bluuebunny/crossref_metadata_2025_split huggingface dataset:
Directing Differentiation of Human Embryonic Stem Cells Toward Anterior Neural Ectoderm Using Small Molecules
Authors: Surmacz Beata , Fox Heather , Gutteridge Alex , Lubitz Sandra , Whiting Paul 
Published: July 2012

AbstractBased on knowledge of early embryo development, where anterior neural ectoderm (ANE) development is regulated by native inhibitors of bone morphogenic protein (BMP) and Nodal/Activin signaling, most published protocols of human embryonic stem cell differentiation to ANE have demonstrated a crucial role for Smad signaling in neural induction. The drawbacks of such protocols include the use of an embryoid body culture step and use of polypeptide secreted factors that are both expensive and, when considering clinical applications, have significant challenges in terms of good manufacturing practices compliancy. The use of small molecules to direct differentiation of pluripotent stem cells toward a specified lineage represents a powerful approach to generate specific cell types for further understanding of biological function, for understanding disease processes, for use in drug discovery, and finally for use in regenerative medicine. We therefore aimed to find controlled and reproducible animal-component-free differentiation conditions that would use only small molecules. Here, we demonstrate that pluripotent stem cells can be reproducibly and efficiently differentiated to PAX6+ (a marker of neuroectoderm) and OCT4− (a marker of pluripotent stem cells) cells with the use of potent small inhibitors of the BMP and Activin/Nodal pathways, and in animal-component-free conditions, replacing the frequently used Noggin and SB431542. We also show by transcript analysis, both at the population level and for the first time at the single-cell level, that differentiated cells express genes characteristic for the development of ANE, in particular for the development of the future forebrain.
Cell‐surface sensors: lighting the cellular environment
Authors: Ali Md Monsur , Kang Dong‐Ku , Tsang Kyle , Fu Moyu , Karp Jeffrey M. , Zhao Weian 
Published: July 2012

AbstractCell‐surface sensors are powerful tools to elucidate cell functions including cell signaling, metabolism, and cell‐to‐cell communication. These sensors not only facilitate our understanding in basic biology but also advance the development of effective therapeutics and diagnostics. While genetically encoded fluorescent protein/peptide sensors have been most popular, emerging cell surface sensor systems including polymer‐, nanoparticle‐, and nucleic acid aptamer‐based sensors have largely expanded our toolkits to interrogate complex cellular signaling and micro‐ or nano‐environments. In particular, cell‐surface sensors that interrogate in vivo cellular microenvironments represent an emerging trend in the development of next generation tools which biologists may routinely apply to elucidate cell biology in vivo and to develop new therapeutics and diagnostics. This review focuses on the most recent development in areas of cell‐surface sensors. We will first discuss some recently reported genetically encoded sensors that were used for monitoring cellular metabolites, proteins, and neurotransmitters. We will then focus on the emerging cell surface sensor systems with emphasis on the use of DNA aptamer sensors for probing cell signaling and cell‐to‐cell communication. WIREs Nanomed Nanobiotechnol 2012, 4:547–561. doi: 10.1002/wnan.1179This article is categorized under:

Diagnostic Tools > Biosensing
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Decoding the functions of post‐transcriptional regulators in the determination of inflammatory states: focus on macrophage activation
Authors: Kafasla Panagiota , Karakasiliotis Ioannis , Kontoyiannis Dimitris L. 
Published: July 2012

AbstractInflammation involves a continuum of intercellular interactions and cellular responses targeting infectious or tissue damage while maintaining homeostasis. At its core, this continuum encompasses the alternating phenotypes of innate immune cells; each phenotype is typified by the expression of molecules which either support host defence or aid tissue restoration and the resolution of inflammation. The aberrant persistence of any such phenotype can drive chronic inflammatory pathology. For macrophages, these phenotypes arise as changes in cellular plasticity because of adaptation. As such their underlying gene expression programs may not be determined by robust transcriptomic and epigenetic programs but by more flexible means like post‐transcriptional mechanisms affecting mRNA use. These mechanisms require the assemblies of RNA‐binding proteins (RBPs) and non‐coding RNAs onto specific elements on their RNA targets in Ribonucleoprotein particles (RNPs) which control mRNA maturation, turnover and translation. The collection of RNPs within a cell defines the ribonome, that is, a high order system of coordinative post‐transcriptional determination. mRNAs involved in the definition of different macrophage activation phenotypes share elements of RBP recognition rendering them amenable to ribonomic regulation. The molecular features of their cognitive RBPs and the pathologies developing in the corresponding mouse mutants support their involvement in inflammatory reactions. We view this information in the context of macrophage activation states to propose that these states can be determined via differential—synergistic or antagonistic—RNP associations. In doing so, we substantiate the need for the use of systems platforms to model RNP hierarchies controlling the continuum of inflammation. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1179This article is categorized under:

Biological Mechanisms > Cell Signaling
Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Biological Mechanisms > Regulatory Biology
Complexity and the reductionism–holism debate in systems biology
Authors: Mazzocchi Fulvio 
Published: July 2012

AbstractReductionism has largely influenced the development of science, culminating in its application to molecular biology. An increasing number of novel research findings have, however, shattered this view, showing how the molecular‐reductionist approach cannot entirely handle the complexity of biological systems. Within this framework, the advent of systems biology as a new and more integrative field of research is described, along with the form which has taken on the debate of reductionism versus holism. Such an issue occupies a central position in systems biology, and nonetheless it is not always clearly delineated. This partly occurs because different dimensions (ontological, epistemological, methodological) are involved, and yet the concerned ones often remain unspecified. Besides, within systems biology different streams can be distinguished depending on the degree of commitment to embrace genuine systemic principles.Some useful insights into the future development of this discipline might be gained from the tradition of complexity and self‐organization. This is especially true with regards the idea of self‐reference, which incorporated into the organizational scheme is able to generate autonomy as an emergent property of the biological whole.WIREs Syst Biol Med2012. doi: 10.1002/wsbm.1181This article is categorized under:Analytical and Computational Methods > Dynamical MethodsModels of Systems Properties and Processes > Mechanistic Models
The Exchange Boundary Framework: Understanding the Evolution of Power within Collaborative Decision‐Making Settings
Authors: Watson Erin R. , Foster-Fishman Pennie G. 
Published: July 2012

AbstractMany community decision‐making bodies encounter challenges in creating conditions where stakeholders from disadvantaged populations can authentically participate in ways that give them actual influence over decisions affecting their lives (Foster‐Fishman et al., Lessons for the journey: Strategies and suggestions for guiding planning, governance, and sustainability in comprehensive community initiatives. W.K. Kellogg Foundation, Battle Creek, MI, 2004). These challenges are often rooted in asymmetrical power dynamics operating within the settings (Prilleltensky, J Commun Psychol 36:116–136, 2008). In response, this paper presents the Exchange Boundary Framework, a new approach for understanding and promoting authentic, empowered participation within collaborative decision‐making settings. The framework expands upon theories currently used in the field of community psychology by focusing on the underlying processes through which power operates in relationships and examining the evolution of power dynamics over time. By integrating concepts from social exchange theory (Emerson, Am Soc Rev 27:31–41, 1962) and social boundaries theory (Hayward, Polity 31(1):1–22, 1998), the framework situates power within parallel processes of resources exchange and social regulation. The framework can be used to understand the conditions leading to power asymmetries within collaborative decisionmaking processes, and guide efforts to promote more equitable and authentic participation by all stakeholders within these settings. In this paper we describe the Exchange Boundary Framework, apply it to three distinct case studies, and discuss key considerations for its application within collaborative community settings.
The role of character strengths in adolescent romantic relationships: An initial study on partner selection and mates' life satisfaction
Authors: Weber Marco , Ruch Willibald 
Published: June 2012

ABSTRACTThe present study investigated the role of 24 character strengths in 87 adolescent romantic relationships focusing on their role in partner selection and their role in mates' life satisfaction. Measures included the Values in Action Inventory of Strengths for Youth, the Students' Life Satisfaction Scale, and an Ideal Partner Profiler for the composition of an ideal partner. Honesty, humor, and love were the most preferred character strengths in an ideal partner. Hope, religiousness, honesty, and fairness showed the most substantial assortment coefficients. Hierarchical regression analyses revealed targets' character strengths as explaining variance in targets' life satisfaction. Furthermore, to a lesser degree, specific character strengths of partners and couples' similarity in certain character strengths explained variance in targets' life satisfaction beyond targets' character strengths. This first research on this topic showed that character strengths play a significant role in adolescent romantic relationships.
Cognitive and structural magnetic resonance imaging features of Lewy body dementia and Alzheimer's disease
Authors: Rodriguez Miriam Jocelyn , Potter Elizabeth , Shen Qian , Barker Warren , Greig‐Custo Maria , Agron Joscelyn , Loewenstein David , Duara Ranjan 
Published: July 2012

AbstractObjectiveTo assess medial temporal atrophy (MTA) and atrophy adjacent to the third ventricle (Peri‐IIIVent) on brain magnetic resonance images as biomarkers for the diagnosis of Alzheimer's disease (AD) and Lewy body dementia (LBD), and to assess the relationship between biomarkers and clinical and functional measures.MethodsSubjects diagnosed with no cognitive impairment (n = 30), AD (n = 30), or LBD (n = 31) were evaluated with the Mini‐Mental State Examination, Multiple Delayed Recall Test, Category Fluency Test, Clinical Dementia Rating Sum of Boxes score, Functional Assessment Questionnaire, and the Unified Parkinson's Disease Rating Scale. A validated visual rating system was used to rate MTA, and volumetric studies were performed to measure total intracranial and hippocampal volumes. Additionally, linear measurements of third ventricle width, Peri‐IIIVent height, and Peri‐IIIVent width were performed.ResultsSubjects with AD and those with LBD were equivalent with respect to age and levels of cognitive impairment. Atrophy in medial temporal and Peri‐IIIVent regions was greater among both patients with AD and those with LBD compared with subjects with no cognitive impairment. The best discriminators of AD from LBD were the severity of MTA, using visual rating, and the severity of memory impairment. Only subjects with LBD showed significant correlations between Unified Parkinson's Disease Rating Scale scores and Peri‐IIIVent atrophy measures.ConclusionsMild AD could be distinguished from mild LBD by the severity of MTA and memory impairment. The severity of parkinsonism was associated with the severity of atrophy in the third ventricular region, but was not a good discriminator between AD and LBD.
Rationale for use of the Clinical Dementia Rating Sum of Boxes as a primary outcome measure for Alzheimer's disease clinical trials
Authors: Cedarbaum Jesse M. , Jaros Mark , Hernandez Chito , Coley Nicola , Andrieu Sandrine , Grundman Michael , Vellas Bruno ,   Alzheimer's Disease Neuroimaging Initiative
Published: July 2012

BackgroundWe used the database of the Alzheimer's Disease Neuroimaging Initiative (ADNI) to explore the psychometric properties of the Clinical Dementia Rating Sum of Boxes (CDR‐SB) to consider its utility as an outcome measure for clinical trials in early and mild, as well as later, stages of Alzheimer's disease (AD).MethodsWe assessed internal consistency, structural validity, convergent validity, and 2‐year internal and external responsiveness of the CDR‐SB using data from 382 subjects with early or mild AD at entry into the ADNI study.ResultsThe CDR‐SB assesses both cognitive and functional domains of AD disability. Mean scores declined nearly linearly; CDR‐SB cognitive and functional subsums contributed equally to total scores at both very mild (early) and mild stages of the disease.ConclusionsThe CDR‐SB has psychometric properties that make it attractive as a primary outcome measure that comprehensively assesses both cognitive and functional disability in AD patients. It may prove particularly useful for studies in early, predementia stages of AD.
Decreased gray matter diffusivity: A potential early Alzheimer's disease biomarker?
Authors: Jacobs Heidi I.L. , van Boxtel Martin P.J. , Gronenschild Ed H.B.M. , Uylings Harry B.M. , Jolles Jelle , Verhey Frans R.J. 
Published: July 2012

BackgroundGray matter atrophy, an important biomarker for early Alzheimer's disease, might be due to white matter changes within gray matter.MethodsTwenty older participants with significant memory decline over a 12‐year period (T12) were matched to 20 nondeclining participants. All participants were magnetic resonance imaging scanned at T12. Cortical thickness and diffusion tensor imaging analyses were performed.ResultsLower cortical thickness values were associated with lower diffusion values in frontal and parietal gray matter areas. This association was only present in the memory decline group. The cortical thickness–diffusion tensor imaging correlations showed significant group differences in the posterior cingulate gyrus, precuneus, and superior frontal gyrus.ConclusionsDecreased gray matter diffusivity in the posterior cingulate/precuneus area might be a disease‐specific process and a potential new biomarker for early Alzheimer's disease. Future studies should validate its potential as a biomarker and focus on cellular changes underlying diffusivity changes in gray matter.
Metabolic syndrome and localization of white matter hyperintensities in the elderly population
Authors: Portet Florence , Brickman Adam M. , Stern Yaakov , Scarmeas Nikolaos , Muraskin Jordan , Provenzano Frank A. , Berr Claudine , Bonafé Alain , Artero Sylvaine , Ritchie Karen , Akbaraly Tasnime N. 
Published: July 2012

BackgroundMetabolic syndrome (MetS) is defined as a clustering of metabolic disorders: abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Although specific components of MetS have been associated with white matter hyperintensities (WMH), less is known about the association between MetS as a whole and WMH, especially in normal aging. We aimed to: (1) investigate this association in a cohort of healthy elderly individuals, and (2) examine the relationship between MetS and the regional distribution of WMH, to further understanding of the relationship between MetS and structural brain changes.MethodsAnalyses were carried out on 308 participants (48.1% men, age: 71.0 ± 3.9 years) from the French longitudinal ESPRIT (Enquête de Santé Psychologique ‐ Risques, Incidence et Traitement) study, who were free of cerebrovascular disease cognitive and functional impairment. Logistic regression models were used to examine the cross‐sectional association between MetS (defined using the National Cholesterol Education Program–Adult Treatment Panel III criteria) and (1) WMH volumes, and (2) WMH volumes according to their localization in insulofrontal and temporoparietal regions.ResultsAfter adjusting for potential confounders, participants with MetS had a twofold increased chance of presenting with high levels of WMH volume compared with those without (odds ratio [OR] = 2.74, 95% confidence interval [CI]: 1.25–6.03). MetS was specifically associated with an increase of temporoparietal WMH volumes, but no association was found between MetS and WMH localized in the insulofrontal region.ConclusionOur findings suggest that effective management of MetS may reduce WMH accumulation in brain areas already vulnerable to the aging process.
The SIRT2 polymorphism rs10410544 and risk of Alzheimer's disease in two Caucasian case–control cohorts
Authors: Polito Letizia , Kehoe Patrick G. , Davin Annalisa , Benussi Luisa , Ghidoni Roberta , Binetti Giuliano , Quadri Pierluigi , Lucca Ugo , Tettamanti Mauro , Clerici Francesca , Bagnoli Silvia , Galimberti Daniela , Nacmias Benedetta , Sorbi Sandro , Guaita Antonio , Scarpini Elio , Mariani Claudio , Forloni Gianluigi , Albani Diego 
Published: July 2012

AbstractBackgroundHuman sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, SIRT2 and SIRT3, affected AD susceptibility.MethodsA genetic case–control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real‐time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (APOE) gene, were genotyped by real‐time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412, and APOE rs429358 were genotyped as mentioned previously.ResultsIn the discovery population, we observed an association between SIRT2 rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.02–1.50, P = .02, after correction for sex, age, and APOE ɛ4 genotype). The association between AD and SIRT2 rs10410544 T allele was only present in APOE ɛ4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03–1.61, P = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02–1.35, P = .02), and only APOE ɛ4 noncarriers were at risk (adjusted OR = 1.2, 95% CI: 1.02–1.43, P = .03).ConclusionsThe SIRT2 rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the APOE ɛ4‐negative Caucasian population.
Lacustrine records of Holocene flood pulse dynamics in the Upper Paraguay River watershed (Pantanal wetlands, Brazil)
Authors: McGlue Michael M. , Silva Aguinaldo , Zani Hiran , Corradini Fabrício A. , Parolin Mauro , Abel Erin J. , Cohen Andrew S. , Assine Mario L. , Ellis Geoffrey S. , Trees Mark A. , Kuerten Sidney , Gradella Frederico dos Santos , Rasbold Giliane Gessica 
Published: June 2012

AbstractThe Pantanal is the world's largest tropical wetland and a biodiversity hotspot, yet its response to Quaternary environmental change is unclear. To address this problem, sediment cores from shallow lakes connected to the Upper Paraguay River (PR) were analyzed and radiocarbon dated to track changes in sedimentary environments. Stratal relations, detrital particle size, multiple biogeochemical indicators, and sponge spicules suggest fluctuating lake-level lowstand conditions between ~ 11,000 and 5300 cal yr BP, punctuated by sporadic and in some cases erosive flood flows. A hiatus has been recorded from ~ 5300 to 2600 cal yr BP, spurred by confinement of the PR within its channel during an episode of profound regional drought. Sustained PR flooding caused a transgression after ~ 2600 cal yr BP, with lake-level highstand conditions appearing during the Little Ice Age. Holocene PR flood pulse dynamics are best explained by variability in effective precipitation, likely driven by insolation and tropical sea-surface temperature gradients. Our results provide novel support for hypotheses on: (1) stratigraphic discontinuity of floodplain sedimentary archives; (2) late Holocene methane flux from Southern Hemisphere wetlands; and (3) pre-colonial indigenous ceramics traditions in western Brazil.
Instability and morphology of polymer solutions coating a fibre
Authors: Boulogne F. , Pauchard L. , Giorgiutti-Dauphiné F. 
Published: July 2012

AbstractWe report an experimental study on the dynamics of a thin film of polymer solution coating a vertical fibre. The liquid film has first a constant thickness and then undergoes the Plateau–Rayleigh instability, which leads to the formation of sequences of drops, separated by a thin film, moving down at a constant velocity. Different polymer solutions are used, i.e. xanthan solutions and polyacrylamide (PAAm) solutions. These solutions both exhibit shear-rate dependence of the viscosity, but for PAAm solutions, there are strong normal stresses in addition to the shear thinning effect. We characterize experimentally and separately the effects of these two non-Newtonian properties on the flow on the fibre. Thus, in the flat film observed before the emergence of the drops, only the shear-thinning effect plays a role, and tends to thin the film compared to the Newtonian case. The effect of the non-Newtonian rheology on the Plateau–Rayleigh instability is then investigated through the measurements of the growth rate and the wavelength of the instability. Results are in good agreement with linear stability analysis for a shear-thinning fluid. The effect of normal stress can be taken into account by considering an effective surface tension, which tends to decrease the growth rate of the instability. Finally, the dependence of the morphology of the drops on normal stress is investigated, and a simplified model including the normal stress within the lubrication approximation provides good quantitative results on the shape of the drops.