bluuebunny/crossref_metadata_2025_split huggingface dataset:
FMO‐MD Simulations on the Hydration of Formaldehyde in Water Solution with Constraint Dynamics
Authors: Sato Makoto , Yamataka Hiroshi , Komeiji Yuto , Mochizuki Yuji 
Published: July 2012

AbstractFull‐quantum mechanical fragment molecular orbital‐based molecular dynamics (FMO‐MD) simulations were applied to the hydration reaction of formaldehyde in water solution under neutral conditions. Two mechanisms, a concerted and a stepwise one, were considered with respect to the nucleophilic addition and the proton transfer. Preliminary molecular orbital calculations by means of polarized continuum model reaction field predicted that the hydration prefers a concerted mechanism. Because the calculated activation barriers were too high for free FMO‐MD simulations to give reactive trajectories spontaneously, a More O’Ferrall–Jencks‐type diagram was constructed from the statistical analysis of the FMO‐MD simulations with constraint dynamics. The diagram showed that the hydration proceeds through a zwitterionic‐like (ZW‐like) structure. The free energy changes along the reaction coordinate calculated by means of the blue moon ensemble for the hydration and the amination of formaldehyde indicated that the hydration proceeds through a concerted process through the ZW‐like structure, whereas the amination goes through a stepwise mechanism with a ZW intermediate. In inspection of the FMO‐MD trajectories, water‐mediated cyclic proton transfers were observed in both reactions on the way from the ZW‐like structure to the product. These proton transfers also have an asynchronous character, in which deprotonation from the nucleophilic oxygen atom (or nitrogen atom for amination) precedes the protonation of the carbonyl oxygen atom. The results showed the strong advantage of the FMO‐MD simulations to obtain detailed information at a molecular level for solution reactions.
Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long‐term enhancement of adult defensive behaviors
Authors: Wright Lisa D. , Muir Katherine E. , Perrot Tara S. 
Published: July 2012

AbstractIn order to characterize the short‐ and long‐term effects of repeated stressor exposure during adolescence, and to compare the effects of using two sources of cat odor as stressor stimuli, male and female adolescent rats (postnatal day (PND) ∼ 38–46) were exposed on five occasions to either a control stimulus, a cloth stimulus containing cat hair/dander, or a section of cat collar previously worn by a cat. Relative to control stimulus exposure, activity was suppressed and defensive behavior enhanced during exposure to either cat odor stimulus (most pervasively in rats exposed to the collar). Only cloth‐exposed rats showed elevated levels of corticosterone (CORT), and only after repeated stressor exposure, but interestingly, rats exposed to the collar stimulus during adolescence continued to show increased behavioral indices of anxiety in adulthood. In this group, the time an individual spent in physical contact with a cagemate during the final adolescent exposure was negatively related to stress‐induced CORT output in adulthood, which suggests that greater use of social support during adolescent stress may facilitate adult behavioral coping, without necessitating increased CORT release. These findings demonstrate that adolescent male and female rats respond defensively to cat odor stimuli across repeated exposures and that exposure to such stressors during adolescence can augment adult anxiety‐like behavior in similar stressful conditions. These findings also suggest a potential role for social behavior during adolescent stressor exposure in mediating long‐term outcomes. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 551–567, 2013
Inbreeding rate modifies the dynamics of genetic load in small populations
Authors: Pekkala Nina , Emily Knott K. , Kotiaho Janne S. , Puurtinen Mikael 
Published: July 2012

AbstractThe negative fitness consequences of close inbreeding are widely recognized, but predicting the long‐term effects of inbreeding and genetic drift due to limited population size is not straightforward. As the frequency and homozygosity of recessive deleterious alleles increase, selection can remove (purge) them from a population, reducing the genetic load. At the same time, small population size relaxes selection against mildly harmful mutations, which may lead to accumulation of genetic load. The efficiency of purging and the accumulation of mutations both depend on the rate of inbreeding (i.e., population size) and on the nature of mutations. We studied how increasing levels of inbreeding affect offspring production and extinction in experimental Drosophila littoralis populations replicated in two sizes, N = 10 and N = 40. Offspring production and extinction were measured over 25 generations concurrently with a large control population. In the N = 10 populations, offspring production decreased strongly at low levels of inbreeding, then recovered only to show a consistent subsequent decline, suggesting early expression and purging of recessive highly deleterious alleles and subsequent accumulation of mildly harmful mutations. In the N = 40 populations, offspring production declined only after inbreeding reached higher levels, suggesting that inbreeding and genetic drift pose a smaller threat to population fitness when inbreeding is slow. Our results suggest that highly deleterious alleles can be purged in small populations already at low levels of inbreeding, but that purging does not protect the small populations from eventual genetic deterioration and extinction.
Phylogenetic assessment of filoviruses: how many lineages ofMarburg virus?
Authors: Peterson A. Townsend , Holder Mark T. 
Published: July 2012

AbstractFiloviruses have to date been considered as consisting of one diverse genus (Ebola viruses) and one undifferentiated genus (Marburg virus). We reconsider this idea by means of detailed phylogenetic analyses of sequence data available for theFiloviridae: using coalescent simulations, we ascertain that two Marburg isolates (termed the “RAVN” strain) represent a quite‐distinct lineage that should be considered in studies of biogeography and host associations, and may merit recognition at the level of species. In contrast, filovirus isolates recently obtained from bat tissues are not distinct from previously known strains, and should be considered as drawn from the same population. Implications for understanding the transmission geography and host associations of these viruses are discussed.
Increased hyaluronan content and stromal cell CD44 associate with HER2 positivity and poor prognosis in human breast cancer
Authors: Auvinen Päivi , Tammi Raija , Kosma Veli‐Matti , Sironen Reijo , Soini Ylermi , Mannermaa Arto , Tumelius Ritva , Uljas Eliisa , Tammi Markku 
Published: July 2012

AbstractPrevious in vitro studies have suggested interactions between hyaluronan (HA), CD44 and HER2. We have studied the expression of HA and CD44 in a material of 278 breast cancer cases, half of which were HER2‐positive. Intense stromal HA staining was associated with HER2 positivity, large tumor size, lymph node positivity, hormone receptor negativity, poor differentiation, a high body mass index, increased relapse rate and shortened overall survival. Among the 139 HER2‐positive cases, the relapse rate was associated with the intensity of stromal HA staining as most of the relapses occurred in the cases with intense stromal HA staining. The presence of HA in the carcinoma cells was related to the frequency of relapses as none of the patients without HA in carcinoma cells experienced a relapse, whereas 33.3% of those with a high percentage of HA‐positive carcinoma cells suffered a relapse. CD44 positivity in carcinoma cells was related to poor differentiation, postmenopausal status and triple negative breast carcinoma. CD44 positivity in stromal cells was associated with HER2 positivity, large tumor size, hormone receptor negativity, poor differentiation, increased relapse rate and shortened overall survival. The association between HER2 positivity and intense stromal HA staining indicates that HA could be one of the factors involved in the unfavorable outcome of HER2‐positive patients. This study also suggests that HA in breast carcinoma cells and CD44 in stromal cells may have clinical significance.
ZEB/miR‐200 feedback loop: At the crossroads of signal transduction in cancer
Authors: Hill Louise , Browne Gareth , Tulchinsky Eugene 
Published: July 2012

AbstractEmbryonic differentiation programs of epithelial–mesenchymal and mesenchymal–epithelial transition (EMT and MET) represent a mechanistic basis for epithelial cell plasticity implicated in cancer. Transcription factors of the ZEB protein family (ZEB1 and ZEB2) and several microRNA species (predominantly miR‐200 family members) form a double negative feedback loop, which controls EMT and MET programs in both development and tumorigenesis. In this article, we review crosstalk between the ZEB/miR‐200 axis and several signal transduction pathways activated at different stages of tumor development. The close association of ZEB proteins with these pathways is indirect evidence for the involvement of a ZEB/miR‐200 loop in tumor initiation, progression and spread. Additionally, the configuration of signaling pathways involving ZEB/miR‐200 loop suggests that ZEB1 and ZEB2 may have different, possibly even opposing, roles in some forms of human cancer.
Functional characterization of the novel BRAF complex mutation, BRAFV600delinsYM, identified in papillary thyroid carcinoma
Authors: Matsuse Michiko , Mitsutake Norisato , Tanimura Susumu , Ogi Tomoo , Nishihara Eijun , Hirokawa Mitsuyoshi , Fuziwara Cesar S. , Saenko Vladimir A. , Suzuki Keiji , Miyauchi Akira , Yamashita Shunichi 
Published: July 2012

AbstractAn activating mutation in the BRAF gene is the most common genetic alteration in papillary thyroid carcinomas (PTCs). The mutation in PTCs is almost a c.1799T>A transversion, resulting in a p.V600E amino acid substitution (BRAFV600E). Here, we report a novel complex BRAF mutation identified in 4/492 Japanese PTC cases (0.81%). The mutation was comprised of one nucleotide substitution at position 1798, followed by an in‐frame insertion of three nucleotides, c.1798delinsTACA in Exon 15, resulting in p.V600delinsYM. In silico three‐dimensional protein structure prediction implied altered kinase activity of this mutant. In vitro kinase assay and western blotting revealed that this mutation conferred high kinase activity on the BRAF protein, leading to constitutive activation of the MAPK signaling pathway. The mutation also showed high transforming ability in focus formation assay using NIH3T3 cells. The degree of all the functional characteristics was comparable to that of BRAFV600E, and treatment with a BRAF inhibitor Sorafenib was also equally effective in this mutant. These findings suggest that the novel BRAF mutation, BRAFV600delinsYM, is a gain‐of‐function mutation and plays an important role in PTC development.
Silencing IDO in dendritic cells: A novel approach to enhance cancer immunotherapy in a murine breast cancer model
Authors: Zheng Xiufen , Koropatnick James , Chen Di , Velenosi Thomas , Ling Hong , Zhang Xusheng , Jiang Nan , Navarro Benjamin , Ichim Thomas E. , Urquhart Bradley , Min Weiping 
Published: July 2012

AbstractCancer immunotherapeutic agents (vaccines) in the form of antigen‐loaded dendritic cells (DCs) reached an important milestone with the recent approval of Provenge, the first DC vaccine for treatment of prostate cancer. Although this heralds a new era of tumor immunotherapy, it also highlights the compelling need to optimize such DC‐based therapies as they are increasingly tested and used to treat human patients. In this study we sought to augment and enhance the antitumor activity of a DC‐based vaccine using siRNA to silence expression of immunosuppressive enzyme indoleamine 2,3‐dioxygenase (IDO) in DCs. We report here that DCs loaded with tumor antigens, but with siRNA‐silenced IDO expression, were introduced into 4T1 breast tumor‐bearing mice, the treatment: (i) lengthened the time required for tumor onset, (ii) decreased tumor size compared to tumors grown for equal lengths of time in mice treated with antigen‐loaded DCs without IDO silencing and (iii) reduced CD4+ and CD8+ T cell apoptosis. Furthermore, immunization with IDO‐silenced DCs enhanced tumor antigen‐specific T cell proliferation and CTL activity, and decreased numbers of CD4+CD25+Foxp3+
Treg. This study provides evidence to support silencing of immunosuppressive genes (IDO) as an effective strategy to enhance the efficacy of DC‐based cancer immunotherapeutic.
Development of disruptive behaviors in young children: A prospective population‐based cohort study
Authors: Baillargeon Raymond H. , Morisset Alexandre , Keenan Kate , Normand Claude L. , Séguin Jean R. , Japel Christa , Cao Guanqiong 
Published: July 2012

AbstractWe know relatively little about the development of disruptive behaviors (DBs), and gender differences therein. The objective of this study was to describe the continuity and discontinuity in the degree to which young children in the general population are reported to exhibit specific DBs over time. Data came from the Québec Longitudinal Study of Child Development. First, the results show that relatively few children exhibit DBs on a frequent basis at 41 months of age. Second, the results show that a majority of children who exhibit a particular DB on a frequent basis at 41 months of age did not do so 1 year earlier. In addition, a majority of children who exhibited a particular DB on a frequent basis at 29 months of age no longer do so 1 year later. Third, gender differences in DBs (boys > girls) are either emerging or at least increasing in magnitude between 29 and 41 months of age. Consistent with the canalization of the behavioral development principle, children who exhibited DBs on a frequent basis at 29 months of age are less likely to stop doing so in the following year if they had exhibited the same behaviors at 17 months of age.
Contextual factors associated with pain response of preterm infants to heel‐stick procedures
Authors: Sellam G. , Engberg S. , Denhaerynck K. , Craig K.D. , Cignacco E.L. 
Published: July 2012

AbstractBackgroundEvidence indicates that medical and demographic contextual factors (cFs) impact pain responses in preterm neonates, but the existing evidence is very heterogeneous.AimTo explore the effect of cFs on pain responses to heel‐stick procedures of preterm infants.MethodsThis study was a secondary analysis of data collected during a randomized controlled trial examining pain response to non‐pharmacological interventions across repeated heel sticks. Five heel sticks across the first 14 days of life were videotaped. Pain response was rated with the Bernese Pain Scale for Neonates (BPSN) by four raters blinded to the heel‐stick phases (baseline, heel stick, recovery). Demographic and medical cFs were extracted from medical charts. Mixed single and multiple regression analyses were performed controlling for the intervention group, site and heel‐stick phase.ResultsApgar scores at 1 min were negatively associated with behavioural (p = 0.002) BPSN scores, while Apgar scores at 5 min after birth were positively associated with behavioural (p = 0.006) scores. Accumulated number of painful procedures (p = 0.002) and gender (p = 0.02) were positively associated with physiological scores while continuous positive airway pressure CPAP (p = 0.009) and mechanical ventilation (p = 0.005) were negatively associated.ConclusionHigher exposure to painful procedures, male infants and having CPAP or mechanical ventilation were cFs associated with physiological response. The only variables significantly associated with behavioural BPSN scores were Apgar scores but these relationships were inconsistent.
The effectiveness of national guidance in changing analgesic prescribing in primary care from 2002 to 2009: An observational database study
Authors: Bedson J. , Belcher J. , Martino O.I. , Ndlovu M. , Rathod T. , Walters K. , Dunn K.M. , Jordan K.P. 
Published: July 2012

AbstractBackgroundNumerous national guidelines have been issued to assist general practitioners’ safe analgesic prescribing. Their effectiveness is unclear. The objective of this study was to examine trends in general practitioners’ prescribing behaviour in relation to national guidelines.MethodsThis was a retrospective observational database study of registered adult patients prescribed an analgesic (2002–2009) from the Consultations in Primary Care Archive – 12 North Staffordshire general practices. Prescribing guidance from the UK Medicines Regulatory Health Authority (MHRA) regarding non‐steroidal anti‐inflammatory drugs (NSAIDs) and co‐proxamol, and the National Institute for Health and Clinical Excellence (NICE) osteoarthritis (OA) management guidelines were considered. Analgesic prescribing rates were examined, arranged according to a classification of six equipotent medication groups: (1) basic analgesics; (2)–(5) increasingly potent opioids and (6) NSAIDs. In each quarter from 2002 to 2009, the number of patients per 10,000 registered population receiving a prescription for the first time from each group was determined. Quarters associated with significant changes in the underlying prescribing trend were determined using joinpoint regression.ResultsA significant decrease in incident co‐proxamol and Cox‐2 prescribing occurred around the time of the first MHRA advice to stop using them and were rarely prescribed thereafter. The new prescribing of weak analgesics (e.g., co‐codamol 8/500) increased at this same time. Initiating topical NSAIDs significantly increased around the time of the NICE OA guidelines.ConclusionsSignificant prescribing changes occurred when national advice and guidelines were issued. The effectiveness of this advice may vary depending upon the content and method of dissemination. Further evaluation of the optimal methods for delivering prescribing guidance is required.
Perfectly registered multiphoton and reflectance confocal video rate imaging of in vivo human skin
Authors: Wang Hequn , Lee Anthony M.D. , Frehlick Zack , Lui Harvey , McLean David I. , Tang Shuo , Zeng Haishan 
Published: July 2012

AbstractWe present a multimodal in vivo skin imaging instrument that is capable of simultaneously acquiring multiphoton and reflectance confocal images at up to 27 frames per second with 256 × 256 pixel resolution without the use of exogenous contrast agents. A single femtosecond laser excitation source is used for all channels ensuring perfect image registration between the two‐photon fluorescence (TPF), second harmonic generation (SHG), and reflectance confocal microscopy (RCM) images. Images and videos acquired with the system show that the three imaging channels provide complementary information in in vivo human skin measurements. In the epidermis, cell boundaries are clearly seen in the RCM channel, while cytoplasm is better seen in the TPF imaging channel, whereas in the dermis, SHG and TPF channels show collagen bundles and elastin fibers, respectively. The demonstrated fast imaging speed and multimodal imaging capabilities of this MPM/RCM instrument are essential features for future clinical application of this technique. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The role of endothelial-mesenchymal transition in heterotopic ossification
Authors: Medici Damian , Olsen Bjorn R 
Published: July 2012

Abstract
Heterotopic ossification (HO) is a process by which bone forms in soft tissues, in response to injury, inflammation, or genetic disease. This usually occurs by initial cartilage formation, followed by endochondral ossification. A rare disease called fibrodysplasia ossificans progressiva (FOP) allows this mechanism to be induced by a combination of genetic mutation and acute inflammatory responses. FOP patients experience progressive HO throughout their lifetime and form an ectopic skeleton. Recent studies on FOP have suggested that heterotopic cartilage and bone is of endothelial origin. Vascular endothelial cells differentiate into skeletal cells through a mesenchymal stem cell intermediate that is generated by endothelial-mesenchymal transition (EndMT). Local inflammatory signals and/or other changes in the tissue microenvironment mediate the differentiation of endothelial-derived mesenchymal stem cells into chondrocytes and osteoblasts to induce HO. We discuss the current evidence for the endothelial contribution to heterotopic bone formation. © 2012 American Society for Bone and Mineral Research.
Overexpression of FABP3 promotes apoptosis through inducing mitochondrial impairment in embryonic cancer cells
Authors: Song Gui Xian , Shen Ya Hui , Liu Yao Qiu , Sun Wei , Miao Li Ping , Zhou Li Juan , Liu Hai Lang , Yang Rong , Kong Xiang Qing , Cao Ke Jiang , Qian Ling Mei , Sheng Yan Hui 
Published: July 2012

AbstractFatty acid‐binding protein 3 (FABP3) is a low‐molecular‐weight protein with a distinct tissue distribution that may play an important role in fatty acid transport, cell growth, cellular signaling, and gene transcription. Previously, we have found that FABP3 was involved in apoptosis‐associated congenital cardiac malformations, but the underlying mechanisms have not yet been described. In the present study, we investigated the characteristics of mitochondrial dysfunction in embryonic cancer cells (P19 cells) that overexpressed FABP3. We demonstrated that in FABP3‐overexpressing P19 cells a lower cellular ATP production was accompanied by a dramatic decrease in mitochondrial membrane potential (MMP), despite the lack of a substantial decrease in the mtDNA copy number. In addition, FABP3 overexpression also led to an imbalance in mitochondrial dynamics and to excess intracellular reactive oxygen species production. Collectively, our results indicated that overexpression of FABP3 in P19 cells caused mitochondrion dysfunction that might be responsible for the development of FABP3‐induced apoptosis. J. Cell. Biochem. 113: 3701–3708, 2012. © 2012 Wiley Periodicals, Inc.
High absorption of endocrine disruptors by Hytrel: towards the development of a two‐phase partitioning bioreactor
Authors: Ouellette Julianne , dos Santos Silvia Cristina Cunha , Lépine François , Juteau Pierre , Déziel Eric , Villemur Richard 
Published: July 2012

AbstractBACKGROUNDEndocrine disruptors (EDs) contribute to the endocrine disrupting potential of urban wastewater because most wastewater treatment plants only partially remove these compounds. Many EDs are present at very low concentrations in wastewater, which explains why most wastewater treatment plants can only partially remove them. The development of a two‐phase partitioning bioreactor (TPPB) could represent an alternative for the extraction of these compounds from water prior to their biodegradation. This study assesses the potential of using the polymer Hytrel used in TPPBs, to extract and concentrate estrone, estradiol, estriol, ethynylestradiol, nonylphenol and bisphenol A from aqueous solutions.RESULTSHytrel demonstrated high capacity absorption for all these EDs. The Hytrel/water partition coefficient for the six EDs was determined. Finally, the capacity of Hytrel to extract a high proportion of these EDs from ED‐spiked, treated wastewater was demonstrated.CONCLUSIONOur results showed that Hytrel has the potential to be used as an effective water‐immiscible phase in the development of a TPPB for the extraction and biodegradation of EDs. Copyright © 2012 Society of Chemical Industry