bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a Novel Dye-Decolorizing Peroxidase (DyP)-Type Enzyme from Irpex lacteus and Its Application in Enzymatic Hydrolysis of Wheat Straw
Authors: Salvachï¿½a Davinia , Prieto Alicia , Martï¿½nez ï¿½ngel T. , Martï¿½nez Marï¿½a Jesï¿½s
Published: May 2013

Irpex lacteus
is a white rot basidiomycete proposed for a wide spectrum of biotechnological applications which presents an interesting, but still scarcely known, enzymatic oxidative system. Among these enzymes, the production, purification, and identification of a new dye-decolorizing peroxidase (DyP)-type enzyme, as well as its physico-chemical, spectroscopic, and catalytic properties, are described in the current work. According to its N-terminal sequence and peptide mass fingerprinting analyses,
I. lacteus
DyP showed high homology (>95%) with the hypothetical (not isolated or characterized) protein cpop21 from an unidentified species of the family
Polyporaceae
. The enzyme had a low optimal pH, was very stable to acid pH and temperature, and showed improved activity and stability at high H
2
O
2
concentrations compared to other peroxidases. Other attractive features of
I. lacteus
DyP were its high catalytic efficiency oxidizing the recalcitrant anthraquinone and azo dyes assayed (
k
cat
/

K
m

of 1.6 ï¿½ 10
6
s
-1
M
-1
) and its ability to oxidize nonphenolic aromatic compounds like veratryl alcohol. In addition, the effect of this DyP during the enzymatic hydrolysis of wheat straw was checked. The results suggest that
I. lacteus
DyP displayed a synergistic action with cellulases during the hydrolysis of wheat straw, increasing significantly the fermentable glucose recoveries from this substrate. These data show a promising biotechnological potential for this enzyme.
A Universally Applicable and Rapid Method for Measuring the Growth of Streptomyces and Other Filamentous Microorganisms by Methylene Blue Adsorption-Desorption
Authors: Fischer Marco , Sawers R. Gary
Published: May 2013

Quantitative assessment of growth of filamentous microorganisms, such as streptomycetes, is generally restricted to determination of dry weight. Here, we describe a straightforward methylene blue-based sorption assay to monitor microbial growth quantitatively, simply, and rapidly. The assay is equally applicable to unicellular and filamentous bacterial and eukaryotic microorganisms.
Zirex: a Novel Zinc-Regulated Expression System for Lactococcus lactis
Authors: Mu Dongdong , Montalbï¿½n-Lï¿½pez Manuel , Masuda Yoshimitsu , Kuipers Oscar P.
Published: May 2013

Here, we report a new zinc-inducible expression system for
Lactococcus lactis
, called Zirex, consisting of the pneumococcal repressor SczA and P

czcD

. P

czcD

tightly regulates the expression of green fluorescent protein in
L. lactis
. We show the applicability of Zirex together with the nisin-controlled expression system, enabling simultaneous but independent regulation of different genes.
Malonate Catabolism Does Not Drive N2Fixation in Legume Nodules
Authors: Karunakaran Ramakrishnan , East Alison K. , Poole Philip S.
Published: May 2013

Malonyl-coenzyme A (CoA) decarboxylase, malonyl-CoA synthetase, and malonate transporter mutants ofRhizobium leguminosarumbv. viciae and trifolii fixed N2at wild-type rates on pea and clover, respectively. Thus, malonate does not drive N2fixation in legume nodules.
Environmental Dissolved Organic Matter Governs Biofilm Formation and Subsequent Linuron Degradation Activity of a Linuron-Degrading Bacterial Consortium
Authors: Horemans Benjamin , Breugelmans Philip , Hofkens Johan , Smolders Erik , Springael Dirk
Published: May 2013

It was examined whether biofilm growth on dissolved organic matter (DOM) of a three-species consortium whose members synergistically degrade the phenylurea herbicide linuron affected the consortium's integrity and subsequent linuron-degrading functionality. Citrate as a model DOM and three environmental DOM (eDOM) formulations of different quality were used. Biofilms developed with all DOM formulations, and the three species were retained in the biofilm. However, biofilm biomass, species composition, architecture, and colocalization of member strains depended on DOM and its biodegradability. To assess the linuron-degrading functionality, biofilms were subsequently irrigated with linuron at 10 mg liter
−1
or 100 μg liter
−1
. Instant linuron degradation, the time needed to attain maximal linuron degradation, and hence the total amount of linuron removed depended on both the DOM used for growth and the linuron concentration. At 10 mg liter
−1
, the final linuron degradation efficiency was as high as previously observed without DOM except for biofilms fed with humic acids which did not degrade linuron. At 100 μg liter
−1
linuron, DOM-grown biofilms degraded linuron less efficiently than biofilms receiving 10 mg liter
−1
linuron. The amount of linuron removed was more correlated with biofilm species composition than with biomass or structure. Based on visual observations, colocalization of consortium members in biofilms after the DOM feed appears essential for instant linuron-degrading activity and might explain the differences in overall linuron degradation. The data show that DOM quality determines biofilm structure and composition of the pesticide-degrading consortium in periods with DOM as the main carbon source and can affect subsequent pesticide-degrading activity, especially at micropollutant concentrations.
The Spatial Distribution of the Exocyst and Actin Cortical Patches Is Sufficient To Organize Hyphal Tip Growth
Authors: Caballero-Lima David , Kaneva Iliyana N. , Watton Simon P. , Sudbery Peter E. , Craven C. Jeremy
Published: May 2013

In the hyphal tip of
Candida albicans
we have made detailed quantitative measurements of (i) exocyst components, (ii) Rho1, the regulatory subunit of (1,3)-β-glucan synthase, (iii) Rom2, the specialized guanine-nucleotide exchange factor (GEF) of Rho1, and (iv) actin cortical patches, the sites of endocytosis. We use the resulting data to construct and test a quantitative 3-dimensional model of fungal hyphal growth based on the proposition that vesicles fuse with the hyphal tip at a rate determined by the local density of exocyst components. Enzymes such as (1,3)-β-glucan synthase thus embedded in the plasma membrane continue to synthesize the cell wall until they are removed by endocytosis. The model successfully predicts the shape and dimensions of the hyphae, provided that endocytosis acts to remove cell wall-synthesizing enzymes at the subapical bands of actin patches. Moreover, a key prediction of the model is that the distribution of the synthase is substantially broader than the area occupied by the exocyst. This prediction is borne out by our quantitative measurements. Thus, although the model highlights detailed issues that require further investigation, in general terms the pattern of tip growth of fungal hyphae can be satisfactorily explained by a simple but quantitative model rooted within the known molecular processes of polarized growth. Moreover, the methodology can be readily adapted to model other forms of polarized growth, such as that which occurs in plant pollen tubes.
The Endosymbiont Amoebophilus asiaticus Encodes an
S
-Adenosylmethionine Carrier That Compensates for Its Missing Methylation Cycle
Authors: Haferkamp Ilka , Penz Thomas , Geier Melanie , Ast Michelle , Mushak Tanja , Horn Matthias , Schmitz-Esser Stephan
Published: May 2013

All organisms require
S
-adenosylmethionine (SAM) as a methyl group donor and cofactor for various biologically important processes. However, certain obligate intracellular parasitic bacteria and also the amoeba symbiont
Amoebophilus asiaticus
have lost the capacity to synthesize this cofactor and hence rely on its uptake from host cells. Genome analyses revealed that
A. asiaticus
encodes a putative SAM transporter. The corresponding protein was functionally characterized in
Escherichia coli
: import studies demonstrated that it is specific for SAM and
S
-adenosylhomocysteine (SAH), the end product of methylation. SAM transport activity was shown to be highly dependent on the presence of a membrane potential, and by targeted analyses, we obtained direct evidence for a proton-driven SAM/SAH antiport mechanism. Sequence analyses suggest that SAM carriers from
Rickettsiales
might operate in a similar way, in contrast to chlamydial SAM transporters. SAM/SAH antiport is of high physiological importance, as it allows for compensation for the missing methylation cycle. The identification of a SAM transporter in
A. asiaticus
belonging to the
Bacteroidetes
phylum demonstrates that SAM transport is more widely spread than previously assumed and occurs in bacteria belonging to three different phyla (
Proteobacteria
,
Chlamydiae
, and
Bacteroidetes
).
Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence
Authors: Jackson Angelyca A. , Gross Maegan J. , Daniels Emily F. , Hampton Thomas H. , Hammond John H. , Vallet-Gely Isabelle , Dove Simon L. , Stanton Bruce A. , Hogan Deborah A.
Published: May 2013

Pseudomonas aeruginosahemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ΔplcHRmutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine betaine (GB), were sufficient to stimulate Anr activity, and their catabolism was required for Anr activation. The addition of choline or GB to glucose-containing medium did not alter Anr protein levels, growth rates, or respiratory activity, and Anr activation could not be attributed to the osmoprotectant functions of GB. The Δanrmutant was defective in virulence in a mouse pneumonia model. Several lines of evidence indicate that Anr is important for the colonization of biotic and abiotic surfaces in bothP. aeruginosaPAO1 and PA14 and that increases in Anr activity resulted in enhanced biofilm formation. Our data suggest that PlcH activity promotes Anr activity in oxic environments and that Anr activity contributes to virulence, even in the acute infection phase, where low oxygen tensions are not expected. This finding highlights the relationships amongin vivobacterial metabolism, the activity of the oxygen-sensitive regulator Anr, and virulence.
Trials of Acupuncture for Drug Dependence: A Recommendation for Hypotheses Based on the Literature
Authors: White Adrian
Published: May 2013

Objectives

After initial promising research into acupuncture for withdrawal from drugs of dependence, two large negative trials were published in 2002 and the use of acupuncture in US rehabilitation facilities fell. However, subsequently it has been maintained, despite a lack of support from systematic reviews. This suggests a mismatch between research and clinical observation, which could be due to the acupuncture technique used, choice of controls or outcome measures. This study aims to explore the mismatch.

Methods

An exploratory review of all 48 clinical trials on alcohol, cocaine, nicotine or opioid dependence included in current reviews.

Results

Studies with sham controls (that could be active) were less likely to be positive (33%) than those with non-acupuncture controls (75%). Positive results were more likely when measuring craving (56%) or withdrawal symptoms (58%) than when measuring abstinence (31%) or attrition (31%). Three treatment variables appeared to be associated with positive results: (1) body acupuncture, used in 13 studies, was associated with positive outcomes for craving and withdrawal symptoms but not for abstinence or attrition; (2) electroacupuncture, used in seven studies, was associated with positive results with all four outcomes; and (3) bilateral needling in 20 studies was associated with effects on abstinence, craving and withdrawal symptoms.

Conclusions

The current evidence suggests that acupuncture may have some effects on drug dependence that have been missed because of choice of outcome in many previous studies, and future studies should use outcomes suggested by clinical experience. Body points and electroacupuncture, used in the original clinical observation, justify further research.
Risk factors and successful interventions for cricket-related low back pain: a systematic review
Authors: Morton Sarah , Barton Christian J , Rice Simon , Morrissey Dylan
Published: May 2013

Background

Low back pain (LBP) is highly prevalent in cricketers, particularly in adolescent fast bowlers. Numerous modifiable risk factors for and interventions to address LBP in cricketers have been proposed in the literature.

Aim

Summarise and critique studies evaluating LBP risk factors in cricketers, and evaluate the effectiveness of interventions designed to prevent or treat such LBP.

Study design

Systematic literature review.

Methods

MEDLINE, ISI Web of Knowledge, CINAHL, SportDiscus and the Cochrane Library were searched from inception using key terms relating to risk factors and interventions in LBP in cricketers. Quality of included studies was assessed using the Downs and Black Quality Index, data were extracted to complete the effect size and OR calculations and evidence levels were established using van Tulder's criteria.

Results

12 studies (6 of high quality) investigating the factors associated with LBP in cricketers and 5 low-quality studies evaluating the interventions for the treatment/prevention of LBP in cricketers were identified. Moderate evidence indicates the presence of acute MRI bone stress as a risk factor for developing lumbar stress fractures. Additionally, moderate evidence indicates increased shoulder counter rotation (associated with mixed bowling actions) and decreased anterior abdominal fascial slide may be associated with LBP in cricketers.

Conclusions

Screening for bone stress on MRI should be considered by clinicians managing developing cricketers to identify the risk of lumbar stress fracture development. Numerous associative factors were outlined, although causality needs establishing to further guide interventions in cricketers with LBP. Intervention studies were of insufficient quality to generate concrete conclusions and these research failings require rapid attention.
Sedentary behaviour and risk of mortality from all-causes and cardiometabolic diseases in adults: evidence from the HUNT3 population cohort
Authors: Chau Josephine Y , Grunseit Anne , Midthjell Kristian , Holmen Jostein , Holmen Turid Lingaas , Bauman Adrian E , Van der Ploeg Hidde P
Published: May 2013

Background

Sedentary behaviour is a potential risk factor for chronic-ill health and mortality, that is, independent of health-enhancing physical activity. Few studies have investigated the risk of mortality associated with multiple contexts of sedentary behaviour.

Objective

To examine the prospective associations of total sitting time, TV-viewing time and occupational sitting with mortality from all causes and cardiometabolic diseases.

Methods

Data from 50 817 adults aged ≥20 years from the Nord-Trøndelag Health Study 3 (HUNT3) in 2006–2008 were linked to the Norwegian Cause of Death Registry up to 31 December 2010. Cox proportional hazards models examined all-cause and cardiometabolic disease-related mortality associated with total sitting time, TV-viewing and occupational sitting, adjusting for multiple potential confounders including physical activity.

Results

After mean follow-up of 3.3 years (137 315.8 person-years), 1068 deaths were recorded of which 388 were related to cardiometabolic diseases. HRs for all-cause mortality associated with total sitting time were 1.12 (95% CI 0.89 to 1.42), 1.18 (95% CI 0.90 to 1.57) and 1.65 (95% CI 1.24 to 2.21) for total sitting time 4−<7, 7−<10 and ≥10 h/day, respectively, relative to <4 h/day after adjusting for confounders (p-trend=0.001). A similar pattern of associations was observed between total sitting time and mortality from cardiometabolic diseases, but TV-viewing time and occupational sitting showed no or borderline significant associations with all-cause or cardiometabolic disease-related mortality over the same follow-up period.

Conclusions

Total sitting time is associated with all-cause and cardiometabolic disease-related mortality in the short term. However, prolonged sitting in specific contexts (ie, watching TV, at work) do not adversely impact health in the same timeframe. These findings suggest that adults should be encouraged to sit less throughout the day to reduce their daily total sitting time.
The challenge of managing tendinopathy in competing athletes
Authors: Cook J L , Purdam C R
Published: May 2013

Managing tendinopathy in season is a challenge for all sports medicine practitioners. Many of the strategies employed to treat tendinopathy in a rehabilitation setting are not suitable because of the time taken to recover. Management strategies that control pain and maintain performance are required. These include load management, both reducing aggravating loads and introducing pain-relieving loads, medications and adequate monitoring to detect a deteriorating tendon. Other interventions such as intratendinous injection therapies and other direct tendon modalities can be provocative at worst and without effect at best. Research to improve the understanding of management in athletes in season is compromised by ethical considerations and access to willing participants. It is likely to remain an area where clinical advances guide future treatments.
Cognitive and motor skills in school-aged children following maternal vitamin A supplementation during pregnancy in rural Nepal: a follow-up of a placebo-controlled, randomised cohort
Authors: Buckley Gillian J , Murray-Kolb Laura E , Khatry Subarna K , LeClerq Steven C , Wu Lee , West Keith P , Christian Parul
Published: May 2013

Objective

To determine the effects of maternal vitamin A supplementation from preconception through postpartum on cognitive and motor development of children at 10–13 years of age in rural Nepal.

Design

Follow-up assessment of children born to women randomly assigned by a village to receive either supplemental vitamin A (7000 µg retinol equivalents) or placebo weekly during a continuous 3.5-year period from 1994–1997. The participants came from 12 wards, a subset of 270 wards in the original trial. Trained staff tested children for cognition by the Universal Nonverbal Intelligence Test (UNIT) and motor ability using four subtests from the Movement Assessment Battery for Children (MABC). Data on schooling, home environment and nutritional and socioeconomic status were also collected.

Setting

Southern plains district of Sarlahi, Nepal.

Participants

390 Nepalese children 10–13 years of age.

Main outcome measures

Raw scores on UNIT and square-root transformed scores on an abridged version of the MABC tests, expressed as cluster-summarised (mean±SD) values to account for the design of the original trial.

Results

There were no differences in UNIT (79.61±5.99 vs 80.69±6.71) or MABC (2.64±0.07 vs 2.49±0.09) test scores in children whose mothers were exposed to vitamin A vs placebo (mean differences: −1.07, 95% CI −7.10 to 9.26, p=0.78; 0.15, 95% CI 0.43 to −0.08, p=0.15), respectively. More children in the placebo group had repeated a grade in school (28% of placebo vs 16.7% of vitamin A, p=0.01).

Conclusions

Preconceptional to postpartum maternal vitamin A supplementation, in an undernourished setting, does not improve cognition or motor development at ages 10–13 years.
Quality of newborn care: a health facility assessment in rural Ghana using survey, vignette and surveillance data
Authors: Vesel Linda , Manu Alexander , Lohela Terhi J , Gabrysch Sabine , Okyere Eunice , ten Asbroek Augustinus H A , Hill Zelee , Agyemang Charlotte Tawiah , Owusu-Agyei Seth , Kirkwood Betty R
Published: May 2013

Objective

To assess the structural capacity for, and quality of, immediate and essential newborn care (ENC) in health facilities in rural Ghana, and to link this with demand for facility deliveries and admissions.

Design

Health facility assessment survey and population-based surveillance data.

Setting

Seven districts in Brong Ahafo Region, Ghana.

Participants

Heads of maternal/neonatal wards in all 64 facilities performing deliveries.

Main outcome measures

Indicators include: the availability of essential infrastructure, newborn equipment and drugs, and personnel; vignette scores and adequacy of reasons given for delayed discharge of newborn babies; and prevalence of key immediate ENC practices that facilities should promote. These are matched to the percentage of babies delivered in and admitted to each type of facility.

Results

70% of babies were delivered in health facilities; 56% of these and 87% of neonatal admissions were in four referral level hospitals. These had adequate infrastructure, but all lacked staff trained in ENC and some essential equipment (including incubators and bag and masks) and/or drugs. Vignette scores for care of very low-birth-weight babies were generally moderate-to-high, but only three hospitals achieved high overall scores for quality of ENC. We estimate that only 33% of babies were born in facilities capable of providing high quality, basic resuscitation as assessed by a vignette plus the presence of a bag and mask. Promotion of immediate ENC practices in facilities was also inadequate, with coverage of early initiation of breastfeeding and delayed bathing both below 50% for babies born in facilities; this represents a lost opportunity.

Conclusions

Unless major gaps in ENC equipment, drugs, staff, practices and skills are addressed, strategies to increase facility utilisation will not achieve their potential to save newborn lives.

Trial registration

http://clinicaltrials.govNCT00623337.
Social media use among patients and caregivers: a scoping review
Authors: Hamm Michele P , Chisholm Annabritt , Shulhan Jocelyn , Milne Andrea , Scott Shannon D , Given Lisa M , Hartling Lisa
Published: May 2013

Objective

To map the state of the existing literature evaluating the use of social media in patient and caregiver populations.

Design

Scoping review.

Data sources

Medline, CENTRAL, ERIC, PubMed, CINAHL Plus Full Text, Academic Search Complete, Alt Health Watch, Health Source, Communication and Mass Media Complete, Web of Knowledge and ProQuest (2000–2012).

Study selection

Studies reporting primary research on the use of social media (collaborative projects, blogs/microblogs, content communities, social networking sites, virtual worlds) by patients or caregivers.

Data extraction

Two reviewers screened studies for eligibility; one reviewer extracted data from relevant studies and a second performed verification for accuracy and completeness on a 10% sample. Data were analysed to describe which social media tools are being used, by whom, for what purpose and how they are being evaluated.

Results

Two hundred eighty-four studies were included. Discussion forums were highly prevalent and constitute 66.6% of the sample. Social networking sites (14.8%) and blogs/microblogs (14.1%) were the next most commonly used tools. The intended purpose of the tool was to facilitate self-care in 77.1% of studies. While there were clusters of studies that focused on similar conditions (eg, lifestyle/weight loss (12.7%), cancer (11.3%)), there were no patterns in the objectives or tools used. A large proportion of the studies were descriptive (42.3%); however, there were also 48 (16.9%) randomised controlled trials (RCTs). Among the RCTs, 35.4% reported statistically significant results favouring the social media intervention being evaluated; however, 72.9% presented positive conclusions regarding the use of social media.

Conclusions

There is an extensive body of literature examining the use of social media in patient and caregiver populations. Much of this work is descriptive; however, with such widespread use, evaluations of effectiveness are required. In studies that have examined effectiveness, positive conclusions are often reported, despite non-significant findings.
Cryptopalaeontology
Authors: Liñán Eladio , Liñán María , Carrasco Joaquín
Published: May 2013

Fossils were credited with magico-medicinal properties in lapidary books written from the second century BCE onwards. The analysis of historical references to fossils in these ancient literary, geological, medical and magical texts has been named Cryptopalaeontology, a discipline that also includes discoveries of fossils at archaeological sites and the study of oral traditions.

Theophrastus'
Perì líthôn
(third century BCE), the four apocryphal Greek lapidaries (
Líthica Orphéôs
,
Orphéôs Líthica Kêrygmata
,
Socrátous Dionísou perì líthôn
and
Damigeron–Evax
: second century BCE), Pliny the Elder's
Historiae Naturae, Dioscorides' De Materia Medica
(first century CE), Isidore of Seville's
Etymologiarum
(seventh century) and Alfonso X's
Libro de las Piedras
(thirteenth century) all contain frequent references to fossils. In this context, these works might be considered the oldest treatises on fossils ever written.

The talismanic use of most of these fossils against a wide range of diseases was based on sympathetic magic. Only a few (e.g. Lapis Gagates, amber and Lapis Bitumen) survive in recent pharmacopoeia.
Terrorism and Democracy
Authors: Chenoweth Erica
Published: May 2013

From 1968 to 1997, wealthy, advanced democracies generally did not suffer from high levels of chronic terrorism, with two exceptions: (a) advanced democracies that interfered in other countries' affairs through military intervention or occupations were frequent targets of transnational terrorism, and (b) poor democracies with territorial conflicts often experienced related domestic terrorist attacks. Intermediately wealthy and transitioning democracies with internally inconsistent institutions were more likely to experience domestic terrorism than advanced democracies and authoritarian regimes. There is very little agreement about why these trends persist. I identify the competing explanations that have emerged within the literature as well as remaining controversies. I also present preliminary evidence suggesting that since 9/11, terrorism persists in the usual pattern but may be increasingly prevalent in nondemocratic countries. I offer five speculative explanations for this and four suggestions for how the field should proceed.
Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries
Authors: Morgan Richard G. , Ives Stephen J. , Lesniewski Lisa A. , Cawthon Richard M. , Andtbacka Robert H. I. , Noyes R. Dirk , Richardson Russell S. , Donato Anthony J.
Published: May 2013

Arterial telomere dysfunction may contribute to chronic arterial inflammation by inducing cellular senescence and subsequent senescence-associated inflammation. Although telomere shortening has been associated with arterial aging in humans, age-related telomere uncapping has not been described in non-cultured human tissues and may have substantial prognostic value. In skeletal muscle feed arteries from 104 younger, middle-aged, and older adults, we assessed the potential role of age-related telomere uncapping in arterial inflammation. Telomere uncapping, measured by p-histone γ-H2A.X (ser139) localized to telomeres (chromatin immunoprecipitation; ChIP), and telomeric repeat binding factor 2 bound to telomeres (ChIP) was greater in arteries from older adults compared with those from younger adults. There was greater tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)-induced senescence, measured by P53 bound to P21 gene promoter (ChIP), and greater expression of P21, interleukin 8, and monocyte chemotactic protein 1 mRNA (RT-PCR) in arteries from older adults compared with younger adults. Telomere uncapping was a highly influential covariate for the age-group difference in P53/P21-induced senescence. Despite progressive age-related telomere shortening in human arteries, mean telomere length was not associated with telomere uncapping or P53/P21-induced senescence. Collectively, these findings demonstrate that advancing age is associated with greater telomere uncapping in arteries, which is linked to P53/P21-induced senescence independent of telomere shortening.
Sexual dimorphism in obesity-mediated left ventricular hypertrophy
Authors: Böhm Christian , Benz Verena , Clemenz Markus , Sprang Christiane , Höft Beata , Kintscher Ulrich , Foryst-Ludwig Anna
Published: May 2013

In the present study we investigated the influence of sex difference on the development of left ventricular hypertrophy (LVH) during obesity. Male and female C57BL/6J mice were fed for 15 and 25 wk with a high-fat diet (HFD) or low-fat control diet (LFD). Analysis of body composition, monitoring of body weight (BW), and echocardiographic analysis were performed, as well as analysis of expression of different adipocytokines in epicardial adipose tissue. The increment in left ventricular mass (LVM) after HFD (25 wk) was significantly stronger in male mice compared with female mice [LVM: male, 116.9 ± 2.9 (LFD) vs. 142.2 ± 9.3 mg (HFD); female, 84.3 ± 3.3 (LFD) vs. 93.9 ± 1.7 mg (HFD), Psex < 0.01]. In parallel, males developed a higher BW and fat mass after 25 wk HFD than female mice [BW: male, 33 ± 0.9 (LFD) vs. 53 ± 0.8 g (HFD); fat mass: male, 8.8 ± 0.9 (LFD) vs. 22.8 ± 0.7 g (HFD); BW: female, 22.5 ± 0.4 (LFD) vs. 33.7 ± 1.3 g (HFD); fat mass: female, 4.0 ± 0.2 (LFD) vs. 13.2 ± 1.2 g (HFD)] ( P < 0.01 for BW+ fat mass female vs. male). The mRNA expression of adipocytokines in epicardial fat after 25 wk of diet showed higher levels of adiponectin (2.8-fold), leptin (4.2-fold), and vaspin (11.9-fold) in male mice compared with female mice ( P < 0.05). To identify new adipose-derived molecular mediators of LVH, we further elucidated the cardiac impact of vaspin. Murine primary cardiac fibroblast proliferation was significantly induced by vaspin (1.8-fold, vaspin 1 μg/l, P < 0.05 vs. control) compared with 1.9-fold induction by angiotensin II (10 μM). The present study demonstrates a sex-dependent regulation of diet-induced LVH associated with sexual dimorphic expression of adipocytokines in epicardial adipose tissue.
Apolipoprotein A-1 mimetic D-4F enhances isoflurane-induced eNOS signaling and cardioprotection during acute hyperglycemia
Authors: Baotic Ines , Ge Zhi-Dong , Sedlic Filip , Coon Adrian , Weihrauch Dorothee , Warltier David C. , Kersten Judy R.
Published: May 2013

Acute hyperglycemia (AHG) decreases the availability of nitric oxide (NO) and impairs anesthetic preconditioning (APC)-elicited protection against myocardial infarction. We investigated whether D-4F, an apolipoprotein A-1 mimetic, rescues the myocardium by promoting APC-induced endothelial NO signaling during AHG. Myocardial infarct size was measured in mice in the absence or presence of APC [isoflurane (1.4%)] with or without AHG [dextrose (2 g/kg ip)] and D-4F (0.12 or 0.6 mg/kg ip). NO production, superoxide generation, protein compartmentalization, and posttranslational endothelial NO synthase (eNOS) modifications were assessed in human coronary artery endothelial cells cultured in 5.5 or 20 mM glucose with or without isoflurane (0.5 mM) in the presence or absence of D-4F (0.5 μg/ml). Myocardial infarct size was significantly decreased by APC (36 ± 3% of risk area) compared with control (54 ± 3%) in the absence, but not presence, of AHG (49 ± 4%). D-4F restored the cardioprotective effect of APC during AHG (36 ± 3% and 30 ± 3%, 0.12 and 0.6 mg/kg, respectively), although D-4F alone had no effect on infarct size (53 ± 3%). Isoflurane promoted caveolin-1 and eNOS compartmentalization within endothelial cell caveolae and eNOS dimerization, concomitant with increased NO production (411 ± 28 vs. 68 ± 10 pmol/mg protein in control). These actions were attenuated by AHG (NO production: 264 ± 18 pmol/mg protein). D-4F reduced superoxide generation and enhanced caveolin-1 and eNOS caveolar compartmentalization and posttranslational eNOS modifications, thus restoring NO production during isoflurane and AHG (418 ± 36 pmol/mg protein). In conclusion, D-4F restored the cardioprotective effect of APC during AHG, possibly by decreasing superoxide generation, which promoted isoflurane-induced eNOS signaling and NO biosynthesis.
Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb
Authors: Heinonen Ilkka , Wendelin-Saarenhovi Maria , Kaskinoro Kimmo , Knuuti Juhani , Scheinin Mika , Kalliokoski Kari K.
Published: May 2013

The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ∼40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min−1·100 g−1 in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min−1·100 g−1) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min−1·100 g−1). During exercise, NE reduced exercising muscle BF by ∼16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT ( P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.
Inhibition of Tumor Cell Migration by LD22-4, an N-Terminal Fragment of 24-kDa FGF2, Is Mediated by Neuropilin 1
Authors: Zhang Ling , Parry Graham C. , Levin Eugene G.
Published: May 2013

LD22-4, an 86-amino acid fragment of the basic fibroblast growth factor, is an inhibitor of cell migration. LD22-4 inhibits the migration of various tumor cells, endothelial cells, and fibroblasts in vitro and suppresses tumor growth and angiogenesis in vivo. LD22-4 is effective in the presence of multiple growth factors, either alone or in combination, as well as haptotactic factors. LD22-4 inhibits the rate of malignant gliomas prepared from U87MG cells in an orthotopic mouse model by 90% compared with untreated mice. Using U87MG cells, we identified the LD22-4 membrane receptor as neuropilin 1 (NRP1). The identification of NRP1 as the LD22-4 receptor was based upon mass spectrometric analysis of proteins that bind to LD22-4, immunoprecipitation of an NRP1–LD22-4 complex formed during incubation of LD22-4 with U87MG cells, LD22-4-NRP1 coimmunoprecipitation studies, and binding of LD22-4 to HEK293 cells expressing NRP1. In contrast, NRP1 binding of an inactive mutant of LD22-4 was substantially reduced. As is typical of NRP1-binding proteins, LD22-4 itself binds to heparin and requires heparan sulfate for binding to cells. The addition of heparin to migration assays increased the inhibitory activity of LD22-4. In addition to a heparin-binding region, LD22-4 contains a 5-amino acid C-terminus that matches an NRP1 consensus binding sequence. Thus, direct binding experiments, dependence on heparan sulfate, and the presence of a NRP1 consensus binding sequence indicate that NRP1 is the binding site of LD22-4 and mediates inhibition of cell migration. Cancer Res; 73(11); 3316–25. ©2013 AACR.
miR-214 Coordinates Melanoma Progression by Upregulating ALCAM through TFAP2 and miR-148b Downmodulation
Authors: Penna Elisa , Orso Francesca , Cimino Daniela , Vercellino Irene , Grassi Elena , Quaglino Elena , Turco Emilia , Taverna Daniela
Published: May 2013

Malignant melanoma is one of the most aggressive human cancers, but the mechanisms governing its metastatic dissemination are not fully understood. Upregulation of miR-214 and ALCAM and the loss of TFAP2 expression have been implicated in this process, with TFAP2 a direct target of miR-214. Here, we link miR-214 and ALCAM as well as identify a core role for miR-214 in organizing melanoma metastasis. miR-214 upregulated ALCAM, acting transcriptionally through TFAP2 and also posttranscriptionally through miR-148b (itself controlled by TFAP2), both negative regulators of ALCAM. We also identified several miR-214–mediated prometastatic functions directly promoted by ALCAM. Silencing ALCAM in miR-214–overexpressing melanoma cells reduced cell migration and invasion without affecting growth or anoikis in vitro, and it also impaired extravasation and metastasis formation in vivo. Conversely, cell migration and extravasation was reduced in miR-214–overexpressing cells by upregulation of either miR-148b or TFAP2. These findings were consistent with patterns of expression of miR-214, ALCAM, and miR-148b in human melanoma specimens. Overall, our results define a pathway involving miR-214, miR-148b, TFAP2, and ALCAM that is critical for establishing distant metastases in melanoma. Cancer Res; 73(13); 4098–111. ©2013 AACR.
Use of Multiple Endpoints and Approval Paths Depicts a Decade of FDA Oncology Drug Approvals
Authors: Shea Michael B. , Roberts Samantha A. , Walrath Jessica C. , Allen Jeff D. , Sigal Ellen V.
Published: May 2013

This study explores the historic use of different endpoints to support regular and accelerated approval of cancer drugs between 2002 and 2012. In the past 10 years, two thirds of oncology regular approvals were based on endpoints other than overall survival. More than three quarters of accelerated approvals were based on response rates. The accelerated approval program has been heavily used over this time period, with one third of all approved oncology indications receiving accelerated approval. At times, critics have characterized the agency as rigid and unpredictable. This research describes the degree of regulatory flexibility that U.S. Food and Drug Administration and drug sponsors have used over the past decade in the development of new treatments for cancer. Clin Cancer Res; 19(14); 3722–31. ©2013 AACR.
Development of a Novel Class of Tubulin Inhibitors with Promising Anticancer Activities
Authors: Xi Jingle , Zhu Xuejun , Feng Yongmei , Huang Na , Luo Guifen , Mao Yongjun , Han Xiaofeng , Tian Wang , Wang Guirong , Han Xiaobing , Luo Rongcheng , Huang Ziwei , An Jing
Published: May 2013

We have developed a novel class (2-amino-4-phenyl-4H-chromene-3-carboxylate) of inhibitors of tubulin assembly by modifying HA14-1, which is a Bcl-2 inhibitor discovered by our group. Three of these compounds, mHA1, mHA6, and mHA11, showed in vitro cytotoxicities against tumor cells that were more potent and more stable than the backbone compound HA14-1, with nM IC50 values. In contrast, the cytotoxic effects of these compounds on normal cells were minimal. Computational docking, colchicine-tubulin competitive binding, and tubulin polymerization studies demonstrated that these compounds bind at the colchicine-binding site on tubulin and inhibit the formation of microtubules. Treatment of HL-60/Bcl-2 leukemia and CRL5908 lung cancer cells with these mHA compounds led to pronounced microtubule density decreases, G2/M cell cycle arrest, and apoptosis, as determined by immunofluorescence microscopy, flow cytometry, and DNA fragmentation analysis. Combined, these data identify a novel class of compounds that inhibit tubulin assembly and limit cancer cell phenotypes.

Implications: This study supports the continued development of novel anti-tubulin assembly inhibitors as potential anticancer agents. Mol Cancer Res; 11(8); 856–64. ©2013 AACR.
The Role of Residential Segregation in Contemporary School Segregation
Authors: Frankenberg Erica
Published: May 2013

Inaction to address housing segregation in metropolitan areas has resulted in persistently high levels of residential segregation. As the Supreme Court has recently limited school districts’ voluntary integration efforts, this article considers the role of residential segregation in maintaining racially isolated schools, namely what is known about the reciprocal relationship between housing and schooling segregation patterns. In addition, it examines the residential and school segregation indices in the largest metropolitan areas since 2000, comparing relationships between the extent of school and residential patterns and changes in each over time. Finally, I consider the legal and policy options for how residential integration efforts might affect school segregation.
The Life and Death of Desegregation Policy in Wake County Public School System and Charlotte-Mecklenburg Schools
Authors: Williams Sheneka M. , Houck Eric A.
Published: May 2013

The state of North Carolina is one of few states in the South in which two large districts committed to desegregating schools in the early 1970s. However, the state’s two largest districts, Charlotte-Mecklenberg Schools (CMS) and Wake County Public School System (WCPSS) have experienced ups and downs in their policy commitment to desegregated schools. This article utilizes a cross-case policy analysis to examine levels of segregation in CMS and WCPSS over a 10-year period. In addition, the authors examine school finance data to determine whether district spending and local and federal contributions have an effect on student outcomes in CMS and WCPSS. The authors also compare district outcomes against the backdrop of student assignment policy within each district. Findings indicate that despite spending mechanisms, both districts have become more segregated over time and that the achievement gap has narrowed between the districts’ students.
Suburban School Districts and Demographic Change
Authors: Holme Jennifer Jellison , Diem Sarah , Welton Anjalé
Published: May 2013

Purpose: Suburban school districts have undergone significant demographic shifts over the past several decades. The research literature to date, however, has yet to explore how suburban district leaders are responding to such changes, or examine the factors that shape response. In this article, we apply a “zone of mediation” framework to examine how the leaders of one large and rapidly changing suburban school district in Texas responded to its changing student population. In our analysis, we consider the technical, normative, and political dimensions of this district’s response to demographic shifts. Research Methods/Approach: We conducted an in-depth qualitative case study of a large and rapidly changing district in the San Antonio Metropolitan area, which we named “Southern Independent School District.” Our data included interviews with 28 district-level and community actors and interviews with 26 educators across three “focus” schools that were undergoing particularly rapid demographic shifts. Findings and Implications: We found that Southern Independent School District’s response to demographic change focused intensely on technical changes in curriculum and instruction. Such technical changes we found were explicitly adopted to address the needs of the increasing proportion of low-income students and students of color within the district. At the same time, we illustrate how the district failed to address the more challenging normative and political dynamics within the district. This failure, we show, placed significant limits upon the technical reforms that were adopted.
Carried or Defeated? Examining the Factors Associated With Passing School District Bond Elections in Texas, 1997-2009
Authors: Bowers Alex J. , Lee Jooyoung
Published: May 2013

Purpose: Across the United States, a large percentage of school districts are in need of facility improvements to provide safe and adequate buildings to facilitate student learning. To finance new construction, school districts traditionally have put proposals before local voters to fund construction through issuing long-term bonds to finance near-term construction. However, past literature indicates that there are few variables that are associated with bond election outcomes that are under the influence of school administrators. The purpose of this study was to examine the factors most associated with passing or failing a school district capital facility finance bond in the state of Texas from 1997 through 2009. Research Methods: We analyzed all proposed school bonds in Texas from 1997 to 2009 ( n = 2,224) using a logistic regression discrete time hazard model to model the probability of passing a bond on the first, second, or third attempt, while controlling for multiple types of variables such as bond, district, and community characteristics, as well as specific election characteristics. Findings: We found that the first attempt of a bond is the mostly likely to succeed, as well as bonds that propose renovations and debt refinancing, or are at the top of the ballot. Also, while percent population over age 65 was negatively related to bond passage, percent Asian and Hispanic students was positively related. Implications for Research and Practice: Using past research and our findings, we propose a mediated model of school bond passage and provide specific recommendations for administrators looking to pass needed facility construction bonds, including focusing on passing the bond on the first attempt and proposing only a single bond that includes all requests.
Applying the Refined Values Theory to Past Data
Authors: Cieciuch Jan , Schwartz Shalom H. , Vecchione Michele
Published: May 2013

The refined theory of basic human values (Schwartz et al., 2012) divides the circular continuum of values into 19 motivationally distinct values. Research with a new questionnaire discriminated these values in 10 countries and demonstrated the benefits of the finer distinctions. We ask, whether researchers can gain by applying the refined theory to the large repository of available data gathered with the 40-Item Portrait Values Questionnaire (PVQ40)? How many, if any, of the more refined values can be distinguished in PVQ40 data, and does this provide improved understanding of the topics studied? We addressed these questions with data from 13 countries on four continents (total N = 7,352). Theory-based multidimensional scaling and confirmatory factor analyses in each country revealed several more narrowly defined values in the PVQ data. Examples from 14 countries demonstrated that these refinements can increase predictive and explanatory power.
More than Words: The Effect of Multi-word Frequency and Constituency on Phonetic Duration
Authors: Arnon Inbal , Cohen Priva Uriel
Published: May 2013

There is mounting evidence that language users are sensitive to the distributional properties of multi-word sequences. Such findings expand the range of information speakers are sensitive to and call for processing models that can represent larger chains of relations. In the current paper we investigate the effect of multi-word statistics on phonetic duration using a combination of experimental and corpus-based research. We ask (a) if phonetic duration is affected by multi-word frequency in both elicited and spontaneous speech, and (b) if syntactic constituency modulates the effect. We show that phonetic durations are reduced in higher frequency sequences, regardless of constituency: duration is shorter for more frequent sequences within and across syntactic boundaries. The effects are not reducible to the frequency of the individual words or substrings. These findings open up a novel set of questions about the interaction between surface distributions and higher order properties, and the resulting need (or lack thereof) to incorporate higher order properties into processing models.