bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple pqqA genes respond differently to environment and one contributes dominantly to pyrroloquinoline quinone synthesis
Authors: Ge Xin , Wang Wenxi , Du Baohua , Wang Jianhua , Xiong Xianghua , Zhang Weicai
Published: July 2013

Pyrroloquinoline quinone is the third redox cofactor after nicotinamide and flavin in bacteria, and its biosynthesis pathway comprise five steps initiated from a precursor peptide PqqA coded by pqqA gene. Methylovorus sp. MP688 is equipped with five copies of pqqA genes. Herein, the transcription of pqqA genes under different conditions by real‐time quantitative PCR and β‐galactosidase reporter genes are reported. Multiple pqqA genes were proved to play significant roles and contribute differently in PQQ synthesis. pqqA1, pqqA2, and pqqA4 were determined to be dominantly transcribed over the others, and correspondingly absence of any of the three genes caused a decrease in PQQ synthesis. Notably, pqqA was up‐regulated in low pH and limited oxygen environment, and it is pqqA2 promoter that could be induced when bacteria were transferred from pH 7.0 to pH 5.5. Deletion analysis revealed a region within pqqA2 promoter inhibiting transcription. PQQ concentration was increased by overexpression of pqq genes under control of truncated pqqA2 promoter. The results not only imply there exist negative transcriptional regulators for pqqA2 but also provide us a new approach to achieve higher PQQ production by deleting the target binding sequence.
Molecular characterization of the planktonic microorganisms in water of two mountain brackish lakes
Authors: Zeng Jun , Deng Li‐Juan , Lou Kai , Zhang Tao , Yang Hong‐Mei , Shi Ying‐Wu , Lin Qing
Published: July 2013

The prokaryotic diversity in two brackish lakes (Sayram Lake and Chaiwopu Lake) was investigated by constructing bacterial and archaeal clone libraries of 16S rRNA genes. Bacterial clones from Sayram Lake were classified into six phyla (Proteobacteria, Verrucomicrobia, Bacteroidetes, Planctomycetes, Acidobacteria, Actinobacteria). Of these, Proteobacteria and Verrucomicrobia were the most dominant, representing 50.4 and 16.8% of the clone library, respectively. Sequences related to Proteobacteria (58.1%), Cyanobacteria (17.2%), Bacteroidetes (15%), Verrucomicrobia (4.3%), Actinobacteria (3.2%) constituted over 97% of the bacterial clone library from Chaiwopu Lake. In addition, 58.8% (Sayram Lake) and 48% (Chaiwopu Lake) of bacterial clones showed high sequence identity to pure cultures. The composition of Archaea was obviously different between the two lakes. Only the Crenarchaeota phylum was found in the Sayram Lake, whereas Archaeal sequences from Chaiwopu Lake were classified into three phyla: Crenarchaeota (5.8%), Thaumarchaeota (81.2%), and Euryarchaeota (13%). Among the archaeal sequences, 94.2% were highly related to cultivable species of the genus Nitrosopumilus, Methanoculleus, and Methanobacterium. These results showed a high diversity of potential cultivable heterotrophic bacteria in Sayram Lake and Chaiwopu Lake. Chaiwopu Lake was a source of potentially novel, cultivable archaea.
Lipid mediator serum profiles in asthmatics significantly shift following dietary supplementation with omega‐3 fatty acids
Authors: Lundström Susanna L. , Yang Jun , Brannan John D. , Haeggström Jesper Z. , Hammock Bruce D. , Nair Parameswaran , O'Byrne Paul , Dahlén Sven‐Erik , Wheelock Craig E.
Published: July 2013

Scope

In contrast to well‐characterized PUFA levels in serum, little is known regarding their downstream metabolic products. However, many of these compounds are lipid mediators with prominent roles during pro‐ and antiinflammatory processes.

Methods and results

In this double blind crossover study on asthmatics, shifts in serum levels of ω‐3 and ω‐6 PUFA‐derived oxidized fatty acids (e.g. eicosanoids, oxylipins) were quantified following dietary fish oil supplementation. Serum was obtained from subjects following fasting at three occasions; (i) prior to supplementation, (ii) following a 3‐week supplement intake of either placebo or fish oil, and (iii) following a 3‐week washout period with a subsequent 3‐week period of either fish oil or placebo supplement. A total of 87 oxylipins representing cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) metabolic pathways were screened via LC‐MS/MS. The primary alterations observed were in CYP‐ and 15‐LOX‐derived EPA‐ and CYP‐derived DHA oxylipins.

Conclusion

The results indicate that intake of an ω‐3 rich diet alters not only the PUFA ratio, but also the ratio of downstream oxylipins. These data further support that dietary manipulation with ω‐3 PUFAs affects not only PUFA levels, but importantly also the downstream metabolic profile.
High‐resolution NMR spectroscopy of human body fluids and tissues in relation to prostate cancer
Authors: Kumar Virendra , Dwivedi Durgesh K. , Jagannathan Naranamangalam R.
Published: July 2013

High‐resolution NMR spectroscopic studies of prostate tissue extracts, prostatic fluid, seminal fluid, serum and urine can be used for the detection of prostate cancer, based on the differences in their metabolic profiles. Useful diagnostic information is obtained by the detection or quantification of as many metabolites as possible and comparison with normal samples. Only a few studies have shown the potential of high‐resolution in vitro NMR of prostate tissues. A survey of the literature has revealed that studies on body fluids, such as urine and serum, in relation to prostate cancer are rare. In addition, the potential of NMR of nuclei other than 1H, such as 13C and 31P, has not been exploited fully. The metabolomic analysis of metabolites, detected by high‐resolution NMR, may help to identify metabolites which could serve as useful biomarkers for prostate cancer detection. Such NMR‐derived biomarkers would not only help in prostate cancer detection and in understanding the in vivo MRS metabolic profile, but also to investigate the biochemical and metabolic changes associated with cancer. Here, we review the published research work on body fluids in relation to prostate and prostate tissue extracts, and highlight the potential of such studies for future work. Copyright © 2013 John Wiley & Sons, Ltd.
Laser‐micromachined cellulose acetate adhesive tape as a low‐cost smart material
Authors: Ochoa Manuel , Chitnis Girish , Ziaie Babak
Published: July 2013

An off‐the‐shelf, moisture‐responsive, acetate‐backed adhesive tape is investigated as a commercially available smart material for fabricating low‐cost, multifunctional, humidity‐responsive millimeter‐scale structures. Laser ablation is used for cutting and thinning‐down the tape to enhance its response. Water‐submerged cantilevers show a radius of curvature of 3 mm or lower (for laser‐thinned cantilevers). Additionally, their humidity response is a function of the angle between the longitudinal axis of the cantilever and polymer orientation. A cut angled at 80° with respect to this orientation results in a tip rotation of up to 25°, enabling the formation of bending cantilevers with twisting behavior. The tape cantilevers are further functionalized with magnetic nanoparticles and used to create four‐finger grippers that close underwater within minutes and can sample 100 µL of liquid. A cyclic humidity monitor is also fabricated using a tape strip that walks unidirectionally on a ratchet‐shaped surface upon exposure to humidity variations. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1263–1267
Synthesis and biomimetic mineralization of l‐proline substituted polyphosphazenes as bulk and nanofiber
Authors: Silva Nykänen Virginia P. , Puska Mervi A. , Nykänen Antti , Ruokolainen Janne
Published: July 2013

This work presents the synthesis of polyphosphazenes bearing L‐proline methyl ester (ProOMe) and 4‐hydroxy‐l‐proline methyl ester (HypOMe), aiming for new bioactive polymers for bone repair. The polymers were characterized by 1H and 31P NMR, FTIR, DSC, and TGA. Electrospun fibers were prepared using poly[bis(l‐proline methyl ester)phosphazene] (PProP), and their potential for biomimetic mineralization, as well as the bulk material, were tested in simulated body fluid (1×SBF). Samples were analyzed between 24 h and 3 weeks of incubation using SEM/EDS and FTIR. After 24 h, spherical and flower‐like shapes of calcium phosphates (CaP) were crystallized on the bulk samples. The nanofibers presented spherical CaP crystals attached to them after 48 h of incubation. The Ca/P molar ratio of the crystals varied from 1.5 to 1.6. According to this study, PProP presents bioactivity in vitro, and its fibers offer sites for CaP nucleation like the collagen fibers in bone. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1318–1327
Distribution of zinc‐blende twins and wurtzite segments in GaAs nanowires probed by X‐ray nanodiffraction
Authors: Biermanns Andreas , Carbone Dina , Breuer Steffen , Jacques Vincent L. R. , Schulli Tobias , Geelhaar Lutz , Pietsch Ullrich
Published: July 2013

magnified image

We study by X‐ray nanodiffraction the statistical distribution of the two possible twinned zinc‐blende (ZB) orientations as well as the occurrence of the wurtzite structure within single GaAs nanowires (NWs) grown by molecular beam epitaxy on Si(111). A fast scanning scheme allowed to perform diffraction experiments on 160 individual NWs. We find that although on average the two ZB orientations show a similar abundance, in 90% of all NWs one ZB orientation dominates and little twinning is observed within each individual NW. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Icariin: Does It Have An Osteoinductive Potential for Bone Tissue Engineering?
Authors: Zhang Xin , Liu Tie , Huang Yuanliang , Wismeijer Daniel , Liu Yuelian
Published: July 2013

Traditional Chinese medicines have been recommended for bone regeneration and repair for thousands of years. Currently, the Herba Epimedii and its multi‐component formulation are the attractive native herbs for the treatment of osteoporosis. Icariin, a typical flavonol glycoside, is considered to be the main active ingredient of the Herba Epimedii from which icariin has been successfully extracted. Most interestingly, it has been reported that icariin can be delivered locally by biomaterials and that it has an osteoinductive potential for bone tissue engineering. This review focuses on the performance of icariin in bone tissue engineering and on blending the information from icariin with the current knowledge relevant to molecular mechanisms and signal pathways. The osteoinductive potential of icariin could be attributed to its multiple functions in the musculoskeletal system which is involved in the regulation of multiple signaling pathways in anti‐osteoporosis, osteogenesis, anti‐osteoclastogenesis, chondrogenesis, angiogenesis, and anti‐inflammation. The osteoinductive potential and the low price of icariin make it a very attractive candidate as a substitute of osteoinductive protein–bone morphogenetic proteins (BMPs), or as a promoter for enhancing the therapeutic effects of BMPs. However, the effectiveness of the local delivery of icariin needs to be investigated further. Copyright © 2013 John Wiley & Sons, Ltd.
Jaguar: A high‐performance quantum chemistry software program with strengths in life and materials sciences
Authors: Bochevarov Art D. , Harder Edward , Hughes Thomas F. , Greenwood Jeremy R. , Braden Dale A. , Philipp Dean M. , Rinaldo David , Halls Mathew D. , Zhang Jing , Friesner Richard A.
Published: July 2013

Jaguar is anab initioquantum chemical program that specializes in fast electronic structure predictions for molecular systems of medium and large size. Jaguar focuses on computational methods with reasonable computational scaling with the size of the system, such as density functional theory (DFT) and local second‐order Møller–Plesset perturbation theory. The favorable scaling of the methods and the high efficiency of the program make it possible to conduct routine computations involving several thousand molecular orbitals. This performance is achieved through a utilization of the pseudospectral approximation and several levels of parallelization. The speed advantages are beneficial for applying Jaguar in biomolecular computational modeling. Additionally, owing to its superior wave function guess for transition‐metal‐containing systems, Jaguar finds applications in inorganic and bioinorganic chemistry. The emphasis on larger systems and transition metal elements paves the way toward developing Jaguar for its use in materials science modeling. The article describes the historical and new features of Jaguar, such as improved parallelization of many modules, innovations inab initiopKa prediction, and new semiempirical corrections for nondynamic correlation errors in DFT. Jaguar applications in drug discovery, materials science, force field parameterization, and other areas of computational research are reviewed. Timing benchmarks and other results obtained from the most recent Jaguar code are provided. The article concludes with a discussion of challenges and directions for future development of the program. © 2013 Wiley Periodicals, Inc.
THE ROLE OF THE BARENTS SEA IN THE ARCTIC CLIMATE SYSTEM
Authors: Smedsrud Lars H. , Esau Igor , Ingvaldsen Randi B. , Eldevik Tor , Haugan Peter M. , Li Camille , Lien Vidar S. , Olsen Are , Omar Abdirahman M. , Otterå Odd H. , Risebrobakken Bjørg , Sandø Anne B. , Semenov Vladimir A. , Sorokina Svetlana A.
Published: July 2013

Present global warming is amplified in the Arctic and accompanied by unprecedented sea ice decline. Located along the main pathway of Atlantic Water entering the Arctic, the Barents Sea is the site of coupled feedback processes that are important for creating variability in the entire Arctic air‐ice‐ocean system. As warm Atlantic Water flows through the Barents Sea, it loses heat to the Arctic atmosphere. Warm periods, like today, are associated with high northward heat transport, reduced Arctic sea ice cover, and high surface air temperatures. The cooling of the Atlantic inflow creates dense water sinking to great depths in the Arctic Basins, and ~60% of the Arctic Ocean carbon uptake is removed from the carbon‐saturated surface this way. Recently, anomalously large ocean heat transport has reduced sea ice formation in the Barents Sea during winter. The missing Barents Sea winter ice makes up a large part of observed winter Arctic sea ice loss, and in 2050, the Barents Sea is projected to be largely ice free throughout the year, with 4°C summer warming in the formerly ice‐covered areas. The heating of the Barents atmosphere plays an important role both in “Arctic amplification” and the Arctic heat budget. The heating also perturbs the large‐scale circulation through expansion of the Siberian High northward, with a possible link to recent continental wintertime cooling. Large air‐ice‐ocean variability is evident in proxy records of past climate conditions, suggesting that the Barents Sea has had an important role in Northern Hemisphere climate for, at least, the last 2500 years.
A security communication model based on certificateless online/offline signcryption for Internet of Things
Authors: Luo Ming , Tu Min , Xu Jianfeng
Published: July 2013

The communication model of Internet of Things (IOT) application has some shortcomings in user privacy protection and information security. To solve these shortcomings, we define the formal models of certificateless online/offline signcryption and propose a concrete certificateless online/offline signcryption scheme for IOT environment. Compared with the existing identity‐based online/offline signcryption schemes that do not require the plaintext and the receiver's identity in the offline phase, our scheme has the great advantage of the offline computation cost, offline storage, ciphertext length, and receiver computation cost. Moreover, our scheme achieves known session‐specific temporary information security, public verifiability with confidentiality and no key escrow problem. Copyright © 2013 John Wiley & Sons, Ltd.
Integrative variable selection via Bayesian model uncertainty
Authors: Quintana M. A. , Conti D. V.
Published: July 2013

We are interested in developing integrative approaches for variable selection problems that incorporate external knowledge on a set of predictors of interest. In particular, we have developed an integrative Bayesian model uncertainty (iBMU) method, which formally incorporates multiple sources of data via a second‐stage probit model on the probability that any predictor is associated with the outcome of interest. Using simulations, we demonstrate that iBMU leads to an increase in power to detect true marginal associations over more commonly used variable selection techniques, such as least absolute shrinkage and selection operator and elastic net. In addition, iBMU leads to a more efficient model search algorithm over the basic BMU method even when the predictor‐level covariates are only modestly informative. The increase in power and efficiency of our method becomes more substantial as the predictor‐level covariates become more informative. Finally, we demonstrate the power and flexibility of iBMU for integrating both gene structure and functional biomarker information into a candidate gene study investigating over 50 genes in the brain reward system and their role with smoking cessation from the Pharmacogenetics of Nicotine Addiction and Treatment Consortium. Copyright © 2013 John Wiley & Sons, Ltd.
Using confidence intervals to compare several correlated areas under the receiver operating characteristic curves
Authors: Zou G. Y. , Yue Li
Published: July 2013

The performance of a diagnostic tool yielding quantitative or ordinal measurements is often assessed in terms of its area under the receiver operating characteristic curve (AUC). As new diagnostic tools are constantly being developed, a frequently occurring task is to compare multiple AUCs as derived from the same group of subjects. For this purpose, previous methods have usually used an omnibus chi‐square test, which may not be very informative. We present here methods for comparing several correlated AUCs using simultaneous confidence intervals. To improve small sample properties, we adopt the method of variance estimates recovery in which confidence limits for each AUC are obtained on the basis of the logit and inverse hyperbolic sine transformations. A simulation study demonstrates the superior performance of the proposed approach. The methods are illustrated with two examples. Copyright © 2013 John Wiley & Sons, Ltd.
Comparison of methods for estimating the effect of salvage therapy in prostate cancer when treatment is given by indication
Authors: Taylor Jeremy M. G. , Shen Jincheng , Kennedy Edward H. , Wang Lu , Schaubel Douglas E.
Published: July 2013

For patients who were previously treated for prostate cancer, salvage hormone therapy is frequently given when the longitudinal marker prostate‐specific antigen begins to rise during follow‐up. Because the treatment is given by indication, estimating the effect of the hormone therapy is challenging. In a previous paper we described two methods for estimating the treatment effect, called two‐stage and sequential stratification. The two‐stage method involved modeling the longitudinal and survival data. The sequential stratification method involves contrasts within matched sets of people, where each matched set includes people who did and did not receive hormone therapy. In this paper, we evaluate the properties of these two methods and compare and contrast them with the marginal structural model methodology. The marginal structural model methodology involves a weighted survival analysis, where the weights are derived from models for the time of hormone therapy. We highlight the different conditional and marginal interpretations of the quantities being estimated by the three methods. Using simulations that mimic the prostate cancer setting, we evaluate bias, efficiency, and accuracy of estimated standard errors and robustness to modeling assumptions. The results show differences between the methods in terms of the quantities being estimated and in efficiency. We also demonstrate how the results of a randomized trial of salvage hormone therapy are strongly influenced by the design of the study and discuss how the findings from using the three methodologies can be used to infer the results of a trial. Copyright © 2013 John Wiley & Sons, Ltd.
A spatial scan statistic for compound Poisson data
Authors: Rosychuk Rhonda J. , Chang Hsing‐Ming
Published: July 2013

The topic of spatial cluster detection gained attention in statistics during the late 1980s and early 1990s. Effort has been devoted to the development of methods for detecting spatial clustering of cases and events in the biological sciences, astronomy and epidemiology. More recently, research has examined detecting clusters of correlated count data associated with health conditions of individuals. Such a method allows researchers to examine spatial relationships of disease‐related events rather than just incident or prevalent cases. We introduce a spatial scan test that identifies clusters of events in a study region. Because an individual case may have multiple (repeated) events, we base the test on a compound Poisson model. We illustrate our method for cluster detection on emergency department visits, where individuals may make multiple disease‐related visits. Copyright © 2013 John Wiley & Sons, Ltd.
Meta‐analysis of clinical trials with early stopping: an investigation of potential bias
Authors: Schou I. Manjula , Marschner Ian C.
Published: July 2013

Clinical trials that stop early for benefit have a treatment difference that overestimates the true effect. The consequences of this fact have been extensively debated in the literature. Some researchers argue that early stopping, or truncation, is an important source of bias in treatment effect estimates, particularly when truncated studies are incorporated into meta‐analyses. Such claims are bound to lead some systematic reviewers to consider excluding truncated studies from evidence synthesis. We therefore investigated the implications of this strategy by examining the properties of sequentially monitored studies conditional on reaching the final analysis. As well as estimation bias, we studied information bias measured by the difference between standard measures of statistical information, such as sample size, and the actual information based on the conditional sampling distribution. We found that excluding truncated studies leads to underestimation of treatment effects and overestimation of information. Importantly, the information bias increases with the estimation bias, meaning that greater estimation bias is accompanied by greater overweighting in a meta‐analysis. Simulations of meta‐analyses confirmed that the bias from excluding truncated studies can be substantial. In contrast, when meta‐analyses included truncated studies, treatment effect estimates were essentially unbiased. Previous analyses comparing treatment effects in truncated and non‐truncated studies are shown not to be indicative of bias in truncated studies. We conclude that early stopping of clinical trials is not a substantive source of bias in meta‐analyses and recommend that all studies, both truncated and non‐truncated, be included in evidence synthesis. Copyright © 2013 John Wiley & Sons, Ltd.
Distinguishability and agreement with continuous data
Authors: Carrasco Josep L. , Caceres Alejandro , Escaramis Georgia , Jover Lluis
Published: July 2013

The analysis of concordance among repeated measures has received a huge amount of attention in the statistical literature leading to a range of different approaches. However, because all the approaches are able to assess the closeness among the readings taken on the same subject, the conclusions about the degree of concordance should be similar regardless the approach applied. Here, two indices to assess the concordance among continuous repeated measures, the intraclass correlation coefficient and the total deviation index, are applied and compared in two case examples. The first example concerns the repeatability of individual nutrient allocation strategy assessed by stable isotope analysis. The second example dealt with the assessment of the concordance of functional magnetic resonance imaging data that shows spatial correlation. The results differ depending upon the approach applied leading to contradictory conclusions about the degree of concordance. The reason behind these results is discussed reaching the conclusion that the total deviation index is just assessing agreement among repeated measurements, whereas the intraclass correlation coefficient assesses the concept of distinguishability among subjects that involves agreement among repeated measurements and spread of subjects at once. Therefore, the best way to select the right approach is to understand the right question behind the research hypothesis. Copyright © 2013 John Wiley & Sons, Ltd.
Using users: When does external knowledge enhance corporate product innovation?
Authors: Chatterji Aaron K. , Fabrizio Kira R.
Published: July 2013

Prior research on corporate innovation highlights the importance of accessing external knowledge from other firms and universities. However, survey evidence indicates that product users are perhaps the most important source of external knowledge. We build on existing theory to identify the conditions under which user knowledge contributes to corporate innovation and when the benefits will be greatest. Using a panel dataset of medical device companies and their collaborative efforts with innovative physicians, we find evidence that inventive collaborations with users enhance corporate product innovation and that the benefits are greatest in new technology areas and in the generation of radical innovations. Copyright © 2013 John Wiley & Sons, Ltd.
Square and Rectangular Symmetry Tiles from Bulk and Thin Film 3‐Miktoarm Star Terpolymers
Authors: Aissou Karim , Nunns Adam , Manners Ian , Ross Caroline A.
Published: July 2013

The directed self assembly of a 3‐miktoarm star terpolymer (polyisoprene‐arm‐polystyrene‐arm‐polyferrocenylethylmethylsilane (3μ‐ISF)) into a (4.82) square symmetry Archimedean tiling pattern is described. Bulk samples of 3μ‐ISF generate equilibrium columnar (4.82) tile patterns (symmetry p 4 mm) on annealing, which is preceded by a metastable c 2 mm centered rectangular structure. In contrast, in thin films of 3μ‐ISF blended with PS homopolymer, the c 2 mm phase is stable with columns oriented out of plane when the film thickness is below 50 nm. However, the 3μ‐ISF/homopolymer blend rapidly forms a p 4 mm symmetry when the film thickness is ∼80 nm, with grain sizes of several μm and excellent order. Defects in the p4mm structure are described.
Ethische und rechtliche Implikationen der Speicherung humaner Genomdaten
Authors: Mathieu N. , Löhnhardt B. , Grütz R. , Weil P. , Drepper J. , Krawczak M.
Published: July 2013

Die Entwicklung der DNA-Sequenzierungstechnologien stellt die humane Genomforschung vor große datenschutzrechtliche und ethische Herausforderungen. Der heute bereits mögliche tiefe Einblick in die genetische Ausstattung eines Menschen kann von enormer Bedeutung für dessen aktuelles und zukünftiges gesundheitliches Befinden sein. Genomische Daten lassen zudem Rückschlüsse auf die Identität und die genetischen Eigenschaften enger Blutsverwandter zu. Wegen ihres inhärenten Personenbezugs bedürfen genomische Daten somit eines besonders sorgfältigen Umgangs. Zentrale Elemente eines verantwortungsvollen Managements von Genomdaten im Rahmen von Forschungsprojekten sind neben der angemessenen Einwilligung der Teilnehmer auch die Anonymisierung/Pseudonymisierung der Daten und die Trennung der Datenhoheit. Außerdem müssen im Sinne der guten wissenschaftlichen Praxis Fristen und Verordnungen für die Aufbewahrung der Daten beachtet werden. Diese Aspekte werden im vorliegenden Artikel dargestellt und hinsichtlich ihrer praktischen Umsetzung diskutiert.
Extracellular cleavage of the p75 neurotrophin receptor is implicated in its pro‐survival effect in breast cancer cells
Authors: Verbeke Stéphanie , Tomellini Elisa , Dhamani Fatima , Meignan Samuel , Adriaenssens Eric , Xuefen Le Bourhis
Published: July 2013

The p75 neurotrophin receptor (p75NTR) undergoes sequential proteolytic cleavages leading to the generation of a carboxyl‐terminal fragment (p75NTR‐CTF) and an intracellular domain (p75NTR‐ICD) in many cellular models. We have previously shown that p75NTR is involved in the survival of breast cancer cells. Here, we demonstrated that p75NTR cleavage occurs also in these cells. Surprisingly, p75NTR‐CTF increased cell survival, whereas p75NTR‐ICD had no effect. The pro‐survival effect of p75NTR‐CTF was associated with a decrease of TNF‐related apoptosis‐inducing ligand (TRAIL)‐induced PARP and caspase 3 cleavages. Finally, our findings indicate that p75NTR could favor cell survival via its carboxyl‐terminal fragment, independently of PI3‐kinase, NF‐κB, or MAP kinase signaling pathways.
Rapamycin enhances eIF4E phosphorylation by activating MAP kinase‐interacting kinase 2a (Mnk2a)
Authors: Stead Rebecca L. , Proud Christopher G.
Published: July 2013

Eukaryotic initiation factor eIF4E and its phosphorylation play key roles in cell transformation and tumorigenesis. eIF4E is phosphorylated by the Mnks (MAP (mitogen‐activated protein) kinase‐interacting kinases). Rapamycin increases eIF4E phosphorylation in cancer cells, potentially limiting their anti‐cancer effects. Here we show that the rapamycin‐induced increase in eIF4E phosphorylation reflects increased activity of Mnk2 but not Mnk1. This activation requires a novel phosphorylation site in Mnk2a, Ser437. Our findings have potentially important implications for the use of rapamycin and its analogues in cancer therapy, suggesting that inhibitors of mTOR and Mnk (or Mnk2) may be more efficacious than rapalogs alone.
The CH2 domain of CBP/p300 is a novel zinc finger
Authors: Park Sangho , Martinez-Yamout Maria A. , Dyson H. Jane , Wright Peter E.
Published: July 2013

The transcriptional co‐regulator CBP (CREB‐binding protein) has a highly conserved cysteine/histidine‐rich region (CH2) whose structure and function remain uncharacterized. Using nuclear magnetic resonance (NMR spectroscopy), sequence alignment, mass spectrometry, and mutagenesis, we show that the CH2 domain is not a canonical plant homeodomain (PHD) finger, as previously proposed, but binds an additional zinc atom through the region N‐terminal to the putative PHD motif. The CH2 domain and the preceding bromodomain interact and mutually stabilize each other, implying a cooperative function. We tested the hypothesis that the bromodomain and the CH2 domain can interact with histones, but found that the CH2 does not participate in histone‐recognition.
The road traveled, the road ahead, or simply on the road? When progress framing affects motivation in goal pursuit
Authors: Wiebenga Jacob H. , Fennis Bob M.
Published: July 2013

The present research examined the dynamic interplay between the framing of one's progress from an initial state toward an end state (i.e., framed as the distance traveled from the initial state to the current state ‐‘to‐date’ versus framed as the distance left from the current state to the end state ‐‘to‐go’) and construal level in influencing motivation in goal pursuit. In three experiments we found that both state and chronic differences in experienced construal level modulate the impact of progress framing on motivation at a specific stage in goal pursuit, i.e., when consumers are halfway between the initial and end state, but is less consequential at the initial or end stages. This modulation shows that type of framing only affected motivation of people with an abstract, but not a concrete mindset. Under these conditions, progress framed in terms of to‐date produced increased motivation compared to a to‐go frame. Moreover, perceived goal distance was found to mediate the impact of progress framing on motivation for individuals with an abstract, but not a concrete mindset.
Second-order ergodic theorem for self-similar tiling systems
Authors: MEDYNETS KONSTANTIN , SOLOMYAK BORIS
Published: July 2013

We consider infinite measure-preserving non-primitive self-similar tiling systems in Euclidean space ${ \mathbb{R} }^{d} $. We establish the second-order ergodic theorem for such systems, with exponent equal to the Hausdorff dimension of a graph-directed self-similar set associated with the substitution rule.
Homomorphisms between diffeomorphism groups
Authors: MANN KATHRYN
Published: July 2013

For $r\geq 3$, $p\geq 2$, we classify all actions of the groups ${ \mathrm{Diff} }_{c}^{r} ( \mathbb{R} )$ and ${ \mathrm{Diff} }_{+ }^{r} ({S}^{1} )$ by ${C}^{p} $-diffeomorphisms on the line and on the circle. This is the same as describing all non-trivial group homomorphisms between groups of compactly supported diffeomorphisms on 1-manifolds. We show that all such actions have an elementary form, which we call topologically diagonal. As an application, we answer a question of Ghys in the 1-manifold case: if $M$ is any closed manifold, and ${\mathrm{Diff} }^{\infty } \hspace{-2.0pt} \mathop{(M)}\nolimits_{0} $ injects into the diffeomorphism group of a 1-manifold, must $M$ be one-dimensional? We show that the answer is yes, even under more general conditions. Several lemmas on subgroups of diffeomorphism groups are of independent interest, including results on commuting subgroups and flows.
Regular consumption of a cocoa product improves the cardiometabolic profile in healthy and moderately hypercholesterolaemic adults
Authors: Sarriá Beatriz , Martínez-López Sara , Sierra-Cinos José Luis , García-Diz Luis , Mateos Raquel , Bravo Laura
Published: July 2013

Cocoa products present great health potential due to their high content of polyphenols, mainly of flavanols. However, the antioxidant, anti-inflammatory and other health effects of regularly consuming cocoa products seem to depend on the intake and health status of the consumer, etc. and need to be further clarified. A randomised, controlled, cross-over, free-living study was carried out in healthy (n24) and moderately hypercholesterolaemic (>2000 mg/l,n20) subjects to assess the influence of regularly consuming (4 weeks) two servings (15 g each) of a cocoa product rich in fibre (containing 33·9 % of total dietary fibre (TDF) and 13·9 mg/g of soluble polyphenols) in milkv.consuming only milk (control) on (1) serum lipid and lipoprotein profile, (2) serum malondialdehyde levels, carbonyl groups, ferric reducing/antioxidant power, oxygen radical absorbance capacity and free radical-scavenging capacity, (3) IL-1β, IL-6, TNF-α, IL-10, IL-8, monocyte chemoattractant protein-1, and vascular and intracellular cell adhesion molecule levels, and (4) systolic and diastolic blood pressure and heart rate. Throughout the study, the diet and physical activity of the volunteers, as well as any possible changes in weight or other anthropometric parameters, were also evaluated. The intake of TDF increased (P< 0·001) to the recommended levels. Serum HDL-cholesterol (HDL-C) levels were increased (P< 0·001), whereas glucose (P= 0·029), IL-1β (P= 0·001) and IL-10 (P= 0·001) levels were decreased. The rest of the studied cardiovascular parameters, as well as the anthropometric ones, remained similar. In conclusion, regularly consuming a cocoa product with milk improves cardiovascular health by increasing HDL-C levels and inducing hypoglycaemic and anti-inflammatory effects in healthy and hypercholesterolaemic individuals without causing weight gain.
Evidence of frugivory and seed dispersal in Oligocene tortoises from South Dakota
Authors: MARRON ALAN O. , MOORE JASON R.
Published: July 2013

Fossilized hackberry (Celtis) seeds were found within the shells of twoStylemysindividuals excavated from Oligocene sediments from South Dakota. The presence ofin situskeletal elements indicates that the tortoises were buried without extensive disarticulation. Abiotic transport of the seeds into the carcasses is unlikely given the anatomically correct placement of both skeletal elements and seeds and the comparative settling velocities of the encasing sediment versus modernCeltisseeds. Ecological evidence from modernCeltisandStylemysanalogues suggests that tortoises are commonly seed dispersal agents. The fossils are therefore interpreted as enterolites, providing the oldest reliable evidence of tortoise frugivory.
Exceptional patients: Narratives of connections
Authors: Engebretson Joan C. , Peterson Noemi E. , Frenkel Moshe
Published: July 2013

Objective:

This study sought to better understand the patient s perspective of the experience of recovery from cancer that appeared to defy medical prognoses.

Methods:

Fourteen cases of medically verified exceptional outcomes were identified. A qualitative approach, employing long narrative interviews was used. Data was analyzed using a cross case thematic analytic approach.

Results:

The major overarching theme was connections, both internal and external. Internal included connections with God or a higher power and with oneself. The external connections, the focus of this paper, included 1) personal connections with friends and family, 2) connections with the medical system: the physician, nurses and other staff, and 3) connections with other patients. They described the nature of these relationships and the importance of frequent contact with family and friends as providing significant emotional and instrumental support. They expressed confidence in receiving care from a reputable clinic, and with very little probing illustrated the importance of the relationship with their providers. They articulated the significance of the compassionate qualities of the physician and identified communication attributes of their physician that were important in establishing this connection. These attributes were demeanor, availability, honesty, sensitivity in the decision making process. They provided examples of positive connections with nurses and other staff as well as with other patients through their illness process.

Significance of results:

The importance of connections in these illness narratives was richly illustrated. These issues often are overlooked in clinical settings; yet they are of crucial importance to the health and well-being of the patients.
Dietary Supplementation of Antioxidants Improves Semen Quality of IVF Patients in Terms of Motility, Sperm Count, and Nuclear Vacuolization
Authors: Wirleitner Barbara , Vanderzwalmen Pierre , Stecher Astrid , Spitzer Dietmar , Schuff Maximilian , Schwerda Delf , Bach Magnus , Schechinger Birgit , Herbert Zech Nicolas
Published: July 2013

Background: This study aimed to investigate the influence of an oral antioxidative supplementation on sperm quality of in vitro fertilization (IVF) patients, as analyzed by sperm motility according to the WHO criteria and motile sperm organelle morphology examination (MSOME). Methods: Semen samples were collected from 147 patients before undergoing an IVF/intracytoplasmic morphologically-selected sperm injection (IMSI) cycle and 2 - 12 months after an antioxidative supplementation. Semen analysis was evaluated according to WHO and MSOME criteria. Spermatozoa were grouped according to the size of nuclear vacuoles within the sperms heads. Patients were divided into oligoasthenoteratozoospermic (OAT) and non-OAT men. Between first and second semen analysis, patients were supplemented orally with an antioxidative preparation. Results: After the antioxidative therapy we observed a significant reduction in the percentage of immotile sperm cells in the patients. Additionally, the percentage of class I spermatozoa according to MSOME criteria was significantly higher after antioxidative supplementation. In OAT patients the percentage of class I sperm was found to be increased, although not significantly. However, we observed a drastic improvement in sperm motility as well as in total sperm count in this group. Conclusion: The results demonstrated a considerable improvement in semen quality, notably in OAT patients. Considering the putative relationship between semen quality on the one hand and reactive oxygen species on the other, the observed changes in the sperm parameters indicate that a decline in semen quality, and even subtle morphological changes, might be associated with oxidative stress. Our findings suggest that an antioxidative and micronutrient supplementation has a remarkable benefit for IVF patients having restricted sperm parameters, in particular.
25(OH) Vitamin D Levels in Premenopausal Women with Polycystic Ovary Syndrome and/or Obesity
Authors: Tsakova Adelina D. , Gateva Antoaneta T. , Kamenov Zdravko A.
Published: July 2013

Background: Insulin resistance, hyperinsulinemia, and obesity play an important role in development of polycystic ovary syndrome (PCOS). Current evidence suggests that vitamin D (VitD) deficiency may contribute to the disturbance in insulin metabolism and the development of the metabolic syndrome. The aim of this study was to investigate VitD levels, measured as 25(OH)D, in Bulgarian women with PCOS and/or obesity. Materials and methods: The study included 103 women, divided into three groups - group 1 Obese (n = 33); group 2 Nonobese PCOS (n = 50), and group 3 Obese PCOS (n = 20). 25(OH)D levels were measured by electrochemiluminescence immunoassay. Results: Almost 2/3 of the women with PCOS and/or obesity appeared to be VitD-deficient. Women with obesity, especially visceral (with or without PCOS), had significantly lower levels of 25(OH)D compared to lean PCOS subjects. Women with and without metabolic syndrome however did not differ significantly in 25(OH)D levels. Women with normal body mass index (BMI) had higher 25(OH)D levels compared to overweight and obese (p = 0.028). There was no correlation between 25(OH)D levels and indices of glucose metabolism - fasting blood glucose and immunoreactive insulin (IRI) and after OGTT and HOMA index.
Diabetic liver injury from streptozotocin is regulated through the caspase-8 homolog cFLIP involving activation of JNK2 and intrahepatic immunocompetent cells
Authors: Kohl T , Gehrke N , Schad A , Nagel M , Wörns M A , Sprinzl M F , Zimmermann T , He Y-W , Galle P R , Schuchmann M , Schattenberg J M
Published: July 2013

The endemic occurrence of obesity and the associated risk factors that constitute the metabolic syndrome have been predicted to lead to a dramatic increase in chronic liver disease. Non-alcoholic steatohepatitis (NASH) has become the most frequent liver disease in countries with a high prevalence of obesity. In addition, hepatic steatosis and insulin resistance have been implicated in disease progression of other liver diseases, including chronic viral hepatitis and hepatocellular carcinoma. The molecular mechanisms underlying the link between insulin signaling and hepatocellular injury are only partly understood. We have explored the role of the antiapoptotic caspase-8 homolog cellular FLICE-inhibitory protein (cFLIP) on liver cell survival in a diabetic model with hypoinsulinemic diabetes in order to delineate the role of insulin signaling on hepatocellular survival. cFLIP regulates cellular injury from apoptosis signaling pathways, and loss of cFLIP was previously shown to promote injury from activated TNF and CD95/Apo-1 receptors. In mice lacking cFLIP in hepatocytes (flip−/−), loss of insulin following streptozotocin treatment resulted in caspase- and c-Jun N-terminal kinase (JNK)-dependent liver injury after 21 days. Substitution of insulin, inhibition of JNK using the SP600125 compound in vivo or genetic deletion of the mitogen-activated protein kinase (MAPK)9 (JNK2) in all tissues abolished the injurious effect. Strikingly, the difference in injury between wild-type and cFLIP-deficient mice occurred only in vivo and was accompanied by liver-infiltrating inflammatory cells with a trend toward increased amounts of NK1.1-positive cells and secretion of proinflammatory cytokines. Transfer of bone marrow from rag-1-deficient mice that are depleted from B and T lymphocytes prevented liver injury in flip−/− mice. These findings support a direct role of insulin on cellular survival by alternating the activation of injurious MAPK, caspases and the recruitment of inflammatory cells to the liver. Thus, increasing resistance to insulin signaling pathways in hepatocytes appears to be an important factor in the initiation and progression of chronic liver disease.
Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma
Authors: Nitta E , Hirooka K , Tenkumo K , Fujita T , Nishiyama A , Nakamura T , Itano T , Shiraga F
Published: July 2013

Glaucoma is conventionally defined as a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Although glaucoma is often associated with elevated intraocular pressure (IOP), significant IOP reduction does not prevent progression of the disease in some glaucoma patients. Thus, exploring IOP-independent mechanisms of RGC loss is important. We describe chronic systemic administration of aldosterone and evaluate its effect on RGCs in rat. Aldosterone was administered via an osmotic minipump that was implanted subcutaneously into the mid-scapular region. Although systemic administration of aldosterone caused RGC loss associated with thinning of the retinal nerve fiber layer without elevated IOP, the other cell layers appeared to be unaffected. After chronic administration of aldosterone, RGC loss was observed at 2 weeks in the peripheral retina and at 4 weeks in the central retina. However, administration of mineralocorticoid receptor blocker prevented RGC loss. These results demonstrate aldosterone is a critical mediator of RGC loss that is independent of IOP. We believe this rat normal-tension glaucoma (NTG) animal model not only offers a powerful system for investigating the mechanism of neurodegeneration in NTG, but can also be used to develop therapies directed at IOP-independent mechanisms of RGC loss.
Hypoxia and P1 receptor activation regulate the high-affinity concentrative adenosine transporter CNT2 in differentiated neuronal PC12 cells
Authors: Medina-Pulido Lorena , Molina-Arcas Míriam , Justicia Carles , Soriano Eduardo , Burgaya Ferran , Planas Anna M. , Pastor-Anglada Marçal
Published: July 2013

Under several adverse conditions, such as hypoxia or ischaemia, extracellular levels of adenosine are elevated because of increased energy demands and ATP metabolism. Because extracellular adenosine affects metabolism through G-protein-coupled receptors, its regulation is of high adaptive importance. CNT2 (concentrative nucleoside transporter 2) may play physiological roles beyond nucleoside salvage in brain as it does in other tissues. Even though nucleoside transport in brain has mostly been seen as being of equilibrative-type, in the present study, we prove that the rat phaeochromocytoma cell line PC12 shows a concentrative adenosine transport of CNT2-type when cells are differentiated to a neuronal phenotype by treatment with NGF (nerve growth factor). Differentiation of PC12 cells was also associated with the up-regulation of adenosine A1 receptors. Addition of adenosine receptor agonists to cell cultures increased CNT2-related activity by a mechanism consistent with A1 and A2A receptor activation. The addition of adenosine to the culture medium also induced the phosphorylation of the intracellular regulatory kinase AMPK (AMP-activated protein kinase), with this effect being dependent upon adenosine transport. CNT2-related activity of differentiated PC12 cells was also dramatically down-regulated under hypoxic conditions. Interestingly, the analysis of nucleoside transporter expression after experimental focal ischaemia in rat brain showed that CNT2 expression was down-regulated in the infarcted tissue, with this effect somehow being restricted to other adenosine transporter proteins such as CNT3 and ENT1 (equilibrative nucleoside transporter 1). In summary, CNT2 is likely to modulate extracellular adenosine and cell energy balance in neuronal tissue.