Areef , Greer Nancy , Taylor Brent C. , Kubes Laurie , Cole Paula , Atwood Melissa , Clothier Barbara , Ercan-Fang Nacide 
Published: June 2011

OBJECTIVE
To determine whether nurse case management with a therapeutic algorithm could effectively improve rates of control for hypertension, hyperglycemia, and hyperlipidemia compared with usual care among veterans with diabetes.

RESEARCH DESIGN AND METHODS
A randomized controlled trial of diabetic patients that had blood pressure (BP) &gt;140/90 mmHg, hemoglobin A1c (HbA1c) &gt;9.0%, or LDL &gt;100 mg/dL. Intervention patients received case management (n = 278) versus usual care (n = 278) over a 1-year period. The primary outcome was the percentage of patients achieving simultaneous control of all three parameters (defined by BP &lt;130/80 mmHg, HbA1c &lt;8.0%, and LDL &lt;100 mg/dL) at 1 year. Secondary outcomes included improvements within each individual component of the composite primary outcome. Differences between groups were analyzed using t tests, Pearson χ2 tests, and linear and logistic regression.

RESULTS
A greater number of individuals assigned to case management achieved the primary study outcome of having all three outcome measures under control (61 [21.9%] compared with 28 [10.1%] in the usual care group [P &lt; 0.01]). In addition, a greater number of individuals assigned to the intervention group achieved the individual treatment goals of HbA1c &lt;8.0% (73.7 vs. 65.8%, P = 0.04) and BP &lt;130/80 mmHg (45.0 vs. 25.4%, P &lt; 0.01), but not for LDL &lt;100 mg/dL (57.6 vs. 55.4%, P = 0.61), compared with those in the usual care group.

CONCLUSIONS
In patients with diabetes, nurse case managers using a treatment algorithm can effectively improve the number of individuals with control of multiple cardiovascular risk factors at 1 year.
Optimal Glycemic Control, Pre-eclampsia, and Gestational Hypertension in Women With Type 1 Diabetes in the Diabetes and Pre-eclampsia Intervention Trial
Authors: Holmes Valerie A. , Young Ian S. , Patterson Christopher C. , Pearson Donald W.M. , Walker James D. , Maresh Michael J.A. , McCance David R. ,   for the Diabetes and Pre-eclampsia Intervention Trial Study Group
Published: June 2011

OBJECTIVE
To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes.

RESEARCH DESIGN AND METHODS
Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal (&lt;6.1%: referent), good (6.1–6.9%), moderate (7.0–7.9%), and poor (≥8.0%) glycemic control, respectively.

RESULTS
Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P &lt; 0.05, respectively). In early pregnancy, A1C ≥8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values ≥6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values ≥7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension.

CONCLUSIONS
Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.
N- Hydroxyphthalimide and transition metal salts as catalysts of the liquid-phase oxidation of 1-methoxy-4-(1-methylethyl)benzene with oxygen
Authors: Orlińska Beata , Romanowska Iwona 
Published: June 2011

Abstract
The oxidation process of 1-methoxy-4-(1-methylethyl)benzene catalysed by N-hydroxyphthalimide (NHPI) or NHPI in combination with Cu(II), Co(II), Mn(II) and Fe(II) salts was studied. The effects of the amount of catalyst and the temperature were determined. 1-Methyl-1-(4-methoxyphenyl)ethyl hydroperoxide was obtained in a yield of 73 mol% when 1-methoxy-4-(1-methylethyl)benzene was oxidised for 3 h at 60°C in acetonitrile as a solvent in the presence of NHPI. 1-(4-Methoxyphenyl)ethanone with high selectivity up to 68–75 mol%, but low yield amounting to 11 mol% was obtained when 1-methoxy-4-(1-methylethyl)benzene was oxidised in the presence of the NHPI/Cu(II) system at 120°C.
Adsorption of nicotinic acid on the surface of nanosized hydroxyapatite and structurally modified hydroxyapatite
Authors: Dancu Alexandra-Cristina , Barabas Reka , Bogya Erzsebet-Sara 
Published: June 2011

Abstract
In the present paper, hydroxyapatite and structurally modified hydroxyapatite were investigated to establish the best material for nicotinic acid adsorption. Structurally modified hydroxyapatite wa prepared by adding sodium silicate in the reaction medium. The influence of silica concentration, presence of small amounts of metal ions, temperature and initial concentrations of nicotinic acid solutions on the adsorption capacity, were studied. Results indicated that structurally modified hydroxyapatite doped with copper adsorbed the highest amount of nicotinic acid. For this material the adsorption capacity was 0.232 mg nicotinic acid / g material, at an initial concentration of 10−4 M nicotinic acid. For all types of materials, best results were obtained at 15°C. The amount of nicotinic acid adsorbed increases with the decrease in temperature and with the increase in the initial concentration of nicotinic acid. Adsorption kinetics data were modeled using pseudo-first and pseudo-second order models while the interference due to diffusion was analyzed with intraparticle diffusion model. The results indicate that pseudo-second order model best describes the adsorption kinetics data, indicating the formation of chemical bonding.
The materials used in this study were characterized by the following methods: IR, Coulter Counter analyzer, Scanning Electron Microscope and BET
Optical properties of ZnO nanoparticles synthesized by varying the sodium hydroxide to zinc acetate molar ratios using a Sol-Gel process
Authors: Dejene Francis , Ali Abdub , Swart Hendrik , Botha Reinhardt , Roro Kittesa , Coetsee Liza , Biggs Mart 
Published: June 2011

Abstract
Material property dependence on the OH−/Zn2+ molar ratio of the precursor was investigated by varying the amount of NaOH during synthesis of ZnO. It was necessary to control the water content and temperature of the mixture to ensure the reproducibility. It was observed that the structural properties, particle size, photoluminescence intensity and wavelength of maximum intensity were influenced by the molar ratio of the precursor. The XRD spectra for ZnO nanoparticles show the entire peaks corresponding to the various planes of wurtzite ZnO, indicating a single phase. UV measurements show the absorption that comes from the ZnO nanoparticles in visible region. The absorption edge of these ZnO nanoparticles are shifted to higher energies and the determined band gap energies are blue shifted as the OH−/Zn2 molar ration increases, due to the quantum confinement effects. The photoluminescence characterization of the ZnO nanostructures exhibited a broad emission band centred at green (600 nm) region for all molar ratios except for OH−/Zn2+ = 1.7 where a second blue emission around 468 nm was also observed. The photoluminescence properties of ZnO nanoparticles were largely determined by the size and surface properties of the nanoparticles.