bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
Authors: Lawson Christopher P. , Füchtbauer Anders F. , Wranne Moa S. , Giraud Tristan , Floyd Thomas , Dumat Blaise , Andersen Nicolai K. , H. El-Sagheer Afaf , Brown Tom , Gradén Henrik , Wilhelmsson L. Marcus , Grøtli Morten 
Published: September 2018

AbstractFluorescent base analogues (FBAs) have emerged as a powerful class of molecular reporters of location and environment for nucleic acids. In our overall mission to develop bright and useful FBAs for all natural nucleobases, herein we describe the synthesis and thorough characterization of bicyclic thymidine (bT), both as a monomer and when incorporated into DNA. We have developed a robust synthetic route for the preparation of the bT DNA monomer and the corresponding protected phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a brightness value of 790 M−1cm−1 in water, which is comparable or higher than most fluorescent thymine analogues reported. When incorporated into DNA, bT pairs selectively with adenine without perturbing the B-form structure, keeping the melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13-fold in single- and double-stranded DNA, respectively). Overall, these properties make bT an interesting thymine analogue for studying DNA and an excellent starting point for the development of brighter bT derivatives.
Residence time of singlet oxygen in membranes
Authors: Sokolov V. S. , Batishchev O. V. , Akimov S. A. , Galimzyanov T. R. , Konstantinova A. N. , Malingriaux E. , Gorbunova Y. G. , Knyazev D. G. , Pohl P. 
Published: September 2018

AbstractPhotodynamic therapy uses photosensitizers (PS) to kill cancer cells by generating reactive oxygen species – like singlet oxygen (SO) - upon illumination with visible light. PS membrane anchoring augments local SO concentration, which in turn increases photodynamic efficiency. The latter may suffer from SO’s escape into the aqueous solution or premature quenching. Here we determined the time constants of SO escape and quenching by target molecules to be in the nanosecond range, the former being threefold longer. We confined PS and dipolar target molecules either to different membrane monolayers or to the same leaflet and assessed their abundance by fluorescence correlation spectroscopy or membrane surface potential measurements. The rate at which the contribution of the dipolar target molecules to membrane dipole potential vanished, served as a measure of the photo-oxidation rate. The solution of the reaction–diffusion equations did not indicate diffusional rate limitations. Nevertheless, reducing the PS-target distance increased photodynamic efficiency by preventing other SO susceptible moieties from protecting the target. Importantly, our analytical model revealed a fourfold difference between SO generation rates per molecule of the two used PSs. Such analysis of PS quantum yield in a membrane environment may help in designing better PSs.
Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance
Authors: Chiou Shin-Heng , Dorsch Madeleine , Kusch Eva , Naranjo Santiago , Kozak Margaret M. , Koong Albert C. , Winslow Monte M. , Grüner Barbara M. 
Published: September 2018

AbstractExpression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here, we characterize the requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in vivo using conditional inactivation of Hmga2 in well-established autochthonous mouse models of PDAC. Overall survival, primary tumour burden, presence of disseminated tumour cells in the peritoneal cavity or circulating tumour cells in the blood, and presence and number of metastases were not significantly different between mice with Hmga2-wildtype or Hmga2-deficient tumours. Treatment of mice with Hmga2-wildtype and Hmga2-deficient tumours with gemcitabine did not uncover a significant impact of Hmga2-deficiency on gemcitabine sensitivity. Hmga1 and Hmga2 overlap in their expression in both human and murine PDAC, however knockdown of Hmga1 in Hmga2-deficient cancer cells also did not decrease metastatic ability. Thus, Hmga2 remains a prognostic marker which identifies a metastatic cancer cell state in primary PDAC, however Hmga2 has limited if any direct functional impact on PDAC progression and therapy resistance.
Features and Associated Factors of the Behavioral Development of 24-month-old Children in Rural China: Follow-up Evaluation of a Randomized Controlled Trial
Authors: Yang Xue , Yin Zhaoyang , Cheng Yue , Yang Wenfang , Zhu Zhonghai , Zhang Min , Li Danyang , Liu Danli , Yan Hong , Zeng Lingxia 
Published: September 2018

AbstractThe aim of this study was to assess the risk factors associated with the behavioral development among 24-month-old children in rural northwestern China. A total of 657 children whose mothers had participated in a double-blinded, randomized, controlled trial of antenatal micronutrient supplementation in western China were followed until 24 months of age. Their mental, psychomotor, and behavioral development were assessed by the Bayley Scales of Infant Development. Multivariate logistic regression models were used to examine the factors associated with infant behavioral development. Six behavioral factors of infants were presented: activity, social adaptability, reactivity, endurance, concentration, and motor coordination. Further analysis demonstrated that maternal malnutrition, exposure to risk factors during pregnancy, and adverse birth outcomes negatively affected the behavioral development of children at 24 months, which is a common co-occurrence with cognitive and emotional problems. These results suggest that strategies to improve infant behavioral development should consider the maternal pregnancy status.
Differential Proteome Analysis of Human Neuroblastoma Xenograft Primary Tumors and Matched Spontaneous Distant Metastases
Authors: Hänel Lorena , Gosau Tobias , Maar Hanna , Valentiner Ursula , Schumacher Udo , Riecken Kristoffer , Windhorst Sabine , Hansen Nils-Owe , Heikaus Laura , Wurlitzer Marcus , Nolte Ingo , Schlüter Hartmut , Lange Tobias 
Published: September 2018

AbstractMetastasis formation is the major cause for cancer-related deaths and the underlying mechanisms remain poorly understood. In this study we describe spontaneous metastasis xenograft mouse models of human neuroblastoma used for unbiased identification of metastasis-related proteins by applying an infrared laser (IR) for sampling primary tumor and metastatic tissues, followed by mass spectrometric proteome analysis. IR aerosol samples were obtained from ovarian and liver metastases, which were indicated by bioluminescence imaging (BLI), and matched subcutaneous primary tumors. Corresponding histology proved the human origin of metastatic lesions. Ovarian metastases were commonly larger than liver metastases indicating differential outgrowth capacities. Among ~1,900 proteins identified at each of the three sites, 55 proteins were differentially regulated in ovarian metastases while 312 proteins were regulated in liver metastases. There was an overlap of 21 and 7 proteins up- and down-regulated at both metastatic sites, respectively, most of which were so far not related to metastasis such as LYPLA2, EIF4B, DPY30, LGALS7, PRPH, and NEFM. Moreover, we established in vitro sublines from primary tumor and metastases and demonstrate differences in cellular protrusions, migratory/invasive potential and glycosylation. Summarized, this work identified several novel putative drivers of metastasis formation that are tempting candidates for future functional studies.
Adjusting risk-taking to the annual cycle of long-distance migratory birds
Authors: Mikula Peter , Díaz Mario , Albrecht Tomáš , Jokimäki Jukka , Kaisanlahti-Jokimäki Marja-Liisa , Kroitero Gal , Møller Anders Pape , Tryjanowski Piotr , Yosef Reuven , Hromada Martin 
Published: September 2018

AbstractLife-history theory predicts that current behaviour affects future reproduction, implying that animals should optimise their escape strategies to reflect fitness costs and benefits of premature escape. Both costs and benefits of escape may change temporally with important consequences for the evolution of escape strategies. Moreover, escape strategies of species may differ according to their positions on slow–fast pace of life gradients. We studied risk-taking in long-distance migratory animals, waders (Charadriiformes), during the annual cycle, i.e., breeding in Europe, stopover in the Middle East and wintering in tropical Africa. Phylogenetically informed comparative analyses revealed that risk-taking (measured as flight initiation distance, FID) changed significantly over the year, being lowest during breeding and peaking at stopover sites. Similarly, relationships between risk-taking and life-history traits changed among stages of the annual cycle. While risk-taking significantly decreased with increasing body mass during breeding, risk-taking–body mass relationship became marginally significant in winter and disappeared during migration. The positive trend of risk-taking along slow–fast pace of life gradient measured as adult survival was only found during breeding. The season-dependent relationships between risk-taking and life history traits suggest that migrating animals respond to fluctuating environments by adopting behavioural plasticity.
Analysis of Racial/Ethnic Representation in Select Basic and Applied Cancer Research Studies
Authors: Guerrero Santiago , López-Cortés Andrés , Indacochea Alberto , García-Cárdenas Jennyfer M. , Zambrano Ana Karina , Cabrera-Andrade Alejandro , Guevara-Ramírez Patricia , González Diana Abigail , Leone Paola E. , Paz-y-Miño César 
Published: September 2018

AbstractOver the past decades, consistent studies have shown that race/ethnicity have a great impact on cancer incidence, survival, drug response, molecular pathways and epigenetics. Despite the influence of race/ethnicity in cancer outcomes and its impact in health care quality, a comprehensive understanding of racial/ethnic inclusion in oncological research has never been addressed. We therefore explored the racial/ethnic composition of samples/individuals included in fundamental (patient-derived oncological models, biobanks and genomics) and applied cancer research studies (clinical trials). Regarding patient-derived oncological models (n = 794), 48.3% have no records on their donor’s race/ethnicity, the rest were isolated from White (37.5%), Asian (10%), African American (3.8%) and Hispanic (0.4%) donors. Biobanks (n = 8,293) hold specimens from unknown (24.56%), White (59.03%), African American (11.05%), Asian (4.12%) and other individuals (1.24%). Genomic projects (n = 6,765,447) include samples from unknown (0.6%), White (91.1%), Asian (5.6%), African American (1.7%), Hispanic (0.5%) and other populations (0.5%). Concerning clinical trials (n = 89,212), no racial/ethnic registries were found in 66.95% of participants, and records were mainly obtained from Whites (25.94%), Asians (4.97%), African Americans (1.08%), Hispanics (0.16%) and other minorities (0.9%). Thus, two tendencies were observed across oncological studies: lack of racial/ethnic information and overrepresentation of Caucasian/White samples/individuals. These results clearly indicate a need to diversify oncological studies to other populations along with novel strategies to enhanced race/ethnicity data recording and reporting.
Serum miR-331-3p predicts tumor recurrence in esophageal adenocarcinoma
Authors: Gu Jianchun , Zhang Jinhua , Zheng Leizhen , Ajani Jaffer A. , Wu Xifeng , Ye Yuanqing 
Published: September 2018

AbstractMicroRNAs (miRNAs) may contribute to the initiation and progression of cancer. The role of circulating miRNAs as predictors of recurrence in esophageal adenocarcinoma (EAC) has not been extensively explored. Here we measured the expressions of 167 miRNAs in serum samples from a discovery cohort of 72 EAC patients (32 patients with recurrence and 40 patients without). A rank sum test was performed to identify differentially expressed miRNAs. Cox regression model was applied to estimate the effect of miRNA expression on recurrence-free survival. The eligible miRNAs were then validated in an independent cohort of 329 EAC patients (132 patients with recurrence and 197 patients without). miR-331-3p was identified and confirmed to be differentially expressed between EAC patients with and without recurrence and associated with recurrence-free survival. In both cohorts, the expression of miR-331-3p was consistently decreased in patients with recurrence compared to those without (P < 0.05). Using patients with low expression of miR-331-3p as reference, those with high expression had HRs for recurrence of 0.45 (95% CI, 0.21-0.96, P = 0.040) and 0.55 (95% CI, 0.38–0.78, P = 0.001) in the discovery and validation cohorts, respectively. Therefore, serum miR-331–3p may be a useful biomarker for identifying EAC patients at high risk of recurrence.
A high content, small molecule screen identifies candidate molecular pathways that regulate rod photoreceptor outer segment renewal
Authors: Campbell Leah J. , West Megan C. , Jensen Abbie M. 
Published: September 2018

AbstractThe outer segment of the vertebrate rod photoreceptor is a highly modified cilium composed of many discrete membranous discs that are filled with the protein machinery necessary for phototransduction. The unique outer segment structure is renewed daily with growth at the base of the outer segment where new discs are formed and shedding at the distal end where old discs are phagocytized by the retinal pigment epithelium. In order to understand how outer segment renewal is regulated to maintain outer segment length and function, we used a small molecule screening approach with the transgenic (hsp70:HA-mCherryTM) zebrafish, which expresses a genetically-encoded marker of outer segment renewal. We identified compounds with known bioactivity that affect five content areas: outer segment growth, outer segment shedding, clearance of shed outer segment tips, Rhodopsin mislocalization, and differentiation at the ciliary marginal zone. Signaling pathways that are targeted by the identified compounds include cyclooxygenase in outer segment growth, γ-Secretase in outer segment shedding, and mTor in RPE phagocytosis. The data generated by this screen provides a foundation for further investigation of the signaling pathways that regulate photoreceptor outer segment renewal.
Increasing Acyl CoA thioesterase activity alters phospholipid profile without effect on insulin action in skeletal muscle of rats
Authors: Bakshi Ishita , Brown Simon H. J. , Brandon Amanda E. , Suryana Eurwin , Mitchell Todd W. , Turner Nigel , Cooney Gregory J. 
Published: September 2018

AbstractIncreased lipid metabolism in muscle is associated with insulin resistance and therefore, many strategies have been employed to alter fatty acid metabolism and study the impact on insulin action. Metabolism of fatty acid requires activation to fatty acyl CoA by Acyl CoA synthases (ACSL) and fatty acyl CoA can be hydrolysed by Acyl CoA thioesterases (Acot). Thioesterase activity is low in muscle, so we overexpressed Acot7 in muscle of chow and high-fat diet (HFD) rats and investigated effects on insulin action. Acot7 overexpression modified specific phosphatidylcholine and phosphatidylethanolamine species in tibialis muscle of chow rats to levels similar to those observed in control HFD muscle. The changes in phospholipid species did not alter glucose uptake in tibialis muscle under hyperinsulinaemic/euglycaemic clamped conditions. Acot7 overexpression in white extensor digitorum longus (EDL) muscle increased complete fatty acid oxidation ex-vivo but was not associated with any changes in glucose uptake in-vivo, however overexpression of Acot7 in red EDL reduced insulin-stimulated glucose uptake in-vivo which correlated with increased incomplete fatty acid oxidation ex-vivo. In summary, although overexpression of Acot7 in muscle altered some aspects of lipid profile and metabolism in muscle, this had no major effect on insulin-stimulated glucose uptake.
Knock-down of AHCY and depletion of adenosine induces DNA damage and cell cycle arrest
Authors: Belužić Lucija , Grbeša Ivana , Belužić Robert , Park Jong Hoon , Kong Hyun Kyung , Kopjar Nevenka , Espadas Guadalupe , Sabidó Eduard , Lepur Adriana , Rokić Filip , Jerić Ivanka , Brkljačić Lidija , Vugrek Oliver 
Published: September 2018

AbstractRecently, functional connections between S-adenosylhomocysteine hydrolase (AHCY) activity and cancer have been reported. As the properties of AHCY include the hydrolysis of S-adenosylhomocysteine and maintenance of the cellular methylation potential, the connection between AHCY and cancer is not obvious. The mechanisms by which AHCY influences the cell cycle or cell proliferation have not yet been confirmed. To elucidate AHCY-driven cancer-specific mechanisms, we pursued a multi-omics approach to investigate the effect of AHCY-knockdown on hepatocellular carcinoma cells. Here, we show that reduced AHCY activity causes adenosine depletion with activation of the DNA damage response (DDR), leading to cell cycle arrest, a decreased proliferation rate and DNA damage. The underlying mechanism behind these effects might be applicable to cancer types that have either significant levels of endogenous AHCY and/or are dependent on high concentrations of adenosine in their microenvironments. Thus, adenosine monitoring might be used as a preventive measure in liver disease, whereas induced adenosine depletion might be the desired approach for provoking the DDR in diagnosed cancer, thus opening new avenues for targeted therapy. Additionally, including AHCY in mutational screens as a potential risk factor may be a beneficial preventive measure.
West Nile virus transmission and human infection risk in Veneto (Italy): a modelling analysis
Authors: Marini Giovanni , Rosà Roberto , Pugliese Andrea , Rizzoli Annapaola , Rizzo Caterina , Russo Francesca , Montarsi Fabrizio , Capelli Gioia 
Published: September 2018

AbstractAn intensified and continuous West Nile virus (WNV) spread across northern Italy has been observed since 2008, which caused more than one hundred reported human infections until 2016. Veneto is one of the Italian regions where WNV is considered endemic, and the greatest intensity of circulation was observed during 2013 and 2016. By using entomological data collected across the region in those years, we calibrated a temperature-driven mathematical model through a Bayesian approach that simulates the WNV infection in an avian population with seasonal demography. We considered two alternative routes of life cycle re-activation of the virus at the beginning of each vector breeding season: in the first one the virus is maintained by infected birds, in the other by diapausing mosquitoes previously infected. Afterwards, we computed seasonal risk curves for human infection and quantified how they translate into reported symptomatic cases. According to our results, WNV is more likely to be re-activated each year via previously infected mosquitoes. The highest probability of human infection is expected to occur in August, consistently with observations. Our epidemiological estimates can be of particular interest for public health authorities, to support decisions in term of designing efficient surveillance plans and preventive measures.
Cryptic introgression: evidence that selection and plasticity mask the full phenotypic potential of domesticated Atlantic salmon in the wild
Authors: Glover Kevin A. , Solberg Monica F. , Besnier Francois , Skaala Øystein 
Published: September 2018

AbstractDomesticated Atlantic salmon grow much faster than wild salmon when reared together in fish tanks under farming conditions (size ratios typically 1:2–3). In contrast, domesticated salmon only display marginally higher growth than wild salmon when reared together in rivers (size ratios typically 1:1–1.2). This begs the question why? Is this a difference in the plastic response driven by divergent energy budgets between the two environments, or is it a result of selection, whereby domesticated salmon that display the greatest growth-potential are those at greatest risk of mortality in the wild? We reared domesticated, hybrid and wild salmon in a river until they smoltified at age 2 or 4, and thereafter in fish tanks for a further 2 years. In the river, there was no difference in the mean size between the groups. In contrast, after being transferred from the river to fish tanks, the domesticated salmon significantly outgrew the wild salmon (maximum size ratio of ~1:1.8). This demonstrates that selection alone cannot be responsible for the lack of growth differences observed between domesticated and wild salmon in rivers. Nevertheless, the final size ratios observed after rearing in tanks were lower than expected in that environment, thus suggesting that plasticity, as for selection, cannot be the sole mechanism. We therefore conclude that a combination of energy-budget plasticity, and selection via growth-potential mortality, cause the differences in growth reaction norms between domesticated and wild salmon across these contrasting environments. Our results imply that if phenotypic changes are not observed in wild populations following introgression of domesticated conspecifics, it does not mean that functional genetic changes have not occurred in the admixed population. Clearly, under the right environmental conditions, the underlying genetic changes will manifest themselves in the phenotype.
Communicative Accessibility in Aphasia: An Investigation of the Interactional Context of Long-Term Care Facilities
Authors: Azios Jamie H. , Damico Jack S. , Roussel Nancye 
Published: September 2018

PurposeThe purpose of this study was to examine the ability of persons with aphasia to access interaction and be included in social encounters in long-term care facilities (LTCFs).MethodFour persons with aphasia were the focus of this investigation. A qualitative research approach using ethnographic methods was used to conduct participant observation, semistructured interviews, and artifact analysis. Expanded field notes from observations, transcribed interviews, and artifacts were then coded to identify patterns in the data.ResultsThe interactional context of LTCFs negatively influenced the ability of persons with aphasia to communicate with others and develop meaningful relationships. Three major themes emerged from the data detailing the contextual elements leading to communication accessibility and inclusion: (a) lack of support, (b) social hierarchy, and (c) focus on performance.ConclusionsFindings highlighted several barriers in LTCFs that worked to discourage persons with aphasia from living social and expressive lives. Specific obstacles included a misunderstanding of aphasia and its influence on communicative exchanges and performance-oriented environment that overlooked psychosocial needs. Speech-language pathologists have an important role for advocacy in LTCFs. Clinical implications for assessment and treatment in institutions are discussed.