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Sample records for early molecular event

  1. Early molecular correlates of adverse events following yellow fever vaccination

    PubMed Central

    Chan, Candice Y.Y.; Chan, Kuan Rong; Chua, Camillus J.H.; nur Hazirah, Sharifah; Ghosh, Sujoy; Ooi, Eng Eong; Low, Jenny G.

    2017-01-01

    The innate immune response shapes the development of adaptive immunity following infections and vaccination. However, it can also induce symptoms such as fever and myalgia, leading to the possibility that the molecular basis of immunogenicity and reactogenicity of vaccination are inseparably linked. To test this possibility, we used the yellow fever live-attenuated vaccine (YFLAV) as a model to study the molecular correlates of reactogenicity or adverse events (AEs). We analyzed the outcome of 68 adults who completed a YFLAV clinical trial, of which 43 (63.2%) reported systemic AEs. Through whole-genome profiling of blood collected before and after YFLAV dosing, we observed that activation of innate immune genes at day 1, but not day 3 after vaccination, was directly correlated with AEs. These findings contrast with the gene expression profile at day 3 that we and others have previously shown to be correlated with immunogenicity. We conclude that although the innate immune response is a double-edged sword, its expression that induces AEs is temporally distinct from that which engenders robust immunity. The use of genomic profiling thus provides molecular insights into the biology of AEs that potentially forms a basis for the development of safer vaccines. PMID:28978802

  2. Early Molecular Events in Murine Gastric Epithelial Cells Mediated by Helicobacter pylori CagA.

    PubMed

    Banerjee, Aditi; Basu, Malini; Blanchard, Thomas G; Chintalacharuvu, Subba R; Guang, Wei; Lillehoj, Erik P; Czinn, Steven J

    2016-10-01

    Murine models of Helicobacter pylori infection are used to study host-pathogen interactions, but lack of severe gastritis in this model has limited its usefulness in studying pathogenesis. We compared the murine gastric epithelial cell line GSM06 to the human gastric epithelial AGS cell line to determine whether similar events occur when cultured with H. pylori. The lysates of cells infected with H. pylori isolates or an isogenic cagA-deficient mutant were assessed for translocation and phosphorylation of CagA and for activation of stress pathway kinases by immunoblot. Phosphorylated CagA was detected in both cell lines within 60 minutes. Phospho-ERK 1/2 was present within several minutes and distinctly present in GSM06 cells at 60 minutes. Similar results were obtained for phospho-JNK, although the 54 kDa phosphoprotein signal was dominant in AGS, whereas the lower molecular weight band was dominant in GSM06 cells. These results demonstrate that early events in H. pylori pathogenesis occur within mouse epithelial cells similar to human cells and therefore support the use of the mouse model for the study of acute CagA-associated host cell responses. These results also indicate that reduced disease in H. pylori-infected mice may be due to lack of the Cag PAI, or by differences in the mouse response downstream of the initial activation events. © 2016 John Wiley & Sons Ltd.

  3. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

    PubMed

    Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

    2009-09-01

    Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

  4. Early molecular events during retinoic acid induced differentiation of neuromesodermal progenitors

    PubMed Central

    Cunningham, Thomas J.; Colas, Alexandre

    2016-01-01

    ABSTRACT Bipotent neuromesodermal progenitors (NMPs) residing in the caudal epiblast drive coordinated body axis extension by generating both posterior neuroectoderm and presomitic mesoderm. Retinoic acid (RA) is required for body axis extension, however the early molecular response to RA signaling is poorly defined, as is its relationship to NMP biology. As endogenous RA is first seen near the time when NMPs appear, we used WNT/FGF agonists to differentiate embryonic stem cells to NMPs which were then treated with a short 2-h pulse of 25 nM RA or 1 µM RA followed by RNA-seq transcriptome analysis. Differential expression analysis of this dataset indicated that treatment with 25 nM RA, but not 1 µM RA, provided physiologically relevant findings. The 25 nM RA dataset yielded a cohort of previously known caudal RA target genes including Fgf8 (repressed) and Sox2 (activated), plus novel early RA signaling targets with nearby conserved RA response elements. Importantly, validation of top-ranked genes in vivo using RA-deficient Raldh2−/− embryos identified novel examples of RA activation (Nkx1-2, Zfp503, Zfp703, Gbx2, Fgf15, Nt5e) or RA repression (Id1) of genes expressed in the NMP niche or progeny. These findings provide evidence for early instructive and permissive roles of RA in controlling differentiation of NMPs to neural and mesodermal lineages. PMID:27793834

  5. Injury of the cell's respiratory system by heat and by formaldehyde. Thermokinetics and early molecular events.

    PubMed

    Johnson, H A; Wiske, P S

    1976-08-01

    This is a study of the manner in which the respiratory system of the cell is injured either by elevated temperature or by exposure to diluted formaldehyde. Molecular mechanisms were identified by thermokinetic measurements. The rates at which respiratory failure developed in mouse liver slices in an injurious environment were measured at various temperatures. The data were fitted to the Arrhenius equation, and the effective activation energies of the injury processes were calculated. These data show that (1) the thermokinetics of injury to the cell's respiratory system, whether by thermal or chemical means, follows the Arrhenius law. (2) Thermal injury of the cell's respiratory system has a high activation energy, indicating that the critical, rate-determining event is a protein denaturation. Other mechanisms such as imbalance of metabolic reaction rates and thermal liquefaction of membrane lipids can be ruled out. (3) Repression of cell respiration by diluted formaldehyde has an activation energy compatible with a chemical reaction but low enough to exclude protein denaturation as a mechanism.

  6. Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.

    PubMed

    Borkar, Aditi Narendra; Rout, Manoj Kumar; Hosur, Ramakrishna V

    2011-01-01

    Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR) was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH) solution and water to study the denaturation process of PR in acetic acid environment. Direct visualization of the denaturation dynamics that is readily available from such simulations has been presented. Our simulations in 9 M AcOH reveal that the PR denaturation begins by separation of dimer into intact monomers and it is only after this separation that the monomer units start denaturing. The denaturation of the monomers is flagged off by the loss of crucial interactions between the α-helix at C-terminal and surrounding β-strands. This causes the structure to transit from the equilibrium dynamics to random non-equilibrating dynamics. Residence time calculations indicate that denaturation occurs via direct interaction of the acetic acid molecules with certain regions of the protein in 9 M AcOH. All these observations have helped to decipher a picture of the early events in acetic acid denaturation of PR and have illustrated that the α-helix and the β-sheet at the C-terminus of a native and functional PR dimer should maintain both the stability and the function of the enzyme and thus present newer targets for blocking PR function.

  7. Early molecular events involved in Pinus pinaster Ait. somatic embryo development under reduced water availability: transcriptomic and proteomic analyses.

    PubMed

    Morel, Alexandre; Teyssier, Caroline; Trontin, Jean-François; Eliášová, Kateřina; Pešek, Bedřich; Beaufour, Martine; Morabito, Domenico; Boizot, Nathalie; Le Metté, Claire; Belal-Bessai, Leila; Reymond, Isabelle; Harvengt, Luc; Cadene, Martine; Corbineau, Françoise; Vágner, Martin; Label, Philippe; Lelu-Walter, Marie-Anne

    2014-09-01

    Maritime pine somatic embryos (SEs) require a reduction in water availability (high gellan gum concentration in the maturation medium) to reach the cotyledonary stage. This key switch, reported specifically for pine species, is not yet well understood. To facilitate the use of somatic embryogenesis for mass propagation of conifers, we need a better understanding of embryo development. Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass spectrometry (MS) identification] of immature SEs, cultured on either high (9G) or low (4G) gellan gum concentration, was performed, together with analysis of water content, fresh and dry mass, endogenous abscisic acid (ABA; gas chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch and confocal laser microscope observations. This multiscale, integrated analysis was used to unravel early molecular and physiological events involved in SE development. Under unfavorable conditions (4G), the glycolytic pathway was enhanced, possibly in relation to cell proliferation that may be antagonistic to SE development. Under favorable conditions (9G), SEs adapted to culture constraint by activating specific protective pathways, and ABA-mediated molecular and physiological responses promoting embryo development. Our results suggest that on 9G, germin-like protein and ubiquitin-protein ligase could be used as predictive markers of SE development, whereas protein phosphatase 2C could be a biomarker for culture adaptive responses. This is the first characterization of early molecular mechanisms involved in the development of pine SEs following an increase in gellan gum concentration in the maturation medium, and it is also the first report on somatic embryogenesis in conifers combining transcriptomic and proteomic datasets. © 2014 Scandinavian Plant Physiology Society.

  8. Early events in the folding of an amphipathic peptide: A multinanosecond molecular dynamics study

    NASA Technical Reports Server (NTRS)

    Chipot, C.; Maigret, B.; Pohorille, A.

    1999-01-01

    Folding of the capped LQQLLQQLLQL peptide is investigated at the water-hexane interface by molecular dynamics simulations for 161.5 ns. Initially placed in the aqueous phase as a beta-strand, the peptide rapidly adsorbs to the interface, where it adopts an amphipathic conformation. The marginal presence of nonamphipathic structures throughout the complete trajectory indicates that the corresponding conformations are strongly disfavored at the interface. It is further suggestive that folding in an interfacial environment proceeds through a pathway of successive amphipathic intermediates. The energetic and entropic penalties involved in the conformational changes along this pathway markedly increase the folding time scales of LQQLLQQLLQL, explaining why the alpha-helix, the hypothesized lowest free energy structure for a sequence with a hydrophobic periodicity of 3.6, has not been reached yet. The formation of a type I beta-turn at the end of the simulation confirms the importance of such motifs as initiation sites allowing the peptide to coalesce towards a secondary structure. Proteins 1999;36:383-399. Copyright 1999 Wiley-Liss, Inc.

  9. Early Events in the Folding of an Amphipathic Peptide A Multi- Nanosecond Molecular Dynamics Study

    NASA Technical Reports Server (NTRS)

    Chipot, Christophe; Maigret, Bernard; Pohorille, Andrew

    1999-01-01

    Folding of the capped LQQLLQQLLQL peptide is investigated at the water-hexane interface by molecular dynamics simulations over 161.5 nanoseconds. Initially placed in the aqueous phase as a beta-strand, the peptide rapidly adsorbs to the interface, where it adopts an amphipathic conformation. The marginal presence of non-amphipathic structures throughout the complete trajectory indicate- that the corresponding conformations are strongly disfavored at the interface. It is further suggestive that folding in an interfacial environment proceeds through a pathway of successive amphipathic intermediates. The energetic and entropic penalties involved in the conformational changes along this pathway markedly increase the folding time-scales of LQQLLQQLLQL, explaining why the alpha-helix, the hypothesized lowest free energy structure for a sequence with a hydrophobic periodicity of 3.6, has not been reached yet. The formation of a type I beta-turn at the end of the simulation confirms the importance of such motifs as initiation sites allowing the peptide to coalesce towards a secondary structure.

  10. Molecular events during the early stages of aggregation of GNNQQNY: An all atom MD simulation study of randomly dispersed peptides.

    PubMed

    Srivastava, Alka; Balaji, Petety V

    2015-12-01

    This study probes the early events during lag phase of aggregation of GNNQQNY using all atom MD simulations in explicit solvent. Simulations were performed by varying system size, temperature and starting configuration. Peptides dispersed randomly in the simulation box come together early on in the simulation and form aggregates. These aggregates are dynamic implying the absence of stabilizing interactions. This facilitates the exploration of alternate arrangements. The constituent peptides sample a variety of conformations, frequently re-orient and re-arrange with respect to each other and dissociate from/re-associate with the aggregate. The size and lifetime of aggregates vary depending upon the number of inter-peptide backbone H-bonds. Most of the aggregates formed are amorphous but crystalline aggregates of smaller size (mainly 2-mers) do appear and sustain for varying durations of time. The peptides in crystalline 2-mers are mostly anti-parallel. The largest crystalline aggregate that appears is a 4-mer in a single sheet and a 4-, 5-, or 6-mer in double layered arrangement. Crystalline aggregates grow either by the sequential addition of peptides, or by the head-on or lateral collision-adhesion of 2-mers. The formation of various smaller aggregates suggests the polymorphic nature of oligomers and heterogeneity in the lag phase. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Early traumatic events in psychopaths.

    PubMed

    Borja, Karina; Ostrosky, Feggy

    2013-07-01

    The relationship between diverse early traumatic events and psychopathy was studied in 194 male inmates. Criminal history transcripts were revised, and clinical interviews were conducted to determine the level of psychopathy using the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory was applied to assess the incidence of abuse before 18 years of age. Psychopathic inmates presented a higher victimization level and were more exposed to certain types of intended abuse than sociopathic inmates, while the sum of events and emotional abuse were associated with the PCL-R score. Our studies support the influence of early adverse events in the development of psychopathic offenders. © 2013 American Academy of Forensic Sciences.

  12. Dose and Effect Thresholds for Early Key Events in a Mode of PPARa-Mediated Action

    EPA Science Inventory

    ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. T...

  13. Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

    PubMed

    Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2017-06-25

    Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Molecular diversity of early foraminifera

    NASA Astrophysics Data System (ADS)

    Holzmann, Maria; Pawlowski, Jan

    2017-04-01

    Monothalamid foraminifera are a diverse group that is characterized by single-chambered agglutinated or organic test. They occur in all marine habitats and are also present in terrestrial and freshwater environments. Monothalamids branch at the base of foraminiferal tree, as a paraphyletic group with some clades branching at the base of Globothalamea and Tubothalamea. We have currently more than 1500 sequences of monothalamids in our database that can be divided in at least 20 clades among which certain are particularly well presented by sequence numbers and/or number of different species. These are members of clade BM that contain Bathysiphon and Micrometula, clade C that contains among others xenophyophorans, saccaminids, and a large variety of organic-walled or agglutinated genera, clade E that contains the genera Psammophaga, Vellaria and Nellya and four clades that contain freshwater foraminifera. In general, the monothalamid clades comprise both agglutinated and organic-walled genera. Some common genera, such as Crithionina, Saccammina, Hippocrepina, are polyphyletic. Our results clearly show that monothalamids are highly diverse and their molecular diversity by far surpasses their morphological variety. Based on phylogenomic studies, monothalamids evolved early in the evolution of eukaryotes, as a part of the supergroup of Rhizaria, comprising also radiolarians and other amoeboid protists. The monothalamids have diverged from ancestral radiolarians, probably about 1000 million years ago, but the exact time is difficult to infer because of the uncertainties concerning a calibration of a eukaryotic phylogenomic tree.

  15. Early events governing memory CD8+ T-cell differentiation.

    PubMed

    Obar, Joshua J; Lefrançois, Leo

    2010-08-01

    Understanding the regulation of the CD8(+) T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8(+) T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8(+) T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8(+) T cells.

  16. Early events in geotropism of seedling shoots

    NASA Technical Reports Server (NTRS)

    Pickard, B. G.

    1985-01-01

    Developments during the first ten minutes of geotropic stimulation in plant seedling shoots are reviewed. Topics include induction and curvature; early processes; the relationship between auxin, electric field, calcium, and differential growth; gravity reception leading to Went-Cholodny transport; and comparison of root and shoot. Early processes reviewed are sedimentation of amyloplasts, release of ethylene, rise of electrical and auxin asymmetry, redistribution of calcium, asymmetric vascular transport, increase in tendency to deposit callose, and simulation of putative exocytotic voltage transients.

  17. Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

    PubMed

    Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

    2014-10-13

    Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

  18. Specific Reaction Patterns to Distinct Positive Emotional Cues Related to Incentive Motivation in Dependence of the Taq1A-Polymorphism: Molecular Genetic Associations of Early and Late Event-Related Potentials.

    PubMed

    Munk, Aisha J L; Wielpuetz, Catrin; Osinsky, Roman; Müller, Erik M; Grant, Phillip; Hennig, Jürgen

    2016-01-01

    Early and late event-related potential (ERP) responses, representing early subconscious and late motivational processes, were recorded for positive emotional words related to 'wanting' and 'liking', in dependence of the dopamine-related Taq1A genotype (ANKK1/DRD2). Research suggests that 'wanting' as opposed to 'liking' is related to dopaminergic processes. Therefore, it was hypothesized that risk allele carriers of the Taq1A polymorphism exhibit late ERP changes in reaction to words representing incentive motivation, i.e. 'wanting' (word categories 'lust' and 'anticipation'), but not to words representing 'liking' ('closeness'). Seventy-two male participants performed an emotional-word Stroop task during EEG recording and were genotyped according to the Taq1A polymorphism of ANKK1/DRD2. Positive emotional words related to anticipation and lust revealed blunted responses in the late positive potential (LPP) in carriers of the A1 allele, an effect absent in response to 'liking'-related words. These differences were not evident in the earlier posterior negativity (EPN). As no differences in dependence of the Taq1A genotype were observed in reaction to 'wanting'- and 'liking'-related words in the EPN, but merely in the LPP, it can be assumed that incentive-motivational stimuli only modify motivation-related ERP responses in carriers of the A1 allele of the Taq1A polymorphism, indicating the role of dopamine in late ERP components. © 2016 S. Karger AG, Basel.

  19. Method for early detection of cooling-loss events

    DOEpatents

    Bermudez, Sergio A.; Hamann, Hendrik; Marianno, Fernando J.

    2015-06-30

    A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

  20. Method for early detection of cooling-loss events

    DOEpatents

    Bermudez, Sergio A.; Hamann, Hendrik F.; Marianno, Fernando J.

    2015-12-22

    A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

  1. Operational early warning platform for extreme meteorological events

    NASA Astrophysics Data System (ADS)

    Mühr, Bernhard; Kunz, Michael

    2015-04-01

    Operational early warning platform for extreme meteorological events Most natural disasters are related to extreme weather events (e.g. typhoons); weather conditions, however, are also highly relevant for humanitarian and disaster relief operations during and after other natural disaster like earthquakes. The internet service "Wettergefahren-Frühwarnung" (WF) provides various information on extreme weather events, especially when these events are associated with a high potential for large damage. The main focus of the platform is on Central Europe, but major events are also monitored worldwide on a daily routine. WF provides high-resolution forecast maps for many weather parameters which allow detailed and reliable predictions about weather conditions during the next days in the affected areas. The WF service became operational in February 2004 and is part of the Center for Disaster Management and Risk Reduction Technology (CEDIM) since 2007. At the end of 2011, CEDIM embarked a new type of interdisciplinary disaster research termed as forensic disaster analysis (FDA) in near real time. In case of an imminent extreme weather event WF plays an important role in CEDIM's FDA group. It provides early and precise information which are always available and updated several times during a day and gives advice and assists with articles and reports on extreme events.

  2. Social anxiety and negative early life events in university students.

    PubMed

    Binelli, Cynthia; Ortiz, Ana; Muñiz, Armando; Gelabert, Estel; Ferraz, Liliana; S Filho, Alaor; Crippa, José Alexandre S; Nardi, Antonio E; Subirà, Susana; Martín-Santos, Rocío

    2012-06-01

    There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

  3. Unveiling molecular events in the brain by noninvasive imaging.

    PubMed

    Klohs, Jan; Rudin, Markus

    2011-10-01

    Neuroimaging allows researchers and clinicians to noninvasively assess structure and function of the brain. With the advances of imaging modalities such as magnetic resonance, nuclear, and optical imaging; the design of target-specific probes; and/or the introduction of reporter gene assays, these technologies are now capable of visualizing cellular and molecular processes in vivo. Undoubtedly, the system biological character of molecular neuroimaging, which allows for the study of molecular events in the intact organism, will enhance our understanding of physiology and pathophysiology of the brain and improve our ability to diagnose and treat diseases more specifically. Technical/scientific challenges to be faced are the development of highly sensitive imaging modalities, the design of specific imaging probe molecules capable of penetrating the CNS and reporting on endogenous cellular and molecular processes, and the development of tools for extracting quantitative, biologically relevant information from imaging data. Today, molecular neuroimaging is still an experimental approach with limited clinical impact; this is expected to change within the next decade. This article provides an overview of molecular neuroimaging approaches with a focus on rodent studies documenting the exploratory state of the field. Concepts are illustrated by discussing applications related to the pathophysiology of Alzheimer's disease.

  4. Molecular Characterization of Transgenic Events Using Next Generation Sequencing Approach.

    PubMed

    Guttikonda, Satish K; Marri, Pradeep; Mammadov, Jafar; Ye, Liang; Soe, Khaing; Richey, Kimberly; Cruse, James; Zhuang, Meibao; Gao, Zhifang; Evans, Clive; Rounsley, Steve; Kumpatla, Siva P

    2016-01-01

    Demand for the commercial use of genetically modified (GM) crops has been increasing in light of the projected growth of world population to nine billion by 2050. A prerequisite of paramount importance for regulatory submissions is the rigorous safety assessment of GM crops. One of the components of safety assessment is molecular characterization at DNA level which helps to determine the copy number, integrity and stability of a transgene; characterize the integration site within a host genome; and confirm the absence of vector DNA. Historically, molecular characterization has been carried out using Southern blot analysis coupled with Sanger sequencing. While this is a robust approach to characterize the transgenic crops, it is both time- and resource-consuming. The emergence of next-generation sequencing (NGS) technologies has provided highly sensitive and cost- and labor-effective alternative for molecular characterization compared to traditional Southern blot analysis. Herein, we have demonstrated the successful application of both whole genome sequencing and target capture sequencing approaches for the characterization of single and stacked transgenic events and compared the results and inferences with traditional method with respect to key criteria required for regulatory submissions.

  5. Impact Constraints on Major Events in Early Mars History

    NASA Technical Reports Server (NTRS)

    Frey, H. V.

    2004-01-01

    MOLA data have revealed a large population of "Quasi-Circular Depressions" (QCDs) with little or no visible expression in image data. These likely buried impact basins have important implications for the age of the lowland crust, how that compares with original highland crust, and when and how the crustal dichotomy may have formed. The buried lowlands are of Early Noachian age, likely slightly younger than the buried highlands but older than the exposed (visible) highland surface. A depopulation of large visible basins at diameters 800 to 1300 km suggests some global scale event early in martian history, maybe related to the formation of the lowlands and/or the development of Tharsis. A suggested early disappearance of the global magnetic field can be placed within a temporal sequence of formation of the very largest impact basins. The global field appears to have disappeared at about the time the lowlands formed. It seems likely the topographic crustal dichotomy was produced very early in martian history by processes which operated very quickly. Thus there appears to have been a northern lowland throughout nearly all of martian history, predating the last of the really large impacts (Hellas, Argyre and Isidis) and their likely very significant environmental consequences.

  6. Bacterial Chemotaxis: The Early Years of Molecular Studies

    PubMed Central

    Hazelbauer, Gerald L.

    2014-01-01

    This review focuses on the early years of molecular studies of bacterial chemotaxis and motility, beginning in the 1960s with Julius Adler's pioneering work. It describes key observations that established the field and made bacterial chemotaxis a paradigm for the molecular understanding of biological signaling. Consideration of those early years includes aspects of science seldom described in journals: the accidental findings, personal interactions, and scientific culture that often drive scientific progress. PMID:22994495

  7. Raman imaging of molecular dynamics during cellular events

    NASA Astrophysics Data System (ADS)

    Fujita, Katsumasa

    2017-07-01

    To overcome the speed limitation in Raman imaging, we have developed a microscope system that detects Raman spectra from hundreds of points in a sample simultaneously. The sample was illuminated by a line-shaped focus, and Raman scattering from the illuminated positions was measured simultaneously by an imaging spectrophotometer. We applied the line-illumination technique to observe the dynamics of intracellular molecules during cellular events. We found that intracellular cytochrome c can be clearly imaged by resonant Raman scattering. We demonstrated label-free imaging of redistribution of cytochrome c during apoptosis and osteoblastic mineralization. We also proposed alkyne-tagged Raman imaging to observe small molecules in living cells. Due to its small size and the unique Raman band, alkyne can tag molecules without strong perturbation to molecular functions and with the capability to be detected separately from endogenous molecules.

  8. Early event related fields during visually evoked pain anticipation.

    PubMed

    Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

    2016-03-01

    Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Early Intravascular Events are Associated with Development of ARDS.

    PubMed

    Abdulnour, Raja-Elie E; Gunderson, Tina; Barkas, Ioanna; Timmons, Jack Y; Barnig, Cindy; Gong, Michelle; Kor, Daryl J; Gajic, Ognjen; Talmor, Daniel; Carter, Rickey E; Levy, Bruce D

    2018-05-21

    The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. To determine select peripheral blood lipid mediator and leukocyte responses in patients at-risk for ARDS. Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin or placebo. Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, 9 subjects developed ARDS after randomization yet prior to study drug initiation, including 7 subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio. Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.

  10. Translational errors as an early event in prion conversion.

    PubMed

    Hatin, I; Bidou, L; Cullin, C; Rousset, J P

    2001-01-01

    A prion is an infectious, altered form of a cellular protein which can self-propagate and affect normal phenotype. Prion conversion has been observed for mammalian and yeast proteins but molecular mechanisms that trigger this process remain unclear. Up to now, only post-translational models have been explored. In this work, we tested the hypothesis that co-translational events may be implicated in the conformation changes of the Ure2p protein of Saccharomyces cerevisiae. This protein can adopt a prion conformation leading to an [URE3] phenotype which can be easily assessed and quantified. We analyzed the effect of two antibiotics, known to affect translation, on [URE3] conversion frequency. For cells treated with G418 we observed a parallel increase of translational errors rate and frequency of [URE3] conversion. By contrast, cycloheximide which was not found to affect translational fidelity, has no influence on the induction of [URE3] phenotype. These results raise the possibility that the mechanism of prion conversion might not only involve alternative structures of strictly identical molecules but also aberrant proteins resulting from translational errors.

  11. Early Warning and Early Action during the 2015-16 El Nino Event

    NASA Astrophysics Data System (ADS)

    Robertson, A. W.; Goddard, L. M.

    2016-12-01

    Strong El Niño events have a marked impact on regional climate worldwide through their influence on large-scale atmospheric circulation. As a result, seasonal climate forecasts show greater skill during El Niño events, which provide communities, governments and humanitarian agencies greater ability to plan and prepare. The scientific community has advanced considerably in the quality and content of information provided about El Niño and its impacts. As a result, society has become better aware of and engaged with this information. This talk will present some details on how we navigate the fine line between expectations and probabilistic forecasts, and how this information was used during the 2015-16 El Niño event. Examples are drawn from the health sector and food security community. Specific attention will be given to the importance of problem-focus and data availability in the appropriate tailoring of climate information for Early Warning/Early Action.

  12. Dose and Effect Thresholds for Early Key Events in a Mode of ...

    EPA Pesticide Factsheets

    ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor-alpha (PPARα). Male B6C3F1 mice were exposed for 7 days to di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), and n-butyl benzyl phthalate (BBP), which vary in PPARα activity and liver tumorigenicity. Each phthalate increased expression of select PPARα target genes at 7 days, while only DEHP significantly increased liver cell proliferation labeling index (LI). Transcriptional benchmark dose (BMDT) estimates for dose-related genomic markers stratified phthalates according to hypothetical tumorigenic potencies, unlike BMDs for non-genomic endpoints (liver weights or proliferation). The 7-day BMDT values for Acot1 as a surrogate measure for PPARα activation were 29, 370, and 676 mg/kg-d for DEHP, DNOP, and BBP, respectively, distinguishing DEHP (liver tumor BMD of 35 mg/kg-d) from non-tumorigenic DNOP and BBP. Effect thresholds were generated using linear regression of DEHP effects at 7 days and 2-year tumor incidence values to anchor early response molec

  13. Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems

    DTIC Science & Technology

    2017-08-01

    Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems The views, opinions and/or findings contained in...University of California - San Diego Title: Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems Report Term...including enzymatic reactions , occurring at the aqueous interfaces of thermotropic LCs show promise as the basis of biomolecular triggers of LC

  14. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

    PubMed

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-11-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. The Relationship Between Early Life Events, Parental Attachment, and Psychopathic Tendencies in Adolescent Detainees.

    PubMed

    Christian, Erica J; Meltzer, Christine L; Thede, Linda L; Kosson, David S

    2017-04-01

    Despite increasing interest in understanding psychopathic traits in youth, the role of early environmental factors in the development of psychopathic traits is not well understood. No prior studies have directly examined the relationship between early life events and psychopathic traits. We examined links between life events in the first 4 years of life and indices of the core affective and interpersonal components of psychopathy. Additionally, we examined relationships between early life events, psychopathic traits, and attachment to parents among 206 adjudicated adolescents. Results indicated that the total number of early life events was positively correlated with indices of the affective component of psychopathy. Moreover, psychopathic traits moderated the relationship between the number of early life events and later reports of attachment to parents. Findings suggest that early environmental factors could have important implications for the development of psychopathic traits and may impact attachment to parents for youth with psychopathic traits.

  16. An Alternative Explanation for "Step-Like" Early VLF Event

    NASA Astrophysics Data System (ADS)

    Moore, R. C.

    2016-12-01

    A newly-deployed array of VLF receivers along the East Coast of the United States is ideally suited for detecting VLF scattering from lightning-induced disturbances to the lower ionosphere. The array was deployed in May 2016, and one VLF receiver was deployed only 20 km from the NAA transmitter (24.0 kHz) in Cutler, Maine. The phase of the NAA signal at this closest site varies significantly with time, due simply to the impedance match of the transmitter varying with time. Additionally, both the amplitude and phase exhibit periods of rapid shifts that could possibly explain at least some "step-like" VLF scattering events. Here, we distinguish between "step-like" VLF scattering events and other events in that "step-like" events are typically not closely associated with a detected causative lightning flash and also tend to exhibit little or no recovery to ambient conditions after the event onset. We present an analysis of VLF observations from the East Coast array that demonstrates interesting examples of step-like VLF events far from the transmitter that are associated with step-like events very close to the transmitter. We conclude that step-like VLF events should be treated with caution, unless definitively associated with a causative lightning flash and/or detected using observations of multiple transmitter signals.

  17. An EAS event observed in the early stage of development

    NASA Astrophysics Data System (ADS)

    Barroso, S. L. C.; Beggio, P. C.; de Carvalho, A. O.; Chinellato, J. A.; Mariano, A.; de Oliveira, R.; Shibuya, E. H.; Brazil-Japan Collaboration of Chacaltaya Emulsion Chamber Experiment

    2008-01-01

    Since 1969 the experiments of Brazil-Japan Collaboration showed the occurrence of a series of events, showing a region with a high concentration of electromagnetic particles, surrounded by isolated and/or groups of showers. These events were named "halo events" or "super-families". Currently, we have more than a dozen of such events. The first of them, due to its aspect, was named "Andromeda". We present here the main characteristics of a similar halo event, named C21S087I075. It has a halo region with many high energy showers in its border. Other small energy showers spread over the central and surrounding blocks (S088, S100, S101, I074). These isolated showers, classified as of hadronic or electromagnetic origin, present a fractional energy distribution compatible with that of a Centauro candidate event (C16S087I037), reported at this symposium [S.L.C. Barroso, P.C. Beggio, J.A. Chinellato, A.O. Carvalho, A. Mariano, R. Oliveira, E.H. Shibuya, in this issue of XIV ISVHECRI]. Moreover, the lateral distribution in the halo region is similar to that observed in other 3 halo events.

  18. Molecular events in skeletal muscle during disuse atrophy

    NASA Technical Reports Server (NTRS)

    Kandarian, Susan C.; Stevenson, Eric J.

    2002-01-01

    This review summarizes the current knowledge of the molecular processes underlying skeletal muscle atrophy due to disuse. Because the processes involved with muscle wasting due to illness are similar to disuse, this literature is used for comparison. Areas that are ripe for further study and that will advance our understanding of muscle atrophy are suggested.

  19. Molecular Imaging of Phosphorylation Events for Drug Development

    PubMed Central

    Chan, C. T.; Paulmurugan, R.; Reeves, R. E.; Solow-Cordero, D.; Gambhir, S. S.

    2014-01-01

    Purpose Protein phosphorylation mediated by protein kinases controls numerous cellular processes. A genetically encoded, generalizable split firefly luciferase (FL)-assisted complementation system was developed for noninvasive monitoring phosphorylation events and efficacies of kinase inhibitors in cell culture and in small living subjects by optical bioluminescence imaging. Procedures An Akt sensor (AST) was constructed to monitor Akt phosphorylation and the effect of different PI-3K and Akt inhibitors. Specificity of AST was determined using a non-phosphorylable mutant sensor containing an alanine substitution (ASA). Results The PI-3K inhibitor LY294002 and Akt kinase inhibitor perifosine led to temporal- and dose-dependent increases in complemented FL activities in 293T human kidney cancer cells stably expressing AST (293T/AST) but not in 293T/ASA cells. Inhibition of endogenous Akt phosphorylation and kinase activities by perifosine also correlated with increase in complemented FL activities in 293T/AST cells but not in 293T/ASA cells. Treatment of nude mice bearing 293T/AST xenografts with perifosine led to a 2-fold increase in complemented FL activities compared to that of 293T/ASA xenografts. Our system was used to screen a small chemical library for novel modulators of Akt kinase activity. Conclusion This generalizable approach for noninvasive monitoring of phosphorylation events will accelerate the discovery and validation of novel kinase inhibitors and modulators of phosphorylation events. PMID:19048345

  20. Iron accumulation in multiple sclerosis: an early pathogenic event.

    PubMed

    LeVine, Steven M; Bilgen, Mehmet; Lynch, Sharon G

    2013-03-01

    Iron has been shown to accumulate in deep gray matter structures in many forms of multiple sclerosis (MS), but detecting its presence early in the disease course (e.g., clinically isolated syndrome [CIS]) has been less clear. Here, we review a recent study where MRI scanning at 7 T together with susceptibility mapping was performed to assess iron deposition in CIS and control subjects. Susceptibility indicative of iron deposition was found to be increased in the globus pallidus, caudate, putamen and pulvinar of CIS patients compared with controls. The findings suggest that iron deposition is a pathological change that occurs early in the development of MS. Identifying the mechanisms of iron accumulation and determining whether iron promotes pathogenesis in MS are important areas of future research.

  1. Molecular clocks and the early evolution of metazoan nervous systems.

    PubMed

    Wray, Gregory A

    2015-12-19

    The timing of early animal evolution remains poorly resolved, yet remains critical for understanding nervous system evolution. Methods for estimating divergence times from sequence data have improved considerably, providing a more refined understanding of key divergences. The best molecular estimates point to the origin of metazoans and bilaterians tens to hundreds of millions of years earlier than their first appearances in the fossil record. Both the molecular and fossil records are compatible, however, with the possibility of tiny, unskeletonized, low energy budget animals during the Proterozoic that had planktonic, benthic, or meiofaunal lifestyles. Such animals would likely have had relatively simple nervous systems equipped primarily to detect food, avoid inhospitable environments and locate mates. The appearance of the first macropredators during the Cambrian would have changed the selective landscape dramatically, likely driving the evolution of complex sense organs, sophisticated sensory processing systems, and diverse effector systems involved in capturing prey and avoiding predation. © 2015 The Author(s).

  2. Event-by-Event Simulations of Early Gluon Fields in High Energy Nuclear Collisions

    NASA Astrophysics Data System (ADS)

    Nickel, Matthew; Rose, Steven; Fries, Rainer

    2017-09-01

    Collisions of heavy ions are carried out at ultra relativistic speeds at the Relativistic Heavy Ion Collider and the Large Hadron Collider to create Quark Gluon Plasma. The earliest stages of such collisions are dominated by the dynamics of classical gluon fields. The McLerran-Venugopalan (MV) model of color glass condensate provides a model for this process. Previous research has provided an analytic solution for event averaged observables in the MV model. Using the High Performance Research Computing Center (HPRC) at Texas A&M, we have developed a C++ code to explicitly calculate the initial gluon fields and energy momentum tensor event by event using the analytic recursive solution. The code has been tested against previously known analytic results up to fourth order. We have also have been able to test the convergence of the recursive solution at high orders in time and studied the time evolution of color glass condensate.

  3. Molecular, Cellular and Functional Events in Axonal Sprouting after Stroke

    PubMed Central

    Kathirvelu, Balachander; Schweppe, Catherine A; Nie, Esther H

    2016-01-01

    Stroke is the leading cause of adult disability. Yet there is a limited degree of recovery in this disease. One of the mechanisms of recovery is the formation of new connections in the brain and spinal cord after stroke: post-stroke axonal sprouting. Studies indicate that post-stroke axonal sprouting occurs in mice, rats, primates and humans. Inducing post-stroke axonal sprouting in specific connections enhances recovery; blocking axonal sprouting impairs recovery. Behavioral activity patterns after stroke modify the axonal sprouting response. A unique regenerative molecular program mediates this aspect of tissue repair in the CNS. The types of connections that are formed after stroke indicate three patterns of axonal sprouting after stroke: Reactive, Reparative and Unbounded Axonal Sprouting. These differ in mechanism, location, relationship to behavioral recovery and, importantly, in their prospect for therapeutic manipulation to enhance tissue repair. PMID:26874223

  4. Early events in copper-ion catalyzed oxidation of α-synuclein.

    PubMed

    Tiwari, Manish K; Leinisch, Fabian; Sahin, Cagla; Møller, Ian Max; Otzen, Daniel E; Davies, Michael J; Bjerrum, Morten J

    2018-04-22

    Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu 2+ /H 2 O 2 /protein and Cu 2+ /H 2 O 2 /ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu 2+ /H 2 O 2 /protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15 min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu 2+ /H 2 O 2 -mediated damage, with carbonyl formation being a minor process. With the Cu 2+ /H 2 O 2 /ascorbate system, rapid protein carbonyl formation was detected with the first 5 min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu 2+ /H 2 O 2 /ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu 2+ /H 2 O 2 -induced α-synuclein modification. Copyright © 2018. Published by Elsevier Inc.

  5. Planck early results. XXV. Thermal dust in nearby molecular clouds

    NASA Astrophysics Data System (ADS)

    Planck Collaboration; Abergel, A.; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Balbi, A.; Banday, A. J.; Barreiro, R. B.; Bartlett, J. G.; Battaner, E.; Benabed, K.; Benoît, A.; Bernard, J.-P.; Bersanelli, M.; Bhatia, R.; Bock, J. J.; Bonaldi, A.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bucher, M.; Burigana, C.; Cabella, P.; Cardoso, J.-F.; Catalano, A.; Cayón, L.; Challinor, A.; Chamballu, A.; Chiang, L.-Y.; Chiang, C.; Christensen, P. R.; Clements, D. L.; Colombi, S.; Couchot, F.; Coulais, A.; Crill, B. P.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Gasperis, G.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Dickinson, C.; Dobashi, K.; Donzelli, S.; Doré, O.; Dörl, U.; Douspis, M.; Dupac, X.; Efstathiou, G.; Enßlin, T. A.; Eriksen, H. K.; Finelli, F.; Forni, O.; Frailis, M.; Franceschi, E.; Galeotta, S.; Ganga, K.; Giard, M.; Giardino, G.; Giraud-Héraud, Y.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Guillet, V.; Hansen, F. K.; Harrison, D.; Henrot-Versillé, S.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hovest, W.; Hoyland, R. J.; Huffenberger, K. M.; Jaffe, A. H.; Jones, A.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knox, L.; Kurki-Suonio, H.; Lagache, G.; Lamarre, J.-M.; Lasenby, A.; Laureijs, R. J.; Lawrence, C. R.; Leach, S.; Leonardi, R.; Leroy, C.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Macías-Pérez, J. F.; MacTavish, C. J.; Maffei, B.; Mandolesi, N.; Mann, R.; Maris, M.; Marshall, D. J.; Martin, P.; Martínez-González, E.; Masi, S.; Matarrese, S.; Matthai, F.; Mazzotta, P.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Mendes, L.; Mennella, A.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Munshi, D.; Murphy, A.; Naselsky, P.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Osborne, S.; Pajot, F.; Paladini, R.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Piacentini, F.; Piat, M.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Ponthieu, N.; Poutanen, T.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Renault, C.; Ricciardi, S.; Riller, T.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Santos, D.; Savini, G.; Scott, D.; Seiffert, M. D.; Shellard, P.; Smoot, G. F.; Starck, J.-L.; Stivoli, F.; Stolyarov, V.; Sudiwala, R.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Torre, J.-P.; Tristram, M.; Tuovinen, J.; Umana, G.; Valenziano, L.; Verstraete, L.; Vielva, P.; Villa, F.; Vittorio, N.; Wade, L. A.; Wandelt, B. D.; Yvon, D.; Zacchei, A.; Zonca, A.

    2011-12-01

    Planck allows unbiased mapping of Galactic sub-millimetre and millimetre emission from the most diffuse regions to the densest parts of molecular clouds. We present an early analysis of the Taurus molecular complex, on line-of-sight-averaged data and without component separation. The emission spectrum measured by Planck and IRAS can be fitted pixel by pixel using a single modified blackbody. Some systematic residuals are detected at 353 GHz and 143 GHz, with amplitudes around -7% and +13%, respectively, indicating that the measured spectra are likely more complex than a simple modified blackbody. Significant positive residuals are also detected in the molecular regions and in the 217 GHz and 100 GHz bands, mainly caused by the contribution of the J = 2 → 1 and J = 1 → 0 12CO and 13CO emission lines. We derive maps of the dust temperature T, the dust spectral emissivity index β, and the dust optical depth at 250 μm τ250. The temperature map illustrates the cooling of the dust particles in thermal equilibrium with the incident radiation field, from 16 - 17 K in the diffuse regions to 13 - 14 K in the dense parts. The distribution of spectral indices is centred at 1.78, with a standard deviation of 0.08 and a systematic error of 0.07. We detect a significant T - β anti-correlation. The dust optical depth map reveals the spatial distribution of the column density of the molecular complex from the densest molecular regions to the faint diffuse regions. We use near-infrared extinction and Hi data at 21-cm to perform a quantitative analysis of the spatial variations of the measured dust optical depth at 250 μm per hydrogen atom τ250/NH. We report an increase of τ250/NH by a factor of about 2 between the atomic phase and the molecular phase, which has a strong impact on the equilibrium temperature of the dust particles. Corresponding author: A. Abergel, e-mail: alain.abergel@ias.u-psud.fr

  6. A New Observation Technique Applied to Early/Fast VLF Scattering Events

    NASA Astrophysics Data System (ADS)

    Kotovsky, D. A.; Moore, R. C.

    2012-12-01

    Early/fast very low frequency (VLF, 3-30 kHz) events are understood to result from ionospheric conductivity changes associated with lightning. Early/fast amplitude and phase perturbations have been observed coincidentally with various optical observations of transient luminous events (TLEs), including elves, sprites, and sprite halos, each of which can have temporal characteristics consistent with those of early/fast VLF events. It is yet unresolved, however, whether a specific type of TLE is directly related to the ionospheric conductivity changes responsible for the typical early/fast event. In this paper, we present spread spectrum VLF scattering observations of early/fast events. The spread spectrum analysis technique determines the amplitude and phase of a subionospherically propagating VLF signal as a function of time during the early/fast event and as a function of frequency across the 200 Hz bandwidth of the VLF transmission. VLF scattering observations, each identified with causative lightning logged by the National Lightning Detection Network (NLDN), are compared with the predictions of the Long-Wave Propagation Capability (LWPC) code, a three-dimensional earth-ionosphere waveguide propagation and scattering model. Theoretical predictions for VLF scattering from ionization changes associated with elves are compared with those associated with sprite halos, and each are compared with experimental observations. Results indicate that the observed frequency dependence of VLF scattering during early/fast events results from the combination of scattering source properties and Earth-ionosphere waveguide propagation effects. Observations are more consistent with the modeled amplitude perturbations associated with sprite halos than those with elves.

  7. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    PubMed

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  8. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus

    PubMed Central

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D.; Saeed, Fahad; Michael Payne, D.; Chen, Shu-Hui; Fenton, Robert A.; Pisitkun, Trairak

    2015-01-01

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI. PMID:26674602

  9. Unraveling the early molecular and physiological mechanisms involved in response to phenanthrene exposure.

    PubMed

    Dumas, Anne-Sophie; Taconnat, Ludivine; Barbas, Evangelos; Rigaill, Guillem; Catrice, Olivier; Bernard, Delphine; Benamar, Abdelilah; Macherel, David; El Amrani, Abdelhak; Berthomé, Richard

    2016-10-21

    Higher plants have to cope with increasing concentrations of pollutants of both natural and anthropogenic origin. Given their capacity to concentrate and metabolize various compounds including pollutants, plants can be used to treat environmental problems - a process called phytoremediation. However, the molecular mechanisms underlying the stabilization, the extraction, the accumulation and partial or complete degradation of pollutants by plants remain poorly understood. Here, we determined the molecular events involved in the early plant response to phenanthrene, used as a model of polycyclic aromatic hydrocarbons. A transcriptomic and a metabolic analysis strongly suggest that energy availability is the crucial limiting factor leading to high and rapid transcriptional reprogramming that can ultimately lead to death. We show that the accumulation of phenanthrene in leaves inhibits electron transfer and photosynthesis within a few minutes, probably disrupting energy transformation. This kinetic analysis improved the resolution of the transcriptome in the initial plant response to phenanthrene, identifying genes that are involved in primary processes set up to sense and detoxify this pollutant but also in molecular mechanisms used by the plant to cope with such harmful stress. The identification of first events involved in plant response to phenanthrene is a key step in the selection of candidates for further functional characterization, with the prospect of engineering efficient ecological detoxification systems for polycyclic aromatic hydrocarbons.

  10. Cosmological Simulations with Molecular Astrochemistry: Water in the Early Universe

    NASA Astrophysics Data System (ADS)

    Wiggins, Brandon K.; Smidt, Joseph

    2018-01-01

    Water is required for the rise of life as we know it throughout the universe, but its origin and the circumstances of its first appearance remain a mystery. The abundance of deuterated water in solar system bodies cannot be explained if all the water in the solar system were created in the protoplanetary disk (Cleeves et al. 2014), suggesting that as much of half of Earth’s water predates the Sun. Water has been observed as early as one sixth the current universe’s age in MG J0414+0534 (Imprellizzeri et al. 2008). It was recently shown that water could, in principle, appear in hot halos barely enriched with heavy elements such as oxygen and carbon (Bialy et al. 2015). So far, no self-consistent calculation of cosmology physics carried out in line with a large chemical reaction network has been carried out to study the first sites of water formation in the universe. We present initial results the first such series of cosmological calculations with a 26 species low metallicity molecular chemical reaction network with Enzo (Bryan et al. 2014) to understand the role of hydrodynamics and radiative feedback on molecule formation in the early universe and to shed light on the cosmological history of this life-giving substance.

  11. Organic geochemistry of the early Toarcian oceanic anoxic event in Hawsker Bottoms, Yorkshire, England

    NASA Astrophysics Data System (ADS)

    French, K. L.; Sepúlveda, J.; Trabucho-Alexandre, J.; Gröcke, D. R.; Summons, R. E.

    2014-03-01

    A comprehensive organic geochemical investigation of the Hawsker Bottoms outcrop section in Yorkshire, England has provided new insights about environmental conditions leading into and during the Toarcian oceanic anoxic event (T-OAE; ∼183 Ma). Rock-Eval and molecular analyses demonstrate that the section is uniformly within the early oil window. Hydrogen index (HI), organic petrography, polycyclic aromatic hydrocarbon (PAH) distributions, and tricyclic terpane ratios mark a shift to a lower relative abundance of terrigenous organic matter supplied to the sampling locality during the onset of the T-OAE and across a lithological transition. Unlike other ancient intervals of anoxia and extinction, biomarker indices of planktonic community structure do not display major changes or anomalous values. Depositional environment and redox indicators support a shift towards more reducing conditions in the sediment porewaters and the development of a seasonally stratified water column during the T-OAE. In addition to carotenoid biomarkers for green sulfur bacteria (GSB), we report the first occurrence of okenane, a marker of purple sulfur bacteria (PSB), in marine samples younger than ∼1.64 Ga. Based on modern observations, a planktonic source of okenane's precursor, okenone, would require extremely shallow photic zone euxinia (PZE) and a highly restricted depositional environment. However, due to coastal vertical mixing, the lack of planktonic okenone production in modern marine sulfidic environments, and building evidence of okenone production in mat-dwelling Chromatiaceae, we propose a sedimentary source of okenone as an alternative. Lastly, we report the first parallel compound-specific δC13 record in marine- and terrestrial-derived biomarkers across the T-OAE. The δC13 records of short-chain n-alkanes, acyclic isoprenoids, and long-chain n-alkanes all encode negative carbon isotope excursions (CIEs), and together, they support an injection of isotopically light

  12. The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

    PubMed

    Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

    2016-04-05

    Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

  13. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    PubMed

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

  14. Development of a tiered screening strategy for a molecular-initiating event: thyroperoxidase inhibition (SOT)

    EPA Science Inventory

    Adverse outcome pathway (AOP) analyses illustrate that some molecular-initiating events (MIEs) for thyroid disruption, including thyroperoxidase (TPO) inhibition, are not evaluated by current ToxCast/Tox21 high-throughput screening (HTS) assays. A novel HTS assay for TPO inhibiti...

  15. Early changes in physical tree characteristics during an oak decline event in the Ozark highlands

    Martin A. Spetich

    2006-01-01

    An oak decline event is severely affecting up to 120 000 ha in the Ozark National Forest of Arkansas. Results of early changes in physical tree characteristics during that event are presented. In the fall and winter of 1999 and 2000, we established research plots on a site that would become a center of severe oak decline. In August 2000, standing trees > 14 cm in...

  16. Modeling a molecular initiating event to population effects: A case study of aromatase inhibition in fathead minnows

    EPA Science Inventory

    An adverse outcome pathway (AOP) conceptually links a molecular initiating event with measureable key events at higher levels of biological organization that ultimately result in an adverse outcome. Development of an AOP requires experimental data and scientific expertise to ide...

  17. Molecular evidence for the early history of living amphibians.

    PubMed

    Feller, A E; Hedges, S B

    1998-06-01

    The evolutionary relationships of the three orders of living amphibians (lissamphibians) has been difficult to resolve, partly because of their specialized morphologies. Traditionally, frogs and salamanders are considered to be closest relatives, and all three orders are thought to have arisen in the Paleozoic (>250 myr). Here, we present evidence from the DNA sequences of four mitochondrial genes (2.7 kilobases) that challenges the conventional hypothesis and supports a salamander-caecilian relationship. This, in light of the fossil record and distribution of the families, suggests a more recent (Mesozoic) origin for salamanders and caecilians directly linked to the initial breakup of the supercontinent Pangaea. We propose that this single geologic event isolated salamanders and archaeobatrachian frogs on the northern continents (Laurasia) and the caecilians and neobatrachian frogs on the southern continents (Gondwana). Among the neobatrachian frog families, molecular evidence supports a South American clade and an African clade, inferred here to be the result of mid-Cretaceous vicariance. Copyright 1998 Academic Press.

  18. Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence.

    PubMed

    Humphreys, Kathryn L; Watts, Emily L; Dennis, Emily L; King, Lucy S; Thompson, Paul M; Gotlib, Ian H

    2018-05-21

    Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

  19. Molecular genetics of early-onset Alzheimer's disease revisited.

    PubMed

    Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

    2016-06-01

    As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Loss of heterozygosity at D8S262: an early genetic event of hepatocarcinogenesis.

    PubMed

    Zhu, Qiao; Gong, Li; Liu, Xiaoyan; Wang, Jun; Ren, Pin; Zhang, Wendong; Yao, Li; Han, Xiujuan; Zhu, Shaojun; Lan, Miao; Li, Yanhong; Zhang, Wei

    2015-06-16

    Hepatocellular carcinoma (HCC) is a multi-factor, multi-step, multi-gene and complicated process resulting from the accumulation of sequential genetic and epigenetic alterations. An important change among them is from precancerous lesions to HCC. However, only few studies have been reported about the sequential genetic changes during hepatocarcinogenesis. We observed firstly molecular karyotypes of 10 matched HCC using Affymetrix single-nucleotide polymorphism (SNP) 6.0 arrays, and found chromosomal fragments with high incidence (more than 70%) of loss of heterozygosity (LOH). Then, we selected 28 microsatellite markers at some gene spanning these chromosomal fragments, and examined the frequency of LOH of 128 matched HCC and 43 matched precancerous lesions-dysplastic nodules (DN) by a PCR-based analysis. Finally, we investigated the expression of proteins encoded by these genes in HCC, DN and the surrounding hepatic tissues. The result of Affymetrix SNP6.0 arrays demonstrated that more than 70% (7/10) cases had chromosomal fragment deletion on 4q13.3-35.1, 8p23.2-21.2, 16q11.2-24.3, and 17p13.3-12. Among 28 microsatellite markers selected, LOH frequencies at D8S262 for DN and HCC were found to be the highest, 51.2% and 72.7%, respectively. Immunohistochemically, the positive rate of its adjacent gene CSMD1 in HCC, DN, and the surrounding hepatic tissues were 27.3% (35/128), 75% (33/44), and 82% (105/128), respectively. LOH at D8S262 may be associated with an early genetic event of hepatocarcinogenesis, and a predictor for the monitor and prevention of HCC. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1557074981159099 .

  1. Characterizing rare-event property distributions via replicate molecular dynamics simulations of proteins.

    PubMed

    Krishnan, Ranjani; Walton, Emily B; Van Vliet, Krystyn J

    2009-11-01

    As computational resources increase, molecular dynamics simulations of biomolecules are becoming an increasingly informative complement to experimental studies. In particular, it has now become feasible to use multiple initial molecular configurations to generate an ensemble of replicate production-run simulations that allows for more complete characterization of rare events such as ligand-receptor unbinding. However, there are currently no explicit guidelines for selecting an ensemble of initial configurations for replicate simulations. Here, we use clustering analysis and steered molecular dynamics simulations to demonstrate that the configurational changes accessible in molecular dynamics simulations of biomolecules do not necessarily correlate with observed rare-event properties. This informs selection of a representative set of initial configurations. We also employ statistical analysis to identify the minimum number of replicate simulations required to sufficiently sample a given biomolecular property distribution. Together, these results suggest a general procedure for generating an ensemble of replicate simulations that will maximize accurate characterization of rare-event property distributions in biomolecules.

  2. Early/fast VLF events produced by the quiescent heating of the lower ionosphere by thunderstorms

    NASA Astrophysics Data System (ADS)

    Kabirzadeh, R.; Marshall, R. A.; Inan, U. S.

    2017-06-01

    Large and easily distinguishable perturbations of the VLF transmitter signals due to interactions with thundercloud-driven ionospheric modifications have been observed and studied for about three decades. These events are called "early/fast VLF" or "early VLF" events due to their immediate detection (˜20 ms) after the causative lightning flash on the ground and the fast rise time of the perturbed signal. Despite many years of study, the physical mechanisms responsible for these perturbations are still under investigation. Modifications of the sustained heating level of the ionosphere due to a lightning flash has been previously proposed as the causative mechanism of early/fast VLF events. The perturbations predicted by this mechanism, however, have been much smaller than experimental observations of 0.2-1 dB or higher. In this study, by using an improved 3-D thundercloud electrostatic upward coupling model which uses a realistic geomagnetic field, we find that the sustained heating model can predict perturbations that are consistent with reported experimental observations. Modifications in the quiescent heating of the lower ionosphere by thundercloud fields by individual lightning flashes may thus account for some observations of early/fast VLF events.

  3. How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2006

    2006-01-01

    Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

  4. Neighborhood Disadvantage, Stressful Life Events, and Adjustment among Mexican American Early Adolescents

    ERIC Educational Resources Information Center

    Roosa, Mark W.; Burrell, Ginger L.; Nair, Rajni L.; Coxe, Stefany; Tein, Jenn-Yun; Knight, George P.

    2010-01-01

    This study examined a stress process model in which stressful life events and association with delinquent peers mediated the relationship of neighborhood disadvantage to Mexican American early adolescents' mental health. The authors also proposed that child gender, child generation, and neighborhood informal social control would moderate the…

  5. The role of parent, teacher, and peer events in maintaining depressive symptoms during early adolescence.

    PubMed

    Herres, Joanna; Kobak, Roger

    2015-02-01

    Negative interpersonal events have been consistently identified as both antecedents and sequalae of adolescent depressive symptoms. However, little is known about the relative contributions of specific domains of interpersonal events (parents, peers or teachers) to the maintenance of depressive symptoms during early adolescence or whether a lack of positive interpersonal interactions plays a direct role in maintaining depressive symptoms. Further, few studies have examined whether positive interpersonal events moderate associations between negative events and adolescents' depressive symptoms. This study combined stress generation and exposure models to evaluate the contribution of daily events to the maintenance of depressive symptoms in a sample of 132 adolescents (53 % female) followed from ages 13 to 15. Daily phone diaries collected at age 14 assessed adolescents' negative and positive interactions with parents, teachers, and peers in a sample of adolescents from economically disadvantaged families. Negative peer events uniquely accounted for the maintenance of depressive symptoms over the 2 years period. Results did not differ by gender; however, positive parent events buffered the effects of negative parent events for females but not for males. Findings highlight the significance of peer relationships during a period of vulnerability for depressive symptoms.

  6. Detection of rain events in radiological early warning networks with spectro-dosimetric systems

    NASA Astrophysics Data System (ADS)

    Dąbrowski, R.; Dombrowski, H.; Kessler, P.; Röttger, A.; Neumaier, S.

    2017-10-01

    Short-term pronounced increases of the ambient dose equivalent rate, due to rainfall are a well-known phenomenon. Increases in the same order of magnitude or even below may also be caused by a nuclear or radiological event, i.e. by artificial radiation. Hence, it is important to be able to identify natural rain events in dosimetric early warning networks and to distinguish them from radiological events. Novel spectrometric systems based on scintillators may be used to differentiate between the two scenarios, because the measured gamma spectra provide significant nuclide-specific information. This paper describes three simple, automatic methods to check whether an dot H*(10) increase is caused by a rain event or by artificial radiation. These methods were applied to measurements of three spectrometric systems based on CeBr3, LaBr3 and SrI2 scintillation crystals, investigated and tested for their practicability at a free-field reference site of PTB.

  7. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    PubMed Central

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

  8. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics

    PubMed Central

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-01-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae–Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. PMID:27604225

  9. Persistence of carbon release events through the peak of early Eocene global warmth

    NASA Astrophysics Data System (ADS)

    Kirtland Turner, Sandra; Sexton, Philip F.; Charles, Christopher D.; Norris, Richard D.

    2014-10-01

    The Early Eocene Climatic Optimum (53-50 million years ago) was preceded by approximately six million years of progressive global warming. This warming was punctuated by a series of rapid hyperthermal warming events triggered by the release of greenhouse gases. Over these six million years, the carbon isotope record suggests that the events became more frequent but smaller in magnitude. This pattern has been suggested to reflect a thermodynamic threshold for carbon release that was more easily crossed as global temperature rose, combined with a decrease in the size of carbon reservoirs during extremely warm conditions. Here we present a continuous, 4.25-million-year-long record of the stable isotope composition of carbonate sediments from the equatorial Atlantic, spanning the peak of early Eocene global warmth. A composite of this and pre-existing records shows that the carbon isotope excursions that identify the hyperthermals exhibit continuity in magnitude and frequency throughout the approximately 10-million-year period covering the onset, peak and termination of the Early Eocene Climate Optimum. We suggest that the carbon cycle processes behind these events, excluding the largest event, the Palaeocene-Eocene Thermal Maximum (about 56 million years ago), were not exceptional. Instead, we argue that the hyperthermals may reflect orbital forcing of the carbon cycle analogous to the mechanisms proposed to operate in the cooler Oligocene and Miocene.

  10. Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy.

    PubMed

    Kong, Bo; Bruns, Philipp; Behler, Nora A; Chang, Ligong; Schlitter, Anna Melissa; Cao, Jing; Gewies, Andreas; Ruland, Jürgen; Fritzsche, Sina; Valkovskaya, Nataliya; Jian, Ziying; Regel, Ivonne; Raulefs, Susanne; Irmler, Martin; Beckers, Johannes; Friess, Helmut; Erkan, Mert; Mueller, Nikola S; Roth, Susanne; Hackert, Thilo; Esposito, Irene; Theis, Fabian J; Kleeff, Jörg; Michalski, Christoph W

    2018-01-01

    The initial steps of pancreatic regeneration versus carcinogenesis are insufficiently understood. Although a combination of oncogenic Kras and inflammation has been shown to induce malignancy, molecular networks of early carcinogenesis remain poorly defined. We compared early events during inflammation, regeneration and carcinogenesis on histological and transcriptional levels with a high temporal resolution using a well-established mouse model of pancreatitis and of inflammation-accelerated Kras G12D -driven pancreatic ductal adenocarcinoma. Quantitative expression data were analysed and extensively modelled in silico. We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer. These data define a transcriptional signature of early pancreatic carcinogenesis and a molecular network driving formation of preneoplastic lesions, which allows for more targeted biomarker development in order to detect cancer earlier in patients with pancreatitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?

    NASA Astrophysics Data System (ADS)

    Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

    2010-05-01

    The Valanginian period is well known for a positive excursion in marine and terrestrial δ13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive δ13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The δ13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian δ13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian δ13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive δ13C excursion. An increase in nutrient input near the onset of the δ13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western

  12. A Further Extension of the Tahiti-Darwin SOI, Early ENSO Events and Darwin Pressure.

    NASA Astrophysics Data System (ADS)

    Allan, Robert J.; Nicholls, Neville; Jones, Phil D.; Butterworth, Ian J.

    1991-07-01

    An extension of the Tahiti minus Darwin Southern Oscillation Index (SOI) from 1882 back to 1876 is reported following the recovery of early Darwin mean sea-level pressure data spanning the period 1865-81. As a result, we are able to compare, for the first time, the major 1877-78 and 1982-83 ENSO events on the basis of this commonly used index. Early Darwin and Jakarta data are also examined in terms of a measure of the Australian response to documented El Niño and/or ENSO events in 1866, 1868, 1871, 1873, 1874 and 1875.The SOI during the 1877-78 ENSO event has a similar temporal response to that in 1982-83, but the index is slightly weaker than in the recent event. Examination of documentary evidence confirms the severity of the drought conditions that affected the Australian continent during the 1877-78 ENSO, and shows that this response is in line with the wider Indo-Pacific impacts reported in the literature. Earlier El Niño phases in 1868 and 1873 are not resolved distinctly in either the Darwin or Jakarta pressure data. This appears to illustrate that El Niño event histories do not always indicate wider ENSO influences in the Indo-Pacific basin, particularly during weak to moderate phases.

  13. [Influence of early childhood stress exposure and traumatic life events on pain perception].

    PubMed

    Tesarz, J; Gerhardt, A; Eich, W

    2018-06-05

    Adult pain perception is influenced substantially by interactions between mind, body, and social environment during early life. Early stress exposure and traumatic life events induce powerful psychophysical stress reactions that exert multiple neurofunctional processes. This has significant implications for pain perception and pain processing. As part of this review, the complex relationships between traumatic stress experiences and associated psychobiological mechanisms of chronic pain will be discussed. Based on selected studies, psychophysiological findings are presented and possible underlying mechanisms are discussed. The article concludes with a discussion of potential implications for treatment.

  14. Constraints on early events in Martian history as derived from the cratering record

    NASA Technical Reports Server (NTRS)

    Barlow, Nadine G.

    1990-01-01

    Constrains on early events in Martian history are derived using the planet's cratering record. Variations in the shapes of the crater size-frequency distribution curves are interpreted as indicative of the size-frequency distribution of the production populations, thus providing information about the age of the unit relative to the end of the heavy bombardment period. Results from the analysis of craters superposed on heavily cratered units across the Martian surface provide constraints on the hemispheric dichotomy and the early erosional conditions on Mars.

  15. Early Events Leading to the Host Protective Th2 Immune Response to an Intestinal Nematode Parasite

    DTIC Science & Technology

    2005-01-01

    expansion, eosinophilia , and IL-4 production (51;52). Similar down regulations of Th2 associated cytokines were observed using monoclonal antibodies...1. Kightlinger,L.K., Seed,J.R., and Kightlinger,M.B., The epidemiology of Ascaris lumbricoides, Trichuris trichiura, and hookworm in children in...Copyright Statement The author hereby certifies that the use of any copyrighted material in the thesis manuscript entitled: “Early Events

  16. Occurrence of early adverse events after vaccination against influenza at a Brazilian reference center.

    PubMed

    Lopes, Marta Heloísa; Mascheretti, Melissa; Franco, Marilia Miranda; Vasconcelos, Ricardo; Gutierrez, Eliana Battaggia

    2008-02-01

    Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

  17. Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

    PubMed Central

    Watt, Richard G.; Tsakos, Georgios

    2014-01-01

    Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

  18. Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

    PubMed

    Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

    2017-05-18

    Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

    PubMed

    Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

    2008-12-01

    This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

  20. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    PubMed Central

    Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle

    2018-01-01

    This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428

  1. Molecular Evolution of Aminoacyl tRNA Synthetase Proteins in the Early History of Life

    NASA Astrophysics Data System (ADS)

    Fournier, Gregory P.; Andam, Cheryl P.; Alm, Eric J.; Gogarten, J. Peter

    2011-12-01

    Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed.

  2. Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

    PubMed Central

    Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

    2011-01-01

    Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

  3. A Simple "Boxed Molecular Kinetics" Approach To Accelerate Rare Events in the Stochastic Kinetic Master Equation.

    PubMed

    Shannon, Robin; Glowacki, David R

    2018-02-15

    The chemical master equation is a powerful theoretical tool for analyzing the kinetics of complex multiwell potential energy surfaces in a wide range of different domains of chemical kinetics spanning combustion, atmospheric chemistry, gas-surface chemistry, solution phase chemistry, and biochemistry. There are two well-established methodologies for solving the chemical master equation: a stochastic "kinetic Monte Carlo" approach and a matrix-based approach. In principle, the results yielded by both approaches are identical; the decision of which approach is better suited to a particular study depends on the details of the specific system under investigation. In this Article, we present a rigorous method for accelerating stochastic approaches by several orders of magnitude, along with a method for unbiasing the accelerated results to recover the "true" value. The approach we take in this paper is inspired by the so-called "boxed molecular dynamics" (BXD) method, which has previously only been applied to accelerate rare events in molecular dynamics simulations. Here we extend BXD to design a simple algorithmic strategy for accelerating rare events in stochastic kinetic simulations. Tests on a number of systems show that the results obtained using the BXD rare event strategy are in good agreement with unbiased results. To carry out these tests, we have implemented a kinetic Monte Carlo approach in MESMER, which is a cross-platform, open-source, and freely available master equation solver.

  4. Multi-model data fusion to improve an early warning system for hypo-/hyperglycemic events.

    PubMed

    Botwey, Ransford Henry; Daskalaki, Elena; Diem, Peter; Mougiakakou, Stavroula G

    2014-01-01

    Correct predictions of future blood glucose levels in individuals with Type 1 Diabetes (T1D) can be used to provide early warning of upcoming hypo-/hyperglycemic events and thus to improve the patient's safety. To increase prediction accuracy and efficiency, various approaches have been proposed which combine multiple predictors to produce superior results compared to single predictors. Three methods for model fusion are presented and comparatively assessed. Data from 23 T1D subjects under sensor-augmented pump (SAP) therapy were used in two adaptive data-driven models (an autoregressive model with output correction - cARX, and a recurrent neural network - RNN). Data fusion techniques based on i) Dempster-Shafer Evidential Theory (DST), ii) Genetic Algorithms (GA), and iii) Genetic Programming (GP) were used to merge the complimentary performances of the prediction models. The fused output is used in a warning algorithm to issue alarms of upcoming hypo-/hyperglycemic events. The fusion schemes showed improved performance with lower root mean square errors, lower time lags, and higher correlation. In the warning algorithm, median daily false alarms (DFA) of 0.25%, and 100% correct alarms (CA) were obtained for both event types. The detection times (DT) before occurrence of events were 13.0 and 12.1 min respectively for hypo-/hyperglycemic events. Compared to the cARX and RNN models, and a linear fusion of the two, the proposed fusion schemes represents a significant improvement.

  5. Current concepts of molecular events during bovine and porcine spermatozoa capacitation.

    PubMed

    Vadnais, Melissa L; Galantino-Homer, Hannah L; Althouse, Gary C

    2007-01-01

    Spermatozoa are required to undergo the processes of capacitation before they obtain fertilizing ability. The molecular changes of capacitation are still not fully understood. However, it is accepted that capacitation is a sequential process involving numerous physiological changes including destabilization of the plasma membrane, alterations of intracellular ion concentrations and membrane potential, and protein phosphorylation. There are no known morphological changes that occur to the spermatozoon during capacitation. The purpose of this review is to summarize current evidence on the molecular aspects of capacitation both in vivo and in vitro in bovine and porcine spermatozoa. For the purpose of this review, the process of sperm capacitation will encompass maturational events that occur following ejaculation up to binding to the zona pellucida, that triggers acrosomal exocytosis and initiates fertilization.

  6. Hard Sphere Simulation by Event-Driven Molecular Dynamics: Breakthrough, Numerical Difficulty, and Overcoming the issues

    NASA Astrophysics Data System (ADS)

    Isobe, Masaharu

    Hard sphere/disk systems are among the simplest models and have been used to address numerous fundamental problems in the field of statistical physics. The pioneering numerical works on the solid-fluid phase transition based on Monte Carlo (MC) and molecular dynamics (MD) methods published in 1957 represent historical milestones, which have had a significant influence on the development of computer algorithms and novel tools to obtain physical insights. This chapter addresses the works of Alder's breakthrough regarding hard sphere/disk simulation: (i) event-driven molecular dynamics, (ii) long-time tail, (iii) molasses tail, and (iv) two-dimensional melting/crystallization. From a numerical viewpoint, there are serious issues that must be overcome for further breakthrough. Here, we present a brief review of recent progress in this area.

  7. Iterative Calibration: A Novel Approach for Calibrating the Molecular Clock Using Complex Geological Events.

    PubMed

    Loeza-Quintana, Tzitziki; Adamowicz, Sarah J

    2018-02-01

    During the past 50 years, the molecular clock has become one of the main tools for providing a time scale for the history of life. In the era of robust molecular evolutionary analysis, clock calibration is still one of the most basic steps needing attention. When fossil records are limited, well-dated geological events are the main resource for calibration. However, biogeographic calibrations have often been used in a simplistic manner, for example assuming simultaneous vicariant divergence of multiple sister lineages. Here, we propose a novel iterative calibration approach to define the most appropriate calibration date by seeking congruence between the dates assigned to multiple allopatric divergences and the geological history. Exploring patterns of molecular divergence in 16 trans-Bering sister clades of echinoderms, we demonstrate that the iterative calibration is predominantly advantageous when using complex geological or climatological events-such as the opening/reclosure of the Bering Strait-providing a powerful tool for clock dating that can be applied to other biogeographic calibration systems and further taxa. Using Bayesian analysis, we observed that evolutionary rate variability in the COI-5P gene is generally distributed in a clock-like fashion for Northern echinoderms. The results reveal a large range of genetic divergences, consistent with multiple pulses of trans-Bering migrations. A resulting rate of 2.8% pairwise Kimura-2-parameter sequence divergence per million years is suggested for the COI-5P gene in Northern echinoderms. Given that molecular rates may vary across latitudes and taxa, this study provides a new context for dating the evolutionary history of Arctic marine life.

  8. The molecular cloud content of early type galaxies

    NASA Technical Reports Server (NTRS)

    Wiklind, Tommy; Henkel, Christian

    1990-01-01

    A survey of the CO content of early type galaxies led to 24 new detections, mostly lenticular galaxies. The galaxies, which are situated in both the Northern and Southern Hemispheres, were selected as being far-IR luminous compared to their blue luminosity, and situated at distances less than about 50 Mpc (H sub o=100 km/s Mpc(-1). Results for some early galaxies (NGC 404, NGC 3593 and NGC 4369 are given.

  9. Novel molecular events associated with altered steroidogenesis induced by exposure to atrazine in the intact and castrate male rat

    EPA Science Inventory

    Toxicology is increasingly focused on molecular events comprising adverse outcome pathways. Atrazine activates the hypothalamic-pituitary adrenal axis, but relationships to gonadal alterations are unknown. We characterized hormone profiles and adrenal (intact and castrate) and te...

  10. Marine ecosystem resilience during extreme deoxygenation: the Early Jurassic oceanic anoxic event.

    PubMed

    Caswell, Bryony A; Frid, Christopher L J

    2017-01-01

    Global warming during the Early Jurassic, and associated widespread ocean deoxygenation, was comparable in scale with the changes projected for the next century. This study quantifies the impact of severe global environmental change on the biological traits of marine communities that define the ecological roles and functions they deliver. We document centennial-millennial variability in the biological trait composition of Early Jurassic (Toarcian) seafloor communities and examine how this changed during the event using biological traits analysis. Environmental changes preceding the global oceanic anoxic event (OAE) produced an ecological shift leading to stressed benthic palaeocommunities with reduced resilience to the subsequent OAE. Changes in traits and ecological succession coincided with major environmental changes; and were of similar nature and magnitude to those in severely deoxygenated benthic communities today despite the very different timescales. Changes in community composition were linked to local redox conditions whereas changes in populations of opportunists were driven by primary productivity. Throughout most of the OAE substitutions by tolerant taxa conserved the trait composition and hence functioning, but periods of severe deoxygenation caused benthic defaunation that would have resulted in functional collapse. Following the OAE recovery was slow probably because the global nature of the event restricted opportunities for recruitment from outside the basin. Our findings suggest that future systems undergoing deoxygenation may initially show functional resilience, but severe global deoxygenation will impact traits and ecosystem functioning and, by limiting the species pool, will slow recovery rates.

  11. The past and the future of Alzheimer's disease CSF biomarkers-a journey toward validated biochemical tests covering the whole spectrum of molecular events.

    PubMed

    Blennow, Kaj; Zetterberg, Henrik

    2015-01-01

    This paper gives a short review on cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD), from early developments to high-precision validated assays on fully automated lab analyzers. We also discuss developments on novel biomarkers, such as synaptic proteins and Aβ oligomers. Our vision for the future is that assaying a set of biomarkers in a single CSF tube can monitor the whole spectrum of AD molecular pathogenic events. CSF biomarkers will have a central position not only for clinical diagnosis, but also for the understanding of the sequence of molecular events in the pathogenic process underlying AD and as tools to monitor the effects of novel drug candidates targeting these different mechanisms.

  12. Molecular clock of HIV-1 envelope genes under early immune selection

    DOE PAGES

    Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.; ...

    2016-06-01

    Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

  13. Molecular clock of HIV-1 envelope genes under early immune selection

    SciT

    Park, Sung Yong; Love, Tanzy M. T.; Perelson, Alan S.

    Here, the molecular clock hypothesis that genes or proteins evolve at a constant rate is a key tool to reveal phylogenetic relationships among species. Using the molecular clock, we can trace an infection back to transmission using HIV-1 sequences from a single time point. Whether or not a strict molecular clock applies to HIV-1’s early evolution in the presence of immune selection has not yet been fully examined.

  14. Giardia lamblia: Molecular Studies of an Early Branching Eukaryote

    The rapid advance in our understanding of the biology of Giardia lamblia over the last several years is due in part to the complete DNA sequencing of the 11.7 Mb genome of this diplomonad. Insight on the molecular nature of G. lamblia has been gained by searching the genome using query sequences fr...

  15. Insights into the Molecular Events That Regulate Heat-Induced Chilling Tolerance in Citrus Fruits.

    PubMed

    Lafuente, María T; Establés-Ortíz, Beatriz; González-Candelas, Luis

    2017-01-01

    Low non-freezing temperature may cause chilling injury (CI), which is responsible for external quality deterioration in many chilling-sensitive horticultural crops. Exposure of chilling-sensitive citrus cultivars to non-lethal high-temperature conditioning may increase their chilling tolerance. Very little information is available about the molecular events involved in such tolerance. In this work, the molecular events associated with the low temperature tolerance induced by heating Fortune mandarin, which is very sensitive to chilling, for 3 days at 37°C prior to cold storage is presented. A transcriptomic analysis reveals that heat-conditioning has an important impact favoring the repression of genes in cold-stored fruit, and that long-term heat-induced chilling tolerance is an active process that requires activation of transcription factors involved in transcription initiation and of the WRKY family. The analysis also shows that chilling favors degradation processes, which affect lipids and proteins, and that the protective effect of the heat-conditioning treatment is more likely to be related to the repression of the genes involved in lipid degradation than to the modification of fatty acids unsaturation, which affects membrane permeability. Another major factor associated with the beneficial effect of the heat treatment on reducing CI is the regulation of stress-related proteins. Many of the genes that encoded such proteins are involved in secondary metabolism and in oxidative stress-related processes.

  16. Energetic atomic and molecular ions of ionospheric origin observed in distant magnetotail flow-reversal events

    NASA Technical Reports Server (NTRS)

    Christon, S. P.; Gloeckler, G.; Williams, D. J.; Mukai, T.; Mcentire, R. W.; Jacquey, C.; Angelopoulos, V.; Lui, A. T. Y.; Kokubun, S.; Fairfield, D. H.

    1994-01-01

    Energetic atomic (O(+1) and N(+1)) and molecular (O2(+1), NO(+1), and N2(+1)) ions of ionospheric origin were observed in Earth's magnetotail at X approximately -146 R(sub E) during two plasma sheet sunward/tailward flow-reversal events measured by instruments on the GEOTAIL spacecraft. These events were associated with concurrent ground-measured geomagnetic disturbance intensification at auroral-and mid-latitudes (Kp = 7(-)). Energetic ions in the sunward-component and tailward flows were from both the solar wind and ionosphere. Plasma and energetic ions participated in the flows. During tailward flow, ionospheric origin ion abundance ratios at approximately 200-900 km/s in the rest frame were N(+1)/O(+1) = approximately 25-30% and ((O2(+1), NO(+1), and N2(+1))/O(+1) = approximately 1-2%. We argue that tailward flow most likely initiated approximately 80-100 R(sub E) tailward of Earth and molecular ions were in the plasma sheet prior to geomagnetic intensification onset.

  17. Coping with a life event in bipolar disorder: ambulatory measurement, signalling and early treatment.

    PubMed

    Knapen, Stefan E; Riemersma-van der Lek, Rixt F; Haarman, Bartholomeus C M; Schoevers, Robert A

    2016-10-13

    Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old woman with bipolar disorder experiencing a life event while wearing an actigraph to measure sleep-wake parameters. The night after the life event the woman had sleep later and shorter sleep duration. Adequate response of both the woman and the treating psychiatrist resulted in two normal nights with the use of 1 mg lorazepam, possibly preventing further mood disturbances. Ambulatory assessment of the biological rhythm can function as an add-on to regular signalling plans for prevention of episodes in patients with bipolar disorder. More research should be conducted to validate clinical applicability, proper protocols and to understand underlying mechanisms. 2016 BMJ Publishing Group Ltd.

  18. Modeling Tool for Decision Support during Early Days of an Anthrax Event.

    PubMed

    Rainisch, Gabriel; Meltzer, Martin I; Shadomy, Sean; Bower, William A; Hupert, Nathaniel

    2017-01-01

    Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat.

  19. Atmospheric pCO2 reconstructed across five early Eocene global warming events

    NASA Astrophysics Data System (ADS)

    Cui, Ying; Schubert, Brian A.

    2017-11-01

    Multiple short-lived global warming events, known as hyperthermals, occurred during the early Eocene (56-52 Ma). Five of these events - the Paleocene-Eocene Thermal Maximum (PETM or ETM1), H1 (or ETM2), H2, I1, and I2 - are marked by a carbon isotope excursion (CIE) within both marine and terrestrial sediments. The magnitude of CIE, which is a function of the amount and isotopic composition of carbon added to the ocean-atmosphere system, varies significantly between marine versus terrestrial substrates. Here we use the increase in carbon isotope fractionation by C3 land plants in response to increased pCO2 to reconcile this difference and reconstruct a range of background pCO2 and peak pCO2 for each CIE, provided two potential carbon sources: methane hydrate destabilization and permafrost-thawing/organic matter oxidation. Although the uncertainty on each pCO2 estimate using this approach is low (e.g., median uncertainty = + 23% / - 18%), this work highlights the potential for significant systematic bias in the pCO2 estimate resulting from sampling resolution, substrate type, diagenesis, and environmental change. Careful consideration of each of these factors is required especially when applying this approach to a single marine-terrestrial CIE pair. Given these limitations, we provide an upper estimate for background early Eocene pCO2 of 463 +248/-131 ppmv (methane hydrate scenario) to 806 +127/-104 ppmv (permafrost-thawing/organic matter oxidation scenario). These results, which represent the first pCO2 proxy estimates directly tied to the Eocene hyperthermals, demonstrate that early Eocene warmth was supported by background pCO2 less than ∼3.5× preindustrial levels and that pCO2 > 1000 ppmv may have occurred only briefly, during hyperthermal events.

  20. Not Just the 8.2 event: Dynamic Early Holocene Climate in Arctic Canada

    NASA Astrophysics Data System (ADS)

    Axford, Y.; Briner, J. P.; Miller, G. H.; Francis, D. R.

    2006-12-01

    Temperature reconstructions from a lake in the eastern Canadian Arctic indicate that peak warmth in the early Holocene was interrupted by two abrupt, short-lived temperature reversals at ~9.l and ~8.5 ka. Summer temperatures at Lake CF8, Baffin Island (~500 km west of Greenland) are inferred from subfossil midge (Chironomidae) assemblages. Our results indicate that the site, like others on Baffin Island, experienced exceptionally warm summers (almost 5°C warmer than present) through much of the early Holocene, presumably in response to enhanced summer insolation. After 1000 years of very warm, stable climate, warmth was interrupted by two discrete cold reversals at ~9.1 and ~8.5 ka, during which multiple cold-stenothermous midge taxa appeared in the lake and summer temperatures dropped more than 3°C. These two clearly-defined reversals, well beyond the range of background variability, were of similar amplitude and duration, and were separated by several centuries of near-peak warmth. The only Holocene events of comparable amplitude at this site are the rapid onset of Holocene warmth, and the more gradual Neoglacial cooling after 8 ka. Abrupt cooling events over the Baffin region are consistent with model simulations of the impacts of freshwater outbursts into the Labrador Sea, such as the Lake Agassiz outburst flood that occurred ~8.4 ka. That there are two discrete events recorded at this site indicates that the "8.2 event" was not uniquely significant in this region; rather, the period between approximately ~9.2 and 8 ka was characterized by repeated climate fluctuations forced by multiple outburst floods or other mechanisms. Thus global correlations among paleoclimate records need not assume that climate perturbations during this time period necessarily correlate with the draining of Lake Agassiz or the 8.2 ka cooling in central Greenland.

  1. Approximate entropy analysis of event-related potentials in patients with early vascular dementia.

    PubMed

    Xu, Jin; Sheng, Hengsong; Lou, Wutao; Zhao, Songzhen

    2012-06-01

    This study investigated differences in event-related potential (ERP) parameters among early vascular dementia (VD) patients, healthy elder controls (ECs), and young controls (YCs). A visual "oddball" color identification task was performed while individuals' electroencephalograms (EEGs) were recorded. Approximate entropy (ApEn), a nonlinear measure, along with P300 latencies and amplitudes were used to analyze ERP data and compare these three groups. The patients with VD showed more complex ERP waveforms and higher ApEn values than did ECs while performing the visual task. It was further found that patients with VD showed reduced P300 amplitudes and increased latencies. The results indicate that patients with VD have fewer attention resources to devote to processing stimuli, lower speed of stimulus classification, and lower synchrony in their cortical activity during the response period. We suggest that ApEn, as a measure of ERP complexity, is a promising marker for early diagnosis of VD.

  2. Preserving the Past: An Early Interview Improves Delayed Event Memory in Children With Intellectual Disabilities

    PubMed Central

    Brown, Deirdre A; Lewis, Charlie N; Lamb, Michael E

    2015-01-01

    The influence of an early interview on children's (N = 194) later recall of an experienced event was examined in children with mild and moderate intellectual disabilities (CWID; 7–12 years) and typically developing (TD) children matched for chronological (7–12 years) or mental (4–9 years) age. Children previously interviewed were more informative, more accurate, and less suggestible. CWID (mild) recalled as much information as TD mental age matches, and were as accurate as TD chronological age matches. CWID (moderate) recalled less than TD mental age matches but were as accurate. Interviewers should elicit CWID's recall as early as possible and consider developmental level and severity of impairments when evaluating eyewitness testimony. PMID:25876042

  3. Early maritime economy and El Nino events at Quebrada Tacahuay, Peru

    Keefer, D.K.; DeFrance, Susan D.; Moseley, M.E.; Richardson, J. B.; Satterlee, D.R.; Day-Lewis, A.

    1998-01-01

    The archaeological site of Quebrada Tacahuay, Peru, dates to 12,700 to 12,500 calibrated years before the present (10,770 to 10,530 carbon-14 years before the present). It contains some of the oldest evidence of maritime- based economic activity in the New World. Recovered materials include a hearth, lithic cutting tools and flakes, and abundant processed marine fauna, primarily seabirds and fish. Sediments below and above the occupation layer were probably generated by El Nino events, indicating that El Nino was active during the Pleistocene as well as during the early and middle Holocene.

  4. Early Detection of Breast Cancer Using Molecular Beacons

    DTIC Science & Technology

    2008-01-01

    a molecular beacon (MB)-based approach for direct examination of gene expression in viable and fixed cells (2, 3). This objective of proposed study ...can be distinguished from normal cells (dark) (Figure 1) (2, 3, 8). Recently, a class of new fluorescent emitting nanoparticles, semiconductor ...morphological classification. This method may offer a simple and fast procedure to detect biomarker gene expression in clinical samples. Our study results

  5. DynamO: a free O(N) general event-driven molecular dynamics simulator.

    PubMed

    Bannerman, M N; Sargant, R; Lue, L

    2011-11-30

    Molecular dynamics algorithms for systems of particles interacting through discrete or "hard" potentials are fundamentally different to the methods for continuous or "soft" potential systems. Although many software packages have been developed for continuous potential systems, software for discrete potential systems based on event-driven algorithms are relatively scarce and specialized. We present DynamO, a general event-driven simulation package, which displays the optimal O(N) asymptotic scaling of the computational cost with the number of particles N, rather than the O(N) scaling found in most standard algorithms. DynamO provides reference implementations of the best available event-driven algorithms. These techniques allow the rapid simulation of both complex and large (>10(6) particles) systems for long times. The performance of the program is benchmarked for elastic hard sphere systems, homogeneous cooling and sheared inelastic hard spheres, and equilibrium Lennard-Jones fluids. This software and its documentation are distributed under the GNU General Public license and can be freely downloaded from http://marcusbannerman.co.uk/dynamo. Copyright © 2011 Wiley Periodicals, Inc.

  6. Divergent response of the neritic carbonate factory to environmental changes during the Early Bajocian Event

    NASA Astrophysics Data System (ADS)

    Bodin, Stephane; Hönig, Martin; Krencker, Francois-Nicolas; Danisch, Jan; Kabiri, Lahcen

    2017-04-01

    The Early Bajocian witnessed a global environmental perturbation, characterized by faunal and floral turnovers and a positive carbon isotope excursion. In Italy, this environmental perturbation coincided with an eutrophication event and a carbonate crisis, but this has so far not been adequately reported from other settings, leaving doubt about the extent and nature of these phenomena. Here, we are reporting on an extensive neritic carbonate factory demise that occurs in the upper Lower Bajocian of the Central High Atlas of Morocco, more precisely in the upper Propinquans - lower Humphriesianum Zones. This demise coincided with the acme of the global carbon isotope perturbation, recorded by a 3‰ positive carbon isotope excursion in the bulk organic matter of Morocco. Recovery of the neritic carbonate system occurs during the Early to Late Bajocian transition. The duration of the neritic carbonate factory demise was therefore in the order of 1 Myr. Furthermore, we observe that the Lower Bajocian of Morocco is relatively enriched in arenitic siliciclastic deposits, suggesting increased weathering and nutrient levels along the northwestern margin of Africa during the Early Bajocian. However, comparison with neighboring European basins highlights the non-uniqueness and different timing of the response of shallow-water carbonates to the Early Bajocian environmental perturbations, as some regions present no sign of carbonate factory crisis. Hence, we postulate that local factors were important in mediating the response of neritic carbonate factories to this global environmental perturbation. We notably highlight the role of large Early Bajocian sea-level fluctuation as a trigger for carbonate factory change and demise in Morocco. Indeed, in the Central High Atlas Basin, transgressive intervals are seeing the development of a mud-dominated carbonate factory whereas regressive intervals are associated with grain-dominated carbonate factory. We speculate that the

  7. The First Molecular Phylogeny of Strepsiptera (Insecta) Reveals an Early Burst of Molecular Evolution Correlated with the Transition to Endoparasitism

    PubMed Central

    McMahon, Dino P.; Hayward, Alexander; Kathirithamby, Jeyaraney

    2011-01-01

    A comprehensive model of evolution requires an understanding of the relationship between selection at the molecular and phenotypic level. We investigate this in Strepsiptera, an order of endoparasitic insects whose evolutionary biology is poorly studied. We present the first molecular phylogeny of Strepsiptera, and use this as a framework to investigate the association between parasitism and molecular evolution. We find evidence of a significant burst in the rate of molecular evolution in the early history of Strepsiptera. The evolution of morphological traits linked to parasitism is significantly correlated with the pattern in molecular rate. The correlated burst in genotypic-phenotypic evolution precedes the main phase of strepsipteran diversification, which is characterised by the return to a low and even molecular rate, and a period of relative morphological stability. These findings suggest that the transition to endoparasitism led to relaxation of selective constraint in the strepsipteran genome. Our results indicate that a parasitic lifestyle can affect the rate of molecular evolution, although other causal life-history traits correlated with parasitism may also play an important role. PMID:21738621

  8. A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

    PubMed

    Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

    2011-10-01

    In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

  9. The early Toarcian anoxic event: what the beginning and the end of the story are?

    NASA Astrophysics Data System (ADS)

    Mattioli, Emanuela; Plancq, Julien; Raucsik, Béla

    2010-05-01

    The early Toarcian anoxic event: what the beginning and the end of the story are? E. Mattioli (1), J. Plancq (1), and B. Rauksik (2) (1) UMR 5125 PEPS, CNRS, France; Université Lyon 1, Campus de la DOUA, Bâtiment Géode, 69622 Villeurbanne Cedex, France (emanuela.mattioli@univ-lyon1.fr) (2) Department of Earth and Environmental Sciences, University of Pannonia, Veszprém, Hungary The early Toarcian anoxic event (T-OAE) and the associated biotic crisis have received much attention in the last decade. However, the events forewarning the crisis as well as its aftermath are still poorly known. The T-OAE coincides with a prominent carbon isotope negative excursion (T-CIE) that is preceded by an excursion of similar intensity at the Pliensbachian-Toarcian boundary (Hesselbo et al., 2007). The onset of T-CIE occurred some 700 kyr later than the end of the Boundary-CIE (Suan et al., 2008a). This succession of events demonstrates that the T-OAE was a complex suite of environmental perturbations. In this work, we focused on calcareous nannofossil assemblages occurring in the Peniche section (Portugal) during the Boundary-CIE with the aim to understand if calcifying plankton reacted in a similar/different way to the two CIEs. Also, two sections and one borehole located along a W-E transect, along the NW-Tethyan shelf (in the Yorkshire coast, in the E Paris Basin, and in Mecsek Basin, respectively), were investigated to assess which way calcareous nannoplankton recovered after the crisis, and if the recovery was a synchronous event. The production by nannoplankton collapsed during the T-CIE, as demonstrated by the lowest absolute abundance of nannofossils measured in Peniche and other studied sites (Mattioli et al., 2008). Besides this nannofossil abundance decrease, also the size of the incertae sedis Schizosphaerella test was drastically reduced (Suan et al., 2008b). If a similar size decrease is also recorded during the Boundary-CIE, calcareous nannofossil abundances are

  10. The role of impact events play in redistributing and sequestering water on Early Mars

    NASA Astrophysics Data System (ADS)

    Osinski, G.; Tornabene, L. L.

    2017-12-01

    Impact cratering is one of the most fundamental geological process in the Solar System. Several workers have considered the effect that impact events may have had on the climate of Early Mars. The proposed effects range from impact-induced precipitation to the production of runaway stable climates to the impact delivery of climatically active gases. The role of impact events in forming hydrated minerals has been touched upon but remains debated. In this contribution, we focus on the role that impact events may have played in redistributing and sequestering water on Early Mars; a record that may still be preserved in the Noachian crust. It has been previously proposed that the sequestration of significant quantities of water may have occurred within various hydrated minerals, in particular clays, in the martian crust. There is undoubtedly no single origin for clay-bearing rocks on Mars and the purpose of this contribution is not to review all the possible formation mechanisms. What we do propose, however, is that it is theoretically possible for impact events to create all known occurrences of clays on Mars. We show that clays can form within and around impact craters in two main ways: through the solid-state devitrification of hydrous impact melts and/or impact-generated hydrothermal alteration. Neither of these mechanisms requires a warmer or wetter climate scenario on Early Mars. Notwithstanding the original origin of clays, any clays may be widely redistributed over the Martian surface in the ejecta deposits of large impact craters. However, ejecta deposits are much more complex than commonly thought, with evidence in many instances for two different types of ejecta deposits around martian craters. The first is a ballistic ejecta layer that is low-shock, melt-poor and low-temperature; it will likely not induce the formation of new clays through the mechanisms described above, but could redistribute pre-impact clays over 100's and 1000's of km over the martian

  11. Characteristics of long recovery early VLF events observed by the North African AWESOME Network

    NASA Astrophysics Data System (ADS)

    Naitamor, S.; Cohen, M. B.; Cotts, B. R. T.; Ghalila, H.; Alabdoadaim, M. A.; Graf, K.

    2013-08-01

    Lightning strokes are capable of initiating disturbances in the lower ionosphere, whose recoveries persist for many minutes. These events are remotely sensed via monitoring subionospherically propagating very low frequency (VLF) transmitter signals, which are perturbed as they pass through the region above the lightning stroke. In this paper we describe the properties and characteristics of the early VLF signal perturbations, which exhibit long recovery times using subionospheric VLF transmitter data from three identical receivers located at Algiers (Algeria), Tunis (Tunisia), and Sebha (Libya). The results indicate that the observation of long recovery events depends strongly on the modal structure of the signal electromagnetic field and the distance from the disturbed region and the receiver or transmitter locations. Comparison of simultaneously collected data at the three sites indicates that the role of the causative lightning stroke properties (e.g., peak current and polarity), or that of transient luminous events may be much less important. The dominant parameter which determines the duration of the recovery time and amplitude appears to be the modal structure of the subionospheric VLF probe signal at the ionospheric disturbance, where scattering occurs, and the subsequent modal structure that propagates to the receiver location.

  12. Irregularities in Early Seismic Rupture Propagation for Large Events in a Crustal Earthquake Model

    NASA Astrophysics Data System (ADS)

    Lapusta, N.; Rice, J. R.; Rice, J. R.

    2001-12-01

    We study early seismic propagation of model earthquakes in a 2-D model of a vertical strike-slip fault with depth-variable rate and state friction properties. Our model earthquakes are obtained in fully dynamic simulations of sequences of instabilities on a fault subjected to realistically slow tectonic loading (Lapusta et al., JGR, 2000). This work is motivated by results of Ellsworth and Beroza (Science, 1995), who observe that for many earthquakes, far-field velocity seismograms during initial stages of dynamic rupture propagation have irregular fluctuations which constitute a "seismic nucleation phase". In our simulations, we find that such irregularities in velocity seismograms can be caused by two factors: (1) rupture propagation over regions of stress concentrations and (2) partial arrest of rupture in neighboring creeping regions. As rupture approaches a region of stress concentration, it sees increasing background stress and its moment acceleration (to which velocity seismographs in the far field are proportional) increases. After the peak in stress concentration, the rupture sees decreasing background stress and moment acceleration decreases. Hence a fluctuation in moment acceleration is created. If rupture starts sufficiently far from a creeping region, then partial arrest of rupture in the creeping region causes a decrease in moment acceleration. As the other parts of rupture continue to develop, moment acceleration then starts to grow again, and a fluctuation again results. Other factors may cause the irregularities in moment acceleration, e.g., phenomena such as branching and/or intermittent rupture propagation (Poliakov et al., submitted to JGR, 2001) which we have not studied here. Regions of stress concentration are created in our model by arrest of previous smaller events as well as by interactions with creeping regions. One such region is deep in the fault zone, and is caused by the temperature-induced transition from seismogenic to creeping

  13. Early events of citrus greening (Huanglongbing) disease development at the ultrastructural level.

    PubMed

    Folimonova, Svetlana Y; Achor, Diann S

    2010-09-01

    Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus Liberibacter asiaticus'. Understanding of the early events in HLB infection is critical for the development of effective measures to control the disease. In this work, we conducted cytopathological studies by following the development of the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing material under greenhouse conditions to examine the correlation between ultrastructural changes and symptom production, with the main objective of characterizing the early events of infection. Based on our observations, one of the first degenerative changes induced upon invasion of the pathogen appears to be swelling of middle lamella between cell walls surrounding sieve elements. This anatomical aberration was often observed in samples from newly growing flushes in inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage of HLB infection. Development of symptoms and their progression correlated with an increasing degree of microscopic aberrations. Remarkably, the ability to observe the bacterium in the infected tissue also correlated with the degree of the disease progression. Large numbers of bacterial cells were found in phloem sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we did not observe the bacteria in highly symptomatic leaf samples, suggesting a possibility that, at more advanced stages of the disease, a major proportion of 'Ca. L. asiaticus' is present in a nonviable state. We trust that observations reported here advance our understanding of how 'Ca. L. asiaticus' causes disease. Furthermore, they may be an important aid in answering a question: when and where within an infected tree the tissue serves as a better inoculum source for acquisition and transmission of the bacterium by its psyllid vector.

  14. Potential of Breastmilk Analysis to Inform Early Events in Breast Carcinogenesis: Rationale and Considerations

    PubMed Central

    Murphy, Jeanne; Sherman, Mark E.; Browne, Eva P.; Caballero, Ana I.; Punska, Elizabeth C.; Pfeiffer, Ruth M.; Yang, Hannah P.; Lee, Maxwell; Yang, Howard; Gierach, Gretchen L.; Arcaro, Kathleen F.

    2016-01-01

    This review summarizes methods related to the study of human breastmilk in etiologic and biomarkers research. Despite the importance of reproductive factors in breast carcinogenesis, factors that act early in life are difficult to study because young women rarely require breast imaging or biopsy, and analysis of critical circulating factors (e.g. hormones) is often complicated by the requirement to accurately account for menstrual cycle date. Accordingly, novel approaches are needed to understand how events such as pregnancy, breastfeeding, weaning, and post-weaning breast remodeling influence breast cancer risk. Analysis of breastmilk offers opportunities to understand mechanisms related to carcinogenesis in the breast, and to identify risk markers that may inform efforts to identify high-risk women early in the carcinogenic process. In addition, analysis of breastmilk could have value in early detection or diagnosis of breast cancer. In this article we describe the potential for using breastmilk to characterize the microenvironment of the lactating breast with the goal of advancing research on risk assessment, prevention, and detection of breast cancer. PMID:27107568

  15. Age-related differences in event-related potentials for early visual processing of emotional faces.

    PubMed

    Hilimire, Matthew R; Mienaltowski, Andrew; Blanchard-Fields, Fredda; Corballis, Paul M

    2014-07-01

    With advancing age, processing resources are shifted away from negative emotional stimuli and toward positive ones. Here, we explored this 'positivity effect' using event-related potentials (ERPs). Participants identified the presence or absence of a visual probe that appeared over photographs of emotional faces. The ERPs elicited by the onsets of angry, sad, happy and neutral faces were recorded. We examined the frontocentral emotional positivity (FcEP), which is defined as a positive deflection in the waveforms elicited by emotional expressions relative to neutral faces early on in the time course of the ERP. The FcEP is thought to reflect enhanced early processing of emotional expressions. The results show that within the first 130 ms young adults show an FcEP to negative emotional expressions, whereas older adults show an FcEP to positive emotional expressions. These findings provide additional evidence that the age-related positivity effect in emotion processing can be traced to automatic processes that are evident very early in the processing of emotional facial expressions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Molecular changes and signaling events occurring in sperm during epididymal maturation

    PubMed Central

    Gervasi, Maria Gracia; Visconti, Pablo E.

    2017-01-01

    After leaving the testis, sperm have not yet acquired the ability to move progressively and are unable to fertilize oocytes. To become fertilization-competent they must go through an epididymal maturation process in the male, and capacitation in the female tract. Epididymal maturation can be defined as those changes occurring to sperm in the epididymis that render the sperm the ability to capacitate in the female tract. As part of this process, sperm cells undergo a series of biochemical and physiological changes that require incorporation of new molecules derived from the epididymal epithelium, as well as post-translational modifications of endogenous proteins synthesized during spermiogenesis in the testis. This review will focus on epididymal maturation events, with emphasis in recent advances in the understanding of the molecular basis of this process. PMID:28297559

  17. A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation.

    PubMed

    Sood, Siddharth; Haifer, Craig; Yu, Lijia; Pavlovic, Julie; Churilov, Leonid; Gow, Paul J; Jones, Robert M; Angus, Peter W; Visvanathan, Kumar; Testro, Adam G

    2017-04-01

    Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study; 55/75 (73.3%) patients experienced a total of 89 clinical events. Most events occurred within the first month. Low week 1 results were significantly associated with risk of early infection (area under the receiver operating characteristic curve [AUROC], 0.74; P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93; sensitivity, 71.4%; specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77; P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection (P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow individualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487-497 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  18. Ab initio molecular dynamics simulations of low energy recoil events in MgO

    NASA Astrophysics Data System (ADS)

    Petersen, B. A.; Liu, B.; Weber, W. J.; Zhang, Y.

    2017-04-01

    Low-energy recoil events in MgO are studied using ab intio molecular dynamics simulations to reveal the dynamic displacement processes and final defect configurations. Threshold displacement energies, Ed, are obtained for Mg and O along three low-index crystallographic directions, [100], [110], and [111]. The minimum values for Ed are found along the [110] direction consisting of the same element, either Mg or O atoms. Minimum threshold values of 29.5 eV for Mg and 25.5 eV for O, respectively, are suggested from the calculations. For other directions, the threshold energies are considerably higher, 65.5 and 150.0 eV for O along [111] and [100], and 122.5 eV for Mg along both [111] and [100] directions, respectively. These results show that the recoil events in MgO are partial-charge transfer assisted processes where the charge transfer plays an important role. There is a similar trend found in other oxide materials, where the threshold displacement energy correlates linearly with the peak partial-charge transfer, suggesting this behavior might be universal in ceramic oxides.

  19. Ab initio molecular dynamics simulations of low energy recoil events in MgO

    DOE PAGES

    Petersen, B. A.; Liu, B.; Weber, W. J.; ...

    2017-01-11

    In this paper, low-energy recoil events in MgO are studied using ab initio molecular dynamics simulations to reveal the dynamic displacement processes and final defect configurations. Threshold displacement energies, E d, are obtained for Mg and O along three low-index crystallographic directions, [100], [110], and [111]. The minimum values for E d are found along the [110] direction consisting of the same element, either Mg or O atoms. Minimum threshold values of 29.5 eV for Mg and 25.5 eV for O, respectively, are suggested from the calculations. For other directions, the threshold energies are considerably higher, 65.5 and 150.0 eVmore » for O along [111] and [100], and 122.5 eV for Mg along both [111] and [100] directions, respectively. These results show that the recoil events in MgO are partial-charge transfer assisted processes where the charge transfer plays an important role. Finally, there is a similar trend found in other oxide materials, where the threshold displacement energy correlates linearly with the peak partial-charge transfer, suggesting this behavior might be universal in ceramic oxides.« less

  20. Diagnostic and molecular evaluation of three iridovirus-associated salamander mortality events

    Docherty, D.E.; Meteyer, C.U.; Wang, Jingyuan; Mao, J.; Case, S.T.; Chinchar, V.G.

    2003-01-01

    In 1998 viruses were isolated from tiger salamander larvae (Ambystoma tigrinum diaboli and A. tigrinum melanostictum) involved in North Dakota and Utah (USA) mortality events and spotted salamander (A. maculatum) larvae in a third event in Maine (USA). Although sympatric caudates and anurans were present at all three sites only ambystomid larvae appeared to be affected. Mortality at the North Dakota site was in the thousands while at the Utah and Maine sites mortality was in the hundreds. Sick larvae were lethargic and slow moving. They swam in circles with obvious buoyancy problems and were unable to remain upright. On the ventral surface, near the gills and hind limbs, red spots or swollen areas were noted. Necropsy findings included: hemorrhages and ulceration of the skin, subcutaneous and intramuscular edema, swollen and pale livers with multifocal hemorrhage, and distended fluid-filled intestines with areas of hemorrhage. Light microscopy revealed intracytoplasmic inclusions, suggestive of a viral infection, in a variety of organs. Electron microscopy of ultra thin sections of the same tissues revealed iridovirus-like particles within the inclusions. These viruses were isolated from a variety of organs, indicating a systemic infection. Representative viral isolates from the three mortality events were characterized using molecular assays. Characterization confirmed that the viral isolates were iridoviruses and that the two tiger salamander isolates were similar and could be distinguished from the spotted salamander isolate. The spotted salamander isolate was similar to frog virus 3, the type species of the genus Ranavirus, while the tiger salamander isolates were not. These data indicate that different species of salamanders can become infected and die in association with different iridoviruses. Challenge assays are required to determine the fish and amphibian host range of these isolates and to assess the susceptibility of tiger and spotted salamanders to

  1. PASBio: predicate-argument structures for event extraction in molecular biology

    PubMed Central

    Wattarujeekrit, Tuangthong; Shah, Parantu K; Collier, Nigel

    2004-01-01

    Background The exploitation of information extraction (IE), a technology aiming to provide instances of structured representations from free-form text, has been rapidly growing within the molecular biology (MB) research community to keep track of the latest results reported in literature. IE systems have traditionally used shallow syntactic patterns for matching facts in sentences but such approaches appear inadequate to achieve high accuracy in MB event extraction due to complex sentence structure. A consensus in the IE community is emerging on the necessity for exploiting deeper knowledge structures such as through the relations between a verb and its arguments shown by predicate-argument structure (PAS). PAS is of interest as structures typically correspond to events of interest and their participating entities. For this to be realized within IE a key knowledge component is the definition of PAS frames. PAS frames for non-technical domains such as newswire are already being constructed in several projects such as PropBank, VerbNet, and FrameNet. Knowledge from PAS should enable more accurate applications in several areas where sentence understanding is required like machine translation and text summarization. In this article, we explore the need to adapt PAS for the MB domain and specify PAS frames to support IE, as well as outlining the major issues that require consideration in their construction. Results We introduce PASBio by extending a model based on PropBank to the MB domain. The hypothesis we explore is that PAS holds the key for understanding relationships describing the roles of genes and gene products in mediating their biological functions. We chose predicates describing gene expression, molecular interactions and signal transduction events with the aim of covering a number of research areas in MB. Analysis was performed on sentences containing a set of verbal predicates from MEDLINE and full text journals. Results confirm the necessity to analyze

  2. Knockin' on pollen's door: live cell imaging of early polarization events in germinating Arabidopsis pollen

    PubMed Central

    Vogler, Frank; Konrad, Sebastian S. A.; Sprunck, Stefanie

    2015-01-01

    Pollen tubes are an excellent system for studying the cellular dynamics and complex signaling pathways that coordinate polarized tip growth. Although several signaling mechanisms acting in the tip-growing pollen tube have been described, our knowledge on the subcellular and molecular events during pollen germination and growth site selection at the pollen plasma membrane is rather scarce. To simultaneously track germinating pollen from up to 12 genetically different plants we developed an inexpensive and easy mounting technique, suitable for every standard microscope setup. We performed high magnification live-cell imaging during Arabidopsis pollen activation, germination, and the establishment of pollen tube tip growth by using fluorescent marker lines labeling either the pollen cytoplasm, vesicles, the actin cytoskeleton or the sperm cell nuclei and membranes. Our studies revealed distinctive vesicle and F-actin polarization during pollen activation and characteristic growth kinetics during pollen germination and pollen tube formation. Initially, the germinating Arabidopsis pollen tube grows slowly and forms a uniform roundish bulge, followed by a transition phase with vesicles heavily accumulating at the growth site before switching to rapid tip growth. Furthermore, we found the two sperm cells to be transported into the pollen tube after the phase of rapid tip growth has been initiated. The method presented here is suitable to quantitatively study subcellular events during Arabidopsis pollen germination and growth, and for the detailed analysis of pollen mutants with respect to pollen polarization, bulging, or growth site selection at the pollen plasma membrane. PMID:25954283

  3. Dynamic crystallography reveals early signalling events in ultraviolet photoreceptor UVR8

    DOE PAGES

    Zeng, Xiaoli; Ren, Zhong; Wu, Qi; ...

    2015-01-08

    Arabidopsis thaliana UVR8 (AtUVR8) is a long-sought-after photoreceptor that undergoes dimer dissociation in response to UV-B light. Crystallographic and mutational studies have identified two crucial tryptophan residues for UV-B responses in AtUVR8. However, the mechanism of UV-B perception and structural events leading up to dimer dissociation remain elusive at the molecular level. We applied dynamic crystallography to capture light-induced structural events in photoactive AtUVR8 crystals. Here we report two intermediate structures at 1.67Å resolution. At the epicenter of UV-B signaling, concerted motions associated with Trp285/Trp233 lead to ejection of a water molecule, which weakens an intricate network of hydrogen bondsmore » and salt bridges at the dimer interface. Partial opening of the β-propeller structure due to thermal relaxation of conformational strains originating in the epicenter further disrupts the dimer interface and leads to dimer dissociation. Ultimately, these dynamic crystallographic observations provide structural insights into the photo-perception and signaling mechanism of UVR8.« less

  4. The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo

    PubMed Central

    Karazisis, Dimitrios; Ballo, Ahmed M; Petronis, Sarunas; Agheli, Hossein; Emanuelsson, Lena; Thomsen, Peter; Omar, Omar

    2016-01-01

    Purpose Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79±6 nm), and distribution (31±2 particles/µm2). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-α, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-α) and

  5. Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

    PubMed

    van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

    2009-01-01

    BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care.

  6. Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice

    PubMed Central

    Hogan, Chad H.; Oldenburg, Darby G.; Kara, Mehmet

    2018-01-01

    Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host. PMID:29390024

  7. Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice.

    PubMed

    Van Skike, Nick D; Minkah, Nana K; Hogan, Chad H; Wu, Gary; Benziger, Peter T; Oldenburg, Darby G; Kara, Mehmet; Kim-Holzapfel, Deborah M; White, Douglas W; Tibbetts, Scott A; French, Jarrod B; Krug, Laurie T

    2018-02-01

    Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host.

  8. Breast cancer and psychosocial factors: early stressful life events, social support, and well-being.

    PubMed

    Ginzburg, Karni; Wrensch, Margaret; Rice, Terri; Farren, Georgianna; Spiegel, David

    2008-01-01

    The allostasis theory postulates that stress causes the body to activate physiologic systems in order to maintain stability. The authors sought to examine the relationship between earlier stress and later development of breast cancer (BC). Authors correlated discrete and interactive relationships of stressful life events, social support, and well-being during childhood and adolescence with the occurrence of BC in adulthood among 300 women with primary BC and 305 matched control subjects. BC patients and control subjects reported similar childhood experiences. Yet, although childhood stressful life events were associated with reports of less family support and well being among the controls, those in the BC group who experienced high stress in early childhood actually expressed higher levels of family support and well-being than did those who had experienced lower levels of stress. These findings may reflect a tendency toward a repressive coping style among the BC group, which may be either a risk factor for the disease or a result of having it.

  9. New Early Jurassic Tetrapod Assemblages Constrain Triassic-Jurassic Tetrapod Extinction Event

    NASA Astrophysics Data System (ADS)

    Olsen, P. E.; Shubin, N. H.; Anders, M. H.

    1987-08-01

    The discovery of the first definitively correlated earliest Jurassic (200 million years before present) tetrapod assemblage (Fundy basin, Newark Supergroup, Nova Scotia) allows reevaluation of the duration of the Triassic-Jurassic tetrapod extinction event. Present are tritheledont and mammal-like reptiles, prosauropod, theropod, and ornithischian dinosaurs, protosuchian and sphenosuchian crocodylomorphs, sphenodontids, and hybodont, semionotid, and palaeonisciform fishes. All of the families are known from Late Triassic and Jurassic strata from elsewhere; however, pollen and spore, radiometric, and geochemical correlation indicate an early Hettangian age for these assemblages. Because all ``typical Triassic'' forms are absent from these assemblages, most Triassic-Jurassic tetrapod extinctions occurred before this time and without the introduction of new families. As was previously suggested by studies of marine invertebrates, this pattern is consistent with a global extinction event at the Triassic-Jurassic boundary. The Manicouagan impact structure of Quebec provides dates broadly compatible with the Triassic-Jurassic boundary and, following the impact theory of mass extinctions, may be implicated in the cause.

  10. Excessive Heat Events and National Security: Building Resilience based on Early Warning Systems

    NASA Astrophysics Data System (ADS)

    Vintzileos, A.

    2017-12-01

    Excessive heat events (EHE) affect security of Nations in multiple direct and indirect ways. EHE are the top cause for morbidity/mortality associated to any atmospheric extremes. Higher energy consumption used for cooling can lead to black-outs and social disorder. EHE affect the food supply chain reducing crop yield and increasing the probability of food contamination during delivery and storage. Distribution of goods during EHE can be severely disrupted due to mechanical failure of transportation equipment. EHE during athletic events e.g., marathons, may result to a high number of casualties. Finally, EHE may also affect military planning by e.g. reducing hours of exercise and by altering combat gear. Early warning systems for EHE allow for building resilience. In this paper we first define EHE as at least two consecutive heat days; a heat day is defined as a day with a maximum heat index with probability of occurrence that exceeds a certain threshold. We then use retrospective forecasts performed with a multitude of operational models and show that it is feasible to forecast EHE at forecast lead of week-2 and week-3 over the contiguous United States. We finally introduce an improved definition of EHE based on an intensity index and investigate forecast skill of the predictive system in the tropics and subtropics.

  11. Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event.

    PubMed

    Willoughby, Karen A; McAndrews, Mary Pat; Rovet, Joanne F

    2014-07-01

    Autobiographical memory (AM) is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO) exposed during gestation to insufficient maternal thyroid hormone (TH), a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH), who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Early event-related brain potentials that reflect interest for content information in the media.

    PubMed

    Adachi, Shinobu; Morikawa, Koji; Nittono, Hiroshi

    2012-03-28

    This study investigated the relationship between event-related brain potentials (ERPs) to abridged content information in the media and the subsequent decisions to view the full content. Student volunteers participated in a task that simulated information selection on the basis of the content information. Screenshots of television clips and headlines of news articles on the Web were used as content information for the image condition and the headline condition, respectively. Following presentation of a stimulus containing content information, participants decided whether or not they would view the full content by pressing a select or a reject button. When the select button was pressed, participants were presented with a television clip or a news article. When the reject button was pressed, participants continued on to the next trial, without viewing further. In comparison with rejected stimuli, selected stimuli elicited a larger negative component, with a peak latency of ∼250 ms. The increase in the negative component was independent of the type of visual stimulus. These results suggest that interest toward content information is reflected in early-stage event-related brain potential responses.

  13. A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.

    PubMed

    Thrower, Edwin C; Yuan, Jingzhen; Usmani, Ashar; Liu, Yannan; Jones, Courtney; Minervini, Samantha N; Alexandre, Martine; Pandol, Stephen J; Guha, Sushovan

    2011-01-01

    Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 μM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 μM), carbachol (CCh, 1 mM), or bombesin (10 μM) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 μM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.

  14. Relationship between early and late stages of information processing: an event-related potential study

    PubMed Central

    Portella, Claudio; Machado, Sergio; Arias-Carrión, Oscar; Sack, Alexander T.; Silva, Julio Guilherme; Orsini, Marco; Leite, Marco Antonio Araujo; Silva, Adriana Cardoso; Nardi, Antonio E.; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

    2012-01-01

    The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP) components, including P200, N200, premotor potential (PMP) and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2), N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) and the reaction time (RT). In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) was found. Therefore, we propose that if the secondary processing of visual input (P200 latency) occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency), motor response processing (PMP latency), reorganization of attention and working memory update (P300 latency), and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude). PMID:23355929

  15. Membrane remodeling, an early event in benzo[alpha]pyrene-induced apoptosis

    SciT

    Tekpli, Xavier; Rissel, Mary; Huc, Laurence

    2010-02-15

    Benzo[alpha]pyrene (B[alpha]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[alpha]P-induced apoptotic process. In this study, we report that B[alpha]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[alpha]P exposure. B[alpha]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[alpha]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[alpha]P-related H{submore » 2}O{sub 2} formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[alpha]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[alpha]P altered the composition of plasma membrane microstructures through AhR and H{sub 2}O{sub 2} dependent-regulation of lipid biosynthesis. In F258 cells, the B[alpha]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.« less

  16. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

  17. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    PubMed Central

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  18. Enhanced tocopherol levels during early germination events in Chamaerops humilis var. humilis seeds.

    PubMed

    Siles, Laura; Alegre, Leonor; Tijero, Verónica; Munné-Bosch, Sergi

    2015-10-01

    Most angiosperms accumulate vitamin E in the form of tocopherols in seeds, exerting a protective antioxidant role. However, several palm trees principally accumulate tocotrienols, rather than tocopherols, in seeds, as it occurs in other monocots. To unravel the protective role of either tocopherols or tocotrienols against lipid peroxidation during seed germination in Chamaerops humilis var. humilis; seed viability, natural and induced germination capacity, seed water content, malondialdehyde levels (as an indicator of the extent of lipid peroxidation) and vitamin E levels (including both tocopherols and tocotrienols) were examined at various germination phases in a simulated, natural seed bank. At the very early stages of germination (operculum removal), malondialdehyde levels increased 2.8-fold, to decrease later up to 74%, thus indicating a transient lipid peroxidation at early stages of germination. Tocopherol levels were absent in quiescent seeds and did not increase during operculum removal, but increased later presumably dampening malondialdehyde accumulation. Thereafter, tocopherols continued increasing, while lipid peroxidation levels decreased. By contrast, tocotrienols levels remained constant or even decreased as germination progressed, showing no correlation with lipid peroxidation levels. We hypothesize that despite their high tocotrienol content, seeds synthesize tocopherols during germination to protect lipids from peroxidation events. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Early spring, severe frost events, and drought induce rapid carbon loss in high elevation meadows.

    PubMed

    Arnold, Chelsea; Ghezzehei, Teamrat A; Berhe, Asmeret Asefaw

    2014-01-01

    By the end of the 20th century, the onset of spring in the Sierra Nevada mountain range of California has been occurring on average three weeks earlier than historic records. Superimposed on this trend is an increase in the presence of highly anomalous "extreme" years, where spring arrives either significantly late or early. The timing of the onset of continuous snowpack coupled to the date at which the snowmelt season is initiated play an important role in the development and sustainability of mountain ecosystems. In this study, we assess the impact of extreme winter precipitation variation on aboveground net primary productivity and soil respiration over three years (2011 to 2013). We found that the duration of snow cover, particularly the timing of the onset of a continuous snowpack and presence of early spring frost events contributed to a dramatic change in ecosystem processes. We found an average 100% increase in soil respiration in 2012 and 2103, compared to 2011, and an average 39% decline in aboveground net primary productivity observed over the same time period. The overall growing season length increased by 57 days in 2012 and 61 days in 2013. These results demonstrate the dependency of these keystone ecosystems on a stable climate and indicate that even small changes in climate can potentially alter their resiliency.

  20. Early life events and motor development in childhood and adolescence: a longitudinal study.

    PubMed

    Grace, Tegan; Bulsara, Max; Robinson, Monique; Hands, Beth

    2016-05-01

    Few studies have reported on early life risk factors for motor development outcomes past childhood. Antenatal, perinatal and neonatal factors affecting motor development from late childhood to adolescence were explored. As sex differences in motor development have been previously reported, males and females were examined separately. Participants (n = 2868) were from the Western Australian Pregnancy Cohort Study. Obstetric and neonatal data were examined to determine factors related to motor development at 10 (n = 1622), 14 (n = 1584) and 17 (n = 1221) years. The Neuromuscular Development Index (NDI) of the McCarron Assessment of Motor Development determined offspring motor proficiency. Linear mixed models were developed to allow for changes in motor development over time. Maternal pre-eclampsia, Caesarean section and low income were negatively related to male and female motor outcomes. Lower percentage of optimal birthweight was related to a lower male NDI. Younger maternal age, smoking during early pregnancy and stress during later pregnancy were related to lower female NDIs. Events experienced during pregnancy were related to motor development into late adolescence. Males and females were influenced differently by antenatal and perinatal risk factors; this may be due to sex-specific developmental pathways. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  1. A catastrophic event in Lake Geneva region during the Early Bronze Age?

    NASA Astrophysics Data System (ADS)

    Kremer, Katrina; Yrro, Blé; Marillier, François; Hilbe, Michael; Corboud, Pierre; Rachoud-Schneider, Anne-Marie; Girardclos, Stéphanie

    2013-04-01

    Similarly to steep oceanic continental margins, lake slopes can collapse, producing large sublacustrine landslides and tsunamis. Lake sediments are excellent natural archives of such mass movements and their study allows the reconstructions of these prehistoric events, such as the 563 AD large tsunami over Lake Geneva (Kremer et al, 2012). In Lake Geneva, more than 100 km of high-resolution seismic reflection profiles reveal the late Holocene sedimentation history. The seismic record shows a succession of five large lens-shaped seismic units (A to I), characterized by transparent/chaotic seismic facies with irregular lower boundaries, and interpreted as mass-movement deposits. These units are interbedded with parallel, continuous and strong amplitude reflections, interpreted as the 'background' lake sediments. The oldest dated mass movement (Unit D) covers a surface of 22 km2 in the deep basin, near the city of Lausanne. This deposit has an estimated minimum volume of 0.18 km3 and thus was very likely tsunamigenic (Kremer et al, 2012). A 12-m-long sediment core confirms the seismic interpretation of the mass movement unit and shows that the uppermost 3 m of Unit D are characterized by deformed hemipelagic sediments topped by a 5 cm thick turbidite. This deposit can be classified as a slump whose scar can be interpreted in the seismic data and visualized by multibeam bathymetry. This slump of Lausanne was likely triggered by an earthquake but a spontaneous slope collapse cannot be excluded (Girardclos et al, 2007). Radiocarbon dating of plant macro-remains reveals that the unit D happened during Early Bronze Age. Three other mass wasting deposits occurred during the same time period and may have been triggered during the same event, either by a single earthquake or by a tsunami generated by the slump of Lausanne. Although the exact trigger mechanism of the all these mass-wasting deposits remains unknown, a tsunami likely generated by this event may have affected the

  2. Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice

    PubMed Central

    Nemmar, Abderrahim; Hemeiri, Ahmed Al; Hammadi, Naser Al; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

    2015-01-01

    Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel” tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are

  3. Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice.

    PubMed

    Nemmar, Abderrahim; Al Hemeiri, Ahmed; Al Hammadi, Naser; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

    2015-03-01

    Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early

  4. Depletion of Key Meiotic Genes and Transcriptome-Wide Abiotic Stress Reprogramming Mark Early Preparatory Events Ahead of Apomeiotic Transition

    PubMed Central

    Shah, Jubin N.; Kirioukhova, Olga; Pawar, Pallavi; Tayyab, Muhammad; Mateo, Juan L.; Johnston, Amal J.

    2016-01-01

    Molecular dissection of apomixis – an asexual reproductive mode – is anticipated to solve the enigma of loss of meiotic sex, and to help fixing elite agronomic traits. The Brassicaceae genus Boechera comprises of both sexual and apomictic species, permitting comparative analyses of meiotic circumvention (apomeiosis) and parthenogenesis. Whereas previous studies reported local transcriptome changes during these events, it remained unclear whether global changes associated with hybridization, polyploidy and environmental adaptation that arose during evolution of Boechera might serve as (epi)genetic regulators of early development prior apomictic initiation. To identify these signatures during vegetative stages, we compared seedling RNA-seq transcriptomes of an obligate triploid apomict and a diploid sexual, both isolated from a drought-prone habitat. Uncovered were several genes differentially expressed between sexual and apomictic seedlings, including homologs of meiotic genes ASYNAPTIC 1 (ASY1) and MULTIPOLAR SPINDLE 1 (MPS1) that were down-regulated in apomicts. An intriguing class of apomict-specific deregulated genes included several NAC transcription factors, homologs of which are known to be transcriptionally reprogrammed during abiotic stress in other plants. Deregulation of both meiotic and stress-response genes during seedling stages might possibly be important in preparation for meiotic circumvention, as similar transcriptional alteration was discernible in apomeiotic floral buds too. Furthermore, we noted that the apomict showed better tolerance to osmotic stress in vitro than the sexual, in conjunction with significant upregulation of a subset of NAC genes. In support of the current model that DNA methylation epigenetically regulates stress, ploidy, hybridization and apomixis, we noted that ASY1, MPS1 and NAC019 homologs were deregulated in Boechera seedlings upon DNA demethylation, and ASY1 in particular seems to be repressed by global DNA

  5. The molecular bacterial load assay replaces solid culture for measuring early bactericidal response to antituberculosis treatment.

    PubMed

    Honeyborne, Isobella; Mtafya, Bariki; Phillips, Patrick P J; Hoelscher, Michael; Ntinginya, Elias N; Kohlenberg, Anke; Rachow, Andrea; Rojas-Ponce, Gabriel; McHugh, Timothy D; Heinrich, Norbert

    2014-08-01

    We evaluated the use of the molecular bacterial load (MBL) assay, for measuring viable Mycobacterium tuberculosis in sputum, in comparison with solid agar and liquid culture. The MBL assay provides early information on the rate of decline in bacterial load and has technical advantages over culture in either form. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Distinct Molecular Events during Secretory Granule Biogenesis Revealed by Sensitivities to Brefeldin A

    PubMed Central

    Fernandez, Carlos J.; Haugwitz, Michael; Eaton, Benjamin; Moore, Hsiao-Ping H.

    1997-01-01

    The biogenesis of peptide hormone secretory granules involves a series of sorting, modification, and trafficking steps that initiate in the trans-Golgi and trans-Golgi network (TGN). To investigate their temporal order and interrelationships, we have developed a pulse–chase protocol that follows the synthesis and packaging of a sulfated hormone, pro-opiomelanocortin (POMC). In AtT-20 cells, sulfate is incorporated into POMC predominantly on N-linked endoglycosidase H-resistant oligosaccharides. Subcellular fractionation and pharmacological studies confirm that this sulfation occurs at the trans-Golgi/TGN. Subsequent to sulfation, POMC undergoes a number of molecular events before final storage in dense-core granules. The first step involves the transfer of POMC from the sulfation compartment to a processing compartment (immature secretory granules, ISGs): Inhibiting export of pulse-labeled POMC by brefeldin A (BFA) or a 20°C block prevents its proteolytic conversion to mature adrenocorticotropic hormone. Proteolytic cleavage products were found in vesicular fractions corresponding to ISGs, suggesting that the processing machinery is not appreciably activated until POMC exits the sulfation compartment. A large portion of the labeled hormone is secreted from ISGs as incompletely processed intermediates. This unregulated secretory process occurs only during a limited time window: Granules that have matured for 2 to 3 h exhibit very little unregulated release, as evidenced by the efficient storage of the 15-kDa N-terminal fragment that is generated by a relatively late cleavage event within the maturing granule. The second step of granule biogenesis thus involves two maturation events: proteolytic activation of POMC in ISGs and a transition of the organelle from a state of high unregulated release to one that favors intracellular storage. By using BFA, we show that the two processes occurring in ISGs may be uncoupled: although the unregulated secretion from ISGs is

  7. Distinct molecular events during secretory granule biogenesis revealed by sensitivities to brefeldin A.

    PubMed

    Fernandez, C J; Haugwitz, M; Eaton, B; Moore, H P

    1997-11-01

    The biogenesis of peptide hormone secretory granules involves a series of sorting, modification, and trafficking steps that initiate in the trans-Golgi and trans-Golgi network (TGN). To investigate their temporal order and interrelationships, we have developed a pulse-chase protocol that follows the synthesis and packaging of a sulfated hormone, pro-opiomelanocortin (POMC). In AtT-20 cells, sulfate is incorporated into POMC predominantly on N-linked endoglycosidase H-resistant oligosaccharides. Subcellular fractionation and pharmacological studies confirm that this sulfation occurs at the trans-Golgi/TGN. Subsequent to sulfation, POMC undergoes a number of molecular events before final storage in dense-core granules. The first step involves the transfer of POMC from the sulfation compartment to a processing compartment (immature secretory granules, ISGs): Inhibiting export of pulse-labeled POMC by brefeldin A (BFA) or a 20 degrees C block prevents its proteolytic conversion to mature adrenocorticotropic hormone. Proteolytic cleavage products were found in vesicular fractions corresponding to ISGs, suggesting that the processing machinery is not appreciably activated until POMC exits the sulfation compartment. A large portion of the labeled hormone is secreted from ISGs as incompletely processed intermediates. This unregulated secretory process occurs only during a limited time window: Granules that have matured for 2 to 3 h exhibit very little unregulated release, as evidenced by the efficient storage of the 15-kDa N-terminal fragment that is generated by a relatively late cleavage event within the maturing granule. The second step of granule biogenesis thus involves two maturation events: proteolytic activation of POMC in ISGs and a transition of the organelle from a state of high unregulated release to one that favors intracellular storage. By using BFA, we show that the two processes occurring in ISGs may be uncoupled: although the unregulated secretion from

  8. Complement inhibition decreases early fibrogenic events in the lung of septic baboons.

    PubMed

    Silasi-Mansat, Robert; Zhu, Hua; Georgescu, Constantin; Popescu, Narcis; Keshari, Ravi S; Peer, Glenn; Lupu, Cristina; Taylor, Fletcher B; Pereira, Heloise Anne; Kinasewitz, Gary; Lambris, John D; Lupu, Florea

    2015-11-01

    Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents. We have been suggested that treatment of septic baboons with compstatin, a C3 convertase inhibitor protects against ARDS-induced fibroproliferation. Baboons challenged with 10(9) cfu/kg (LD50) live E. coli by intravenous infusion were treated or not with compstatin at the time of challenge or 5 hrs thereafter. Changes in the fibroproliferative response at 24 hrs post-challenge were analysed at both transcript and protein levels. Gene expression analysis showed that sepsis induced fibrotic responses in the lung as early as 24 hrs post-bacterial challenge. Immunochemical and biochemical analysis revealed enhanced collagen synthesis, induction of profibrotic factors and increased cell recruitment and proliferation. Specific inhibition of complement with compstatin down-regulated sepsis-induced fibrosis genes, including transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinase 1 (TIMP1), various collagens and chemokines responsible for fibrocyte recruitment (e.g. chemokine (C-C motif) ligand 2 (CCL2) and 12 (CCL12)). Compstatin decreased the accumulation of myofibroblasts and proliferating cells, reduced the production of fibrosis mediators (TGF-β, phospho-Smad-2 and CTGF) and inhibited collagen deposition. Our data demonstrate that complement inhibition effectively attenuates collagen deposition and fibrotic responses in the lung after severe sepsis. Inhibiting complement could prove an attractive strategy for preventing sepsis-induced fibrosis of the lung. © 2015 The Authors

  9. Characterizing single isolated radiation-damage events from molecular dynamics via virtual diffraction methods

    DOE PAGES

    Stewart, James A.; Brookman, G.; Price, Patrick Michael; ...

    2018-04-25

    In this study, the evolution and characterization of single-isolated-ion-strikes are investigated by combining atomistic simulations with selected-area electron diffraction (SAED) patterns generated from these simulations. Five molecular dynamics simulations are performed for a single 20 keV primary knock-on atom in bulk crystalline Si. The resulting cascade damage is characterized in two complementary ways. First, the individual cascade events are conventionally quantified through the evolution of the number of defects and the atomic (volumetric) strain associated with these defect structures. These results show that (i) the radiation damage produced is consistent with the Norgett, Robinson, and Torrens model of damage productionmore » and (ii) there is a net positive volumetric strain associated with the cascade structures. Second, virtual SAED patterns are generated for the resulting cascade-damaged structures along several zone axes. The analysis of the corresponding diffraction patterns shows the SAED spots approximately doubling in size, on average, due to broadening induced by the defect structures. Furthermore, the SAED spots are observed to exhibit an average radial outward shift between 0.33% and 0.87% depending on the zone axis. Finally, this characterization approach, as utilized here, is a preliminary investigation in developing methodologies and opportunities to link experimental observations with atomistic simulations to elucidate microstructural damage states.« less

  10. Insights into molecular and metabolic events associated with fruit response to post-harvest fungal pathogens

    PubMed Central

    Alkan, Noam; Fortes, Ana M.

    2015-01-01

    Due to post-harvest losses more than 30% of harvested fruits will not reach the consumers’ plate. Fungal pathogens play a key role in those losses, as they cause most of the fruit rots and the customer complaints. Many of the fungal pathogens are already present in the unripe fruit but remain quiescent during fruit growth until a particular phase of fruit ripening and senescence. The pathogens sense the developmental change and switch into the devastating necrotrophic life style that causes fruit rotting. Colonization of unripe fruit by the fungus initiates defensive responses that limit fungal growth and development. However, during fruit ripening several physiological processes occur that correlate with increased fruit susceptibility. In contrast to plant defenses in unripe fruit, the defense posture of ripe fruit entails a different subset of defense responses that will end with fruit rotting and losses. This review will focus on several aspects of molecular and metabolic events associated with fleshy fruit responses induced by post-harvest fungal pathogens during fruit ripening. PMID:26539204

  11. The Molecular and Cellular Events That Take Place during Craniofacial Distraction Osteogenesis

    PubMed Central

    Rachmiel, Adi

    2014-01-01

    Summary: Gradual bone lengthening using distraction osteogenesis principles is the gold standard for the treatment of hypoplastic facial bones. However, the long treatment time is a major disadvantage of the lengthening procedures. The aim of this study is to review the current literature and summarize the cellular and molecular events occurring during membranous craniofacial distraction osteogenesis. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biological processes that may include differentiation of pluripotential tissue, angiogenesis, osteogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Studies have implicated number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (transforming growth factor-β, bone morphogenetic proteins, insulin-like growth factor-1, and fibroblast growth factor-2) and extracellular matrix proteins (osteonectin, osteopontin) during distraction osteogenesis has been best characterized and discussed. Understanding the biomolecular mechanisms that mediate membranous distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone regeneration that may lead to shorten the treatment duration. PMID:25289295

  12. Characterizing single isolated radiation-damage events from molecular dynamics via virtual diffraction methods

    SciT

    Stewart, James A.; Brookman, G.; Price, Patrick Michael

    In this study, the evolution and characterization of single-isolated-ion-strikes are investigated by combining atomistic simulations with selected-area electron diffraction (SAED) patterns generated from these simulations. Five molecular dynamics simulations are performed for a single 20 keV primary knock-on atom in bulk crystalline Si. The resulting cascade damage is characterized in two complementary ways. First, the individual cascade events are conventionally quantified through the evolution of the number of defects and the atomic (volumetric) strain associated with these defect structures. These results show that (i) the radiation damage produced is consistent with the Norgett, Robinson, and Torrens model of damage productionmore » and (ii) there is a net positive volumetric strain associated with the cascade structures. Second, virtual SAED patterns are generated for the resulting cascade-damaged structures along several zone axes. The analysis of the corresponding diffraction patterns shows the SAED spots approximately doubling in size, on average, due to broadening induced by the defect structures. Furthermore, the SAED spots are observed to exhibit an average radial outward shift between 0.33% and 0.87% depending on the zone axis. Finally, this characterization approach, as utilized here, is a preliminary investigation in developing methodologies and opportunities to link experimental observations with atomistic simulations to elucidate microstructural damage states.« less

  13. Characterizing single isolated radiation-damage events from molecular dynamics via virtual diffraction methods

    NASA Astrophysics Data System (ADS)

    Stewart, J. A.; Brookman, G.; Price, P.; Franco, M.; Ji, W.; Hattar, K.; Dingreville, R.

    2018-04-01

    The evolution and characterization of single-isolated-ion-strikes are investigated by combining atomistic simulations with selected-area electron diffraction (SAED) patterns generated from these simulations. Five molecular dynamics simulations are performed for a single 20 keV primary knock-on atom in bulk crystalline Si. The resulting cascade damage is characterized in two complementary ways. First, the individual cascade events are conventionally quantified through the evolution of the number of defects and the atomic (volumetric) strain associated with these defect structures. These results show that (i) the radiation damage produced is consistent with the Norgett, Robinson, and Torrens model of damage production and (ii) there is a net positive volumetric strain associated with the cascade structures. Second, virtual SAED patterns are generated for the resulting cascade-damaged structures along several zone axes. The analysis of the corresponding diffraction patterns shows the SAED spots approximately doubling in size, on average, due to broadening induced by the defect structures. Furthermore, the SAED spots are observed to exhibit an average radial outward shift between 0.33% and 0.87% depending on the zone axis. This characterization approach, as utilized here, is a preliminary investigation in developing methodologies and opportunities to link experimental observations with atomistic simulations to elucidate microstructural damage states.

  14. Using Wavelet Analysis To Assist in Identification of Significant Events in Molecular Dynamics Simulations.

    PubMed

    Heidari, Zahra; Roe, Daniel R; Galindo-Murillo, Rodrigo; Ghasemi, Jahan B; Cheatham, Thomas E

    2016-07-25

    Long time scale molecular dynamics (MD) simulations of biological systems are becoming increasingly commonplace due to the availability of both large-scale computational resources and significant advances in the underlying simulation methodologies. Therefore, it is useful to investigate and develop data mining and analysis techniques to quickly and efficiently extract the biologically relevant information from the incredible amount of generated data. Wavelet analysis (WA) is a technique that can quickly reveal significant motions during an MD simulation. Here, the application of WA on well-converged long time scale (tens of μs) simulations of a DNA helix is described. We show how WA combined with a simple clustering method can be used to identify both the physical and temporal locations of events with significant motion in MD trajectories. We also show that WA can not only distinguish and quantify the locations and time scales of significant motions, but by changing the maximum time scale of WA a more complete characterization of these motions can be obtained. This allows motions of different time scales to be identified or ignored as desired.

  15. Senescent fibroblasts enhance early skin carcinogenic events via a paracrine MMP-PAR-1 axis.

    PubMed

    Malaquin, Nicolas; Vercamer, Chantal; Bouali, Fatima; Martien, Sébastien; Deruy, Emeric; Wernert, Nicolas; Chwastyniak, Maggy; Pinet, Florence; Abbadie, Corinne; Pourtier, Albin

    2013-01-01

    The incidence of carcinoma increases greatly with aging, but the cellular and molecular mechanisms underlying this correlation are only partly known. It is established that senescent fibroblasts promote the malignant progression of already-transformed cells through secretion of inflammatory mediators. We investigated here whether the senescent fibroblast secretome might have an impact on the very first stages of carcinogenesis. We chose the cultured normal primary human epidermal keratinocyte model, because after these cells reach the senescence plateau, cells with transformed and tumorigenic properties systematically and spontaneously emerge from the plateau. In the presence of medium conditioned by autologous senescent dermal fibroblasts, a higher frequency of post-senescence emergence was observed and the post-senescence emergent cells showed enhanced migratory properties and a more marked epithelial-mesenchymal transition. Using pharmacological inhibitors, siRNAs, and blocking antibodies, we demonstrated that the MMP-1 and MMP-2 matrix metalloproteinases, known to participate in late stages of cancer invasion and metastasis, are responsible for this enhancement of early migratory capacity. We present evidence that MMPs act by activating the protease-activated receptor 1 (PAR-1), whose expression is specifically increased in post-senescence emergent keratinocytes. The physiopathological relevance of these results was tested by analyzing MMP activity and PAR-1 expression in skin sections. Both were higher in skin sections from aged subjects than in ones from young subjects. Altogether, our results suggest that during aging, the dermal and epidermal skin compartments might be activated coordinately for initiation of skin carcinoma, via a paracrine axis in which MMPs secreted by senescent fibroblasts promote very early epithelial-mesenchymal transition of keratinocytes undergoing transformation and oversynthesizing the MMP-activatable receptor PAR-1.

  16. Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

    PubMed Central

    Jayasooriya, Shamanthi; de Silva, Thushan I.; Njie-jobe, Jainaba; Sanyang, Chilel; Leese, Alison M.; Bell, Andrew I.; McAulay, Karen A.; Yanchun, Peng; Long, Heather M.; Dong, Tao; Whittle, Hilton C.; Rickinson, Alan B.; Rowland-Jones, Sarah L.; Hislop, Andrew D.; Flanagan, Katie L.

    2015-01-01

    Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14–18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms. PMID:25816224

  17. Reflections on some early events related to behavior analysis of child development

    PubMed Central

    Bijou, Sidney W.

    1996-01-01

    A series of events related to the early application of behavioral principles to child behavior and development is described. The events began in the 1930s at Columbia University with a solicited letter from John B. Watson suggesting a master's degree thesis problem, and continued through the 1950s and 1960s at the University of Washington. Specifically, these happenings resulted in (a) research demonstrating that Skinner's laboratory method for studying nonhuman organisms could be profitably applied to the laboratory study of young normal children; (b) a demonstration that by successive approximations, a normal child can be operantly conditioned to respond to an arbitrary situation; (c) research showing that the effects of simple schedules of reinforcement obtained with nonhuman organisms could be duplicated in young normal and retarded children; (d) the demonstration that Skinner's operant laboratory method could be adapted to study young children in field situations; (e) research showing that operant principles can be successfully applied to the treatment of a young autistic boy with a serious visual handicap; (f) laboratory studies showing that mothers can be trained to treat their own young children who have behavior problems; (g) an in-home study demonstrating that a mother can treat her own child who has behavior problems; (h) a demonstration that operant principles can be applied effectively to teaching reading, writing, and arithmetic to children with retardation; and (i) publication of a book, Child Development: A Systematic and Empirical Theory, in collaboration with Donald M. Baer, by Prentice Hall in their Century Psychological Series. PMID:22478239

  18. Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I.

    PubMed

    Heppner, Jonathan M; Zaucke, Frank; Clarke, Lorne A

    2015-02-01

    Progressive skeletal and connective tissue disease represents a significant clinical burden in all of the mucopolysaccharidoses. Despite the introduction of enzyme replacement strategies for many of the mucopolysaccharidoses, symptomatology related to bone and joint disease appears to be recalcitrant to current therapies. In order to address these unmet medical needs a clearer understanding of skeletal and connective tissue disease pathogenesis is required. Historically the pathogenesis of the mucopolysaccharidoses has been assumed to directly relate to progressive storage of glycosaminoglycans. It is now apparent for many lysosomal storage disorders that more complex pathogenic mechanisms underlie patients' clinical symptoms. We have used proteomic and genome wide expression studies in the murine mucopolysaccharidosis I model to identify early pathogenic events occurring in micro-dissected growth plate tissue. Studies were conducted using 3 and 5-week-old mice thus representing a time at which no obvious morphological changes of bone or joints have taken place. An unbiased iTRAQ differential proteomic approach was used to identify candidates followed by validation with multiple reaction monitoring mass spectrometry and immunohistochemistry. These studies reveal significant decreases in six key structural and signaling extracellular matrix proteins; biglycan, fibromodulin, PRELP, type I collagen, lactotransferrin, and SERPINF1. Genome-wide expression studies in embryonic day 13.5 limb cartilage and 5 week growth plate cartilage followed by specific gene candidate qPCR studies in the 5week growth plate identified fourteen significantly deregulated mRNAs (Adamts12, Aspn, Chad, Col2a1, Col9a1, Hapln4, Lum, Matn1, Mmp3, Ogn, Omd, P4ha2, Prelp, and Rab32). The involvement of biglycan, PRELP and fibromodulin; all members of the small leucine repeat proteoglycan family is intriguing, as this protein family is implicated in the pathogenesis of late onset osteoarthritis

  19. Imaging of early acceleration phase of the 2013-2014 Boso slow slip event

    NASA Astrophysics Data System (ADS)

    Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.

    2014-12-01

    Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip event (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in early December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from early to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. Early slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the

  20. The Early Toarcian Oceanic Anoxic Event: A Southern Hemisphere record from Chile

    NASA Astrophysics Data System (ADS)

    Fantasia, Alicia; Föllmi, Karl B.; Adatte, Thierry; Spangenberg, Jorge E.; Bernárdez, Enrique; Mattioli, Emanuela

    2016-04-01

    The Early Toarcian was marked by important environmental changes, marine oxygen deficiency and extensive organic-rich sediment deposition (T-OAE; ˜182 Ma, Early Jurassic). The T-OAE coincides with a marked negative carbon isotope excursion (CIE) recorded in marine carbonate, and marine and terrestrial organic carbon. This is commonly attributed to the massive release of isotopically light carbon to the atmospheric and oceanic reservoirs derived from the destabilization of methane hydrates from marine sediments and/or the emissions of thermogenic methane from the eruption of the Karoo-Ferrar LIP (e.g., Hesselbo et al., 2000; Kemp et al., 2005; Svensen et al., 2007; Mazzini et al., 2010). Moreover, in most documented marine sections, this episode is marked by a generalized crisis in carbonate production and marine invertebrate extinctions (e.g. Jenkyns, 1988; Röhl et al., 2005; Suan et al., 2001). Several studies of the T-OAE have been conducted on sediments in central and northwest Europe, but only few data are available from the Southern Hemisphere, leading to large uncertainty concerning the exact expression of this event in this part of the world. The aims of this study are to characterize the sediments deposited during the Andean equivalents of the tenuicostatum and falciferum European Zones and establish in which way the T-OAE affected this region. In the Early Jurassic, the Andean basin was in a back-arc setting with marine corridors connected to Panthalassa. In this study, we have generated new high-resolution sedimentological, geochemical and mineralogical data from the sections of El Peñon and Quebrada Asiento, located in Chile in the northeastern area of the city of Copiapó, Atacama region. The biostratigraphy of these sections has been studied by von Hillebrandt and Schidt-Effing (1981) and complemented here by a biostratigraphy based on calcareous nannofossils. The sections consist of a succession of marl, limestone and siltstone of Pliensbachian and

  1. Eye coding mechanisms in early human face event-related potentials.

    PubMed

    Rousselet, Guillaume A; Ince, Robin A A; van Rijsbergen, Nicola J; Schyns, Philippe G

    2014-11-10

    In humans, the N170 event-related potential (ERP) is an integrated measure of cortical activity that varies in amplitude and latency across trials. Researchers often conjecture that N170 variations reflect cortical mechanisms of stimulus coding for recognition. Here, to settle the conjecture and understand cortical information processing mechanisms, we unraveled the coding function of N170 latency and amplitude variations in possibly the simplest socially important natural visual task: face detection. On each experimental trial, 16 observers saw face and noise pictures sparsely sampled with small Gaussian apertures. Reverse-correlation methods coupled with information theory revealed that the presence of the eye specifically covaries with behavioral and neural measurements: the left eye strongly modulates reaction times and lateral electrodes represent mainly the presence of the contralateral eye during the rising part of the N170, with maximum sensitivity before the N170 peak. Furthermore, single-trial N170 latencies code more about the presence of the contralateral eye than N170 amplitudes and early latencies are associated with faster reaction times. The absence of these effects in control images that did not contain a face refutes alternative accounts based on retinal biases or allocation of attention to the eye location on the face. We conclude that the rising part of the N170, roughly 120-170 ms post-stimulus, is a critical time-window in human face processing mechanisms, reflecting predominantly, in a face detection task, the encoding of a single feature: the contralateral eye. © 2014 ARVO.

  2. Early Events in Insulin Fibrillization Studied by Time-Lapse Atomic Force Microscopy

    PubMed Central

    Podestà, Alessandro; Tiana, Guido; Milani, Paolo; Manno, Mauro

    2006-01-01

    The importance of understanding the mechanism of protein aggregation into insoluble amyloid fibrils lies not only in its medical consequences, but also in its more basic properties of self-organization. The discovery that a large number of uncorrelated proteins can form, under proper conditions, structurally similar fibrils has suggested that the underlying mechanism is a general feature of polypeptide chains. In this work, we address the early events preceding amyloid fibril formation in solutions of zinc-free human insulin incubated at low pH and high temperature. Here, we show by time-lapse atomic force microscopy that a steady-state distribution of protein oligomers with a quasiexponential tail is reached within a few minutes after heating. This metastable phase lasts for a few hours, until fibrillar aggregates are observable. Although for such complex systems different aggregation mechanisms can occur simultaneously, our results indicate that the prefibrillar phase is mainly controlled by a simple coagulation-evaporation kinetic mechanism, in which concentration acts as a critical parameter. These experimental facts, along with the kinetic model used, suggest a critical role for thermal concentration fluctuations in the process of fibril nucleation. PMID:16239333

  3. Redox signaling is an early event in the pathogenesis of renovascular hypertension.

    PubMed

    Hartono, Stella P; Knudsen, Bruce E; Zubair, Adeel S; Nath, Karl A; Textor, Stephen J; Lerman, Lilach O; Grande, Joseph P

    2013-09-10

    Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3⁺ T cells and F4/80⁺ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

  4. Impact of early and late winter icing events on sub-arctic dwarf shrubs.

    PubMed

    Preece, C; Phoenix, G K

    2014-01-01

    Polar regions are predicted to undergo large increases in winter temperature and an increased frequency of freeze-thaw cycles, which can cause ice layers in the snow pack and ice encasement of vegetation. Early or late winter timing of ice encasement could, however, modify the extent of damage caused to plants. To determine impacts of the date of ice encasement, a novel field experiment was established in sub-arctic Sweden, with icing events simulated in January and March 2008 and 2009. In the subsequent summers, reproduction, phenology, growth and mortality, as well as physiological indicators of leaf damage were measured in the three dominant dwarf shrubs: Vaccinium uliginosum, Vaccinium vitis-idaea and Empetrum nigrum. It was hypothesised that January icing would be more damaging compared to March icing due to the longer duration of ice encasement. Following 2 years of icing, E. nigrum berry production was 83% lower in January-iced plots compared to controls, and V. vitis-idaea electrolyte leakage was increased by 69%. Conversely, electrolyte leakage of E. nigrum was 25% lower and leaf emergence of V. vitis-idaea commenced 11 days earlier in March-iced plots compared to control plots in 2009. There was no effect of icing on any of the other parameters measured, indicating that overall these study species have moderate to high tolerance to ice encasement. Even much longer exposure under the January icing treatment does not clearly increase damage. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  5. A Time Scale for Major Events in Early Mars Crustal Evolution

    NASA Technical Reports Server (NTRS)

    Frey, Herbert V.

    2004-01-01

    The population of visible and buried impact basins > 200 km diameter revealed by high resolution gridded MOLA data and the cumulative frequency curves derived for these pvide a basis for a chronology of major events in early martian history. The relative chronology can be given in terms of N(200) crater retention ages; 'absolute ages' can be assigued using the Hartmann-Neukum (H&N) model chronology. In terms of billions of H&N years, the crustal dichotomy formed by large impact basins at 4.12 +/- 0.08 BYA (N(200) = 3.0-3.2) and the global magnetic field died at about or slightly before the same time (4.15 +/- 0.08 BYA (N(200) = 3.5). In this chronology, the buried lowlands are approx. 120 my younger than the buried highlands, approx. 160 my younger than the highlands overall and approx. 340 my younger than the oldest crater retention surface we see, defined by the largest impact basins.

  6. Fractal analysis of GPS time series for early detection of disastrous seismic events

    NASA Astrophysics Data System (ADS)

    Filatov, Denis M.; Lyubushin, Alexey A.

    2017-03-01

    A new method of fractal analysis of time series for estimating the chaoticity of behaviour of open stochastic dynamical systems is developed. The method is a modification of the conventional detrended fluctuation analysis (DFA) technique. We start from analysing both methods from the physical point of view and demonstrate the difference between them which results in a higher accuracy of the new method compared to the conventional DFA. Then, applying the developed method to estimate the measure of chaoticity of a real dynamical system - the Earth's crust, we reveal that the latter exhibits two distinct mechanisms of transition to a critical state: while the first mechanism has already been known due to numerous studies of other dynamical systems, the second one is new and has not previously been described. Using GPS time series, we demonstrate efficiency of the developed method in identification of critical states of the Earth's crust. Finally we employ the method to solve a practically important task: we show how the developed measure of chaoticity can be used for early detection of disastrous seismic events and provide a detailed discussion of the numerical results, which are shown to be consistent with outcomes of other researches on the topic.

  7. Early Tertiary mammals from North Africa reinforce the molecular Afrotheria clade

    PubMed Central

    Tabuce, Rodolphe; Marivaux, Laurent; Adaci, Mohammed; Bensalah, Mustapha; Hartenberger, Jean-Louis; Mahboubi, Mohammed; Mebrouk, Fateh; Tafforeau, Paul; Jaeger, Jean-Jacques

    2007-01-01

    The phylogenetic pattern and timing of the radiation of mammals, especially the geographical origins of major crown clades, are areas of controversy among molecular biologists, morphologists and palaeontologists. Molecular phylogeneticists have identified an Afrotheria clade, which includes several taxa as different as tenrecs (Tenrecidae), golden moles (Chrysochloridae), elephant-shrews (Macroscelididae), aardvarks (Tubulidentata) and paenungulates (elephants, sea cows and hyracoids). Molecular data also suggest a Cretaceous African origin for Afrotheria within Placentalia followed by a long period of endemic evolution on the Afro-Arabian continent after the mid-Cretaceous Gondwanan breakup (approx. 105–25 Myr ago). However, there was no morphological support for such a natural grouping so far. Here, we report new dental and postcranial evidence of Eocene stem hyrax and macroscelidid from North Africa that, for the first time, provides a congruent phylogenetic view with the molecular Afrotheria clade. These new fossils imply, however, substantial changes regarding the historical biogeography of afrotheres. Their long period of isolation in Africa, as assumed by molecular inferences, is now to be reconsidered inasmuch as Eocene paenungulates and elephant-shrews are here found to be related to some Early Tertiary Euramerican ‘hyopsodontid condylarths’ (archaic hoofed mammals). As a result, stem members of afrotherian clades are not strictly African but also include some Early Paleogene Holarctic mammals. PMID:17329227

  8. Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

    PubMed

    Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

    2018-06-16

    To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P < 0.01), with fewer ophthalmic vascular events (early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P < 0.01), including peripheral retinal nonperfusion (5% vs. 2% per eye, P = 0.50), vitreous hemorrhage (9% vs. 2%, P = 0.20), subretinal hemorrhage (0% vs. 2%, P = 0.99), branch retinal vein occlusion (5% vs. 0%, P = 0.29), choroidal ischemia (14% vs. 4%, P = 0.14), and ophthalmic artery spasm/occlusion (27% vs. 0%, P < 0.01). Events did not correlate to patient age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era

  9. Molecular snapshot of an intracellular freezing event in an Antarctic nematode.

    PubMed

    Thorne, Michael A S; Seybold, Anna; Marshall, Craig; Wharton, David

    2017-04-01

    The Antarctic nematode, Panagrolaimus sp. DAW1 (formerly called Panagrolaimus davidi), is the best documented example of an organism able to survive intracellular ice formation in all of its compartments. Not only is it able to survive such extreme physiological disruption, but it is able to produce progeny once thawed from such a state. In addition, under slower rates, or less extreme degrees, of cooling, its body remains unfrozen and the vapour pressure difference between the supercooled body fluids and the surrounding ice leads to a process termed cryoprotective dehydration. In contrast to a fairly large body of work in building up our molecular understanding of cryoprotective dehydration, no comparable work has been undertaken on intracellular freezing. This paper describes an experiment subjecting cultures of Panagrolaimus sp. DAW1 to a range of temperatures including a rapid descent to -10 °C, in a medium just prior to, and after, freezing. Through deep sequencing of RNA libraries we have gained a snapshot of which genes are highly abundant when P. sp. DAW1 is undergoing an intracellular freezing event. The onset of freezing correlated with a high production of genes involved in cuticle formation and subsequently, after 24 h in a frozen state, protease production. In addition to the mapping of RNA sequencing, we have focused on a select set of genes arising both from the expression profiles, as well as implicated from other cold tolerance studies, to undertake qPCR. Among the most abundantly represented transcripts in the RNA mapping is the zinc-metalloenzyme, neprilysin, which also shows a particularly strong upregulated signal through qPCR once the nematodes have frozen. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.

    PubMed

    Handley, Renee R; Reid, Suzanne J; Brauning, Rudiger; Maclean, Paul; Mears, Emily R; Fourie, Imche; Patassini, Stefano; Cooper, Garth J S; Rudiger, Skye R; McLaughlan, Clive J; Verma, Paul J; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2017-12-26

    The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin ( HTT ) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73 -line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

  11. Surface-mediated molecular events in material-induced blood-plasma coagulation

    NASA Astrophysics Data System (ADS)

    Chatterjee, Kaushik

    Coagulation and thrombosis persist as major impediments associated with the use of blood-contacting medical devices. We are investigating the molecular mechanism underlying material-induced blood-plasma coagulation focusing on the role of the surface as a step towards prospective development of improved hemocompatible biomaterials. A classic observation in hematology is that blood/blood-plasma in contact with clean glass surface clots faster than when in contact with many plastic surfaces. The traditional biochemical theory explaining the underlying molecular mechanism suggests that hydrophilic surfaces, like that of glass, are specific activators of the coagulation cascade because of the negatively-charged groups on the surface. Hydrophobic surfaces are poor procoagulants or essentially "benign" because they lack anionic groups. Further, these negatively-charged surfaces are believed to not only activate blood factor XII (FXII), the key protein in contact activation, but also play a cofactor role in the amplification and propagation reactions that ultimately lead to clot formation. In sharp contrast to the traditional theory, our investigations indicate a need for a paradigm shift in the proposed sequence of contact activation events to incorporate the role of protein adsorption at the material surfaces. These studies have lead to the central hypothesis for this work proposing that protein adsorption to hydrophobic surfaces attenuates the contact activation reactions so that poorly-adsorbent hydrophilic surfaces appear to be stronger procoagulants relative to hydrophobic surfaces. Our preliminary studies measuring the plasma coagulation response of activated FXII (FXIIa) on different model surfaces suggested that the material did not play a cofactor role in the processing of this enzyme dose through the coagulation pathway. Therefore, we focused our efforts on studying the mechanism of initial production of enzyme at the procoagulant surface. Calculations for the

  12. EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

    EPA Science Inventory

    Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.

    Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.

    Environmental exposure to arsenic is a m...

  13. Developing Fluorescence Sensor Systems for Early Detection of Nitrification Events in Chloraminated Drinking Water Distribution Systems

    EPA Science Inventory

    Detection of nitrification events in chloraminated drinking water distribution systems remains an ongoing challenge for many drinking water utilities, including Dallas Water Utilities (DWU) and the City of Houston (CoH). Each year, these utilities experience nitrification events ...

  14. Toward an orbital chronology for the early Aptian Oceanic Anoxic Event (OAE1a, ~ 120 Ma)

    NASA Astrophysics Data System (ADS)

    Li, Yong-Xiang; Bralower, Timothy J.; Montañez, Isabel P.; Osleger, David A.; Arthur, Michael A.; Bice, David M.; Herbert, Timothy D.; Erba, Elisabetta; Premoli Silva, Isabella

    2008-07-01

    The early Aptian Oceanic Anoxic Event (OAE1a, 120 Ma) represents a geologically brief time interval in the mid-Cretaceous greenhouse world that is characterized by increased organic carbon accumulation in marine sediments, sudden biotic changes, and abrupt carbon-isotope excursions indicative of significant perturbations to global carbon cycling. The brevity of these drastic environmental changes (< 10 6 year) and the typically 10 6 year temporal resolution of the available chronologies, however, represent a critical gap in our knowledge of OAE1a. We have conducted a high-resolution investigation of three widely distributed sections, including the Cismon APTICORE in Italy, Santa Rosa Canyon in northeastern Mexico, and Deep Sea Drilling Project (DSDP) Site 398 off the Iberian margin in the North Atlantic Ocean, which represent a range of depositional environments where condensed and moderately expanded OAE1a intervals are recorded. The objectives of this study are to establish orbital chronologies for these sections and to construct a common, high-resolution timescale for OAE1a. Spectral analyses of the closely-spaced (corresponding to ~ 5 to 10 kyr) measurements of calcium carbonate content of the APTICORE, magnetic susceptibility (MS) and anhysteretic remanent magnetization (ARM) of the Santa Rosa samples, and MS, ARM and ARM/IRM, where IRM is isothermal remanent magnetization, of Site 398 samples reveal statistically significant cycles. These cycles exhibit periodicity ratios and modulation patterns similar to those of the mid-Cretaceous orbital cycles, suggesting that orbital variations may have modulated depositional processes. Orbital control allows us to estimate the duration of unique, globally identifiable stages of OAE1a. Although OAE1a had a duration of ~ 1.0 to 1.3 Myr, the initial perturbation represented by the negative carbon-isotope excursion was rapid, lasting for ~ 27-44 kyr. This estimate could serve as a basis for constraining triggering

  15. Shorter Exposures to Harder X-Rays Trigger Early Apoptotic Events in Xenopus laevis Embryos

    PubMed Central

    Dong, JiaJia; Mury, Sean P.; Drahos, Karen E.; Moscovitch, Marko

    2010-01-01

    Background A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. Methodology/Principal Findings We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. Conclusions/Significance Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic

  16. Evaluation of an early warning system for glacial lake outburst flood (GLOF) events in Huaraz, Peru

    NASA Astrophysics Data System (ADS)

    McKinney, D. C.; Somos-Valenzuela, M. A.

    2014-12-01

    People in Cordillera Blanca range in Peru have a long history dealing with natural disasters associated to high mountains; particularly Glacier Lakes Outburst Flood (GLOF). Examples in the Cordillera Blanca vary from a GLOF that occurred in 1941 that killed more than 5000 people in the city of Huaraz to recent events from Lake Artison Baja in 2012 and Lake 513 on 2010, which were not devastating thanks to safety systems previously installed in those lakes. However, glaciers continue melting leaving new lakes or changing the characteristics of lakes that were previously controlled making safety systems obsolete that worked successfully in the past protecting communities downstream. Lake Palcacocha has evolved from being safe after the installation of a safety system in 1970 to an imminent source of GLOF risk due to the expansion that has occurred during the last 40 years increasing from a volume of 500,000 to 17 million m3. In response to this risk the community in Huaraz is planning an Early Warning System (EWS) that will allow the population to mobilize to a safe area in case a GLOF occurs. In this work we present an adaptation of the LifeSIM model to calculate the benefits from such an EWS using 2007 census data and a FLO-2D flood simulation model. The outputs are the number of people in Huaraz that could lose their life due to a GLOF. Our results indicate that without an EWS around 19,773 people could lose their life; whereas, if an EWS is installed the number of victims reduces to 7344. Finally, if mobilization of the affected population is improved the value reduces to 2865. The results show the importance of the EWS as well as informing and training the population to how to react if a GLOF occurs.

  17. Molecular Diagnostics of Copper-Transporting Protein Mutations Allows Early Onset Individual Therapy of Menkes Disease.

    PubMed

    Králík, L; Flachsová, E; Hansíková, H; Saudek, V; Zeman, J; Martásek, P

    2017-01-01

    Menkes disease is a severe X-linked recessive disorder caused by a defect in the ATP7A gene, which encodes a membrane copper-transporting ATPase. Deficient activity of the ATP7A protein results in decreased intestinal absorption of copper, low copper level in serum and defective distribution of copper in tissues. The clinical symptoms are caused by decreased activities of copper-dependent enzymes and include neurodegeneration, connective tissue disorders, arterial changes and hair abnormalities. Without therapy, the disease is fatal in early infancy. Rapid diagnosis of Menkes disease and early start of copper therapy is critical for the effectiveness of treatment. We report a molecular biology-based strategy that allows early diagnosis of copper transport defects and implementation of individual therapies before the full development of pathological symptoms. Low serum copper and decreased activity of copperdependent mitochondrial cytochrome c oxidase in isolated platelets found in three patients indicated a possibility of functional defects in copper-transporting proteins, especially in the ATPA7 protein, a copper- transporting P-type ATPase. Rapid mutational screening of the ATP7A gene using high-resolution melting analysis of DNA indicated presence of mutations in the patients. Molecular investigation for mutations in the ATP7A gene revealed three nonsense mutations: c.2170C>T (p.Gln724Ter); c.3745G>T (p.Glu1249Ter); and c.3862C>T (p.Gln1288Ter). The mutation c.3745G>T (p.Glu1249Ter) has not been identified previously. Molecular analysis of the ATOX1 gene as a possible modulating factor of Menkes disease did not reveal presence of pathogenic mutations. Molecular diagnostics allowed early onset of individual therapies, adequate genetic counselling and prenatal diagnosis in the affected families.

  18. Sildenafil ameliorates right ventricular early molecular derangement during left ventricular pressure overload.

    PubMed

    Imai, Yousuke; Kariya, Taro; Iwakiri, Masaki; Yamada, Yoshitsugu; Takimoto, Eiki

    2018-01-01

    Right ventricular (RV) dysfunction following left ventricular (LV) failure is associated with poor prognosis. RV remodeling is thought initiated by the increase in the afterload of RV due to secondary pulmonary hypertension (PH) to impaired LV function; however, RV molecular changes might occur in earlier stages of the disease. cGMP (cyclic guanosine monophosphate)-phosphodiesterase 5 (PDE5) inhibitors, widely used to treat PH through their pulmonary vasorelaxation properties, have shown direct cardiac benefits, but their impacts on the RV in LV diseases are not fully determined. Here we show that RV molecular alterations occur early in the absence of RV hemodynamic changes during LV pressure-overload and are ameliorated by PDE5 inhibition. Two-day moderate LV pressure-overload (transverse aortic constriction) neither altered RV pressure/ function nor RV weight in mice, while it induced only mild LV hypertrophy. Importantly, pathological molecular features were already induced in the RV free wall myocardium, including up-regulation of gene markers for hypertrophy and inflammation, and activation of extracellular signal-regulated kinase (ERK) and calcineurin. Concomitant PDE5 inhibition (sildenafil) prevented induction of such pathological genes and activation of ERK and calcineurin in the RV as well as in the LV. Importantly, dexamethasone also prevented these RV molecular changes, similarly to sildenafil treatment. These results suggest the contributory role of inflammation to the early pathological interventricular interaction between RV and LV. The current study provides the first evidence for the novel early molecular cross-talk between RV and LV, preceding RV hemodynamic changes in LV disease, and supports the therapeutic strategy of enhancing cGMP signaling pathway to treat heart diseases.

  19. The Early Toarcian Oceanic Anoxic Event and its sedimentary record in Switzerland

    NASA Astrophysics Data System (ADS)

    Fantasia, Alicia; Föllmi, Karl B.; Adatte, Thierry; Spangenberg, Jorge E.; Montero-Serrano, Jean-Carlos

    2015-04-01

    In the Jurassic period, the Early Toarcian Oceanic Anoxic Event (T-OAE), about 183 Ma ago, was a global perturbation of paleoclimatic and paleoenvironmental conditions. This episode was associated with a crisis in marine carbonate accumulation, climate warming, an increase in sea level, ocean acidification, enhanced continental weathering, whereas organic-rich sediments are noticeable for example in the Atlantic and in the Tethys. This episode is associated with a negative carbon excursion, which is recorded both in marine and terrestrial environments. The cause(s) of this environmental crisis remain(s) still controversial. Nevertheless, the development of negative δ13C excursions is commonly interpreted as due to the injection of isotopically-light carbon associated with gas hydrate dissociation, the thermal metamorphism of carbon-rich sediments and input of thermogenic and volcanogenic carbon related to the formation of the Karoo-Ferrar basaltic province in southern Gondwana (Hesselbo et al., 2000, 2007; Beerling et al., 2002; Cohen et al., 2004, 2007; McElwain et al., 2005, Beerling and Brentnall, 2007; Svensen et al., 2007; Hermoso et al., 2009, 2012; Mazzini et al., 2010). Several studies of the T-OAE have been conducted on sediments in central and northwest Europe, but only few data are available concerning the Swiss sedimentary records. Therefore, we focused on two sections in the Jura Plateau (canton Aargau): the Rietheim section (Montero-Serrano et al., submitted) and the Gipf section (current study). A multidisciplinary approach has been chosen and the tools to be used are based on sedimentological observations (sedimentary condensation, etc.), biostratigraphy, mineralogy (bulk-rock composition), facies and microfacies analysis (presence or absence of benthos), clay-mineralogy composition (climatic conditions), major and trace-element analyses (productivity, redox conditions, etc.), phosphorus (trophic levels, anoxia), carbon isotopes and organic

  20. Finding the signal in the noise: Could social media be utilized for early hospital notification of multiple casualty events?

    PubMed Central

    Moore, Sara; Wakam, Glenn; Hubbard, Alan E.; Cohen, Mitchell J.

    2017-01-01

    Introduction Delayed notification and lack of early information hinder timely hospital based activations in large scale multiple casualty events. We hypothesized that Twitter real-time data would produce a unique and reproducible signal within minutes of multiple casualty events and we investigated the timing of the signal compared with other hospital disaster notification mechanisms. Methods Using disaster specific search terms, all relevant tweets from the event to 7 days post-event were analyzed for 5 recent US based multiple casualty events (Boston Bombing [BB], SF Plane Crash [SF], Napa Earthquake [NE], Sandy Hook [SH], and Marysville Shooting [MV]). Quantitative and qualitative analysis of tweet utilization were compared across events. Results Over 3.8 million tweets were analyzed (SH 1.8 m, BB 1.1m, SF 430k, MV 250k, NE 205k). Peak tweets per min ranged from 209–3326. The mean followers per tweeter ranged from 3382–9992 across events. Retweets were tweeted a mean of 82–564 times per event. Tweets occurred very rapidly for all events (<2 mins) and represented 1% of the total event specific tweets in a median of 13 minutes of the first 911 calls. A 200 tweets/min threshold was reached fastest with NE (2 min), BB (7 min), and SF (18 mins). If this threshold was utilized as a signaling mechanism to place local hospitals on standby for possible large scale events, in all case studies, this signal would have preceded patient arrival. Importantly, this threshold for signaling would also have preceded traditional disaster notification mechanisms in SF, NE, and simultaneous with BB and MV. Conclusions Social media data has demonstrated that this mechanism is a powerful, predictable, and potentially important resource for optimizing disaster response. Further investigated is warranted to assess the utility of prospective signally thresholds for hospital based activation. PMID:28982201

  1. Early Verb Learning: How Do Children Learn How to Compare Events?

    PubMed Central

    Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin

    2015-01-01

    An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions, however comparing events is difficult. Two studies test whether children benefit from initially seeing a pair of similar events (‘progressive alignment’) while learning new verbs, and whether this influence changes with age. In Study 1, 2 ½- and 3 ½-year-old children participated in an interactive task. Children who saw a pair of similar events and then varied events were able to extend verbs at test, differing from a control group; children who saw two pairs of varied events did not differ from the control group. In Study 2, events were presented on a monitor. Following the initial pair of events that varied by condition, a Tobii x120 eye tracker recorded 2 ½-, 3 ½- and 4 ½-year-olds’ fixations to specific elements of events (AOIs) during the second pair of events, which were the same across conditions. After seeing the pair of events that were highly similar, 2 ½-year-olds showed significantly longer fixation durations to agents and to affected objects as compared to the all varied condition. At test, 3 ½-year-olds were able to extend the verb, but only in the progressive alignment condition. These results are important because they show children’s visual attention to relevant elements in dynamic events is influenced by their prior comparison experience, and they show that young children benefit from seeing similar events as they learn to compare events to each other. PMID:27092030

  2. Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

    PubMed

    Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

    1999-01-15

    Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P < 0.001) than in paired normal tissue specimens (4.3+/-0.5 vs. 1.8+/-0.1). In 12 papillary and 10 follicular carcinomas, IR content was significantly higher (P < 0.001) than in the adjacent normal thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage

  3. IDENTIFICATION OF EARLY MOLECULAR EVENTS AFTER PEROXISOME PROLIFERATOR EXPOSURE IN THE RODENT LIVER

    EPA Science Inventory

    Peroxisome proliferators (PP) are a large class of structurally diverse chemicals that mediate their effects in the liver mainly through the PP-activated receptor α(PPARα). Development of PP induced hepatocarcinogenesis in mouse liver is known to be dependent on PPARα but do...

  4. Measures of maturation in early fossil hominins: events at the first transition from australopiths to early Homo

    PubMed Central

    Dean, M. Christopher

    2016-01-01

    An important question in palaeoanthropology is whether, among the australopiths and the first fossil hominins attributed to early Homo, there was a shift towards a more prolonged period of growth that can be distinguished from that of the living great apes and whether between the end of weaning and the beginning of puberty there was a slow period of growth as there is in modern humans. Evidence for the pace of growth in early fossil hominins comes from preserved tooth microstructure. A record of incremental growth in enamel and dentine persists, which allows us to reconstruct tooth growth and compare key measures of dental maturation with modern humans and living great apes. Despite their diverse diets and way of life, it is currently difficult to identify any clear differences in the timing of dental development among living great apes, australopiths and the earliest hominins attributed to the genus Homo. There is, however, limited evidence that some early hominins may have attained a greater proportion of their body mass and stature relatively earlier in the growth period than is typical of modern humans today. This article is part of the themed issue ‘Major transitions in human evolution’. PMID:27298465

  5. Early Verb Learning: How Do Children Learn How to Compare Events?

    ERIC Educational Resources Information Center

    Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin P.

    2016-01-01

    An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions; however, comparing events is difficult. In 2 studies, researchers tested whether children benefit from initially seeing a pair of similar events ("progressive alignment") while learning new…

  6. Gender Differences in Early Mother-Child Interactions: Talking about an Imminent Event.

    ERIC Educational Resources Information Center

    Eisenmann, Barbara

    1997-01-01

    Examines maternal modes of organizing an imminent emotional event, a brief separation from the child. Finds that the mothers displayed two ways of structuring the future event, and these different modes were related statistically to the gender of the child. Investigates how the mother directs the child's mental processes by using augments of…

  7. Formaldehyde in Absorption: Tracing Molecular Gas in Early-Type Galaxies

    NASA Astrophysics Data System (ADS)

    Dollhopf, Niklaus M.; Donovan Meyer, Jennifer

    2016-01-01

    Early-Type Galaxies (ETGs) have been long-classified as the red, ellipsoidal branch of the classic Hubble tuning fork diagram of galactic structure. In part with this classification, ETGs are thought to be molecular and atomic gas-poor with little to no recent star formation. However, recent efforts have questioned this ingrained classification. Most notably, the ATLAS3D survey of 260 ETGs within ~40 Mpc found 22% contain CO, a common tracer for molecular gas. The presence of cold molecular gas also implies the possibility for current star formation within these galaxies. Simulations do not accurately predict the recent observations and further studies are necessary to understand the mechanisms of ETGs.CO traces molecular gas starting at densities of ~102 cm-3, which makes it a good tracer of bulk molecular gas, but does little to constrain the possible locations of star formation within the cores of dense molecular gas clouds. Formaldehyde (H2CO) traces molecular gas on the order of ~104 cm-3, providing a further constraint on the location of star-forming gas, while being simple enough to possibly be abundant in gas-poor ETGs. In cold molecular clouds at or above ~104 cm-3 densities, the structure of formaldehyde enables a phenomenon in which rotational transitions have excitation temperatures driven below the temperature of the cosmic microwave background (CMB), ~2.7 K. Because the CMB radiates isotropically, formaldehyde can be observed in absorption, independent of distance, as a tracer of moderately-dense molecular clouds and star formation.This novel observation technique of formaldehyde was incorporated for observations of twelve CO-detected ETGs from the ATLAS3D sample, including NGC 4710 and PGC 8815, to investigate the presence of cold molecular gas, and possible star formation, in ETGs. We present images from the Very Large Array, used in its C-array configuration, of the J = 11,0 - 11,1 transition of formaldehyde towards these sources. We report our

  8. Molecular dynamics simulation of low-energy recoil events in titanate pyrochlores

    SciT

    Dong, Liyuan; Setyawan, Wahyu; Li, Yuhong

    2017-01-01

    Molecular dynamics simulations of low-energy displacements in titanate pyrochlores have been carried out along three main directions, to determineE dfor A, Ti and O, corresponding defect configurations, and defect formation dynamics.

  9. Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

    NASA Astrophysics Data System (ADS)

    Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

    2016-06-01

    Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual

  10. Molecular evidence of keratin and melanosomes in feathers of the Early Cretaceous bird Eoconfuciusornis.

    PubMed

    Pan, Yanhong; Zheng, Wenxia; Moyer, Alison E; O'Connor, Jingmai K; Wang, Min; Zheng, Xiaoting; Wang, Xiaoli; Schroeter, Elena R; Zhou, Zhonghe; Schweitzer, Mary H

    2016-12-06

    Microbodies associated with feathers of both nonavian dinosaurs and early birds were first identified as bacteria but have been reinterpreted as melanosomes. Whereas melanosomes in modern feathers are always surrounded by and embedded in keratin, melanosomes embedded in keratin in fossils has not been demonstrated. Here we provide multiple independent molecular analyses of both microbodies and the associated matrix recovered from feathers of a new specimen of the basal bird Eoconfuciusornis from the Early Cretaceous Jehol Biota of China. Our work represents the oldest ultrastructural and immunological recognition of avian beta-keratin from an Early Cretaceous (∼130-Ma) bird. We apply immunogold to identify protein epitopes at high resolution, by localizing antibody-antigen complexes to specific fossil ultrastructures. Retention of original keratinous proteins in the matrix surrounding electron-opaque microbodies supports their assignment as melanosomes and adds to the criteria employable to distinguish melanosomes from microbial bodies. Our work sheds new light on molecular preservation within normally labile tissues preserved in fossils.

  11. Molecular evidence of keratin and melanosomes in feathers of the Early Cretaceous bird Eoconfuciusornis

    PubMed Central

    Pan, Yanhong; Zheng, Wenxia; Moyer, Alison E.; O’Connor, Jingmai K.; Zheng, Xiaoting; Wang, Xiaoli; Schroeter, Elena R.; Zhou, Zhonghe; Schweitzer, Mary H.

    2016-01-01

    Microbodies associated with feathers of both nonavian dinosaurs and early birds were first identified as bacteria but have been reinterpreted as melanosomes. Whereas melanosomes in modern feathers are always surrounded by and embedded in keratin, melanosomes embedded in keratin in fossils has not been demonstrated. Here we provide multiple independent molecular analyses of both microbodies and the associated matrix recovered from feathers of a new specimen of the basal bird Eoconfuciusornis from the Early Cretaceous Jehol Biota of China. Our work represents the oldest ultrastructural and immunological recognition of avian beta-keratin from an Early Cretaceous (∼130-Ma) bird. We apply immunogold to identify protein epitopes at high resolution, by localizing antibody–antigen complexes to specific fossil ultrastructures. Retention of original keratinous proteins in the matrix surrounding electron-opaque microbodies supports their assignment as melanosomes and adds to the criteria employable to distinguish melanosomes from microbial bodies. Our work sheds new light on molecular preservation within normally labile tissues preserved in fossils. PMID:27872291

  12. Microgravity Effects on the Early Events of Biological Nitrogen Fixation in Medicago Truncatula: Results from the SyNRGE Experiment

    NASA Technical Reports Server (NTRS)

    Stutte, Gary W.; Roberts, Michael

    2012-01-01

    SyNRGE (Symbiotic Nodulation in a Reduced Gravity Environment) was a sortie mission on STS-135 in the Biological Research in Canisters (BRIC) hardware to study the effect of microgravity on a plant-microbe symbiosis resulting in biological nitrogen fixation. Medicago truncatula, a model species for th legume family, was inoculated with its bacterial symbiont, Sinorhizobium meliloti, to observe early biomolecular events associated with infection and nodulation in Petri Dish Fixation Units (PDFU's).

  13. Infection of Brachypodium distachyon by Formae Speciales of Puccinia graminis: Early Infection Events and Host-Pathogen Incompatibility

    PubMed Central

    Figueroa, Melania; Alderman, Stephen; Garvin, David F.; Pfender, William F.

    2013-01-01

    Puccinia graminis causes stem rust, a serious disease of cereals and forage grasses. Important formae speciales of P. graminis and their typical hosts are P. graminis f. sp. tritici (Pg-tr) in wheat and barley, P. graminis f. sp. lolii (Pg-lo) in perennial ryegrass and tall fescue, and P. graminis f. sp. phlei-pratensis (Pg-pp) in timothy grass. Brachypodium distachyon is an emerging genetic model to study fungal disease resistance in cereals and temperate grasses. We characterized the P. graminis-Brachypodium pathosystem to evaluate its potential for investigating incompatibility and non-host resistance to P. graminis. Inoculation of eight Brachypodium inbred lines with Pg-tr, Pg-lo or Pg-pp resulted in sporulating lesions later accompanied by necrosis. Histological analysis of early infection events in one Brachypodium inbred line (Bd1-1) indicated that Pg-lo and Pg-pp were markedly more efficient than Pg-tr at establishing a biotrophic interaction. Formation of appressoria was completed (60–70% of germinated spores) by 12 h post-inoculation (hpi) under dark and wet conditions, and after 4 h of subsequent light exposure fungal penetration structures (penetration peg, substomatal vesicle and primary infection hyphae) had developed. Brachypodium Bd1-1 exhibited pre-haustorial resistance to Pg-tr, i.e. infection usually stopped at appressorial formation. By 68 hpi, only 0.3% and 0.7% of the Pg-tr urediniospores developed haustoria and colonies, respectively. In contrast, development of advanced infection structures by Pg-lo and Pg-pp was significantly more common; however, Brachypodium displayed post-haustorial resistance to these isolates. By 68 hpi the percentage of urediniospores that only develop a haustorium mother cell or haustorium in Pg-lo and Pg-pp reached 8% and 5%, respectively. The formation of colonies reached 14% and 13%, respectively. We conclude that Brachypodium is an apt grass model to study the molecular and genetic components of incompatiblity

  14. Modeling Temporal Processes in Early Spacecraft Design: Application of Discrete-Event Simulations for Darpa's F6 Program

    NASA Technical Reports Server (NTRS)

    Dubos, Gregory F.; Cornford, Steven

    2012-01-01

    While the ability to model the state of a space system over time is essential during spacecraft operations, the use of time-based simulations remains rare in preliminary design. The absence of the time dimension in most traditional early design tools can however become a hurdle when designing complex systems whose development and operations can be disrupted by various events, such as delays or failures. As the value delivered by a space system is highly affected by such events, exploring the trade space for designs that yield the maximum value calls for the explicit modeling of time.This paper discusses the use of discrete-event models to simulate spacecraft development schedule as well as operational scenarios and on-orbit resources in the presence of uncertainty. It illustrates how such simulations can be utilized to support trade studies, through the example of a tool developed for DARPA's F6 program to assist the design of "fractionated spacecraft".

  15. A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

    PubMed

    Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

    2018-04-25

    Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

  16. [Eventful life stories. Members of student fraternities persecuted in Silesia in the early 19th century].

    PubMed

    Schmidt, Walter

    2003-01-01

    This study supplemented by three charts and a list of biographies, is, for the first time, encompassing their life-data, their resumés and even their professional careers as well as political commitments shown by more than 200 Silesian students. They, at the University of Breslau, but also at other German universities, had joined the student fraternities in the 20-ies and early 30-ies of the 19th century and, in consequence, were persecuted by state authorities, notably in Prussia and, in the majority of cases, had been sentenced to prison terms of varying degrees. The first demagogic persecution, which happened in the first half of the twenties, culminating in 1822 in the Breslau Arminen Trail and ending up with the staging of the Youth-Association-Trail in 1826, had implicated about 100 Silesians, with a smaller portion of them - apart from teh three Youth-Association Silesians who were sentenced to five years imprisonment in a fortress - getting away with a relatively short "political fortress imprisonment". Later a considerable part of them made a career in the prussian judicial authority, in the institutions of higher learning, as parish priests, physicians and scientists, whereas any political engagement remained a rare exception. Out of the 137 Silesian members of the student fraternities affected by the second wave of persecution, the overwhelming majority of them being Protestants and originating partly from the middle classes, mostly artisans, and from intellectual background, with about a hundred of them being given essentially higher sentences ranging from six years up to capital punishment and, in the event of reprieves, they had to serve their sentences between six months and four-to-six years in a fortress. The majority of them made a medium-level professional career, never exceeding the medium ranks, as judicial officers, lawyers in state or communal services, parish priests, teachers or physicians. However, from this group of persecuted persons, a

  17. Early Holocene hydroclimate of Baffin Bay: Understanding the interplay between abrupt climate change events and ice sheet fluctuations

    NASA Astrophysics Data System (ADS)

    Corcoran, M. C.; Thomas, E. K.; Castañeda, I. S.; Briner, J. P.

    2017-12-01

    Understanding the causes of ice sheet fluctuations resulting in sea level rise is essential in today's warming climate. In high-latitude ice-sheet-proximal environments such as Baffin Bay, studying both the cause and the rate of ice sheet variability during past abrupt climate change events aids in predictions. Past climate reconstructions are used to understand ice sheet responses to changes in temperature and precipitation. The 9,300 and 8,200 yr BP events are examples of abrupt climate change events in the Baffin Bay region during which there were multiple re-advances of the Greenland and Laurentide ice sheets. High-resolution (decadal-scale) hydroclimate variability near the ice sheet margins during these abrupt climate change events is still unknown. We will generate a decadal-scale record of early Holocene temperature and precipitation using leaf wax hydrogen isotopes, δ2Hwax, from a lake sediment archive on Baffin Island, western Baffin Bay, to better understand abrupt climate change in this region. Shifts in temperature and moisture source result in changes in environmental water δ2H, which in turn is reflected in δ2Hwax, allowing for past hydroclimate to be determined from these compound-specific isotopes. The combination of terrestrial and aquatic δ2Hwax is used to determine soil evaporation and is ultimately used to reconstruct moisture variability. We will compare our results with a previous analysis of δ2Hwax and branched glycerol dialkyl glycerol tetraethers, a temperature and pH proxy, in lake sediment from western Greenland, eastern Baffin Bay, which indicates that cool and dry climate occurred in response to freshwater forcing events in the Labrador Sea. Reconstructing and comparing records on both the western and eastern sides of Baffin Bay during the early Holocene will allow for a spatial understanding of temperature and moisture balance changes during abrupt climate events, aiding in ice sheet modeling and predictions of future sea level

  18. HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events

    PubMed Central

    Buhler, Stéphane; Sanchez-Mazas, Alicia

    2011-01-01

    Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies. Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the

  19. Is epigenetics an important link between early life events and adult disease?

    Epigenetic mechanisms provide one potential explanation for how environmental influences in early life cause long-term changes in chronic disease susceptibility. Whereas epigenetic dysregulation is increasingly implicated in various rare developmental syndromes and cancer, the role of epigenetics in...

  20. Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers.

    PubMed

    Aljakna, Aleksandra; Fracasso, Tony; Sabatasso, Sara

    2018-03-01

    Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.

  1. Slow slip events in the early part of the earthquake cycle

    NASA Astrophysics Data System (ADS)

    Voss, Nicholas K.; Malservisi, Rocco; Dixon, Timothy H.; Protti, Marino

    2017-08-01

    In February 2014 a Mw = 7.0 slow slip event (SSE) took place beneath the Nicoya Peninsula, Costa Rica. This event occurred 17 months after the 5 September 2012, Mw = 7.6, earthquake and along the same subduction zone segment, during a period when significant postseismic deformation was ongoing. A second SSE occurred in the middle of 2015, 21 months after the 2014 SSE and 38 months after the earthquake. The recurrence interval for Nicoya SSEs was unchanged by the earthquake. However, the spatial distribution of slip for the 2014 event differed significantly from previous events, having only deep ( 40 km) slip, compared to previous events, which had both deep and shallow slip. The 2015 SSE marked a return to the combination of deep plus shallow slip of preearthquake SSEs. However, slip magnitude in 2015 was nearly twice as large (Mw = 7.2) as preearthquake SSEs. We employ Coulomb Failure Stress change modeling in order to explain these changes. Stress changes associated with the earthquake and afterslip were highest near the shallow portion of the megathrust, where preearthquake SSEs had significant slip. Lower stress change occurred on the deeper parts of the plate interface, perhaps explaining why the deep ( 40 km) region for SSEs remained unchanged. The large amount of shallow slip in the 2015 SSE may reflect lack of shallow slip in the prior SSE. These observations highlight the variability of aseismic strain release rates throughout the earthquake cycle.Plain Language SummaryWe analyzed small signals in continuous GPS time series. By averaging many GPS measurements over a day, we are able to get very precise measurements of the motion of the ground. We found two <span class="hlt">events</span> in the Nicoya Peninsula of Costa Rica where the GPS changed direction and began moving toward the oceanic trench in the opposite direction of subduction plate motion. These <span class="hlt">events</span> are called slow</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11277825','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11277825"><span>Effects of atorvastatin on <span class="hlt">early</span> recurrent ischemic <span class="hlt">events</span> in acute coronary syndromes: the MIRACL study: a randomized controlled trial.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schwartz, G G; Olsson, A G; Ezekowitz, M D; Ganz, P; Oliver, M F; Waters, D; Zeiher, A; Chaitman, B R; Leslie, S; Stern, T</p> <p>2001-04-04</p> <p>Patients experience the highest rate of death and recurrent ischemic <span class="hlt">events</span> during the <span class="hlt">early</span> period after an acute coronary syndrome, but it is not known whether <span class="hlt">early</span> initiation of treatment with a statin can reduce the occurrence of these <span class="hlt">early</span> <span class="hlt">events</span>. To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic <span class="hlt">events</span>. A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Primary end point <span class="hlt">event</span> defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. A primary end point <span class="hlt">event</span> occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://pubs.er.usgs.gov/publication/70025735','USGSPUBS'); return false;" href="https://pubs.er.usgs.gov/publication/70025735"><span>Middle Devonian to <span class="hlt">Early</span> Carboniferous <span class="hlt">event</span> stratigraphy of Devils Gate and Northern Antelope Range sections, Nevada, U.S.A</span></a></p> <p><a target="_blank" href=""></a></p> <p>Sandberg, C.A.; Morrow, J.R.; Poole, F.G.; Ziegler, W.</p> <p>2003-01-01</p> <p>The classic type section of the Devils Gate Limestone at Devils Gate Pass is situated on the eastern slope of a proto-Antler forebulge that resulted from convergence of the west side of the North American continent with an ocean plate. The original Late Devonian forebulge, the site of which is now located between Devils Gate Pass and the Northern Antelope Range, separated the continental-rise to deep-slope Woodruff basin on the west from the backbulge Pilot basin on the east. Two connections between these basins are recorded by deeper water siltstone beds at Devils Gate; the older one is the lower tongue of the Woodruff Formation, which forms the basal unit of the upper member of the type Devils Gate, and the upper one is the overlying, thin lower member of the Pilot Shale. The forebulge and the backbulge Pilot basin originated during the middle Frasnian (<span class="hlt">early</span> Late Devonian) <span class="hlt">Early</span> hassi Zone, shortly following the Alamo Impact within the punctata Zone in southern Nevada. Evidence of this impact is recorded by coeval and reworked shocked quartz grains in the Northern Antelope Range and possibly by a unique bypass-channel or megatsunami-uprush sandy diamictite within carbonate-platform rocks of the lower member of the type Devils Gate Limestone. Besides the Alamo Impact and three regional <span class="hlt">events</span>, two other important global <span class="hlt">events</span> are recorded in the Devils Gate section. The semichatovae eustatic rise, the maximum Late Devonian flooding <span class="hlt">event</span>, coincides with the sharp lithogenetic change at the discordant boundary above the lower member of the Devils Gate Limestone. Most significantly, the Devils Gate section contains the thickest and most complete rock record in North America across the late Frasnian linguiformis Zone mass extinction <span class="hlt">event</span>. Excellent exposures include not only the extinction shale, but also a younger. <span class="hlt">Early</span> triangularis Zone tsunamite breccia, produced by global collapse of carbonate platforms during a shallowing <span class="hlt">event</span> that continued into the next</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2562610','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2562610"><span>Suicidal Ideation and Its Recurrence in Boys and Men from <span class="hlt">Early</span> Adolescence to <span class="hlt">Early</span> Adulthood: An <span class="hlt">Event</span> History Analysis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kerr, David C. R.; Owen, Lee. D.; Capaldi, Deborah M.</p> <p>2008-01-01</p> <p>Occurrence and recurrences of suicidal ideation (SI) were modeled among boys/men assessed annually from ages 12 to 29 years. Multiple-spell discrete-time <span class="hlt">event</span> history analyses permitted (a) determination of whether risk for SI escalates with prior experiences of SI (Spell effects), (b) while accounting for changes in risk with time (Period effects), and (c) controlling for vulnerability factors. Self-reported SI (presence/absence in past week), depressive symptoms, alcohol/substance use, and antisocial behavior, and official arrest records were collected annually from 205 boys recruited on the basis of community risk for delinquency. Parents’ self-reported psychopathology and SES were collected in childhood. Period effects supported decreasing risk for SI over time. Spell and time-varying, 1-year lagged substance use and depressive symptoms independently predicted increased risk for SI. Models involving SI with intent were explored. Consistent with interpersonal psychological theory, risk for young men’s SI increases with past experience of SI, even with key propensities controlled; however, risk also decays over time. Targeting conditions that confer risk for SI is essential. Preventing and delaying SI occurrence and recurrence may represent independent mechanisms by which prevention efforts operate. PMID:18729614</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29635145','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29635145"><span>Treatment decisions and the impact of adverse <span class="hlt">events</span> before and during extended endocrine therapy in postmenopausal <span class="hlt">early</span> breast cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H</p> <p>2018-05-01</p> <p>Extended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with <span class="hlt">early</span> treatment discontinuation, and how this influenced survival outcome. In the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive <span class="hlt">early</span> breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for <span class="hlt">early</span> treatment discontinuation and the effect of <span class="hlt">early</span> treatment discontinuation on disease-free survival (DFS). Nodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse <span class="hlt">events</span> (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with <span class="hlt">early</span> treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with <span class="hlt">early</span> treatment discontinuation. <span class="hlt">Early</span> treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76-1.37). In this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to <span class="hlt">early</span> treatment discontinuation, with no effect on DFS. Copyright © 2018 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3019846','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3019846"><span>Global Profiling and <span class="hlt">Molecular</span> Characterization of Alternative Splicing <span class="hlt">Events</span> Misregulated in Lung Cancer ▿ †</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Misquitta-Ali, Christine M.; Cheng, Edith; O'Hanlon, Dave; Liu, Ni; McGlade, C. Jane; Tsao, Ming Sound; Blencowe, Benjamin J.</p> <p>2011-01-01</p> <p>Alternative splicing (AS) is a widespread mechanism underlying the generation of proteomic and regulatory complexity. However, which of the myriad of human AS <span class="hlt">events</span> play important roles in disease is largely unknown. To identify frequently occurring AS <span class="hlt">events</span> in lung cancer, we used AS microarray profiling and reverse transcription-PCR (RT-PCR) assays to survey patient-matched normal and adenocarcinoma tumor tissues from the lungs of 29 individuals diagnosed with non-small cell lung cancer (NSCLC). Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients. These <span class="hlt">events</span> affected transcripts from the VEGFA, MACF1, APP, and NUMB genes. Similar AS changes were detected in NUMB and APP transcripts in primary breast and colon tumors. Tumor-associated increases in NUMB exon 9 inclusion correlated with reduced levels of NUMB protein expression and activation of the Notch signaling pathway, an <span class="hlt">event</span> that has been linked to tumorigenesis. Moreover, short hairpin RNA (shRNA) knockdown of NUMB followed by isoform-specific rescue revealed that expression of the exon 9-skipped (nontumor) isoform represses Notch target gene activation whereas expression of the exon 9-included (tumor) isoform lacks this activity and is capable of promoting cell proliferation. The results thus reveal widespread AS changes in NSCLC that impact cell signaling in a manner that likely contributes to tumorigenesis. PMID:21041478</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21041478','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21041478"><span>Global profiling and <span class="hlt">molecular</span> characterization of alternative splicing <span class="hlt">events</span> misregulated in lung cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Misquitta-Ali, Christine M; Cheng, Edith; O'Hanlon, Dave; Liu, Ni; McGlade, C Jane; Tsao, Ming Sound; Blencowe, Benjamin J</p> <p>2011-01-01</p> <p>Alternative splicing (AS) is a widespread mechanism underlying the generation of proteomic and regulatory complexity. However, which of the myriad of human AS <span class="hlt">events</span> play important roles in disease is largely unknown. To identify frequently occurring AS <span class="hlt">events</span> in lung cancer, we used AS microarray profiling and reverse transcription-PCR (RT-PCR) assays to survey patient-matched normal and adenocarcinoma tumor tissues from the lungs of 29 individuals diagnosed with non-small cell lung cancer (NSCLC). Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients. These <span class="hlt">events</span> affected transcripts from the VEGFA, MACF1, APP, and NUMB genes. Similar AS changes were detected in NUMB and APP transcripts in primary breast and colon tumors. Tumor-associated increases in NUMB exon 9 inclusion correlated with reduced levels of NUMB protein expression and activation of the Notch signaling pathway, an <span class="hlt">event</span> that has been linked to tumorigenesis. Moreover, short hairpin RNA (shRNA) knockdown of NUMB followed by isoform-specific rescue revealed that expression of the exon 9-skipped (nontumor) isoform represses Notch target gene activation whereas expression of the exon 9-included (tumor) isoform lacks this activity and is capable of promoting cell proliferation. The results thus reveal widespread AS changes in NSCLC that impact cell signaling in a manner that likely contributes to tumorigenesis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA471730','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA471730"><span>Evaluation of Genomic Instability as an <span class="hlt">Early</span> <span class="hlt">Event</span> in the Progression of Breast Cancer</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2007-04-01</p> <p>theory of marginotomy. J. Theor. Biol. 41:181-90. 8. Watson, J. D. 1972. The origin of concatemeric T7 DNA. Nat. New Biol. 239:197-201. 9. Karlseder...concentrations were measured 6 using the Picogreen® dsDNA quantitation assay (<span class="hlt">Molecular</span> Probes, Eugene, OR) using a λ phage DNA as the standard as</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28398139','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28398139"><span>The association between high on-treatment platelet reactivity and <span class="hlt">early</span> recurrence of ischemic <span class="hlt">events</span> after minor stroke or TIA.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin</p> <p>2017-08-01</p> <p>To evaluate the role of HTPR in predicting <span class="hlt">early</span> recurrence of ischemic <span class="hlt">events</span> in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic <span class="hlt">events</span> was assessed 3 months after onset. The incidence of recurrent ischemic <span class="hlt">events</span> was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic <span class="hlt">events</span>. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic <span class="hlt">events</span> compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic <span class="hlt">events</span>. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic <span class="hlt">events</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28945748','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28945748"><span>Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-<span class="hlt">molecular</span> <span class="hlt">events</span> between insertion sequences.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pilla, Giulia; McVicker, Gareth; Tang, Christoph M</p> <p>2017-09-01</p> <p>Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30 kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segregational killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR). Our aim was to define the <span class="hlt">molecular</span> <span class="hlt">events</span> in Shigella flexneri that cause loss of Type III secretion (T3S), and to examine whether TA systems exert positional effects on pINV. During growth at 37°C, we found that deletions of regions of the plasmid including the PAI lead to the emergence of CR-negative colonies; deletions occur through intra-<span class="hlt">molecular</span> recombination <span class="hlt">events</span> between insertion sequences (ISs) flanking the PAI. Furthermore, by repositioning MvpAT (which belongs to the VapBC family of TA systems) near the PAI, we demonstrate that the location of this TA system alters the rearrangements that lead to loss of T3S, indicating that MvpAT acts both globally (by reducing loss of pINV through PSK) as well as locally (by preventing loss of adjacent sequences). During growth at environmental temperatures, we show for the first time that pINV spontaneously integrates into different sites in the chromosome, and this is mediated by inter-<span class="hlt">molecular</span> <span class="hlt">events</span> involving IS1294. Integration leads to reduced PAI gene expression and impaired secretion through the T3SS, while excision of pINV from the chromosome restores T3SS function. Therefore, pINV integration provides a reversible mechanism for Shigella to circumvent the metabolic burden imposed by pINV. Intra- and inter-<span class="hlt">molecular</span> <span class="hlt">events</span> between ISs, which are abundant in Shigella spp., mediate plasticity of S. flexneri pINV.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23755184','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23755184"><span>Polycyclic aromatic hydrocarbon-induced signaling <span class="hlt">events</span> relevant to inflammation and tumorigenesis in lung cells are dependent on <span class="hlt">molecular</span> structure.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Osgood, Ross S; Upham, Brad L; Hill, Thomas; Helms, Katherine L; Velmurugan, Kalpana; Babica, Pavel; Bauer, Alison K</p> <p>2014-01-01</p> <p>Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental and occupational toxicants, which are a major human health concern in the U.S. and abroad. Previous research has focused on the genotoxic <span class="hlt">events</span> caused by high <span class="hlt">molecular</span> weight PAHs, but not on non-genotoxic <span class="hlt">events</span> elicited by low <span class="hlt">molecular</span> weight PAHs. We used an isomeric pair of low <span class="hlt">molecular</span> weight PAHs, namely 1-Methylanthracene (1-MeA) and 2-Methylanthracene (2-MeA), in which only 1-MeA possessed a bay-like region, and hypothesized that 1-MeA, but not 2-MeA, would affect non-genotoxic endpoints relevant to tumor promotion in murine C10 lung cells, a non-tumorigenic type II alveolar pneumocyte and progenitor cell type of lung adenocarcinoma. The non-genotoxic endpoints assessed were dysregulation of gap junction intercellular communication function and changes in the major pulmonary connexin protein, connexin 43, using fluorescent redistribution and immunoblots, activation of mitogen activated protein kinases (MAPK) using phosphospecific MAPK antibodies for immunoblots, and induction of inflammatory genes using quantitative RT-PCR. 2-MeA had no effect on any of the endpoints, but 1-MeA dysregulated gap junctional communication in a dose and time dependent manner, reduced connexin 43 protein expression, and altered membrane localization. 1-MeA also activated ERK1/2 and p38 MAP kinases. Inflammatory genes, such as cyclooxygenase 2, and chemokine ligand 2 (macrophage chemoattractant 2), were also upregulated in response to 1-MeA only. These results indicate a possible structure-activity relationship of these low <span class="hlt">molecular</span> weight PAHs relevant to non-genotoxic endpoints of the promoting aspects of cancer. Therefore, our novel findings may improve the ability to predict outcomes for future studies with additional toxicants and mixtures, identify novel targets for biomarkers and chemotherapeutics, and have possible implications for future risk assessment for these PAHs.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3317068','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3317068"><span>A New Experimental Polytrauma Model in Rats: <span class="hlt">Molecular</span> Characterization of the <span class="hlt">Early</span> Inflammatory Response</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus</p> <p>2012-01-01</p> <p>Background. The <span class="hlt">molecular</span> mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the <span class="hlt">early</span> <span class="hlt">molecular</span> inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the <span class="hlt">early</span> immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=Clinical+AND+trials+AND+PTSD&pg=2&id=EJ936794','ERIC'); return false;" href="https://eric.ed.gov/?q=Clinical+AND+trials+AND+PTSD&pg=2&id=EJ936794"><span>Traumatic and Stressful <span class="hlt">Events</span> in <span class="hlt">Early</span> Childhood: Can Treatment Help Those at Highest Risk?</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Ippen, Chandra Ghosh; Harris, William W.; Van Horn, Patricia; Lieberman, Alicia F.</p> <p>2011-01-01</p> <p>Objective: This study involves a reanalysis of data from a randomized controlled trial to examine whether child-parent psychotherapy (CPP), an empirically based treatment focusing on the parent-child relationship as the vehicle for child improvement, is efficacious for children who experienced multiple traumatic and stressful life <span class="hlt">events</span> (TSEs).…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=separate+AND+work+AND+home+AND+teachers&id=EJ828153','ERIC'); return false;" href="https://eric.ed.gov/?q=separate+AND+work+AND+home+AND+teachers&id=EJ828153"><span>It's the Little Things: Exploring the Importance of Commonplace <span class="hlt">Events</span> for <span class="hlt">Early</span>-Career Teachers' Motivation</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Kitching, Karl; Morgan, Mark; O'Leary, Michael</p> <p>2009-01-01</p> <p>This paper seeks to provide a rationale for further researching the everyday <span class="hlt">events</span> that keep teachers motivated or that discourage them. We put forward the idea that routine Affect Triggering Incidents (ATIs) are an important area for researchers to investigate in terms of how they impact teacher motivation and resilience. Two groups of…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=Hot+AND+papers&pg=5&id=EJ957137','ERIC'); return false;" href="https://eric.ed.gov/?q=Hot+AND+papers&pg=5&id=EJ957137"><span>Riding the Wave to Reach the Masses: Natural <span class="hlt">Events</span> in <span class="hlt">Early</span> Twentieth Century Portuguese Daily Press</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Simoes, Ana; Carneiro, Ana; Diogo, Maria Paula</p> <p>2012-01-01</p> <p>This paper brings together science communicated in newspapers in Portugal by looking at how news on natural <span class="hlt">events</span> were communicated in two different newspapers--the capital newspaper "Diario de Noticias" ("Daily News") and the "Diario dos Acores" ("Azores Daily"). In particular, we look at how the 1900…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=papas&id=EJ897745','ERIC'); return false;" href="https://eric.ed.gov/?q=papas&id=EJ897745"><span>Exposure to Potentially Traumatic <span class="hlt">Events</span> in <span class="hlt">Early</span> Childhood: Differential Links to Emergent Psychopathology</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Briggs-Gowan, Margaret J.; Carter, Alice S.; Clark, Roseanne; Augustyn, Marilyn; McCarthy, Kimberly J.; Ford, Julian D.</p> <p>2010-01-01</p> <p>Research NeedsObjective: To examine associations between exposure to potentially traumatic <span class="hlt">events</span> (PTEs) and clinical patterns of symptoms and disorders in preschool children. Method: Two hundred and thirteen referred and non-referred children, ages 24 to 48 months (MN = 34.9, SD = 6.7 months) were studied. Lifetime exposure to PTEs (family…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26753931','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26753931"><span>Seismology-based <span class="hlt">early</span> identification of dam-formation landquake <span class="hlt">events</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua</p> <p>2016-01-12</p> <p>Flooding resulting from the bursting of dams formed by landquake <span class="hlt">events</span> such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake <span class="hlt">events</span> which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten <span class="hlt">events</span>, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake <span class="hlt">events</span> (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=hope+AND+life&id=EJ1099060','ERIC'); return false;" href="https://eric.ed.gov/?q=hope+AND+life&id=EJ1099060"><span>Origins of <span class="hlt">Early</span> Adolescents' Hope: Personality, Parental Attachment, and Stressful Life <span class="hlt">Events</span></span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Otis, Kristin L.; Huebner, E. Scott; Hills, Kimberly J.</p> <p>2016-01-01</p> <p>Psychology has recently increased attention to identifying psychological qualities in individuals that indicate positive mental health, such as hope. In an effort to understand further the origins of hope, we examined the relations among parental attachment, stressful life <span class="hlt">events</span>, personality variables, and hope in a sample of 647 middle school…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=risk+AND+profile&pg=5&id=EJ741426','ERIC'); return false;" href="https://eric.ed.gov/?q=risk+AND+profile&pg=5&id=EJ741426"><span>Mood Reactivity to Daily Negative <span class="hlt">Events</span> in <span class="hlt">Early</span> Adolescence: Relationship to Risk for Psychopathology</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Schneiders, Josien; Nicolson, Nancy A.; Berkhof, Johannes; Feron, Frans J.; van Os, Jim; deVries, Marten W.</p> <p>2006-01-01</p> <p>Emotional responses to negative daily experiences in young adolescents may provide important clues to the development of psychopathology, but research is lacking. This study assessed momentary mood reactivity to daily <span class="hlt">events</span> as a function of risk profile in a school sample, ages 11-14. High-risk (HR, n = 25) and low-risk (LR, n = 106) subgroups…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=338409&Lab=NHEERL&keyword=brain&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=338409&Lab=NHEERL&keyword=brain&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>A Network of AOPs for reduced thyroid hormone synthesis derived from inhibition of Thyroperoxidase - A common <span class="hlt">Molecular</span> Initiating <span class="hlt">Event</span> Leading to Species-Specific Indices of Adversity.</span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the <span class="hlt">molecular</span>-initiating <span class="hlt">event</span> (MIE), results in decreased thyroid hormone (TH) synthesis, a...</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_9");'>9</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li class="active"><span>11</span></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_11 --> <div id="page_12" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li class="active"><span>12</span></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="221"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4714149','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4714149"><span><span class="hlt">Molecular</span> approach to genetic and epigenetic pathogenesis of <span class="hlt">early</span>-onset colorectal cancer</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Tezcan, Gulcin; Tunca, Berrin; Ak, Secil; Cecener, Gulsah; Egeli, Unal</p> <p>2016-01-01</p> <p>Colorectal cancer (CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that <span class="hlt">early</span>-onset CRC (EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the <span class="hlt">molecular</span> mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the <span class="hlt">molecular</span> basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, MutYH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about <span class="hlt">molecular</span> genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach. PMID:26798439</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4508003','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4508003"><span>MMP-13 In-Vivo <span class="hlt">Molecular</span> Imaging Reveals <span class="hlt">Early</span> Expression in Lung Adenocarcinoma</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.</p> <p>2015-01-01</p> <p>Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for <span class="hlt">molecular</span> imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence <span class="hlt">molecular</span> tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in <span class="hlt">early</span> pulmonary invasive adenocarcinomas and may be a potential target for <span class="hlt">molecular</span> imaging of lung cancer. PMID:26193700</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3362053','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3362053"><span><span class="hlt">Early</span> Decrease in Respiration and Uncoupling <span class="hlt">Event</span> Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Berghella, Libera; Ferraro, Elisabetta</p> <p>2012-01-01</p> <p>Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the <span class="hlt">early</span> stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling <span class="hlt">event</span>, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling <span class="hlt">event</span> is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile <span class="hlt">event</span>. These findings may contribute to understand the mechanisms affecting mitochondria during the <span class="hlt">early</span> stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26946460','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26946460"><span>Cytokine Signatures Associated With <span class="hlt">Early</span> Onset, Active Lesions and Late Cicatricial <span class="hlt">Events</span> of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Béla, Samantha Ribeiro; Costa, Julia Gatti Ladeia; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-Dos-Reis, Jordana Grazziela; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis</p> <p>2016-06-15</p> <p>Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological <span class="hlt">events</span> that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during <span class="hlt">early</span> and late immunological <span class="hlt">events</span>. This specific proinflammatory pattern is associated with <span class="hlt">early</span> <span class="hlt">events</span> and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25306527','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25306527"><span>Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. I. Multimode effect on <span class="hlt">early</span> membrane <span class="hlt">events</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rocher, Françoise; Dédaldéchamp, Fabienne; Saeedi, Saed; Fleurat-Lessard, Pierrette; Chollet, Jean-Francois; Roblin, Gabriel</p> <p>2014-11-01</p> <p>A study of the structure-activity relationship carried out on several benzoic acid-related phenolics indicates that this type of compounds hinders the osmocontractile reaction of pulvinar cells in the range of 0-100%. Tentatively, we tried to find a way that could explain this differential action. With this aim, the relationship between the inhibitory effect and important <span class="hlt">molecular</span> physico-chemical parameters (namely lipophilicity and degree of dissociation) was drawn. In addition, the effect of a variety of these compounds was investigated on their capacity to modify the electrical transmembrane potential and induce modifications in proton fluxes. Finally, using plasma membrane vesicles purified from pulvinar tissues, we examined the effects of some selected compounds on the proton pump activity and catalytic activity of the plasma membrane H(+)-ATPase. Taken together, the results indicate that a modification of the <span class="hlt">molecular</span> structure of phenolics may induce important variation in the activity of the compound on these <span class="hlt">early</span> membrane <span class="hlt">events</span>. Among the tested phenolics, salicylic acid (SA) and acetylsalicylic acid (ASA, aspirin) are of particuler note, as they showed atypical effects on the physiological processes studied. Copyright © 2014 Elsevier Masson SAS. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=family+AND+beliefs&pg=5&id=EJ875145','ERIC'); return false;" href="https://eric.ed.gov/?q=family+AND+beliefs&pg=5&id=EJ875145"><span>Family Support for <span class="hlt">Early</span> Literacy and Numeracy: Examining <span class="hlt">Events</span> in the Home and Community</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Kennedy, Anne</p> <p>2010-01-01</p> <p><span class="hlt">Early</span> childhood educators often make assumptions about the nature of families' understandings and what they do at home to support their young children's literacy and numeracy development and learning. Sometimes educator's have a limited understanding of children's every day experiences at home or in their community and the potential for these to…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25026534','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25026534"><span>Spiders do not evoke greater <span class="hlt">early</span> posterior negativity in the <span class="hlt">event</span>-related potential as snakes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>He, Hongshen; Kubo, Kenta; Kawai, Nobuyuki</p> <p>2014-09-10</p> <p>It has been long believed that both snakes and spiders are archetypal fear stimuli for humans. Furthermore, snakes have been assumed as stronger threat cues for nonhuman primates. However, it is still unclear whether spiders hold a special status in human perception. The current study explored to what extent spider pictures draw <span class="hlt">early</span> visual attention [as assessed with <span class="hlt">early</span> posterior negativity (EPN)] when compared with insects similar to spiders. To measure the EPN, participants watched a random rapid serial presentation of pictures, which consisted of two conditions: spider condition (spider, wasp, bumblebee, beetle) and snake condition (snake, bird). EPN amplitudes revealed no significant difference between spider, wasp, bumblebee, and beetle pictures, whereas EPN amplitudes were significantly larger for snake pictures relative to bird pictures. In addition, EPN amplitudes were significantly larger for snake pictures relative to spider pictures. These results suggest that the <span class="hlt">early</span> visual attentional capture of animate objects is stronger for snakes, whereas spiders do not appear to hold special <span class="hlt">early</span> attentional value.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017Icar..288...10T','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017Icar..288...10T"><span>3D modelling of the climatic impact of outflow channel formation <span class="hlt">events</span> on <span class="hlt">early</span> Mars</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Turbet, Martin; Forget, Francois; Head, James W.; Wordsworth, Robin</p> <p>2017-05-01</p> <p>Mars was characterized by cataclysmic groundwater-sourced surface flooding that formed large outflow channels and that may have altered the climate for extensive periods during the Hesperian era. In particular, it has been speculated that such <span class="hlt">events</span> could have induced significant rainfall and caused the formation of late-stage valley networks. We present the results of 3-D Global Climate Model simulations reproducing the short and long term climatic impact of a wide range of outflow channel formation <span class="hlt">events</span> under cold ancient Mars conditions. We find that the most intense of these <span class="hlt">events</span> (volumes of water up to 107 km3 and released at temperatures up to 320 K) cannot trigger long-term greenhouse global warming, regardless of how favorable are the external conditions (e.g. obliquity and seasons). Furthermore, the intensity of the response of the <span class="hlt">events</span> is significantly affected by the atmospheric pressure, a parameter not well constrained for the Hesperian era. Thin atmospheres (P < 80 mbar) can be heated efficiently because of their low volumetric heat capacity, triggering the formation of a convective plume that is very efficient in transporting water vapor and ice at the global scale. Thick atmospheres (P > 0.5 bar) have difficulty in producing precipitation far from the water flow area, and are more efficient in generating snowmelt. In any case, outflow channel formation <span class="hlt">events</span> at any atmospheric pressure are unable to produce rainfall or significant snowmelt at latitudes below 40°N. As an example, for an outflow channel <span class="hlt">event</span> (under a 0.2 bar atmospheric pressure and 45° obliquity) releasing 106 km3 of water heated at 300 K and at a discharge rate of 109 m3 s-1 , the flow of water reaches the lowest point of the northern lowlands (around ∼70°N, 30°W) after ∼3 days and forms a 200 m deep lake of 4.2 × 106 km2 after ∼20 days; the lake becomes entirely covered by an ice layer after ∼500 days. Over the short term, such an <span class="hlt">event</span> leaves 6.5 × 103 km3</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4446388','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4446388"><span>Alterations in <span class="hlt">molecular</span> pathways in the retina of <span class="hlt">early</span> experimental glaucoma eyes</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Cao, Li; Wang, Lin; Cull, Grant; Zhou, An</p> <p>2015-01-01</p> <p>Glaucoma is a multifactorial, neurodegenerative disease. The <span class="hlt">molecular</span> mechanisms that underlie the pathophysiological changes in glaucomatous eyes, especially at the <span class="hlt">early</span> stage of the disease, are poorly understood. Here, we report the findings from a quantitative proteomic analysis of retinas from experimental glaucoma (EG) eyes. An <span class="hlt">early</span> stage of EG was modeled on unilateral eyes of five nonhuman primates (NHP) by laser treatment-induced elevation of intraocular pressure (IOP). Retinal proteins were extracted from individual EG eyes and their contralateral control eyes of the same animals, respectively, and analyzed by quantitative mass spectrometry (MS). As a result, a total, 475 retinal proteins were confidently identified and quantified. Results of bioinformatic analysis of proteins that showed an increase in the EG eyes suggested changes in apoptosis, DNA damage, immune response, cytoskeleton rearrangement and cell adhesion processes. Interestingly, hemoglobin subunit alpha (HBA) and Ras related C3 botulinum toxin substrate 1 (Rac1) were among the increased proteins. Results of <span class="hlt">molecular</span> modeling of HBA- and Rac1-associated signaling network implicated the involvement of Mitogen-Activated Protein Kinase (MAPK) pathway in the EG, through which Rac1 may exert a regulatory role on HBA. This is the first observation of this potentially novel signaling network in the NHP retina and in EG. Results of Western blot analyses for Rac1, HBA and a selected MAPK pathway protein indicated synergistic changes in all three proteins in the EG eyes. Further, results of hierarchical cluster analysis of proteomes of control eyes revealed a clear age-proteome relationship, and such relationship appeared disrupted in the EG eyes. In conclusion, our results suggested an increased presence of a potentially novel signaling network at the <span class="hlt">early</span> stage of glaucoma, and age might be one of the determinant factors in retinal proteomic characteristics under normal conditions. PMID</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2714155','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2714155"><span><span class="hlt">Early</span> and long-standing rheumatoid arthritis: distinct <span class="hlt">molecular</span> signatures identified by gene-expression profiling in synovia</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe</p> <p>2009-01-01</p> <p>Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying <span class="hlt">molecular</span> mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the <span class="hlt">molecular</span> profiles of <span class="hlt">early</span> and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 <span class="hlt">early</span> untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of <span class="hlt">early</span>, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, <span class="hlt">early</span> from LS RA, and <span class="hlt">early</span> or LS RA from healthy synovia. We identified several gene clusters and distinct <span class="hlt">molecular</span> signatures specifically expressed during <span class="hlt">early</span> or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions <span class="hlt">Early</span> and LS RA have distinct <span class="hlt">molecular</span> signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/1422327-molecular-chemistry-atmospheric-brown-carbon-inferred-from-nationwide-biomass-burning-event','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/1422327-molecular-chemistry-atmospheric-brown-carbon-inferred-from-nationwide-biomass-burning-event"><span><span class="hlt">Molecular</span> Chemistry of Atmospheric Brown Carbon Inferred from a Nationwide Biomass Burning <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Lin, Peng; Bluvshtein, Nir; Rudich, Yinon</p> <p></p> <p>Lag Ba'Omer, a nationwide bonfire festival in Israel, was chosen as a case study to investigate the influence of a major biomass burning <span class="hlt">event</span> on the light absorption properties of atmospheric brown carbon (BrC). The chemical composition and optical properties of BrC chromophores were investigated using a high performance liquid chromatography (HPLC) platform coupled to photo diode array (PDA) and high resolution mass spectrometry (HRMS) detectors. Substantial increase of BrC light absorption coefficient was observed during the night-long biomass burning <span class="hlt">event</span>. Most chromophores observed during the <span class="hlt">event</span> were attributed to nitroaromatic compounds, comprising 28 elemental formulas of at least 63more » structural isomers. The NAC, in combination, accounted for 50-80% of the total visible light absorption (> 400 nm) by solvent extractable BrC. The results highlight that NAC, particular nitrophenols, are important light absorption contributors of biomass burning organic aerosol (BBOA), suggesting that night time chemistry of ·NO 3 and N 2O 5 with particles may play a significant role in atmospheric transformations of BrC. Nitrophenols and related compounds were especially important chromophores of BBOA. The absorption spectra of the BrC chromophores are influenced by the extraction solvent and solution pH, implying that the aerosol acidity is an important factor controlling the light absorption properties of BrC.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1422327-molecular-chemistry-atmospheric-brown-carbon-inferred-from-nationwide-biomass-burning-event','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1422327-molecular-chemistry-atmospheric-brown-carbon-inferred-from-nationwide-biomass-burning-event"><span><span class="hlt">Molecular</span> Chemistry of Atmospheric Brown Carbon Inferred from a Nationwide Biomass Burning <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Lin, Peng; Bluvshtein, Nir; Rudich, Yinon; ...</p> <p>2017-08-26</p> <p>Lag Ba'Omer, a nationwide bonfire festival in Israel, was chosen as a case study to investigate the influence of a major biomass burning <span class="hlt">event</span> on the light absorption properties of atmospheric brown carbon (BrC). The chemical composition and optical properties of BrC chromophores were investigated using a high performance liquid chromatography (HPLC) platform coupled to photo diode array (PDA) and high resolution mass spectrometry (HRMS) detectors. Substantial increase of BrC light absorption coefficient was observed during the night-long biomass burning <span class="hlt">event</span>. Most chromophores observed during the <span class="hlt">event</span> were attributed to nitroaromatic compounds, comprising 28 elemental formulas of at least 63more » structural isomers. The NAC, in combination, accounted for 50-80% of the total visible light absorption (> 400 nm) by solvent extractable BrC. The results highlight that NAC, particular nitrophenols, are important light absorption contributors of biomass burning organic aerosol (BBOA), suggesting that night time chemistry of ·NO 3 and N 2O 5 with particles may play a significant role in atmospheric transformations of BrC. Nitrophenols and related compounds were especially important chromophores of BBOA. The absorption spectra of the BrC chromophores are influenced by the extraction solvent and solution pH, implying that the aerosol acidity is an important factor controlling the light absorption properties of BrC.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27378911','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27378911"><span>Magnetic Resonance Imaging to Detect <span class="hlt">Early</span> <span class="hlt">Molecular</span> and Cellular Changes in Alzheimer's Disease.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Knight, Michael J; McCann, Bryony; Kauppinen, Risto A; Coulthard, Elizabeth J</p> <p>2016-01-01</p> <p>Recent pharmaceutical trials have demonstrated that slowing or reversing pathology in Alzheimer's disease is likely to be possible only in the earliest stages of disease, perhaps even before significant symptoms develop. Pathology in Alzheimer's disease accumulates for well over a decade before symptoms are detected giving a large potential window of opportunity for intervention. It is therefore important that imaging techniques detect subtle changes in brain tissue before significant macroscopic brain atrophy. Current diagnostic techniques often do not permit <span class="hlt">early</span> diagnosis or are too expensive for routine clinical use. Magnetic Resonance Imaging (MRI) is the most versatile, affordable, and powerful imaging modality currently available, being able to deliver detailed analyses of anatomy, tissue volumes, and tissue state. In this mini-review, we consider how MRI might detect patients at risk of future dementia in the <span class="hlt">early</span> stages of pathological change when symptoms are mild. We consider the contributions made by the various modalities of MRI (structural, diffusion, perfusion, relaxometry) in identifying not just atrophy (a late-stage AD symptom) but more subtle changes reflective of <span class="hlt">early</span> dementia pathology. The sensitivity of MRI not just to gross anatomy but to the underlying "health" at the cellular (and even <span class="hlt">molecular</span>) scales, makes it very well suited to this task.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4428449','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4428449"><span>Nanoparticle-facilitated functional and <span class="hlt">molecular</span> imaging for the <span class="hlt">early</span> detection of cancer</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei</p> <p>2014-01-01</p> <p>Cancer detection in its <span class="hlt">early</span> stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. <span class="hlt">Molecular</span> imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the <span class="hlt">early</span> diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the <span class="hlt">early</span> detection of cancer. PMID:25988156</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20060021587','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20060021587"><span>Ar-Ar Dating of Martian Meteorite, Dhofar 378: An <span class="hlt">Early</span> Shock <span class="hlt">Event</span>?</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Park, J.; Bogard, D. D.</p> <p>2006-01-01</p> <p>Martian meteorite, Dhofar 378 (Dho378) is a basaltic shergottite from Oman, weighing 15 g, and possessing a black fusion crust. Chemical similarities between Dho378 and the Los Angeles 001 shergottite suggests that they might have derived from the same Mars locale. The plagioclase in other shergottites has been converted to maskelenite by shock, but Dho378 apparently experienced even more intense shock heating, estimated at 55-75 GPa. Dho378 feldspar (approximately 43 modal %) melted, partially flowed and vesiculated, and then partially recrystallized. Areas of feldspathic glass are appreciably enriched in K, whereas individual plagioclases show a range in the Or/An ratio of approximately 0.18-0.017. Radiometric dating of martian shergottites indicate variable formation times of 160-475 Myr, whereas cosmic ray exposure (CRE) ages of shergottites indicate most were ejected from Mars within the past few Myr. Most determined Ar-39-Ar-40 ages of shergottites appear older than other radiometric ages because of the presence of large amounts of martian atmosphere or interior Ar-40. Among all types of meteorites and returned lunar rocks, the impact <span class="hlt">event</span> that initiated the CRE age very rarely reset the Ar-Ar age. This is because a minimum time and temperature is required to facilitate Ar diffusion loss. It is generally assumed that the shock-texture characteristics in martian meteorites were produced by the impact <span class="hlt">events</span> that ejected the rocks from Mars, although the time of these shock <span class="hlt">events</span> (as opposed to CRE ages) are not directly dated. Here we report Ar-39-Ar-40 dating of Dho378 plagioclase. We suggest that the determined age dates the intense shock heating <span class="hlt">event</span> this meteorite experienced, but that it was not the impact that initiated the CRE age.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24289463','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24289463"><span>Stressful life <span class="hlt">events</span> and neuroticism as predictors of late-life versus <span class="hlt">early</span>-life depression.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Weber, Kerstin; Giannakopoulos, Panteleimon; Herrmann, François R; Bartolomei, Javier; Digiorgio, Sergio; Ortiz Chicherio, Nadia; Delaloye, Christophe; Ghisletta, Paolo; Lecerf, Thierry; De Ribaupierre, Anik; Canuto, Alessandra</p> <p>2013-12-01</p> <p>The occurrence of depression in younger adults is related to the combination of long-standing factors such as personality traits (neuroticism) and more acute factors such as the subjective impact of stressful life <span class="hlt">events</span>. Whether an increase in physical illnesses changes these associations in old age depression remains a matter of debate. We compared 79 outpatients with major depression and 102 never-depressed controls; subjects included both young (mean age: 35 years) and older (mean age: 70 years) adults. Assessments included the Social Readjustment Rating Scale, NEO Personality Inventory and Cumulative Illness Rating Scale. Logistic regression models analyzed the association between depression and subjective impact of stressful life <span class="hlt">events</span> while controlling for neuroticism and physical illness. Patients and controls experienced the same number of stressful life <span class="hlt">events</span> in the past 12 months. However, in contrast to the controls, patients associated the <span class="hlt">events</span> with a subjective negative emotional impact. Negative stress impact and levels of neuroticism, but not physical illness, significantly predicted depression in young age. In old age, negative stress impact was weakly associated with depression. In this age group, depressive illness was also determined by physical illness burden and neuroticism. Our data suggest that the subjective impact of life stressors, although rated as of the same magnitude, plays a less important role in accounting for depression in older age compared to young age. They also indicate an increasing weight of physical illness burden in the prediction of depression occurrence in old age. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25684790','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25684790"><span>Evidence for nucleosynthetic enrichment of the protosolar <span class="hlt">molecular</span> cloud core by multiple supernova <span class="hlt">events</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schiller, Martin; Paton, Chad; Bizzarro, Martin</p> <p>2015-01-15</p> <p>The presence of isotope heterogeneity of nucleosynthetic origin amongst meteorites and their components provides a record of the diverse stars that contributed matter to the protosolar <span class="hlt">molecular</span> cloud core. Understanding how and when the solar system's nucleosynthetic heterogeneity was established and preserved within the solar protoplanetary disk is critical for unraveling the earliest formative stages of the solar system. Here, we report calcium and magnesium isotope measurements of primitive and differentiated meteorites as well as various types of refractory inclusions, including refractory inclusions (CAIs) formed with the canonical 26 Al/ 27 Al of ~5 × 10 -5 ( 26 Al decays to 26 Mg with a half-life of ~0.73 Ma) and CAIs that show fractionated and unidentified nuclear effects (FUN-CAIs) to understand the origin of the solar system's nucleosynthetic heterogeneity. Bulk analyses of primitive and differentiated meteorites along with canonical and FUN-CAIs define correlated, mass-independent variations in 43 Ca, 46 Ca and 48 Ca. Moreover, sequential dissolution experiments of the Ivuna carbonaceous chondrite aimed at identifying the nature and number of presolar carriers of isotope anomalies within primitive meteorites have detected the presence of multiple carriers of the short-lived 26 Al nuclide as well as carriers of anomalous and uncorrelated 43 Ca, 46 Ca and 48 Ca compositions, which requires input from multiple and recent supernovae sources. We infer that the solar system's correlated nucleosynthetic variability reflects unmixing of old, galactically-inherited homogeneous dust from a new, supernovae-derived dust component formed shortly prior to or during the evolution of the giant <span class="hlt">molecular</span> cloud parental to the protosolar <span class="hlt">molecular</span> cloud core. This implies that similarly to 43 Ca, 46 Ca and 48 Ca, the short-lived 26 Al nuclide was heterogeneously distributed in the inner solar system at the time of CAI formation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27339368','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27339368"><span>Indirect Effects of Attributional Style for Positive <span class="hlt">Events</span> on Depressive Symptoms Through Self-Esteem During <span class="hlt">Early</span> Adolescence.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rueger, Sandra Yu; George, Rachel</p> <p>2017-04-01</p> <p>Research on adolescent depression has overwhelmingly focused on risk factors, such as stressful negative <span class="hlt">events</span> and cognitive vulnerabilities, but much important information can be gained by focusing on protective factors. Thus, the current study aimed to broaden understanding on adolescent depression by considering the role of two positive elements as protective factors, attributional style for positive <span class="hlt">events</span> and self-esteem, in a model of depression. The sample included 491 middle school students (52 % female; n = 249) with an age range from 12 to 15 years (M = 13.2, SD = .70). The sample was ethnically/racially diverse, with 55 % White, 22 % Hispanic, 10 % Asian American, 3 % African American, and 10 % Biracial/Other. Correlational analyses indicated significant cross-sectional and longitudinal associations between an enhancing attributional style (internal, stable, global attributions for positive <span class="hlt">events</span>), self-esteem and depressive symptoms. Further, prospective analyses using bootstrapping methodology demonstrated significant indirect effects of an enhancing attributional style on decreases in depressive symptoms through its effects on self-esteem. These findings highlight the importance of considering attributional style for positive <span class="hlt">events</span> as a protective factor in the developmental course of depressive symptoms during <span class="hlt">early</span> adolescence.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018JSeis.tmp...53M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018JSeis.tmp...53M"><span>The instrumental seismicity of the Barents and Kara sea region: relocated <span class="hlt">event</span> catalog from <span class="hlt">early</span> twentieth century to 1989</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Morozov, Alexey Nikolaevich; Vaganova, Natalya V.; Asming, Vladimir E.; Konechnaya, Yana V.; Evtyugina, Zinaida A.</p> <p>2018-05-01</p> <p>We have relocated seismic <span class="hlt">events</span> registered within the Barents and Kara sea region from <span class="hlt">early</span> twentieth century to 1989 with a view to creating a relocated catalog. For the relocation, we collected all available seismic bulletins from the global network using data from the ISC Bulletin (International Seismological Centre), ISC-GEM project (International Seismological Centre-Global Earthquake Model), EuroSeismos project, and by Soviet seismic stations from Geophysical Survey of the Russian Academy of Sciences. The location was performed by applying a modified method of generalized beamforming. We have considered several travel time models and selected one with the best location accuracy for ground truth <span class="hlt">events</span>. Verification of the modified method and selection of the travel time model were performed using data on four nuclear explosions that occurred in the area of the Novaya Zemlya Archipelago and in the north of the European part of Russia. The modified method and the Barents travel time model provide sufficient accuracy for <span class="hlt">event</span> location in the region. The relocation procedure was applied to 31 of 36 seismic <span class="hlt">events</span> registered within the Barents and Kara sea region.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=428463','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=428463"><span><span class="hlt">Early</span> <span class="hlt">events</span> in speciation: Polymorphism for hybrid male sterility in Drosophila</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Reed, Laura K.; Markow, Therese A.</p> <p>2004-01-01</p> <p>Capturing the process of speciation <span class="hlt">early</span> enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an <span class="hlt">early</span> stage. PMID:15184657</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li class="active"><span>12</span></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_12 --> <div id="page_13" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li class="active"><span>13</span></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="241"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15184657','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15184657"><span><span class="hlt">Early</span> <span class="hlt">events</span> in speciation: polymorphism for hybrid male sterility in Drosophila.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Reed, Laura K; Markow, Therese A</p> <p>2004-06-15</p> <p>Capturing the process of speciation <span class="hlt">early</span> enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an <span class="hlt">early</span> stage.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3650896','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3650896"><span>Role of intestinal inflammation as an <span class="hlt">early</span> <span class="hlt">event</span> in obesity and insulin resistance</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ding, Shengli; Lund, Pauline K.</p> <p>2013-01-01</p> <p>Purpose of review To highlight recent evidence supporting a concept that intestinal inflammation is a mediator or contributor to development of obesity and insulin resistance. Recent findings Current views suggest that obesity-associated systemic and adipose tissue inflammation promote insulin resistance, which underlies many obesity-linked health risks. Diet-induced changes in gut microbiota also contribute to obesity. Recent findings support a concept that high fat diet and bacteria interact to promote <span class="hlt">early</span> inflammatory changes in the small intestine that contribute to development of or susceptibility to obesity and insulin resistance. This review summarizes the evidence supporting a role of intestinal inflammation in diet-induced obesity and insulin resistance and discusses mechanisms. Summary The role of diet-induced intestinal inflammation as an <span class="hlt">early</span> biomarker and mediator of obesity, and insulin resistance warrants further study. PMID:21587067</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18556935','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18556935"><span>Temporally selective attention modulates <span class="hlt">early</span> perceptual processing: <span class="hlt">event</span>-related potential evidence.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sanders, Lisa D; Astheimer, Lori B</p> <p>2008-05-01</p> <p>Some of the most important information we encounter changes so rapidly that our perceptual systems cannot process all of it in detail. Spatially selective attention is critical for perception when more information than can be processed in detail is presented simultaneously at distinct locations. When presented with complex, rapidly changing information, listeners may need to selectively attend to specific times rather than to locations. We present evidence that listeners can direct selective attention to time points that differ by as little as 500 msec, and that doing so improves target detection, affects baseline neural activity preceding stimulus presentation, and modulates auditory evoked potentials at a perceptually <span class="hlt">early</span> stage. These data demonstrate that attentional modulation of <span class="hlt">early</span> perceptual processing is temporally precise and that listeners can flexibly allocate temporally selective attention over short intervals, making it a viable mechanism for preferentially processing the most relevant segments in rapidly changing streams.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2007AGUFMGP43C1487G','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2007AGUFMGP43C1487G"><span>Paleomagnetic and Geochronologic Data from Central Asia: Inferences for <span class="hlt">Early</span> Paleozoic Tectonic Evolution and Timing of Worldwide Glacial <span class="hlt">Events</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Gregory, L. C.; Meert, J. G.; Levashova, N.; Grice, W. C.; Gibsher, A.; Rybanin, A.</p> <p>2007-12-01</p> <p>The Neoproterozoic to <span class="hlt">early</span> Paleozoic Ural-Mongol belt that runs through Central Asia is crucial for determining the enigmatic amalgamation of microcontinents that make up the Eurasian subcontinent. Two unique models have been proposed for the evolution of Ural-Mongol belt. One involves a complex assemblage of cratonic blocks that have collided and rifted apart during diachronous opening and closing of Neoproterozoic to Devonian aged ocean basins. The opposing model of Sengor and Natal"in proposes a long-standing volcanic arc system that connected Central Asian blocks with the Baltica continent. The Aktau-Mointy and Dzabkhan microcontinents in Kazakhstan and Central Mongolia make up the central section of the Ural-Mongol belt, and both contain glacial sequences characteristic of the hypothesized snowball earth <span class="hlt">event</span>. These worldwide glaciations are currently under considerable debate, and paleomagnetic data from these microcontients are a useful contribution to the snowball controversy. We have sampled volcanic and sedimentary sequences in Central Mongolia, Kazakhstan and Kyrgyzstan for paleomagnetic and geochronologic study. U-Pb data, 13C curves and abundant fossil records place age constraints on sequences that contain glacial deposits of the hypothesized snowball earth <span class="hlt">events</span>. Carbonates in the Zavkhan Basin in Mongolia are likely remagnetized, but fossil evidence within the sequence suggests a readjusted age control on two glacial <span class="hlt">events</span> that were previously labeled as Sturtian and Marinoan. U-Pb ages from both Kazakhstan and Mongolian volcanic sequences imply a similar evolution history of the areas as part of the Ural-Mongol fold belt, and these ages paired with paleomagnetic and 13C records have important tectonic implications. We will present these data in order to place better constraints on the Precambrian to <span class="hlt">early</span> Paleozoic tectonic evolution of Central Asia and the timing of glacial <span class="hlt">events</span> recorded in the area.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26640507','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26640507"><span>Stressful Life <span class="hlt">Events</span> and Predictors of Post-traumatic Growth among High-Risk <span class="hlt">Early</span> Emerging Adults.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Arpawong, Thalida E; Rohrbach, Louise A; Milam, Joel E; Unger, Jennifer B; Land, Helen; Sun, Ping; Spruijt-Metz, Donna; Sussman, Steve</p> <p>2016-01-01</p> <p>Stressful life <span class="hlt">events</span> (SLEs) may elicit positive psychosocial change among youth, referred to as Post-traumatic Growth (PTG). We assessed types of SLEs experienced, degree to which participants reported PTG, and variables predicting PTG across 24 months among a sample of high risk, ethnically diverse <span class="hlt">early</span> emerging adults. Participants were recruited from alternative high schools ( n = 564; mean age=16.8; 65% Hispanic). Multi-level regression models were constructed to examine the impact of environmental (SLE quantity, severity) and personal factors (hedonic ability, perceived stress, developmental stage, future time orientation) on a composite score of PTG. The majority of participants reported positive changes resulted from their most life-altering SLE of the past two years. Predictors of PTG included fewer SLEs, less general stress, having a future time perspective, and greater identification with the developmental stage of Emerging Adulthood. Findings suggest intervention targets to foster positive adaptation among <span class="hlt">early</span> emerging adults who experience frequent SLEs.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21903250','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21903250"><span>Does silent reading speed in normal adult readers depend on <span class="hlt">early</span> visual processes? evidence from <span class="hlt">event</span>-related brain potentials.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Korinth, Sebastian Peter; Sommer, Werner; Breznitz, Zvia</p> <p>2012-01-01</p> <p>Little is known about the relationship of reading speed and <span class="hlt">early</span> visual processes in normal readers. Here we examined the association of the <span class="hlt">early</span> P1, N170 and late N1 component in visual <span class="hlt">event</span>-related potentials (ERPs) with silent reading speed and a number of additional cognitive skills in a sample of 52 adult German readers utilizing a Lexical Decision Task (LDT) and a Face Decision Task (FDT). Amplitudes of the N170 component in the LDT but, interestingly, also in the FDT correlated with behavioral tests measuring silent reading speed. We suggest that reading speed performance can be at least partially accounted for by the extraction of essential structural information from visual stimuli, consisting of a domain-general and a domain-specific expertise-based portion. © 2011 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22402544-early-warning-indicator-atmospheric-blocking-events-using-transfer-operators','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22402544-early-warning-indicator-atmospheric-blocking-events-using-transfer-operators"><span>An <span class="hlt">early</span> warning indicator for atmospheric blocking <span class="hlt">events</span> using transfer operators</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Tantet, Alexis, E-mail: a.j.j.tantet@uu.nl; Burgt, Fiona R. van der; Dijkstra, Henk A.</p> <p></p> <p>The existence of persistent midlatitude atmospheric flow regimes with time-scales larger than 5–10 days and indications of preferred transitions between them motivates to develop <span class="hlt">early</span> warning indicators for such regime transitions. In this paper, we use a hemispheric barotropic model together with estimates of transfer operators on a reduced phase space to develop an <span class="hlt">early</span> warning indicator of the zonal to blocked flow transition in this model. It is shown that the spectrum of the transfer operators can be used to study the slow dynamics of the flow as well as the non-Markovian character of the reduction. The slowest motionsmore » are thereby found to have time scales of three to six weeks and to be associated with meta-stable regimes (and their transitions) which can be detected as almost-invariant sets of the transfer operator. From the energy budget of the model, we are able to explain the meta-stability of the regimes and the existence of preferred transition paths. Even though the model is highly simplified, the skill of the <span class="hlt">early</span> warning indicator is promising, suggesting that the transfer operator approach can be used in parallel to an operational deterministic model for stochastic prediction or to assess forecast uncertainty.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20050198881','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20050198881"><span>Age Dating Merger <span class="hlt">Events</span> in <span class="hlt">Early</span> Type Galaxies via the Detection of AGB Light</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Bothun, G.</p> <p>2005-01-01</p> <p>A thorough statistical analysis of the J-H vs. H-K color plane of all detected <span class="hlt">early</span> type galaxies in the 2MASS catalog with velocities less than 5000 km/s has been performed. This all sky survey is not sensitive to one particular galactic environment and therefore a representative range of <span class="hlt">early</span> type galaxy environments have been sampled. Virtually all N-body simulation so major mergers produces a central starburst due to rapid collection of gas. This central starburst is of sufficient amplitude to change the stellar population in the central regions of the galaxy. Intermediate age populations are given away by the presence of AGB stars which will drive the central colors redder in H-K relative to the J- H baseline. This color anomaly has a lifetime of 2-5 billion years depending on the amplitude of the initial starburst Employing this technique on the entire 2MASS sample (several hundred galaxies) reveals that the AGB signature occurs less than 1% of the time. This is a straightforward indication that virtually all nearby <span class="hlt">early</span> type galaxies have not had a major merger occur within the last few billion years.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AGUFM.S44C..07F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AGUFM.S44C..07F"><span>Performance of Earthquake <span class="hlt">Early</span> Warning Systems during the Major <span class="hlt">Events</span> of the 2016-2017 Central Italy Seismic Sequence.</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Festa, G.; Picozzi, M.; Alessandro, C.; Colombelli, S.; Cattaneo, M.; Chiaraluce, L.; Elia, L.; Martino, C.; Marzorati, S.; Supino, M.; Zollo, A.</p> <p>2017-12-01</p> <p>Earthquake <span class="hlt">early</span> warning systems (EEWS) are systems nowadays contributing to the seismic risk mitigation actions, both in terms of losses and societal resilience, by issuing an alert promptly after the earthquake origin and before the ground shaking impacts the targets to be protected. EEWS systems can be grouped in two main classes: network based and stand-alone systems. Network based EEWS make use of dense seismic networks surrounding the fault (e.g. Near Fault Observatory; NFO) generating the <span class="hlt">event</span>. The rapid processing of the P-wave <span class="hlt">early</span> portion allows for the location and magnitude estimation of the <span class="hlt">event</span> then used to predict the shaking through ground motion prediction equations. Stand-alone systems instead analyze the <span class="hlt">early</span> P-wave signal to predict the ground shaking carried by the late S or surface waves, through empirically calibrated scaling relationships, at the recording site itself. We compared the network-based (PRESTo, PRobabilistic and Evolutionary <span class="hlt">early</span> warning SysTem, www.prestoews.org, Satriano et al., 2011) and the stand-alone (SAVE, on-Site-Alert-leVEl, Caruso et al., 2017) systems, by analyzing their performance during the 2016-2017 Central Italy sequence. We analyzed 9 earthquakes having magnitude 5.0 < M < 6.5 at about 200 stations located within 200 km from the epicentral area, including stations of The Altotiberina NFO (TABOO). Performances are evaluated in terms of rate of success of ground shaking intensity prediction and available lead-time, i.e. the time available for security actions. PRESTo also evaluated the accuracy of location and magnitude. Both systems well predict the ground shaking nearby the <span class="hlt">event</span> source, with a success rate around 90% within the potential damage zone. The lead-time is significantly larger for the network based system, increasing to more than 10s at 40 km from the <span class="hlt">event</span> epicentre. The stand-alone system better performs in the near-source region showing a positive albeit small lead-time (<3s). Far away from</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4909766','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4909766"><span>Parental Substance Abuse As an <span class="hlt">Early</span> Traumatic <span class="hlt">Event</span>. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs <span class="hlt">Early</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Parolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, Marianna; Cristofalo, Patrizia</p> <p>2016-01-01</p> <p>Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic <span class="hlt">events</span>. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of <span class="hlt">early</span> exposure to drugs as a traumatic <span class="hlt">event</span>, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs <span class="hlt">early</span> in their family context. The research involved three groups, each consisting of 15 young adults (aged 18–24): a group of inpatients diagnosed with SUDs and exposed to drugs <span class="hlt">early</span>, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4489862','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4489862"><span>Impaired <span class="hlt">Early</span> Attentional Processes in Parkinson’s Disease: A High-Resolution <span class="hlt">Event</span>-Related Potentials Study</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bocquillon, Perrine; Bourriez, Jean-Louis; Palmero-Soler, Ernesto; Defebvre, Luc; Derambure, Philippe; Dujardin, Kathy</p> <p>2015-01-01</p> <p>Introduction The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. A previous study using the P3 component of the <span class="hlt">event</span>-related potentials suggested that a reduced ability to resist interference could be responsible for attention disorders at <span class="hlt">early</span> stages of Parkinson’s disease (PD), with a possible role of the dorsolateral prefrontal cortex (DLPFC). Methods Our objective was to better determine the origin of this impairment, by studying an earlier ERP component, the N2, and its subcomponents, as they reflect <span class="hlt">early</span> inhibition processes and as they are known to have sources in the anterior cingulate cortex (ACC), which is involved together with the DLPFC in inhibition processes. Fifteen <span class="hlt">early</span>-stage PD patients and 15 healthy controls (HCs) performed a three-stimulus visual oddball paradigm, consisting in detecting target inputs amongst standard stimuli, while resisting interference from distracter ones. A 128-channel electroencephalogram was recorded during this task and the generators of the N2 subcomponents were identified using standardized weighted low-resolution electromagnetic tomography (swLORETA). Results PD patients displayed fewer N2 generators than HCs in both the DLPFC and the ACC, for all types of stimuli. In contrast to controls, PD patients did not show any differences between their generators for different N2 subcomponents. Conclusion Our data suggest that impaired inhibition in PD results from dysfunction of the DLPFC and the ACC during the <span class="hlt">early</span> stages of attentional processes. PMID:26135906</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5754647','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5754647"><span>Clinical and <span class="hlt">molecular</span> characterization of KCNT1-related severe <span class="hlt">early</span>-onset epilepsy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Nair, Umesh; Malhotra, Sony; Meyer, Esther; Trump, Natalie; Gazina, Elena V.; Papandreou, Apostolos; Ngoh, Adeline; Ackermann, Sally; Ambegaonkar, Gautam; Appleton, Richard; Desurkar, Archana; Eltze, Christin; Kneen, Rachel; Kumar, Ajith V.; Lascelles, Karine; Montgomery, Tara; Ramesh, Venkateswaran; Samanta, Rajib; Scott, Richard H.; Tan, Jeen; Whitehouse, William; Poduri, Annapurna; Scheffer, Ingrid E.; Chong, W.K. “Kling”; Cross, J. Helen; Topf, Maya; Petrou, Steven</p> <p>2018-01-01</p> <p>Objective To characterize the phenotypic spectrum, <span class="hlt">molecular</span> genetic findings, and functional consequences of pathogenic variants in <span class="hlt">early</span>-onset KCNT1 epilepsy. Methods We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS <span class="hlt">early</span>-onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. When possible, we performed homology modeling to predict the putative effects of variants on protein structure and function. We undertook electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model system. Results We identified pathogenic variants in KCNT1 in 12 patients, 4 of which are novel. Most variants occurred de novo. Ten patients had a clinical diagnosis of EIMFS, and the other 2 presented with <span class="hlt">early</span>-onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in 1 patient. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. Conclusions Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in <span class="hlt">early</span> infancy. Currently, genotype-phenotype correlations are unclear, although clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy. PMID:29196579</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24670416','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24670416"><span>Quantification of pancreatic cancer proteome and phosphorylome: indicates <span class="hlt">molecular</span> <span class="hlt">events</span> likely contributing to cancer and activity of drug targets.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Britton, David; Zen, Yoh; Quaglia, Alberto; Selzer, Stefan; Mitra, Vikram; Löβner, Christopher; Jung, Stephan; Böhm, Gitte; Schmid, Peter; Prefot, Petra; Hoehle, Claudia; Koncarevic, Sasa; Gee, Julia; Nicholson, Robert; Ward, Malcolm; Castellano, Leandro; Stebbing, Justin; Zucht, Hans Dieter; Sarker, Debashis; Heaton, Nigel; Pike, Ian</p> <p>2014-01-01</p> <p>LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex <span class="hlt">molecular</span> <span class="hlt">events</span> that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application. Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological <span class="hlt">events</span> from the complex dataset. Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power. Here we provided critical information enabling us to identify the common and unique <span class="hlt">molecular</span> <span class="hlt">events</span> likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27325739','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27325739"><span><span class="hlt">Molecular</span> <span class="hlt">events</span> during translocation and proofreading extracted from 200 static structures of DNA polymerase.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ren, Zhong</p> <p>2016-09-06</p> <p>DNA polymerases in family B are workhorses of DNA replication that carry out the bulk of the job at a high speed with high accuracy. A polymerase in this family relies on a built-in exonuclease for proofreading. It has not been observed at the atomic resolution how the polymerase advances one nucleotide space on the DNA template strand after a correct nucleotide is incorporated, that is, a process known as translocation. It is even more puzzling how translocation is avoided after the primer strand is excised by the exonuclease and returned back to the polymerase active site once an error occurs. The structural <span class="hlt">events</span> along the bifurcate pathways of translocation and proofreading have been unwittingly captured by hundreds of structures in Protein Data Bank. This study analyzes all available structures of a representative member in family B and reveals the orchestrated <span class="hlt">event</span> sequence during translocation and proofreading. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1204285','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1204285"><span>Transformation of Chloroplast Ribosomal RNA Genes in Chlamydomonas: <span class="hlt">Molecular</span> and Genetic Characterization of Integration <span class="hlt">Events</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Newman, S. M.; Boynton, J. E.; Gillham, N. W.; Randolph-Anderson, B. L.; Johnson, A. M.; Harris, E. H.</p> <p>1990-01-01</p> <p>Transformation of chloroplast ribosomal RNA (rRNA) genes in Chlamydomonas has been achieved by the biolistic process using cloned chloroplast DNA fragments carrying mutations that confer antibiotic resistance. The sites of exchange employed during the integration of the donor DNA into the recipient genome have been localized using a combination of antibiotic resistance mutations in the 16S and 23S rRNA genes and restriction fragment length polymorphisms that flank these genes. Complete or nearly complete replacement of a region of the chloroplast genome in the recipient cell by the corresponding sequence from the donor plasmid was the most common integration <span class="hlt">event</span>. Exchange <span class="hlt">events</span> between the homologous donor and recipient sequences occurred preferentially near the vector:insert junctions. Insertion of the donor rRNA genes and flanking sequences into one inverted repeat of the recipient genome was followed by intramolecular copy correction so that both copies of the inverted repeat acquired identical sequences. Increased frequencies of rRNA gene transformants were achieved by reducing the copy number of the chloroplast genome in the recipient cells and by decreasing the heterology between donor and recipient DNA sequences flanking the selectable markers. In addition to producing bona fide chloroplast rRNA transformants, the biolistic process induced mutants resistant to low levels of streptomycin, typical of nuclear mutations in Chlamydomonas. PMID:1981764</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20060049104&hterms=parents&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D30%26Ntt%3Dparents','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20060049104&hterms=parents&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D30%26Ntt%3Dparents"><span>Ar-39-Ar-40 Evidence for <span class="hlt">Early</span> Impact <span class="hlt">Events</span> on the LL Parent Body</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Dixon, E. T.; Bogard, D. D.; Garrison, D. H.; Rubin, A. E.</p> <p>2006-01-01</p> <p>We determined Ar-39-Ar-40 ages of eight LL chondrites, and one igneous inclusion from an LL chondrite, with the object of understanding the thermal history of the LL-chondrite parent body. The meteorites in this study have a range of petrographic types from LL3.3 to LL6, and shock stages from S1 to S4. These meteorites reveal a range of K-Ar ages from 23.66 to 24.50 Ga, and peak ages from 23.74 to 24.55 Ga. Significantly, three of the eight chondrites (LL4, 5, 6) have K-Ar ages of -4.27 Ga. One of these (MIL99301) preserves an Ar-39-Ar-40 age of 4.23 +/- 0.03 Ga from low-temperature extractions, and an older age of 4.52 +/- 0.08 Ga from the highest temperature extractions. In addition, an igneous-textured impact melt DOM85505,22 has a peak Ar-39-Ar-40 age of >= 4.27 Ga. We interpret these results as evidence for impact <span class="hlt">events</span> that occurred at about 4.27 Ga on the LL parent body that produced local impact melts, reset the Ar-39-Ar-40 ages of some meteorites, and exhumed (or interred) others, resulting in a range of cooling ages. The somewhat younger peak age of 3.74 Ga from GR095658 (LL3.3) suggests an additional impact <span class="hlt">event</span> close to timing of impact-reset ages of some other ordinary chondrites between 3.6-3.8 Ga. The results from MIL99301 suggest that some apparently unshocked (Sl) chondrites may have substantially reset Ar-39-Ar-40 ages. A previous petrographic investigation of MIL99301 suggested that reheating to temperatures less than or equal to type 4 petrographic conditions (600C) caused fractures in olivine to anneal, resulting in a low apparent shock stage of S1 (unshocked). The Ar-39-Ar-40 age spectrum of MIL99301 is consistent with this interpretation. Older ages from high-T extractions may date an earlier impact <span class="hlt">event</span> at 4.52 +/- 0.08 Ga, whereas younger ages from lower-T extractions date a later impact <span class="hlt">event</span> at 4.23 Ar-39-Ar-40 0.03 Ga that may have caused annealing of feldspar and olivine</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4025992','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4025992"><span>The onset of childhood amnesia in childhood: A prospective investigation of the course and determinants of forgetting of <span class="hlt">early</span>-life <span class="hlt">events</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bauer, Patricia J.; Larkina, Marina</p> <p>2013-01-01</p> <p>The present research was an examination of the onset of childhood amnesia and how it relates to maternal narrative style, an important determinant of autobiographical memory development. Children and their mothers discussed unique <span class="hlt">events</span> when the children were 3 years of age. Different subgroups of children were tested for recall of the <span class="hlt">events</span> at ages 5, 6, 7, 8, and 9 years. At the later session, they were interviewed by an experimenter about the <span class="hlt">events</span> discussed 2 to 6 years previously with their mothers (<span class="hlt">early</span>-life <span class="hlt">events</span>). Children ages 5, 6, and 7 remembered 60% or more of the <span class="hlt">early</span>-life <span class="hlt">events</span>. In contrast, children ages 8 and 9 years remembered fewer than 40% of the <span class="hlt">early</span>-life <span class="hlt">events</span>. Overall maternal narrative style predicted children's contributions to mother-child conversations at age 3 years; it did not have cross-lagged relations to memory for <span class="hlt">early</span>-life <span class="hlt">events</span> at ages 5 to 9 years. Maternal deflections of the conversational turn to the child predicted the amount of information children later reported about the <span class="hlt">early</span>-life <span class="hlt">events</span>. The findings have implications for our understanding of the onset of childhood amnesia and the achievement of an adult-like distribution of memories in the school years. They highlight the importance of forgetting processes in explanations of the amnesia. PMID:24236647</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3597714','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3597714"><span>Impact of Prior Traumatic Life <span class="hlt">Events</span> on Parental <span class="hlt">Early</span> Stage Reactions following a Child's Cancer</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Boman, Krister K.; Kjällander, Ylva; Eksborg, Staffan; Becker, Jeremy</p> <p>2013-01-01</p> <p>Background In pediatric oncology, effective clinic–based management of acute and long–term distress in families calls for investigation of determinants of parents' psychological response to the child's cancer. We examined the relationship between parents' prior exposure to traumatic life <span class="hlt">events</span> (TLE) and the occurrence of posttraumatic stress symptoms (PTSS) following their child's cancer diagnosis. Factors mediating the TLE–PTSS relationship were analyzed. Methodology The study comprised 169 parents (97 mothers, 72 fathers) of 103 cancer diagnosed children (median age: 5,9 years; range 0.1–19.7 years). Thirty five parents were of immigrant origin (20.7%). Prior TLE were collated using a standardized questionnaire, PTSS was assessed using the Impact of Events–Revised (IES–R) questionnaire covering intrusion, avoidance and hyperarousal symptoms. The predictive significance of prior TLE on PTSS was tested in adjusted regression models. Results Mothers demonstrated more severe PTSS across all symptom dimensions. TLE were associated with significantly increased hyperarousal symptoms. Parents' gender, age and immigrant status did not significantly influence the TLE–PTSS relationship. Conclusions Prior traumatic life–<span class="hlt">events</span> aggravate posttraumatic hyperarousal symptoms. In clinic–based psychological care of parents of high–risk pediatric patients, attention needs to be paid to life history, and to heightened vulnerability to PTSS associated with female gender. PMID:23516408</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5237696-early-paleozoic-magmatic-events-eastern-klamath-mountains-northern-california','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5237696-early-paleozoic-magmatic-events-eastern-klamath-mountains-northern-california"><span><span class="hlt">Early</span> Paleozoic magmatic <span class="hlt">events</span> in the eastern Klamath Mountains, northern California</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Wallin, E.T.; Mattinson, J.M.; Potter, A.W.</p> <p>1988-02-01</p> <p>New U-Pb zircon ages for nine samples of tonalite and pegmatitic trondhjemite from the Trinity ophiolite and associated melange reveal a complex history of magmatic activity extending back into the earliest Cambrian, much older than previously believed. Earlier investigations, based on limited data, recognized lower Paleozoic crustal elements in the eastern Klamath terrane (EKT) ranging in age from Middle Ordovician to <span class="hlt">Early</span> to Middle Devonian. The new work in the Yreka-Callahan area of the EKT confirms the Ordovician (440-475 Ma) and younger ages, but reveals for the first time the presence of tonalitic rocks that crystallized during a narrow timemore » interval at about 565-570 Ma. The authors also recognize younger, Late Silurian magmatism at 412 Ma. In the context of available mapping, these ages indicate that the Trinity ophiolite is broadly polygenetic because parts of it yield crystallization ages that span approximately 150 m.y. Superjacent dismembered units of probable <span class="hlt">early</span> Paleozoic age may be tectonostratigraphically equivalent to the Sierra City melange in the northern Sierra Nevada.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27885062','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27885062"><span>Quantifying risk of <span class="hlt">early</span> relapse in patients with first demyelinating <span class="hlt">events</span>: Prediction in clinical practice.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Spelman, Tim; Meyniel, Claire; Rojas, Juan Ignacio; Lugaresi, Alessandra; Izquierdo, Guillermo; Grand'Maison, Francois; Boz, Cavit; Alroughani, Raed; Havrdova, Eva; Horakova, Dana; Iuliano, Gerardo; Duquette, Pierre; Terzi, Murat; Grammond, Pierre; Hupperts, Raymond; Lechner-Scott, Jeannette; Oreja-Guevara, Celia; Pucci, Eugenio; Verheul, Freek; Fiol, Marcela; Van Pesch, Vincent; Cristiano, Edgardo; Petersen, Thor; Moore, Fraser; Kalincik, Tomas; Jokubaitis, Vilija; Trojano, Maria; Butzkueven, Helmut</p> <p>2017-09-01</p> <p>Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of <span class="hlt">early</span> second attack and could benefit the most from <span class="hlt">early</span> disease-modifying drugs (DMDs). To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion. Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices. A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities. This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li class="active"><span>13</span></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_13 --> <div id="page_14" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li class="active"><span>14</span></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="261"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27190065','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27190065"><span><span class="hlt">Early</span> coagulation <span class="hlt">events</span> induce acute lung injury in a rat model of blunt traumatic brain injury.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yasui, Hideki; Donahue, Deborah L; Walsh, Mark; Castellino, Francis J; Ploplis, Victoria A</p> <p>2016-07-01</p> <p>Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as <span class="hlt">early</span> as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as <span class="hlt">early</span> as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI. Copyright © 2016 the American Physiological Society.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013EGUGA..15.5612M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013EGUGA..15.5612M"><span>Astrochronology of the Valanginian Stage (<span class="hlt">Early</span> Cretaceous) : implications for the origin of the Weissert <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Martinez, Mathieu; Deconinck, Jean-François; Pellenard, Pierre; Reboulet, Stéphane; Riquier, Laurent</p> <p>2013-04-01</p> <p>Due to the scarcity of available radioisotopic ages in the Lower Cretaceous, the Geologic Time Scale presents uncertainties that impact palaeoceanographic and palaeoclimatic reconstructions. Particularly, the chronological relationship between the Mid-Valanginian carbon-isotope excursion (namely the 'Weissert <span class="hlt">Event</span>') and the activity of the Paraná-Etendeka Large Igneous Province is debated. To better constrain this relationship, an astrochronology of the Valanginian Stage is proposed based on high-resolution gamma-ray spectrometry measurements performed on five biostratigraphically well-constrained sections throughout the Vocontian Basin (SE France). The Valanginian sediments of the Vocontian Basin are composed of decimetric hemipelagic marl-limestone alternations. These lithologic cycles are attributed to orbital forcing because marls and limestones display significant differences within clay mineralogy, geochemistry and faunal assemblages and these marl-limestone alternations are correlated throughout the Western Tethys and the Atlantic Ocean. Among the analyzed sections, Vergol (GSSP candidate for the Berriasian-Valanginian boundary), La Charce (GSSP candidate for the Valanginian-Hauterivian boundary) and Angles (Valanginian Hypostratotype) are standard sections for the Valanginian Stage since all ammonite zones and subzones are precisely identified and bounded. Spectral analyses were performed using the multi-taper method and amplitude spectrograms on the gamma-ray signals. The comparison between sedimentary frequency ratios derived from the spectral analyses and orbital frequency ratios calculated from astronomical solutions allows the identification of a pervasive dominance of the precession and the 405 kyr-eccentricity cycles throughout the Valanginian Stage. A duration of 5.1 myr is proposed for the Valanginian Stage on the base of the recognition of the 405 kyr-eccentricity cycles. This duration is in agreement with the orbital calibration proposed from </p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29604063','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29604063"><span>Somatic POLE exonuclease domain mutations are <span class="hlt">early</span> <span class="hlt">events</span> in sporadic endometrial and colorectal carcinogenesis, determining driver mutational landscape, clonal neoantigen burden and immune response.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Temko, Daniel; Van Gool, Inge C; Rayner, Emily; Glaire, Mark; Makino, Seiko; Brown, Matthew; Chegwidden, Laura; Palles, Claire; Depreeuw, Jeroen; Beggs, Andrew; Stathopoulou, Chaido; Mason, John; Baker, Ann-Marie; Williams, Marc; Cerundolo, Vincenzo; Rei, Margarida; Taylor, Jenny C; Schuh, Anna; Ahmed, Ahmed; Amant, Frédéric; Lambrechts, Diether; Smit, Vincent Thbm; Bosse, Tjalling; Graham, Trevor A; Church, David N; Tomlinson, Ian</p> <p>2018-03-31</p> <p>Genomic instability, which is a hallmark of cancer, is generally thought to occur in the middle to late stages of tumourigenesis, following the acquisition of permissive <span class="hlt">molecular</span> aberrations such as TP53 mutation or whole genome doubling. Tumours with somatic POLE exonuclease domain mutations are notable for their extreme genomic instability (their mutation burden is among the highest in human cancer), distinct mutational signature, lymphocytic infiltrate, and excellent prognosis. To what extent these characteristics are determined by the timing of POLE mutations in oncogenesis is unknown. Here, we have shown that pathogenic POLE mutations are detectable in non-malignant precursors of endometrial and colorectal cancer. Using genome and exome sequencing, we found that multiple driver mutations in POLE-mutant cancers show the characteristic POLE mutational signature, including those in genes conventionally regarded as initiators of tumourigenesis. In POLE-mutant cancers, the proportion of monoclonal predicted neoantigens was similar to that in other cancers, but the absolute number was much greater. We also found that the prominent CD8 + T-cell infiltrate present in POLE-mutant cancers was evident in their precursor lesions. Collectively, these data indicate that somatic POLE mutations are <span class="hlt">early</span>, quite possibly initiating, <span class="hlt">events</span> in the endometrial and colorectal cancers in which they occur. The resulting <span class="hlt">early</span> onset of genomic instability may account for the striking immune response and excellent prognosis of these tumours, as well as their <span class="hlt">early</span> presentation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017APS..DPPTO6009F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017APS..DPPTO6009F"><span>A model of <span class="hlt">early</span> formation of uranium <span class="hlt">molecular</span> oxides in laser-ablated plasmas</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Finko, Mikhail; Curreli, Davide; Azer, Magdi; Weisz, David; Crowhurst, Jonathan; Rose, Timothy; Koroglu, Batikan; Radousky, Harry; Zaug, Joseph; Armstrong, Mike</p> <p>2017-10-01</p> <p>An important problem within the field of nuclear forensics is fractionation: the formation of post-detonation nuclear debris whose composition does not reflect that of the source weapon. We are investigating uranium fractionation in rapidly cooling plasma using a combined experimental and modeling approach. In particular, we use laser ablation of uranium metal samples to produce a low-temperature plasma with physical conditions similar to a condensing nuclear fireball. Here we present a first plasma-chemistry model of uranium <span class="hlt">molecular</span> species formation during the <span class="hlt">early</span> stage of laser ablated plasma evolution in atmospheric oxygen. The system is simulated using a global kinetic model with rate coefficients calculated according to literature data and the application of reaction rate theory. The model allows for a detailed analysis of the evolution of key uranium <span class="hlt">molecular</span> species and represents the first step in producing a uranium fireball model that is kinetically validated against spatially and temporally resolved spectroscopy measurements. This project was sponsored by the DoD, Defense Threat Reduction Agency, Grant HDTRA1-16- 1-0020. This work was performed in part under the auspices of the U.S. DoE by Lawrence Livermore National Laboratory under Contract DE-AC52- 07NA27344.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17420766','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17420766"><span>Lack of serotonin1B receptor expression leads to age-related motor dysfunction, <span class="hlt">early</span> onset of brain <span class="hlt">molecular</span> aging and reduced longevity.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sibille, E; Su, J; Leman, S; Le Guisquet, A M; Ibarguen-Vargas, Y; Joeyen-Waldorf, J; Glorioso, C; Tseng, G C; Pezzone, M; Hen, R; Belzung, C</p> <p>2007-11-01</p> <p>Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-HT) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-HT system would reveal its contribution to age-related processes and investigated behavioral and <span class="hlt">molecular</span> changes throughout adult life in mice lacking the regulatory presynaptic 5-HT(1B) receptor (5-HT(1B)R), a candidate gene for 5-HT-mediated age-related functions. We show that the lack of 5-HT(1B)R (Htr1b(KO) mice) induced an <span class="hlt">early</span> age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an <span class="hlt">early</span> and global shift of the gene expression signature of aging in the brain of Htr1b(KO) mice. Moreover, <span class="hlt">molecular</span> changes reached an apparent maximum effect at 18-months in Htr1b(KO) mice, corresponding to the onset of <span class="hlt">early</span> death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the <span class="hlt">early</span> onset of <span class="hlt">molecular</span> aging in Htr1b(KO) mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems (IGF-1, sirtuins). In summary, our findings suggest that the onset of age-related <span class="hlt">events</span> can be influenced by altered 5-HT function, thus identifying 5-HT as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-HT.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014PhDT........37Y','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014PhDT........37Y"><span>In situ sensing and modeling of <span class="hlt">molecular</span> <span class="hlt">events</span> at the cellular level</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Yang, Ruiguo</p> <p></p> <p>We developed the Atomic Force Microscopy (AFM) based nanorobot in combination with other nanomechanical sensors for the investigation of cell signaling pathways. The AFM nanorobotics hinge on the superior spatial resolution of AFM in imaging and extends it into the measurement of biological processes and manipulation of biological matters. A multiple input single output control system was designed and implemented to solve the issues of nanomanipulation of biological materials, feedback, response frequency and nonlinearity. The AFM nanorobotic system therefore provide the human-directed position, velocity and force control with high frequency feedback, and more importantly it can feed the operator with the real-time imaging of manipulation result from the fast-imaging based local scanning. The use of the system has taken the study of cellular process at the <span class="hlt">molecular</span> scale into a new level. The cellular response to the physiological conditions can be significantly manifested in cellular mechanics. Dynamic mechanical property has been regarded as biomarkers, sometimes even regulators of the signaling and physiological processes, thus the name mechanobiology. We sought to characterize the relationship between the structural dynamics and the <span class="hlt">molecular</span> dynamics and the role of them in the regulation of cell behavior. We used the AFM nanorobotics to investigate the mechanical properties in real-time of cells that are stimulated by different chemical species. These reagents could result in similar ion channel responses but distinctive mechanical behaviors. We applied these measurement results to establish a model that describes the cellular stimulation and the mechanical property change, a "two-hit" model that comprises the loss of cell adhesion and the initiation of cell apoptosis. The first hit was verified by functional experiments: depletion of Calcium and nanosurgery to disrupt the cellular adhesion. The second hit was tested by a labeling of apoptotic markers that</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018AAS...23142302B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018AAS...23142302B"><span>Circumnuclear <span class="hlt">Molecular</span> Disks in <span class="hlt">Early</span>-type Galaxies: Physical Properties and Precision Black Hole Mass Measurements</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Boizelle, Benjamin</p> <p>2018-01-01</p> <p>ALMA is now capable of providing the most precise determinations of the masses of supermassive black holes in <span class="hlt">early</span>-type galaxies (ETGs). In ALMA Cycle 2 we began a program to map the <span class="hlt">molecular</span> gas kinematics in nearby ETGs that host central dust disks as seen in Hubble Space Telescope imaging. These initial observations targeted CO(2-1) emission at ~0.3" resolution, corresponding roughly to the projected radii of influence of the central black holes. In all cases we detect significant (~108 M⊙) <span class="hlt">molecular</span> gas reservoirs that are in dynamically cold rotation, providing the most sensitive probes of the inner gravitational potentials of luminous ETGs. Using these gas kinematics, we verify that these <span class="hlt">molecular</span> disks are formally stable against gravitational fragmentation and collapse. In several galaxies we detect central high-velocity gas rotation that provides direct kinematic evidence for a black hole. For two of these targets, NGC 1332 and NGC 3258, we have obtained higher-resolution observations (0.044" and 0.09") in Cycles 3 and 4 that more fully map out the gas rotation within the gravitational sphere of influence. We present dynamical modeling results for these targets, demonstrating that ALMA observations can enable black hole mass measurements at a precision of 10% or better, with minimal susceptibility to the systematic uncertainties that affect other methods of black hole mass measurement in ETGs. We discuss the impact of future high-resolution ALMA observations on black hole demographics and their potential to refine the high-mass end of the black hole-host galaxy scaling relationships.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017LaPhy..27d5601B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017LaPhy..27d5601B"><span>Raman spectroscopy based investigation of <span class="hlt">molecular</span> changes associated with an <span class="hlt">early</span> stage of dengue virus infection</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan</p> <p>2017-04-01</p> <p>Raman spectroscopy based investigations of the <span class="hlt">molecular</span> changes associated with an <span class="hlt">early</span> stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775-875 cm-1, lectins at 1003, 1238, 1340, 1449 and 1672 cm-1, DNA in the region 1040-1140 cm-1 and alpha and beta structures of proteins in the region 933-967 cm-1 have been identified in the regression vector for their role in an <span class="hlt">early</span> stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28493069','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28493069"><span>Comparison of <span class="hlt">molecular</span> marker expression in <span class="hlt">early</span> zebrafish brain development following chronic ethanol or morpholino treatment.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhang, Chengjin; Boa-Amponsem, Oswald; Cole, Gregory J</p> <p>2017-08-01</p> <p>This study was undertaken to ascertain whether defined markers of <span class="hlt">early</span> zebrafish brain development are affected by chronic ethanol exposure or morpholino knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors, four signaling molecules that are suggested to be ethanol sensitive. Zebrafish embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha, aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during <span class="hlt">early</span> brain development. Our results showed that pax6a mRNA expression was decreased in eye, forebrain, and hindbrain of both chronic ethanol exposed and select MO treatments. Epha4a expression in rhombomere R1 boundary was decreased in chronic ethanol exposure and aldh1a3 morphants, lost in fgf8a morphants, but largely unaffected in agrin and shha morphants. Ectopic pax6a and epha4a expression in midbrain was only found in fgf8a morphants. These results suggest that while chronic ethanol induces obvious morphological change in brain architecture, many <span class="hlt">molecular</span> markers of these brain structures are relatively unaffected by ethanol exposure.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29207216','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29207216"><span>The roles of cellular and <span class="hlt">molecular</span> components of a hematoma at <span class="hlt">early</span> stage of bone healing.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shiu, Hoi Ting; Leung, Ping Chung; Ko, Chun Hay</p> <p>2018-04-01</p> <p>Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the <span class="hlt">early</span> healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and <span class="hlt">molecular</span> components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an <span class="hlt">early</span> hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23373850','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23373850"><span>Safety evaluation of laninamivir octanoate hydrate through analysis of adverse <span class="hlt">events</span> reported during <span class="hlt">early</span> post-marketing phase vigilance.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nakano, Takashi; Okumura, Akihisa; Tanabe, Takuya; Niwa, Shimpei; Fukushima, Masato; Yonemochi, Rie; Eda, Hisano; Tsutsumi, Hiroyuki</p> <p>2013-06-01</p> <p>Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir <span class="hlt">early</span>, based on post-marketing experiences. Spontaneous safety reports collected in the <span class="hlt">early</span> post-marketing phase vigilance were analyzed. Adverse <span class="hlt">events</span> of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious <span class="hlt">events</span> were intensively reviewed by the Safety Evaluation Committee. Abnormal behavior/delirium was a frequently reported <span class="hlt">event</span>. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4472151','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4472151"><span>TGF-β/BMP signaling and other <span class="hlt">molecular</span> <span class="hlt">events</span>: regulation of osteoblastogenesis and bone formation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Rahman, Md Shaifur; Akhtar, Naznin; Jamil, Hossen Mohammad; Banik, Rajat Suvra; Asaduzzaman, Sikder M</p> <p>2015-01-01</p> <p>Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the <span class="hlt">molecular</span> mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics. PMID:26273537</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21256894','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21256894"><span>Origin of microbial life: Nano- and <span class="hlt">molecular</span> <span class="hlt">events</span>, thermodynamics/entropy, quantum mechanisms and genetic instructions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Trevors, J T</p> <p>2011-03-01</p> <p>Currently, there are no agreed upon mechanisms and supporting evidence for the origin of the first microbial cells on the Earth. However, some hypotheses have been proposed with minimal supporting evidence and experimentation/observations. The approach taken in this article is that life originated at the nano- and <span class="hlt">molecular</span> levels of biological organization, using quantum mechanic principles that became manifested as classical microbial cell(s), allowing the origin of microbial life on the Earth with a core or minimal, organic, genetic code containing the correct instructions for cell(s) for growth and division, in a micron dimension environment, with a local entropy range conducive to life (present about 4 billion years ago), and obeying the laws of thermodynamics. An integrated approach that explores all encompassing factors necessary for the origin of life, may bring forth plausible hypotheses (and mechanisms) with much needed supporting experimentation and observations for an origin of life theory. Copyright © 2010 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21118421','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21118421"><span><span class="hlt">Molecular</span> <span class="hlt">events</span> of apical bud formation in white spruce, Picea glauca.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>El Kayal, Walid; Allen, Carmen C G; Ju, Chelsea J-T; Adams, Eri; King-Jones, Susanne; Zaharia, L Irina; Abrams, Suzanne R; Cooke, Janice E K</p> <p>2011-03-01</p> <p>Bud formation is an adaptive trait that temperate forest trees have acquired to facilitate seasonal synchronization. We have characterized transcriptome-level changes that occur during bud formation of white spruce [Picea glauca (Moench) Voss], a primarily determinate species in which preformed stem units contained within the apical bud constitute most of next season's growth. Microarray analysis identified 4460 differentially expressed sequences in shoot tips during short day-induced bud formation. Cluster analysis revealed distinct temporal patterns of expression, and functional classification of genes in these clusters implied <span class="hlt">molecular</span> processes that coincide with anatomical changes occurring in the developing bud. Comparing expression profiles in developing buds under long day and short day conditions identified possible photoperiod-responsive genes that may not be essential for bud development. Several genes putatively associated with hormone signalling were identified, and hormone quantification revealed distinct profiles for abscisic acid (ABA), cytokinins, auxin and their metabolites that can be related to morphological changes to the bud. Comparison of gene expression profiles during bud formation in different tissues revealed 108 genes that are differentially expressed only in developing buds and show greater transcript abundance in developing buds than other tissues. These findings provide a temporal roadmap of bud formation in white spruce. © 2011 Blackwell Publishing Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/874329','DOE-PATENT-XML'); return false;" href="https://www.osti.gov/servlets/purl/874329"><span>Dopant profile modeling by rare <span class="hlt">event</span> enhanced domain-following <span class="hlt">molecular</span> dynamics</span></a></p> <p><a target="_blank" href="http://www.osti.gov/doepatents">DOEpatents</a></p> <p>Beardmore, Keith M.; Jensen, Niels G.</p> <p>2002-01-01</p> <p>A computer-implemented <span class="hlt">molecular</span> dynamics-based process simulates a distribution of ions implanted in a semiconductor substrate. The properties of the semiconductor substrate and ion dose to be simulated are first initialized, including an initial set of splitting depths that contain an equal number of virtual ions implanted in each substrate volume determined by the splitting depths. A first ion with selected velocity is input onto an impact position of the substrate that defines a first domain for the first ion during a first timestep, where the first domain includes only those atoms of the substrate that exert a force on the ion. A first position and velocity of the first ion is determined after the first timestep and a second domain of the first ion is formed at the first position. The first ion is split into first and second virtual ions if the first ion has passed through a splitting interval. The process then follows each virtual ion until all of the virtual ions have come to rest. A new ion is input to the surface and the process repeats until all of the ion dose has been input. The resulting ion rest positions form the simulated implant distribution.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017JGRA..122.7761K','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017JGRA..122.7761K"><span>Modeling long recovery <span class="hlt">early</span> <span class="hlt">events</span> (LOREs) produced by lightning-induced ionization of the nighttime upper mesosphere</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Kotovsky, D. A.; Moore, R. C.</p> <p>2017-07-01</p> <p>We present results of a cylindrically symmetric, coupled electrodynamic, and photochemical model which simulates diffuse ionization of the middle atmosphere induced by strong lightning discharges (peak currents >150 kA). Scattering of subionospherically propagating, very low frequency radio waves is then evaluated using the Long-Wave Propagation Capability code. Some modeled sprite halos exhibit continued electron density growth up to timescales of seconds due to O- detachment, though it is not yet clear how this might relate to the slower onset durations (>20 ms) of some <span class="hlt">early</span> VLF <span class="hlt">events</span>. Modeled electron density enhancements in sprite halos, capable of strong VLF scattering, can persist for long periods of time (greater than hundreds of seconds) even at lower altitudes where their recovery is initially controlled by fast attachment processes. Consequently, our modeling results indicate that both typical recovery (20 to 240 s) and long recovery (LOREs, >300 s) VLF scattering <span class="hlt">events</span> can be explained by scattering from conductivity changes associated with sprite halos. In contrast, modeled scattered fields resulting from elve-associated conductivity changes, though exhibiting long recovery times, are too weak to sufficiently explain typical LORE observations. Theoretical scattering from structured ionization <span class="hlt">events</span> (e.g., sprites columns and gigantic jets) is not considered in this work.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2006QuRes..66..401W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2006QuRes..66..401W"><span>Climate forcing due to the 8200 cal yr BP <span class="hlt">event</span> observed at <span class="hlt">Early</span> Neolithic sites in the eastern Mediterranean</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Weninger, Bernhard; Alram-Stern, Eva; Bauer, Eva; Clare, Lee; Danzeglocke, Uwe; Jöris, Olaf; Kubatzki, Claudia; Rollefson, Gary; Todorova, Henrieta; van Andel, Tjeerd</p> <p>2006-11-01</p> <p>We explore the hypothesis that the abrupt drainage of Laurentide lakes and associated rapid switch of the North Atlantic thermohaline circulation 8200 yr ago had a catastrophic influence on Neolithic civilisation in large parts of southeastern Europe, Anatolia, Cyprus, and the Near East. The <span class="hlt">event</span> at 8200 cal yr BP is observed in a large number of high-resolution climate proxies in the Northern Hemisphere, and in many cases corresponds to markedly cold and arid conditions. We identify the relevant archaeological levels of major Neolithic settlements in Central Anatolia, Cyprus, Greece and Bulgaria, and examine published stratigraphic, architectural, cultural and geoarchaeological studies for these sites. The specific archaeological <span class="hlt">events</span> and processes we observe at a number of these sites during the study interval 8400-8000 cal yr BP lead us to refine some previously established Neolithisation models. The introduction of farming to South-East Europe occurs in all study regions (Thrace, Macedonia, Thessaly, Bulgaria) near 8200 cal yr BP. We observe major disruptions of Neolithic cultures in the Levant, North Syria, South-East Anatolia, Central Anatolia and Cyprus, at the same time. We conclude that the 8200 cal yr BP aridity <span class="hlt">event</span> triggered the spread of <span class="hlt">early</span> farmers, by different routes, out of West Asia and the Near East into Greece and Bulgaria.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15203055','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15203055"><span>Dipole source localization of <span class="hlt">event</span>-related brain activity indicative of an <span class="hlt">early</span> visual selective attention deficit in ADHD children.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H</p> <p>2004-07-01</p> <p>This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific <span class="hlt">early</span> selective attention deficits in the visual modality with the aid of <span class="hlt">event</span>-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an <span class="hlt">early</span> selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific <span class="hlt">early</span> filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040172850&hterms=recruitment&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Drecruitment','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040172850&hterms=recruitment&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D60%26Ntt%3Drecruitment"><span><span class="hlt">Molecular</span> <span class="hlt">events</span> underlying skeletal muscle atrophy and the development of effective countermeasures</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Booth, F. W.; Criswell, D. S.</p> <p>1997-01-01</p> <p>Skeletal muscle adapts to loading; atrophying when exposed to unloading on Earth or in spaceflight. Significant atrophy (decreases in muscle fiber cross-section of 11-24%) in humans has been noted after only 5 days in space. Since muscle strength is determined both by muscle cross-section and synchronization of motor unit recruitment, a loss in muscle size weakens astronauts, which would increase risks to their safety if an emergency required maximal muscle force. Numerous countermeasures have been tested to prevent atrophy. Resistant exercise together with growth hormone and IGF-I are effective countermeasures to unloading as most atrophy is prevented in animal models. The loss of muscle protein is due to an <span class="hlt">early</span> decrease in protein synthesis rate and a later increase in protein degradation. The initial decrease in protein synthesis is a result of decreased protein translation, caused by a prolongation in the elongation rate. A decrease in HSP70 by a sight increase in ATP may be the factors prolonging elongation rate. Increases in the activities of proteolytic enzymes and in ubiquitin contribute to the increased protein degradation rate in unloaded muscle. Numerous mRNA concentrations have been shown to be altered in unloaded muscles. Decreases in mRNAs for contractile proteins usually occur after the initial fall in protein synthesis rates. Much additional research is needed to determine the mechanism by which muscle senses the absence of gravity with an adaptive atrophy. The development of effective countermeasures to unloading atrophy will require more research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2012Sc%26Ed..21..311S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2012Sc%26Ed..21..311S"><span>Riding the Wave to Reach the Masses: Natural <span class="hlt">Events</span> in <span class="hlt">Early</span> Twentieth Century Portuguese Daily Press</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Simões, Ana; Carneiro, Ana; Diogo, Maria Paula</p> <p>2012-03-01</p> <p>This paper brings together science communicated in newspapers in Portugal by looking at how news on natural <span class="hlt">events</span> were communicated in two different newspapers—the capital newspaper Diário de Notícias ( Daily News) and the Diário dos Açores ( Azores Daily). In particular, we look at how the 1900 solar eclipse, a hot topic throughout Europe, was reported by the capital newspaper, and how news on seismology were conveyed in the period 1907-1910 in the newspaper published in Azores, an archipelago with a significant seismic and volcanic activity. We argue that the importance conceded to these scientific news was related to their overwhelming features, that their dissimilar presentation stemmed from their local relevance allied to their different nature, predictable in the case of eclipses, and unpredictable in the case of earthquakes, and that behind these two instances of science journalism laid an attempt by the scientific and political communities to gain the support of the general public to such an extent that these two specific instances of science journalism transcended their usual features to become successful forms of expository science.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li class="active"><span>14</span></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_14 --> <div id="page_15" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li class="active"><span>15</span></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="281"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28649335','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28649335"><span><span class="hlt">Early</span> <span class="hlt">events</span> in speciation: Cryptic species of Drosophila aldrichi.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Castro Vargas, Cynthia; Richmond, Maxi Polihronakis; Ramirez Loustalot Laclette, Mariana; Markow, Therese Ann</p> <p>2017-06-01</p> <p>Understanding the earliest <span class="hlt">events</span> in speciation remains a major challenge in evolutionary biology. Thus identifying species whose populations are beginning to diverge can provide useful systems to study the process of speciation. Drosophila aldrichi , a cactophilic fruit fly species with a broad distribution in North America, has long been assumed to be a single species owing to its morphological uniformity. While previous reports either of genetic divergence or reproductive isolation among different D. aldrichi strains have hinted at the existence of cryptic species, the evolutionary relationships of this species across its range have not been thoroughly investigated. Here we show that D. aldrichi actually is paraphyletic with respect to its closest relative, Drosophila wheeleri , and that divergent D. aldrichi lineages show complete hybrid male sterility when crossed. Our data support the interpretation that there are at least two species of D. aldrichi, making these flies particularly attractive for studies of speciation in an ecological and geographical context.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017E%26ES...96a2015R','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017E%26ES...96a2015R"><span>Droughts and Excessive Moisture <span class="hlt">Events</span> in Southern Siberia in the Late XXth - <span class="hlt">Early</span> XXIst Centuries</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Ryazanova, A. A.; Voropay, N. N.</p> <p>2017-11-01</p> <p>In recent years much research has been devoted to global and regional climate changes. Special attention was paid to climate extremes, such as droughts and excessive moisture <span class="hlt">events</span>. In this study the moisture and aridity of Southern Siberia are estimated using web-GIS called “CLIMATE”. The system “CLIMATE” is part of a hardware and software cloud storage complex for data analysis of various climatic data sets, with algorithms for searching, extracting, processing, and visualizing the data. The ECMWF ERA-Interim reanalysis data for Southern Siberia (50-65°N, 60-120°E) from 1979 to 2010 with a grid cell of 0.75×0.75° is used. Some hydrothermal conditions are estimated using the so-called Ped index (Si), which is a normalized indicator of the ratio of air temperature to precipitation. The mountain regions of Eastern Siberia are becoming more and more arid each month during the last 30 years. In Western Siberia, aridity increases in May and decreases in June, in the other months positive and negative trends are found. The greatest differences between the trends of the aridity index (Si), air temperature, and precipitation are observed in July.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AGUFMPP23B1308W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AGUFMPP23B1308W"><span>A Possible Late Paleocene-<span class="hlt">Early</span> Eocene Ocean Acidification <span class="hlt">Event</span> Recoded in the Adriatic Carbonate Platform</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Weiss, A.; Martindale, R. C.; Kosir, A.; Oefinger, J.</p> <p>2017-12-01</p> <p>The Paleocene-Eocene Thermal Maximum (PETM) <span class="hlt">event</span> ( 56.3 Ma) was a period of massive carbon release into the Earth system, resulting in significant shifts in ocean chemistry. It has been proposed that ocean acidification - a decrease in the pH and carbonate saturation state of the water as a result of dissolved carbon dioxide in sea water - occurred in both the shallow and deep marine realms. Ocean acidification would have had a devastating impact on the benthic ecosystem, and has been proposed as the cause of decreased carbonate deposition in marine sections and coral reef collapse during the late Paleocene. To date, however, the only physical evidence of Paleocene-Eocene ocean acidification has been shown for offshore sites (i.e., a shallow carbonate compensation depth), but isotope analysis (i.e. B, I/Ca) suggests that acidification occurred in the shallow shelves as well. Several sites in the Kras region of Slovenia, has been found to contain apparent erosion surfaces coeval with the Paleocene-Eocene Boundary. We have investigated these potentially acidified horizons using petrography, stable carbon isotopes, cathodoluminescence, and elemental mapping. These datasets will inform whether the horizons formed by seafloor dissolution in an acidified ocean, or are due to subaerial exposure, or burial diagenesis (i.e. stylotization). Physical erosion and diagenesis can easily be ruled out based on field relationships and petrography, but the other potential causes must be analyzed more critically.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20105590','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20105590"><span>Cholangiocyte apoptosis is an <span class="hlt">early</span> <span class="hlt">event</span> during induced metamorphosis in the sea lamprey, Petromyzon marinus L.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Boomer, Laura A; Bellister, Seth A; Stephenson, Linda L; Hillyard, Stanley D; Khoury, Joseph D; Youson, John H; Gosche, John R</p> <p>2010-01-01</p> <p>Research in biliary atresia has been hindered by lack of a suitable animal model. Lampreys are primitive vertebrates with distinct larval and adult life cycle stages. During metamorphosis the biliary system of the larval lamprey disappears. Lamprey metamorphosis has been proposed as a model for biliary atresia. We have begun to explore cellular <span class="hlt">events</span> during lamprey metamorphosis by assessing for cholangiocyte apoptosis. Sea lamprey larvae were housed under controlled environmental conditions. Premetamorphic larvae were induced to undergo metamorphosis by exposure to 0.01% KClO(4). Animals were photographed weekly, and the stage of metamorphosis was assigned based upon external features. Livers were harvested and processed for routine histology and immunohistochemistry. DNA fragmentation was detected using deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays and cholangiocytes were identified with antibodies to cytokeratin-19. Percent TUNEL+ cholangiocytes at different stages of metamorphosis was determined. The percentage of TUNEL+ cholangiocytes was 10% in premetamorphic (stage 0) lamprey (n = 6), 51% at stage 1 (n = 6), 40% at stage 2 (n = 5), 18% at stage 3 (n = 5), and 9% stage 4 (n = 4). Routine hemotoxylin and eosin stained paraffin-embedded tissue sections revealed frequent apoptotic bodies at stages 3 and 4 of metamorphosis without histologic evidence of necrosis. DNA fragmentation is identified at the earliest stages of metamorphosis during induced metamorphosis in lampreys. Additional studies are necessary to validate this potentially valuable animal model. Copyright 2010 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22865782','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22865782"><span>Relationship between specific adverse <span class="hlt">events</span> and efficacy of exemestane therapy in <span class="hlt">early</span> postmenopausal breast cancer patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fontein, D B Y; Houtsma, D; Hille, E T M; Seynaeve, C; Putter, H; Meershoek-Klein Kranenbarg, E; Guchelaar, H J; Gelderblom, H; Dirix, L Y; Paridaens, R; Bartlett, J M S; Nortier, J W R; van de Velde, C J H</p> <p>2012-12-01</p> <p>Many adverse <span class="hlt">events</span> (AEs) associated with aromatase inhibitors (AIs) involve symptoms related to the depletion of circulating estrogens, and may be related to efficacy. We assessed the relationship between specific AEs [hot flashes (HF) and musculoskeletal AEs (MSAE)] and survival outcomes in Dutch and Belgian patients treated with exemestane (EXE) in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Additionally, the relationship between hormone receptor expression and AEs was assessed. Efficacy end points were relapse-free survival (RFS), overall survival (OS) and breast cancer-specific mortality (BCSM), starting at 6 months after starting EXE treatment. AEs reported in the first 6 months of treatment were included. Specific AEs comprised HF and/or MSAE. Landmark analyses and Cox proportional hazards models assessed survival differences up to 5 years. A total of 1485 EXE patients were included. Patients with HF had a better RFS than patients without HF [multivariate hazard ratio (HR) 0.393, 95% confidence interval (CI) 0.19-0.813; P = 0.012]. The occurrence of MSAE versus no MSAE did not relate to better RFS (multivariate HR 0.677, 95% CI 0.392-1.169; P = 0.162). Trends were maintained for OS and BCSM. Quantitative hormone receptor expression was not associated with specific AEs. Some AEs associated with estrogen depletion are related to better outcomes and may be valuable biomarkers in AI treatment.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28472989','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28472989"><span>Circulating mutational portrait of cancer: manifestation of aggressive clonal <span class="hlt">events</span> in both <span class="hlt">early</span> and late stages.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, Meng; Topaloglu, Umit; Petty, W Jeffrey; Pagni, Matthew; Foley, Kristie L; Grant, Stefan C; Robinson, Mac; Bitting, Rhonda L; Thomas, Alexandra; Alistar, Angela T; Desnoyers, Rodwige J; Goodman, Michael; Albright, Carol; Porosnicu, Mercedes; Vatca, Mihaela; Qasem, Shadi A; DeYoung, Barry; Kytola, Ville; Nykter, Matti; Chen, Kexin; Levine, Edward A; Staren, Edgar D; D'Agostino, Ralph B; Petro, Robin M; Blackstock, William; Powell, Bayard L; Abraham, Edward; Pasche, Boris; Zhang, Wei</p> <p>2017-05-04</p> <p>Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs) and circulating tumor DNAs (ctDNA). Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins. Deep sequencing using the Guardant360 test was performed to identify mutations in 73 clinically actionable genes, and the results were associated with clinical characteristics of the patient. The mutation profiles of 37 lung cancer cases with paired ctDNA and tumor genomic DNA sequencing were used to evaluate clonal representation of tumor in circulation. Five lung cancer cases with longitudinal ctDNA sampling were monitored for cancer progression or response to treatments. Mutations in TP53, EGFR, and KRAS genes are most prevalent in our cohort. Mutation rates of ctDNA are similar in <span class="hlt">early</span> (I and II) and late stage (III and IV) cancers. Mutation in DNA repair genes BRCA1, BRCA2, and ATM are found in 18.1% (32/177) of cases. Patients with higher mutation rates had significantly higher mortality rates. Lung cancer of never smokers exhibited significantly higher ctDNA mutation rates as well as higher EGFR and ERBB2 mutations than ever smokers. Comparative analysis of ctDNA and tumor DNA mutation data from the same patients showed that key driver mutations could be detected in plasma even when they were present at a minor clonal population in the tumor. Mutations of key genes found in the tumor tissue could remain in circulation even after frontline radiotherapy and chemotherapy suggesting these mutations represented resistance mechanisms. Longitudinal sampling of five lung cancer cases showed distinct changes in ctDNA mutation portraits that are consistent with cancer progression or response</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29211792','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29211792"><span>The prognostic role of tumor size in <span class="hlt">early</span> breast cancer in the era of <span class="hlt">molecular</span> biology.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kasangian, Anaid Anna; Gherardi, Giorgio; Biagioli, Elena; Torri, Valter; Moretti, Anna; Bernardin, Elena; Cordovana, Andrea; Farina, Gabriella; Bramati, Annalisa; Piva, Sheila; Dazzani, Maria Chiara; Paternò, Emanuela; La Verde, Nicla Maria</p> <p>2017-01-01</p> <p>The prognosis of <span class="hlt">early</span> breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors. The primary objective is to evaluate the association between tumor dimensions and overall survival (OS) / disease free survival (DFS), in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated using the following formula: 4/3π x a x b x c. 341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52-31.651.2). 44 patients (12.9%) relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and <span class="hlt">molecular</span> subtype. The multivariate analysis confirmed the statistically significant association only for <span class="hlt">molecular</span> subtype (p 0.005), with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34-5.22). Likewise for OS, an association was shown by the multivariate analysis solely for <span class="hlt">molecular</span> subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46-5.49; p 0.002). In our study, the only parameter that strongly influences survival is <span class="hlt">molecular</span> subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria but on</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017APS..MARA49005T','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017APS..MARA49005T"><span>Real-time visualization of <span class="hlt">early</span> metastasis <span class="hlt">events</span> in Danio rerio</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Tanner, Kandice</p> <p></p> <p>Metastasis, the process by which cancer cells travel from a primary tumor to establish lesions in distant organs, is the cause of most cancer-related deaths. One critical process during metastasis is the transit of cells from a primary tumor and through the vasculature or lymphatic systems to a distant site prior to metastatic colonization. However, visualization of cellular behavior in the vasculature is difficult in most model systems, where final cell destination is not known beforehand. Here, we used bone- and brain-tropic subclones of MDA-MB-231 breast adenocarcinoma cells (231BO and 231BR, respectively) injected into the circulation of embryonic zebrafish as a model xenograft system of metastasis. The zebrafish vasculature contains vessels on the scale of human capillaries. Real-time intravital imaging revealed metastatic spread to be an inefficient process, with less than 20% of cells passing through a given organ remaining there following 14 h of imaging. Additionally, there was no significant difference in the organ-specific residence time or migration speed of single 231BO and 231BR cells in the organ vasculature. Instead, cell capture was dependent on vessel topography and the function of integrin β1. Interestingly, a fraction of cells extravasated from the vasculature and survived in a perivascular position in the head and caudal venous plexus for up to two weeks. In conclusion, use of the zebrafish vasculature as a model capillary bed has revealed critical steps in <span class="hlt">early</span> metastasis that are difficult to capture in other systems.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28673401','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28673401"><span>An exposome perspective: <span class="hlt">Early</span>-life <span class="hlt">events</span> and immune development in a changing world.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Renz, Harald; Holt, Patrick G; Inouye, Michael; Logan, Alan C; Prescott, Susan L; Sly, Peter D</p> <p>2017-07-01</p> <p>Advances in metagenomics, proteomics, metabolomics, and systems biology are providing a new emphasis in research; interdisciplinary work suggests that personalized medicine is on the horizon. These advances are illuminating sophisticated interactions between human-associated microbes and the immune system. The result is a transformed view of future prevention and treatment of chronic noncommunicable diseases, including allergy. Paradigm-shifting gains in scientific knowledge are occurring at a time of rapid global environmental change, urbanization, and biodiversity losses. Multifactorial and multigenerational implications of total environmental exposures, the exposome, require coordinated interdisciplinary efforts. It is clear that the genome alone cannot provide answers to urgent questions. Here we review the historical origins of exposome research and define a new concept, the metaexposome, which considers the bidirectional effect of the environment on human subjects and the human influence on all living systems and their genomes. The latter is essential for human health. We place the metaexposome in the context of <span class="hlt">early</span>-life immune functioning and describe how various aspects of a changing environment, especially through microbiota exposures, can influence health and disease over the life course. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3350749','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3350749"><span>Multiple cytokines are involved in the <span class="hlt">early</span> <span class="hlt">events</span> leading to the Alzheimer’s disease pathology</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wilberding, Akiko; Morimoto, Kaori; Satoh, Haruhisa; Harano, Keiko; Harano, Teruo; Arita, Seizaburo; Tooyama, Ikuo; Konishi, Yoshihiro</p> <p>2009-01-01</p> <p>It is likely that neuroinflammation begins well before detectable cognitive impairment in Alzheimer’s disease (AD) occurs. Clarifying the alterations occurring prior to the clinical manifestation of overt AD dementia may provide valuable insight into the <span class="hlt">early</span> diagnosis and management of AD. Herein, to address the issue that neuroinflammation precedes development of AD pathology, we analyzed cytokine expression profiles of the brain, with focus on non-demented control patients with increasing AD pathology, referred to as high pathology control (HPC) cases, who provide an intermediate subset between AD and normal control cases referred to as low pathology control (LPC) cases. With a semi-quantitative analysis of cytokine mRNA, among 15 cytokines and their related molecules tested, we found the involvement of eight: interleukin-1(IL-1) receptor antagonist (IL-1ra), IL-1 converting enzyme (ICE), IL-2, IL-6, IL-8, tumor necrosis factor (TNF) α, macrophage-colony stimulating factor (M-CSF) and transforming growth factor (TGF) β1 during the development from LPC to HPC, while decreases in IL-1ra, IL-8, MCP-1 and TNFα, and an increase in TACE were implicated in the later development from HPC to AD. These findings indicate that neuroinflammation precedes the clinical manifestation of overt dementia, rather than being involved at the later stages of AD. PMID:22586434</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040120343&hterms=jj&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D20%26Ntt%3Djj','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040120343&hterms=jj&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D20%26Ntt%3Djj"><span>A comparative study of diversification <span class="hlt">events</span>: the <span class="hlt">early</span> Paleozoic versus the Mesozoic</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Erwin, D. H.; Valentine, J. W.; Sepkoski, J. J. Jr; Sepkoski JJ, J. r. (Principal Investigator)</p> <p>1987-01-01</p> <p>We compare two major long-term diversifications of marine animal families that began during periods of low diversity but produced strikingly different numbers of phyla, classes, and orders. The first is the <span class="hlt">early</span>-Paleozoic diversification (late Vendian-Ordovician; 182 MY duration) and the other the Mesozoic phase of the post-Paleozoic diversification (183 MY duration). The earlier diversification was associated with a great burst of morphological invention producing many phyla, classes, and orders and displaying high per taxon rates of family origination. The later diversification lacked novel morphologies recognized as phyla and classes, produced fewer orders, and displayed lower per taxon rates of family appearances. The chief difference between the diversifications appears to be that the earlier one proceeded from relatively narrow portions of adaptive space, whereas the latter proceeded from species widely scattered among adaptive zones and representing a variety of body plans. This difference is believed to explain the major differences in the products of these great radiations. Our data support those models that hold that evolutionary opportunity is a major factor in the outcome of evolutionary processes.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29067033','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29067033"><span><span class="hlt">Events</span> Associated with <span class="hlt">Early</span> Age-Related Decline in Adventitious Rooting Competence of Eucalyptus globulus Labill.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Aumond, Márcio L; de Araujo, Artur T; de Oliveira Junkes, Camila F; de Almeida, Márcia R; Matsuura, Hélio N; de Costa, Fernanda; Fett-Neto, Arthur G</p> <p>2017-01-01</p> <p>The development of adventitious roots is affected by several factors, including the age of the cutting donor plant, which negatively affects rooting capacity. Eucalyptus globulus quickly loses rooting capacity of cuttings as the donor plant ages, although the <span class="hlt">molecular</span> and biochemical mechanisms behind this process are still unclear. To better understand the bases of rooting competence loss in E. globulus , the time required for a significant decline in rhizogenic ability without exogenous auxin was determined in microcuttings derived from donor plants of different ages after sowing. Tip cuttings of donor plants were severed before and after loss of rooting competence of microcuttings to test the hypothesis that auxin and carbohydrate homeostasis regulate rooting competence decline. There were no significant changes in concentration of carbohydrates, flavonoids, or proteins before and after the loss of rooting capacity. Peroxidase (EC 1.11.1.7) total activity increased with loss of rooting competence. Auxin concentration showed the opposite pattern. In good agreement, TAA1 , a key gene in auxin biosynthesis, had lower expression after loss of rooting capacity. The same applied to the auxin receptor gene TIR1 , suggesting reduced auxin sensitivity. On the other hand, genes associated with auxin response repression ( TPL , IAA12 ) or with the action of cytokinins, the rhizogenesis inhibitor-related ARR1 , showed higher expression in plants with lower rooting competence. Taken together, data suggest that age negatively affects E. globulus rooting by a combination of factors. Decreased endogenous auxin concentration, possibly caused by less biosynthesis, lower auxin sensitivity, higher expression of genes inhibiting auxin action, as well as of genes related to the action of cytokinins, appear to play roles in this process.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5641372','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5641372"><span><span class="hlt">Events</span> Associated with <span class="hlt">Early</span> Age-Related Decline in Adventitious Rooting Competence of Eucalyptus globulus Labill</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Aumond, Márcio L.; de Araujo, Artur T.; de Oliveira Junkes, Camila F.; de Almeida, Márcia R.; Matsuura, Hélio N.; de Costa, Fernanda; Fett-Neto, Arthur G.</p> <p>2017-01-01</p> <p>The development of adventitious roots is affected by several factors, including the age of the cutting donor plant, which negatively affects rooting capacity. Eucalyptus globulus quickly loses rooting capacity of cuttings as the donor plant ages, although the <span class="hlt">molecular</span> and biochemical mechanisms behind this process are still unclear. To better understand the bases of rooting competence loss in E. globulus, the time required for a significant decline in rhizogenic ability without exogenous auxin was determined in microcuttings derived from donor plants of different ages after sowing. Tip cuttings of donor plants were severed before and after loss of rooting competence of microcuttings to test the hypothesis that auxin and carbohydrate homeostasis regulate rooting competence decline. There were no significant changes in concentration of carbohydrates, flavonoids, or proteins before and after the loss of rooting capacity. Peroxidase (EC 1.11.1.7) total activity increased with loss of rooting competence. Auxin concentration showed the opposite pattern. In good agreement, TAA1, a key gene in auxin biosynthesis, had lower expression after loss of rooting capacity. The same applied to the auxin receptor gene TIR1, suggesting reduced auxin sensitivity. On the other hand, genes associated with auxin response repression (TPL, IAA12) or with the action of cytokinins, the rhizogenesis inhibitor-related ARR1, showed higher expression in plants with lower rooting competence. Taken together, data suggest that age negatively affects E. globulus rooting by a combination of factors. Decreased endogenous auxin concentration, possibly caused by less biosynthesis, lower auxin sensitivity, higher expression of genes inhibiting auxin action, as well as of genes related to the action of cytokinins, appear to play roles in this process. PMID:29067033</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010AGUFMNH33A1371C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010AGUFMNH33A1371C"><span>CISN ShakeAlert: Faster Warning Information Through Multiple Threshold <span class="hlt">Event</span> Detection in the Virtual Seismologist (VS) <span class="hlt">Early</span> Warning Algorithm</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Cua, G. B.; Fischer, M.; Caprio, M.; Heaton, T. H.; Cisn Earthquake Early Warning Project Team</p> <p>2010-12-01</p> <p>The Virtual Seismologist (VS) earthquake <span class="hlt">early</span> warning (EEW) algorithm is one of 3 EEW approaches being incorporated into the California Integrated Seismic Network (CISN) ShakeAlert system, a prototype EEW system that could potentially be implemented in California. The VS algorithm, implemented by the Swiss Seismological Service at ETH Zurich, is a Bayesian approach to EEW, wherein the most probable source estimate at any given time is a combination of contributions from a likehihood function that evolves in response to incoming data from the on-going earthquake, and selected prior information, which can include factors such as network topology, the Gutenberg-Richter relationship or previously observed seismicity. The VS codes have been running in real-time at the Southern California Seismic Network since July 2008, and at the Northern California Seismic Network since February 2009. We discuss recent enhancements to the VS EEW algorithm that are being integrated into CISN ShakeAlert. We developed and continue to test a multiple-threshold <span class="hlt">event</span> detection scheme, which uses different association / location approaches depending on the peak amplitudes associated with an incoming P pick. With this scheme, an <span class="hlt">event</span> with sufficiently high initial amplitudes can be declared on the basis of a single station, maximizing warning times for damaging <span class="hlt">events</span> for which EEW is most relevant. Smaller, non-damaging <span class="hlt">events</span>, which will have lower initial amplitudes, will require more picks to initiate an <span class="hlt">event</span> declaration, with the goal of reducing false alarms. This transforms the VS codes from a regional EEW approach reliant on traditional location estimation (and the requirement of at least 4 picks as implemented by the Binder Earthworm phase associator) into an on-site/regional approach capable of providing a continuously evolving stream of EEW information starting from the first P-detection. Real-time and offline analysis on Swiss and California waveform datasets indicate that the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25643818','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25643818"><span><span class="hlt">Molecular</span> detection of a putatively novel cyprinid herpesvirus in sichel (Pelecus cultratus) during a mass mortality <span class="hlt">event</span> in Hungary.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Doszpoly, Andor; Papp, Melitta; Deákné, Petra P; Glávits, Róbert; Ursu, Krisztina; Dán, Ádám</p> <p>2015-05-01</p> <p>In the <span class="hlt">early</span> summer of 2014, mass mortality of sichel (Pelecus cultratus) was observed in Lake Balaton, Hungary. Histological examination revealed degenerative changes within the tubular epithelium, mainly in the distal tubules and collecting ducts in the kidneys and multifocal vacuolisation in the brain stem and cerebellum. Routine <span class="hlt">molecular</span> investigations showed the presence of the DNA of an unknown alloherpesvirus in some specimens. Subsequently, three genes of the putative herpesviral genome (DNA polymerase, terminase, and helicase) were amplified and partially sequenced. A phylogenetic tree reconstruction based on the concatenated sequence of these three conserved genes implied that the virus belongs to the genus Cyprinivirus within the family Alloherpesviridae. The sequences of the sichel herpesvirus differ markedly from those of the cypriniviruses CyHV-1, CyHV-2 and CyHV-3, putatively representing a fifth species in the genus.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27397682','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27397682"><span>Complex epithelial remodeling underlie the fusion <span class="hlt">event</span> in <span class="hlt">early</span> fetal development of the human penile urethra.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shen, Joel; Overland, Maya; Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence</p> <p></p> <p>We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion <span class="hlt">events</span>, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. Copyright © 2016 International Society</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018GPC...162...53F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018GPC...162...53F"><span>The <span class="hlt">Early</span> Toarcian oceanic anoxic <span class="hlt">event</span>: Paleoenvironmental and paleoclimatic change across the Alpine Tethys (Switzerland)</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Fantasia, Alicia; Föllmi, Karl B.; Adatte, Thierry; Spangenberg, Jorge E.; Montero-Serrano, Jean-Carlos</p> <p>2018-03-01</p> <p>Paleoenvironmental and paleoclimatic change associated with the Toarcian oceanic anoxic <span class="hlt">event</span> (T-OAE) was evaluated in five successions located in Switzerland. They represent different paleogeographic settings across the Alpine Tethys: the northern shelf (Gipf, Riniken and Rietheim), the Sub-Briançonnais basin (Creux de l'Ours), and the Lombardian basin (Breggia). The multi-proxy approach chosen (whole-rock and clay mineralogy, phosphorus, major and trace elements) shows that local environmental conditions modulated the response to the T-OAE across the Alpine Tethys. On the northern shelf and in the Sub-Briançonnais basin, high kaolinite contents and detrital proxies (detrital index, Ti, Zr, Si) in the T-OAE interval suggest a change towards a warmer and more humid climate coupled with an increase in the chemical weathering rates. In contrast, low kaolinite content in the Lombardian basin is likely related to a more arid climate along the southern Tethys margin and/or to a deeper and more distal setting. Redox-sensitive trace-element (V, Mo, Cu, Ni) enrichments in the T-OAE intervals reveal that dysoxic to anoxic conditions developed on the northern shelf, whereas reducing conditions were less severe in the Sub-Briançonnais basin. In the Lombardian basin well-oxygenated bottom water conditions prevailed. Phosphorus (P) speciation analysis was performed at Riniken and Creux de l'Ours. This is the first report of P speciation data for T-OAE sections, clearly suggesting that high P contents during this time interval are mainly linked to the presence of an authigenic phases and fish remains. The development of oxygen-depleted conditions during the T-OAE seems to have promoted the release of the organic-bound P back into the water column, thereby further sustaining primary productivity in a positive feedback loop.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28366424','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28366424"><span>Alcohol Intake More than Doubles the Risk of <span class="hlt">Early</span> Cardiovascular <span class="hlt">Events</span> in Young Hypertensive Smokers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Palatini, Paolo; Fania, Claudio; Mos, Lucio; Mazzer, Adriano; Saladini, Francesca; Casiglia, Edoardo</p> <p>2017-08-01</p> <p>An interactive effect of tobacco and alcohol use has been described for cancer. The aim of this study was to investigate the joint effect of smoking and alcohol intake on major adverse cardiovascular and renal <span class="hlt">events</span> (MACE) in young subjects screened for stage 1 hypertension. A total of 1204 untreated patients aged from 18 to 45 years (mean 33.1) were included in this prospective cohort study. Subjects were classified into 4 categories of cigarette smoking and 3 classes of alcohol use. Main outcome variable was risk for MACE. During a 12.6-year follow-up, there were 74 fatal and nonfatal MACE. In multivariable Cox models, current smoking and alcohol drinking were associated with risk of MACE. In a multivariable model also including follow-up changes in blood pressure and body weight, hazard ratio (HR) was 1.48 (95% confidence interval [CI], 1.20-1.83) for smoking and was 1.82 (95% CI, 1.05-3.15) for alcohol use. In addition, an interactive effect was found between smoking and alcohol on risk of MACE (P <.001). Among the 142 smokers who also drank alcoholic beverages, the risk of MACE (HR 4.02; 95% CI, 1.98-8.15) was more than doubled compared with the 112 smokers who abstained from drinking (HR 1.64; 95% CI, 0.63-4.27). In the group of heavy smokers who also were alcohol drinkers (n = 51), the risk of MACE was even quadrupled (HR 7.79; 95% CI, 4.22-14.37). Alcohol use potentiates the deleterious cardiovascular effects of heavy smoking in stage 1 hypertensive subjects younger than 45 years. These results call for prompt intervention addressed to improve unhealthy behaviors in these subjects. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26446379','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26446379"><span>Prior chronic clopidogrel therapy is associated with increased adverse <span class="hlt">events</span> and <span class="hlt">early</span> stent thrombosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Asher, Elad; Fefer, Paul; Sabbag, Avi; Herscovici, Romana; Regev, Ehud; Mazin, Israel; Shlomo, Nir; Zahger, Doron; Atar, Shaul; Hammerman, Haim; Polak, Arthur; Beigel, Roy; Matetzky, Shlomi</p> <p>2016-01-01</p> <p>Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular <span class="hlt">events</span> (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014EGUGA..1613072C','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014EGUGA..1613072C"><span>The PRESSCA operational <span class="hlt">early</span> warning system for landslide forecasting: the 11-12 November 2013 rainfall <span class="hlt">event</span> in Central Italy.</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Ciabatta, Luca; Brocca, Luca; Ponziani, Francesco; Berni, Nicola; Stelluti, Marco; Moramarco, Tommaso</p> <p>2014-05-01</p> <p>The Umbria Region, located in Central Italy, is one of the most landslide risk prone area in Italy, almost yearly affected by landslides <span class="hlt">events</span> at different spatial scales. For <span class="hlt">early</span> warning procedures aimed at the assessment of the hydrogeological risk, the rainfall thresholds represent the main tool for the Italian Civil Protection System. As shown in previous studies, soil moisture plays a key-role in landslides triggering. In fact, acting on the pore water pressure, soil moisture influences the rainfall amount needed for activating a landslide. In this work, an operational physically-based <span class="hlt">early</span> warning system, named PRESSCA, that takes into account soil moisture for the definition of rainfall thresholds is presented. Specifically, the soil moisture conditions are evaluated in PRESSCA by using a distributed soil water balance model that is recently coupled with near real-time satellite soil moisture product obtained from ASCAT (Advanced SCATterometer) and from in-situ monitoring data. The integration of three different sources of soil moisture information allows to estimate the most accurate possible soil moisture condition. Then, both observed and forecasted rainfall data are compared with the soil moisture-based thresholds in order to obtain risk indicators over a grid of ~ 5 km. These indicators are then used for the daily hydrogeological risk evaluation and management by the Civil Protection regional service, through the sharing/delivering of near real-time landslide risk scenarios (also through an open source web platform: www.cfumbria.it). On the 11th-12th November, 2013, Umbria Region was hit by an exceptional rainfall <span class="hlt">event</span> with up to 430mm/72hours that resulted in significant economic damages, but fortunately no casualties among the population. In this study, the results during the rainfall <span class="hlt">event</span> of PRESSCA system are described, by underlining the model capability to reproduce, two days in advance, landslide risk scenarios in good spatial and temporal</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li class="active"><span>15</span></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_15 --> <div id="page_16" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li class="active"><span>16</span></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="301"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28849724','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28849724"><span><span class="hlt">Molecular</span>-genetic diagnostics of von Hippel-Lindau syndrome (VHL) in Bulgaria: first complex mutation <span class="hlt">event</span> in the VHL gene.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Glushkova, Maria; Dimova, Petia; Yordanova, Iglika; Todorov, Tihomir; Tourtourikov, Ivan; Mitev, Vanyo; Todorova, Albena</p> <p>2018-02-01</p> <p>Von Hippel-Lindau syndrome is an autosomal-dominant disease characterized by the formation of various tumours and cysts in many different parts of the body. Von Hippel-Lindau syndrome is caused by VHL gene mutations leading to production of impaired tumor suppressor Von Hippel-Lindau syndrome protein or its complete absence. To study five patients with clinically suspected Von Hippel-Lindau syndrome, who were referred for <span class="hlt">molecular</span> genetic testing. Sanger sequencing of the coding regions of the VHL gene. Five clinically relevant germline mutations were detected. One of the pathogenic variants has not been previously reported. This novel mutation is a complex mutation <span class="hlt">event</span> combining a duplication and an indel, rearranging exon 3 of the VHL gene - c. [516_517dupGTCAAGCCT; 532_542delCTGGACATCGTinsATTA], p. (Glu173Serfs*4). Overall, our results showed that the diagnosis of Von Hippel-Lindau syndrome in our country is difficult most probably because of its heterogeneous clinical manifestation and insufficient knowledge on the diagnostic criteria for the disease. From genetic point of view our results add some novel data on the mutation profile of the VHL gene. In order to prove or revise the diagnosis, <span class="hlt">early</span> genetic testing is strongly recommended in affected patients and their family members to ensure appropriate follow-up and treatment of the malignancies.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=366456','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=366456"><span>The Effect of Arsenate and Other Inhibitors on <span class="hlt">Early</span> <span class="hlt">Events</span> during the Germination of Lettuce Seeds (Lactuca sativa L.)</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Speer, Henry L.</p> <p>1973-01-01</p> <p>The effect of arsenate, arsenite, 2,4-dinitrophenol, and anaerobiosis on <span class="hlt">early</span> <span class="hlt">events</span> in seed germination was investigated using both intact and punched seeds of lettuce (Lactuca sativa L.). It was found that punching the seed removes penetration barriers to the entrance of inhibitors without an undue loss of germination or light responses. The kinetics of the action of germination inhibitors were established by 2-hour pulse experiments. Arsenate and 2, 4-dinitrophenol have very different kinetics. The inhibition of germination in punched seeds by arsenate given in conjunction with phosphate compared with the lack of inhibition of arsenate plus phosphate on the growing seedling, suggest a distinct metabolic change in the germinating embryo at some time between the onset of germination and subsequent seedling growth. Images PMID:16658515</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5075782','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5075782"><span><span class="hlt">Early</span> nucleation <span class="hlt">events</span> in the polymerization of actin, probed by time-resolved small-angle x-ray scattering</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Oda, Toshiro; Aihara, Tomoki; Wakabayashi, Katsuzo</p> <p>2016-01-01</p> <p>Nucleators generating new F-actin filaments play important roles in cell activities. Detailed information concerning the <span class="hlt">events</span> involved in nucleation of actin alone in vitro is fundamental to understanding these processes, but such information has been hard to come by. We addressed the <span class="hlt">early</span> process of salt-induced polymerization of actin using the time-resolved synchrotron small-angle X-ray scattering (SAXS). Actin molecules in low salt solution maintain a monomeric state by an electrostatic repulsive force between molecules. On mixing with salts, the repulsive force was rapidly screened, causing an immediate formation of many of non-polymerizable dimers. SAXS kinetic analysis revealed that tetramerization gives the highest energetic barrier to further polymerization, and the major nucleation is the formation of helical tetramers. Filaments start to grow rapidly with the formation of pentamers. These findings suggest an acceleration mechanism of actin assembly by a variety of nucleators in cells. PMID:27775032</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/81013','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/81013"><span>The Center for the Study of <span class="hlt">Early</span> <span class="hlt">Events</span> in Photosynthesis. Final report, September 1, 1988--August 31, 1994</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Orr, L.A.</p> <p></p> <p>The ASU Center for the Study of <span class="hlt">Early</span> <span class="hlt">Events</span> in Photosynthesis was established in 1988 with funding through a five-year grant from the USDA/DOE/NSF Plant Science Center program and a grant from the NSF Biological Facilities program. Its scientific objective is to elucidate the basic principles that govern photosynthetic energy collection and storage. Understanding these principles is vital to mankind, as photosynthesis provides most of our food, fiber and energy needs. The Center attempts to fulfill this objective through research of the highest standard, coupled inextricably with quality education at the undergraduate, graduate and postdoctoral levels. These goals are metmore » via a network of collaborative, interdisciplinary research groups comprising 100 personnel within the Department of Chemistry and Biochemistry, the Department of Botany, and the Department of Physics and Astronomy. The work of these research groups is facilitated by the Center through a variety of important infrastructural functions.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013AGUFM.A41I..08B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013AGUFM.A41I..08B"><span>The Intense Arctic Cyclone of <span class="hlt">Early</span> August 2012: A Dynamically Driven Cyclogenesis <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Bosart, L. F.; Turchioe, A.; Adamchcik, E.</p> <p>2013-12-01</p> <p>A series of surface cyclones formed along an anomalously strong northeast-southwest oriented baroclinic zone over north-central Russia on 1-3 August 2012. These cyclones moved northeastward, intensified slowly, and crossed the coast of Russia by 4 August. The last cyclone in the series strengthened rapidly as it moved poleward over the Arctic Ocean on 5-6 August, achieved a minimum sea level pressure of < 965 hPa by 6 August, and was arguably the most intense storm system to impact the Arctic Ocean in the modern data record going back to the International Geophysical Year in 1957-1958. The purpose of this presentation is to illustrate the structure and life cycle of this Arctic Ocean cyclone from a multiscale perspective. Anticyclonic wave breaking in the upper troposphere across Russia in late July and very <span class="hlt">early</span> August 2012 created an anomalously strong baroclinic zone across northern Asia between 60-80°N. During 1-5 August, negative 850 hPa temperature anomalies between -2° and -4°C were found poleward of 70-75°N between 90°E and the Dateline over the Arctic Ocean while positive 850 hPa temperature anomalies of 8-9°C were found over eastern Russia near 60°N. The associated anomalously strong 850 hPa meridional temperature gradient of ~10°C (2000 km)-1 helped to sustain an anomalously strong (20-30 m s-1) 250 hPa jet along the coast of northeastern Russia. A local wind speed maximum (~50 m s-1 ) embedded in this 250 hPa jet corridor contributed to the extreme intensity of the trailing (last) surface cyclone in the series. Although the dominant surface cyclone in the series of surface cyclones intensified most rapidly over the relatively ice free Arctic Ocean, the impact of surface heat and moisture fluxes appeared to be secondary to jet-driven dynamical processes in the deepening process. Anomalously high observed 1000-500 hPa thickness values between 564-570 dam, precipitable water values between 30-40 mm, and CAPE values between 500-1000 J kg-1 in the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16813575','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16813575"><span>A C2H2-type zinc finger protein, SGR5, is involved in <span class="hlt">early</span> <span class="hlt">events</span> of gravitropism in Arabidopsis inflorescence stems.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Morita, Miyo T; Sakaguchi, Keitaro; Kiyose, Shin-Ichiro; Taira, Kensuke; Kato, Takehide; Nakamura, Moritaka; Tasaka, Masao</p> <p>2006-08-01</p> <p>Plants can sense the direction of gravity and change the growth orientation of their organs. To elucidate the <span class="hlt">molecular</span> mechanisms of gravity perception and the signal transduction of gravitropism, we have characterized a number of shoot gravitropism (sgr) mutants of Arabidopsis. The sgr5-1 mutant shows reduced gravitropism in the inflorescence stem but its root and hypocotyl have normal gravitropism. SGR5 encodes a zinc finger protein with a coiled-coil motif. The SGR5-GFP fusion protein is localized in the nucleus of Arabidopsis protoplasts, suggesting that SGR5 may act as a transcription factor. Analysis of GUS expression under the control of the SGR5 promoter revealed that SGR5 is mainly expressed in the endodermis, the gravity-sensing tissue in inflorescence stems. Furthermore, the observation that endodermis-specific expression of SGR5 using the SCR promoter in the sgr5-1 mutant restores shoot gravitropism indicates that it could function in the gravity-sensing endodermal cell layer. In contrast to other sgr mutants reported previously, almost all amyloplasts in the endodermal cells of the sgr5-1 mutant sedimented in the direction of gravity. Taken together, our results suggest that SGR5 may be involved in an <span class="hlt">early</span> <span class="hlt">event</span> in shoot gravitropism such as gravity perception and/or a signaling process subsequent to amyloplast sedimentation as a putative transcription factor in gravity-perceptive cells.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28507167','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28507167"><span><span class="hlt">Early</span> activation of deleterious <span class="hlt">molecular</span> pathways in the kidney in experimental heart failure with atrial remodeling.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ichiki, Tomoko; Huntley, Brenda K; Harty, Gail J; Sangaralingham, S Jeson; Burnett, John C</p> <p>2017-05-01</p> <p>Heart failure (HF) is a major health problem with worsening outcomes when renal impairment is present. Therapeutics for <span class="hlt">early</span> phase HF may be effective for cardiorenal protection, however the detailed characteristics of the kidney in <span class="hlt">early</span>-stage HF (ES-HF), and therefore treatment for potential renal protection, are poorly defined. We sought to determine the gene and protein expression profiles of specific maladaptive pathways of ES-HF in the kidney and heart. Experimental canine ES-HF, characterized by de-novo HF with atrial remodeling but not ventricular fibrosis, was induced by right ventricular pacing for 10 days. Kidney cortex (KC), medulla (KM), left ventricle (LV), and left atrial (LA) tissues from ES-HF versus normal canines ( n  = 4 of each) were analyzed using RT-PCR microarrays and protein assays to assess genes and proteins related to inflammation, renal injury, apoptosis, and fibrosis. ES-HF was characterized by increased circulating natriuretic peptides and components of the renin-angiotensin-aldosterone system and decreased sodium and water excretion with mild renal injury and up-regulation of CNP and renin genes in the kidney. Compared to normals, widespread genes, especially genes of the inflammatory pathways, were up-regulated in KC similar to increases seen in LA Protein expressions related to inflammatory cytokines were also augmented in the KC Gene and protein changes were less prominent in the LV and KM The ES-HF displayed mild renal injury with widespread gene changes and increased inflammatory cytokines. These changes may provide important clues into the pathophysiology of ES-HF and for therapeutic <span class="hlt">molecular</span> targets in the kidney of ES-HF. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5020184','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5020184"><span>Simple <span class="hlt">Molecular</span> Methods for <span class="hlt">Early</span> Detection of Chloroquine Drug Resistance in Plasmodium vivax and Plasmodium falciparum</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Singh, Raksha; Urhehar, Anant Dattatraya</p> <p>2016-01-01</p> <p>Introduction Malaria is a human disease of which causes high morbidity and mortality. In Plasmodium falciparum malaria, the resistance to antimalarial drugs, especially chloroquine (CQ) is one of the paramount factors contributing to the global increase in morbidity and mortality, due to malaria. Hence, there is a need for detection of chloroquine drug resistance genes i.e., pfcrt-o (Plasmodium falciparum chloroquine resistance transporter-o) and pfmdr-1 (Plasmodium falciparum multidrug resistance-1) of P. falciparum and pvcrt-o (Plasmodium vivax chloroquine resistance transporter-o) and pvmdr-1 (Plasmodium vivax multidrug resistance-1) of P. vivax by using <span class="hlt">molecular</span> methods to prevent mortality in malarial cases. Aim To standardize chloroquine drug sensitivity testing by <span class="hlt">molecular</span> method so as to provide reports of chloroquine within 6-8 hours to physicians for better treatment. Materials and Methods This study was conducted over a period of one year from January to December 2014. A Total of 300 blood samples were collected from malaria suspected patient attending MGM Hospital, Kamothe, Navi Mumbai, India. Out of 300 blood samples, 44 were malaria positive as assessed by Thick and Thin blood smear stained, by Leishman’s method and examination with light microscope. Chloroquine drug sensitivity testing was performed using WHO III plate method (micro test). Nested PCR was done for detection of pfcrt-o and pfmdr-1 for P. falciparum and pvcrt-o, pvmdr-1 genes for P. vivax. Results Total 44 samples were included in this study, out of which 22 samples confirmed for Plasmodium falciparum and 22 samples confirmed for Plasmodium vivax. Out of 22 P. falciparum 15 (68.18%) samples were chloroquine resistant. P. vivax showed chloroquine resistance to 5 samples (22.73%) by method similar to WHO III plate method (micro test) and nested PCR. Conclusion Drug resistance testing by <span class="hlt">molecular</span> methods is useful for <span class="hlt">early</span> detection of antimalarial drug resistance. pfmdr-1 along with</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27988471','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27988471"><span><span class="hlt">Early</span> histological, hormonal, and <span class="hlt">molecular</span> changes during pineapple (Ananas comosus (L.) Merrill) artificial flowering induction.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Espinosa, Maita Eulalia Ávila; Moreira, Rafael Oliveira; Lima, André Almeida; Ságio, Solange Aparecida; Barreto, Horllys Gomes; Luiz, Sara Lazara Pérez; Abreu, Carlos Eduardo Aragón; Yanes-Paz, Ermis; Ruíz, Yanelis Capdesuñer; González-Olmedo, Justo Lorenzo; Chalfun-Júnior, Antonio</p> <p>2017-02-01</p> <p>Natural flowering can cause serious scheduling problems in the pineapple (Ananas comosus) industry and increase harvest costs. Pineapple flowering is thought to be triggered by increased ethylene levels and artificial forcing of pineapple flowering is a common practice to promote flowering synchronisation. However, little is known about the <span class="hlt">early</span> hormonal and <span class="hlt">molecular</span> changes of pineapple flowering induction and development. Here, we aimed to analyse the <span class="hlt">molecular</span>, hormonal, and histological changes during artificial pineapple flowering by Ethrel ® 48 treatment. Histological analyses of the shoot apical meristem, leaf gibberellic acid (GA 3 ), and ethylene quantification were carried out during the first 72h after Ethrel ® 48 treatment. Expression profiles from ethylene biosynthesis (AcACS2 and AcACO1), gibberellin metabolism (AcGA2-ox1 and AcDELLA1), and flower development (FT-like gene (AcFT), LFY-like gene (AcLFY), and a PISTILLATA-like gene (AcPI)) genes were analysed during the first 24h after Ethrel ® 48 treatment. Differentiation processes of the shoot apical meristem into flower buds were already present in the first 72h after Ethrel ® 48 treatment. Ethrel ® 48 lead to a reduction in GA 3 levels, probably triggered by elevated ethylene levels and the positive regulation AcGA2-ox1. AcLFY activation upon Ethrel ® 48 may also have contributed to the reduction of GA 3 levels and, along with the up-regulation of AcPI, are probably associated with the flower induction activation. AcFT and AcDELLA1 do not seem to be regulated by GA 3 and ethylene. Decreased GA 3 and increased ethylene levels suggest an accumulation of AcDELLA1, which may display an important role in pineapple flowering induction. Thus, this study shows that <span class="hlt">molecular</span>, hormonal, and histological changes are present right after Ethrel ® 48 treatment, providing new insights into how pineapple flowering occurs under natural conditions. Copyright © 2016 Elsevier GmbH. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009AGUFM.S22A..02F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009AGUFM.S22A..02F"><span>Multiple-Threshold <span class="hlt">Event</span> Detection and Other Enhancements to the Virtual Seismologist (VS) Earthquake <span class="hlt">Early</span> Warning Algorithm</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Fischer, M.; Caprio, M.; Cua, G. B.; Heaton, T. H.; Clinton, J. F.; Wiemer, S.</p> <p>2009-12-01</p> <p>The Virtual Seismologist (VS) algorithm is a Bayesian approach to earthquake <span class="hlt">early</span> warning (EEW) being implemented by the Swiss Seismological Service at ETH Zurich. The application of Bayes’ theorem in earthquake <span class="hlt">early</span> warning states that the most probable source estimate at any given time is a combination of contributions from a likelihood function that evolves in response to incoming data from the on-going earthquake, and selected prior information, which can include factors such as network topology, the Gutenberg-Richter relationship or previously observed seismicity. The VS algorithm was one of three EEW algorithms involved in the California Integrated Seismic Network (CISN) real-time EEW testing and performance evaluation effort. Its compelling real-time performance in California over the last three years has led to its inclusion in the new USGS-funded effort to develop key components of CISN ShakeAlert, a prototype EEW system that could potentially be implemented in California. A significant portion of VS code development was supported by the SAFER EEW project in Europe. We discuss recent enhancements to the VS EEW algorithm. We developed and continue to test a multiple-threshold <span class="hlt">event</span> detection scheme, which uses different association / location approaches depending on the peak amplitudes associated with an incoming P pick. With this scheme, an <span class="hlt">event</span> with sufficiently high initial amplitudes can be declared on the basis of a single station, maximizing warning times for damaging <span class="hlt">events</span> for which EEW is most relevant. Smaller, non-damaging <span class="hlt">events</span>, which will have lower initial amplitudes, will require more picks to be declared an <span class="hlt">event</span> to reduce false alarms. This transforms the VS codes from a regional EEW approach reliant on traditional location estimation (and it requirement of at least 4 picks as implemented by the Binder Earthworm phase associator) to a hybrid on-site/regional approach capable of providing a continuously evolving stream of EEW</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26058698','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26058698"><span><span class="hlt">Early</span> disrupted neurovascular coupling and changed <span class="hlt">event</span> level hemodynamic response function in type 2 diabetes: an fMRI study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel</p> <p>2015-10-01</p> <p>Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an <span class="hlt">event</span>-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in <span class="hlt">early</span> stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in <span class="hlt">event</span>-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2692014','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2692014"><span>Co-ordination of <span class="hlt">early</span> and late ripening <span class="hlt">events</span> in apples is regulated through differential sensitivities to ethylene</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Johnston, Jason W.; Gunaseelan, Kularajathaven; Pidakala, Paul; Wang, Mindy; Schaffer, Robert J.</p> <p>2009-01-01</p> <p>In this study, it is shown that anti-sense suppression of Malus domestica 1-AMINO-CYCLOPROPANE-CARBOXYLASE OXIDASE (MdACO1) resulted in fruit with an ethylene production sufficiently low to be able to assess ripening in the absence of ethylene. Exposure of these fruit to different concentrations of exogenous ethylene showed that flesh softening, volatile biosynthesis, and starch degradation, had differing ethylene sensitivity and dependency. <span class="hlt">Early</span> ripening <span class="hlt">events</span> such as the conversion of starch to sugars showed a low dependency for ethylene, but a high sensitivity to low concentrations of ethylene (0.01 μl l−1). By contrast, later ripening <span class="hlt">events</span> such as flesh softening and ester volatile production showed a high dependency for ethylene but were less sensitive to low concentrations (needing 0.1 μl l−1 for a response). A sustained exposure to ethylene was required to maintain ripening, indicating that the role of ethylene may go beyond that of ripening initiation. These results suggest a conceptual model for the control of individual ripening characters in apple, based on both ethylene dependency and sensitivity. PMID:19429839</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22594531-early-stage-oxynitridation-process-si-surface-gas-reactive-molecular-dynamics-simulation-study','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22594531-early-stage-oxynitridation-process-si-surface-gas-reactive-molecular-dynamics-simulation-study"><span><span class="hlt">Early</span> stage oxynitridation process of Si(001) surface by NO gas: Reactive <span class="hlt">molecular</span> dynamics simulation study</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Cao, Haining; Kim, Seungchul; Lee, Kwang-Ryeol, E-mail: krlee@kist.re.kr</p> <p>2016-03-28</p> <p>Initial stage of oxynitridation process of Si substrate is of crucial importance in fabricating the ultrathin gate dielectric layer of high quality in advanced MOSFET devices. The oxynitridation reaction on a relaxed Si(001) surface is investigated via reactive <span class="hlt">molecular</span> dynamics (MD) simulation. A total of 1120 <span class="hlt">events</span> of a single nitric oxide (NO) molecule reaction at temperatures ranging from 300 to 1000 K are statistically analyzed. The observed reaction kinetics are consistent with the previous experimental or calculation results, which show the viability of the reactive MD technique to study the NO dissociation reaction on Si. We suggest the reaction pathwaymore » for NO dissociation that is characterized by the inter-dimer bridge of a NO molecule as the intermediate state prior to NO dissociation. Although the energy of the inter-dimer bridge is higher than that of the intra-dimer one, our suggestion is supported by the ab initio nudged elastic band calculations showing that the energy barrier for the inter-dimer bridge formation is much lower. The growth mechanism of an ultrathin Si oxynitride layer is also investigated via consecutive NO reactions simulation. The simulation reveals the mechanism of self-limiting reaction at low temperature and the time evolution of the depth profile of N and O atoms depending on the process temperature, which would guide to optimize the oxynitridation process condition.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4677922','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4677922"><span>Changes in the Phosphoproteome and Metabolome Link <span class="hlt">Early</span> Signaling <span class="hlt">Events</span> to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis1</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Chen, Yanmei; Hoehenwarter, Wolfgang</p> <p>2015-01-01</p> <p>Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The <span class="hlt">molecular</span> and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture <span class="hlt">early</span> signaling <span class="hlt">events</span> with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K+ and Na+ transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between <span class="hlt">early</span> signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. PMID:26471895</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/1198284-differential-network-analyses-alzheimers-disease-identify-early-events-alzheimers-disease-pathology','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/1198284-differential-network-analyses-alzheimers-disease-identify-early-events-alzheimers-disease-pathology"><span>Differential Network Analyses of Alzheimer’s Disease Identify <span class="hlt">Early</span> <span class="hlt">Events</span> in Alzheimer’s Disease Pathology</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Xia, Jing; Rocke, David M.; Perry, George</p> <p></p> <p>In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and <span class="hlt">early</span> characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very <span class="hlt">early</span> <span class="hlt">events</span> occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3566377','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3566377"><span><span class="hlt">Early</span> psychosocial interventions after disasters, terrorism and other shocking <span class="hlt">events</span>: is there a gap between norms and practice in Europe?</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Te Brake, Hans</p> <p>2013-01-01</p> <p>Background Internationally, several initiatives exist to describe standards for post-disaster psychosocial care. Objective This study explored the level of consensus of experts within Europe on a set of recommendations on <span class="hlt">early</span> psychosocial intervention after shocking <span class="hlt">events</span> (Dutch guidelines), and to what degree these standards are implemented into mental health care practice. Methods Two hundred and six (mental) health care professionals filled out a questionnaire to assess the extent to which they consider the guidelines’ scope and recommendations relevant and part of the regular practice in their own country. Forty-five European experts from 24 EU countries discussed the guidelines at an international seminar. Results The data suggest overall agreement on the standards although many of the recommendations appear not (yet) to be embedded in everyday practice. Conclusions Although large consensus exists on standards for <span class="hlt">early</span> psychosocial care, a chasm between norms and practice appears to exist throughout the EU, stressing the general need for investments in guideline development and implementation. PMID:23393613</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1198284-differential-network-analyses-alzheimers-disease-identify-early-events-alzheimers-disease-pathology','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1198284-differential-network-analyses-alzheimers-disease-identify-early-events-alzheimers-disease-pathology"><span>Differential Network Analyses of Alzheimer’s Disease Identify <span class="hlt">Early</span> <span class="hlt">Events</span> in Alzheimer’s Disease Pathology</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Xia, Jing; Rocke, David M.; Perry, George; ...</p> <p>2014-01-01</p> <p>In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and <span class="hlt">early</span> characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very <span class="hlt">early</span> <span class="hlt">events</span> occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25867962','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25867962"><span>Implicit processing of heroin and emotional cues in abstinent heroin users: <span class="hlt">early</span> and late <span class="hlt">event</span>-related potential effects.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, Ling; Zhang, Jianxun; Zhao, Xin</p> <p>2015-05-01</p> <p>The abnormal cognitive processing of drug cues is a core characteristic of drug dependence. Previous research has suggested that the late positive potential (LPP) of heroin users is increased by heroin-related stimuli because of the attention-grabbing nature of such stimuli. The present research used a modified emotional Stroop (eStroop) task to examine whether there was an <span class="hlt">early</span> posterior negativity (EPN) modulation to heroin cues compared with emotional or neutral stimuli in heroin dependent subjects. Fifteen former heroin users and 15 matched controls performed the eStroop task, which was composed of positive, negative, heroin-related, and neutral pictures with superimposed color squares. Participants responded to the color of the square and not to the picture while behavioral data and <span class="hlt">event</span>-related potentials were recorded. There were no significant differences of EPN amplitudes to emotional and neutral stimuli between heroin users and controls. However, heroin users displayed increased EPN modulation for heroin cues, whereas this modulation was absent in controls. Drug-related cues acquire motivational salience and automatically capture the attention of heroin users at <span class="hlt">early</span> processing stages, even when engaged in a non-drug-related task. The EPN to heroin cues could represent a novel electrophysiological index with clinical implications for selecting abstinent drug users who are at increased risk of relapse or to evaluate treatment interventions.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2012AGUFMPP11C2035H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2012AGUFMPP11C2035H"><span>Timing of the Toarcian Ocean Anoxic <span class="hlt">Event</span> (<span class="hlt">Early</span> Jurassic) from correlation of astronomically forced global stratigraphic sections</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Huang, C.; Hinnov, L. A.; Hesselbo, S. P.</p> <p>2012-12-01</p> <p>The <span class="hlt">Early</span> Toarcian Oceanic Anoxic <span class="hlt">Event</span> (OAE) in the <span class="hlt">Early</span> Jurassic Period is associated with a major negative carbon isotope excursion (CIE), mass extinction, marine transgression and global warming. The Toarcian OAE is thought to have been caused by flood basalt magmatism, and may have been a trigger for mass extinction. However, these proposed causes of the Toarcian OAE and associated biotic crisis are not adequately resolved by a precise chronology. The duration of the Toarcian OAE has been estimated to be anywhere from ~0.12 to ~0.9 Myr, most recently 0.74 to 3.26 Myr from U-Pb dating. The CIE associated with the Toarcian OAE has a similar pattern at numerous localities, and there is evidence for astronomical forcing of marine carbon isotopes. Here we estimate a duration of ~625 kyr for the main negative CIE, ~860 kyr for the polymorphum zone and >1.58 Myr for the levisoni zone based on 405-kyr astronomical eccentricity tuning of the marine section at Peniche (Portugal). This 405-kyr tuned series provides a ~2.5 Myr continuous high-resolution chronology through the <span class="hlt">Early</span> Toarcian. There are 6, or possibly 7 short eccentricity cycles in the main CIE interval at Peniche. To confirm this astronomically based estimate, we analyzed five other sections at Yorkshire (UK), Dotternhausen (Germany), Valdorbia (Italy), Mechowo (Poland) and Serrucho, Neuquén (Argentina), from marine and terrestrial carbon isotopic series. These six stratigraphic sections from <span class="hlt">Early</span> Jurassic western Tethys and eastern Panthalassa record the Toarcian OAE with ~6 prominent carbon isotope cycles in the CIE that provide us a 600 ± 100 kyr duration. The Peniche 405 kyr-tuned series indicates that the pre- and post-CIE intervals experienced strong precession-eccentricity-forced climate change, whereas the CIE interval is marked by dominant obliquity forcing. These dramatic and abrupt changes in astronomical response in the carbon isotopes point to fundamental shifting in the <span class="hlt">Early</span> Toarcian</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3918912','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3918912"><span><span class="hlt">Early</span>-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, <span class="hlt">molecular</span>, and epigenetic mechanisms</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Huang, Li-Tung</p> <p>2014-01-01</p> <p><span class="hlt">Early</span>-life stress includes prenatal, postnatal, and adolescence stress. <span class="hlt">Early</span>-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and <span class="hlt">molecular</span> changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and <span class="hlt">molecular</span> changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, <span class="hlt">early</span>-life stress, and epilepsy are discussed. PMID:24574961</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li class="active"><span>16</span></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_16 --> <div id="page_17" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="321"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4928817','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4928817"><span><span class="hlt">Early</span>-Life <span class="hlt">Events</span>, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan</p> <p>2016-01-01</p> <p>Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in <span class="hlt">early</span> life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as <span class="hlt">early</span> colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in <span class="hlt">early</span> life and the succession process and the evolution of the microbial community as a function of time and <span class="hlt">events</span> occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27362264','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27362264"><span><span class="hlt">Early</span>-Life <span class="hlt">Events</span>, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan</p> <p>2016-01-01</p> <p>Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in <span class="hlt">early</span> life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as <span class="hlt">early</span> colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in <span class="hlt">early</span> life and the succession process and the evolution of the microbial community as a function of time and <span class="hlt">events</span> occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009JPCM...21X5101H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009JPCM...21X5101H"><span><span class="hlt">Early</span> structural development in melt-quenched polymer PTT from atomistic <span class="hlt">molecular</span> dynamic simulations</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hsieh, Min-Kang; Lin, Shiang-Tai</p> <p>2009-12-01</p> <p><span class="hlt">Molecular</span> dynamics simulations are performed to study the initial structural development in poly(trimethylene terephthalate) (PTT) when quenched below its melting point. The development of local ordering has been observed in our simulations. The thermal properties, such as the glass transition temperature (Tg) and the melting temperature (Tm), determined from our simulations are in reasonable agreement with experimental values. It is found that, between these two temperatures, the number of local structures quickly increases during the thermal relaxation period soon after the system is quenched and starts to fluctuate afterwards. The formation and development of local structures is found to be driven mainly by the torsional and van der Waals forces and follows the classical nucleation-growth mechanism. The variation of local structures' fraction with temperature exhibits a maximum between Tg and Tm, resembling the temperature dependence of the crystallization rate for most polymers. In addition, the backbone torsion distribution for segments within the local structures preferentially reorganizes to the trans-gauche-gauche-trans (t-g-g-t) conformation, the same as that in the crystalline state. As a consequence, we believe that such local structural ordering could be the baby nuclei that have been suggested to form in the <span class="hlt">early</span> stage of polymer crystallization.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27966594','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27966594"><span>Meteorite Impact-Induced Rapid NH3 Production on <span class="hlt">Early</span> Earth: Ab Initio <span class="hlt">Molecular</span> Dynamics Simulation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shimamura, Kohei; Shimojo, Fuyuki; Nakano, Aiichiro; Tanaka, Shigenori</p> <p>2016-12-14</p> <p>NH 3 is an essential molecule as a nitrogen source for prebiotic amino acid syntheses such as the Strecker reaction. Previous shock experiments demonstrated that meteorite impacts on ancient oceans would have provided a considerable amount of NH 3 from atmospheric N 2 and oceanic H 2 O through reduction by meteoritic iron. However, specific production mechanisms remain unclear, and impact velocities employed in the experiments were substantially lower than typical impact velocities of meteorites on the <span class="hlt">early</span> Earth. Here, to investigate the issues from the atomistic viewpoint, we performed multi-scale shock technique-based ab initio <span class="hlt">molecular</span> dynamics simulations. The results revealed a rapid production of NH 3 within several picoseconds after the shock, indicating that shocks with greater impact velocities would provide further increase in the yield of NH 3 . Meanwhile, the picosecond-order production makes one expect that the important nitrogen source precursors of amino acids were obtained immediately after the impact. It was also observed that the reduction of N 2 proceeded according to an associative mechanism, rather than a dissociative mechanism as in the Haber-Bosch process.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22267883-risk-cerebrovascular-events-elderly-patients-after-radiation-therapy-versus-surgery-early-stage-glottic-cancer','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22267883-risk-cerebrovascular-events-elderly-patients-after-radiation-therapy-versus-surgery-early-stage-glottic-cancer"><span>Risk of Cerebrovascular <span class="hlt">Events</span> in Elderly Patients After Radiation Therapy Versus Surgery for <span class="hlt">Early</span>-Stage Glottic Cancer</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai</p> <p></p> <p>Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for <span class="hlt">early</span>-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with <span class="hlt">early</span>-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular <span class="hlt">events</span>, and SEER data for stroke as the causemore » of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with <span class="hlt">early</span>-stage laryngeal cancer have a high burden of cerebrovascular <span class="hlt">events</span> after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25017101','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25017101"><span>Ritonavir binds to and downregulates estrogen receptors: <span class="hlt">molecular</span> mechanism of promoting <span class="hlt">early</span> atherosclerosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Xiang, Jin; Wang, Ying; Su, Ke; Liu, Min; Hu, Peng-Chao; Ma, Tian; Li, Jia-Xi; Wei, Lei; Zheng, Zhongliang; Yang, Fang</p> <p>2014-10-01</p> <p>Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist for E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and <span class="hlt">early</span> <span class="hlt">events</span> of atherosclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5710845','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5710845"><span><span class="hlt">Early</span> Experiences Porting the NAMD and VMD <span class="hlt">Molecular</span> Simulation and Analysis Software to GPU-Accelerated OpenPOWER Platforms</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Stone, John E.; Hynninen, Antti-Pekka; Phillips, James C.; Schulten, Klaus</p> <p>2017-01-01</p> <p>All-atom <span class="hlt">molecular</span> dynamics simulations of biomolecules provide a powerful tool for exploring the structure and dynamics of large protein complexes within realistic cellular environments. Unfortunately, such simulations are extremely demanding in terms of their computational requirements, and they present many challenges in terms of preparation, simulation methodology, and analysis and visualization of results. We describe our <span class="hlt">early</span> experiences porting the popular <span class="hlt">molecular</span> dynamics simulation program NAMD and the simulation preparation, analysis, and visualization tool VMD to GPU-accelerated OpenPOWER hardware platforms. We report our experiences with compiler-provided autovectorization and compare with hand-coded vector intrinsics for the POWER8 CPU. We explore the performance benefits obtained from unique POWER8 architectural features such as 8-way SMT and its value for particular <span class="hlt">molecular</span> modeling tasks. Finally, we evaluate the performance of several GPU-accelerated <span class="hlt">molecular</span> modeling kernels and relate them to other hardware platforms. PMID:29202130</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014EGUGA..16.7249H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014EGUGA..16.7249H"><span>Subsurface warming in the subpolar North Atlantic during rapid climate <span class="hlt">events</span> in the <span class="hlt">Early</span> and Mid-Pleistocene</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hernández-Almeida, Iván; Sierro, Francisco; Cacho, Isabel; Abel Flores, José</p> <p>2014-05-01</p> <p>A new high-resolution reconstruction of the temperature and salinity of the subsurface waters using paired Mg/Ca-δ18O measurements on the planktonic foraminifera Neogloboquadrina pachyderma sinistrorsa (sin.) was conducted on a deep-sea sediment core in the subpolar North Atlantic (Site U1314). This study aims to reconstruct millennial-scale subsurface hydrography variations during the <span class="hlt">Early</span> and Mid-Pleistocene (MIS 31-19). These rapid climate <span class="hlt">events</span> are characterized by abrupt shifts between warm/cold conditions, and ice-sheet oscillations, as evidenced by major ice rafting <span class="hlt">events</span> recorded in the North Atlantic sediments (Hernández-Almeida et al., 2012), similar to those found during the Last Glacial period (Marcott et al, 2011). The Mg/Ca derived paleotemperature and salinity oscillations prior and during IRD discharges at Site U1314 are related to changes in intermediate circulation. The increases in Mg/Ca paleotemperatures and salinities during the IRD <span class="hlt">event</span> are preceded by short episodes of cooling and freshening of subsurface waters. The response of the AMOC to this perturbation is an increased of warm and salty water coming from the south, transported to high latitudes in the North Atlantic beneath the thermocline. This process is accompanied by a southward shift in the convection cell from the Nordic Seas to the subpolar North Atlantic and better ventilation of the North Atlantic at mid-depths. Poleward transport of warm and salty subsurface subtropical waters causes intense basal melting and thinning of marine ice-shelves, that culminates in large-scale instability of the ice sheets, retreat of the grounding line and iceberg discharge. The mechanism proposed involves the coupling of the AMOC with ice-sheet dynamics, and would explain the presence of these fluctuations before the establishment of high-amplitude 100-kyr glacial cycles. Hernández-Almeida, I., Sierro, F.J., Cacho, I., Flores, J.A., 2012. Impact of suborbital climate changes in the North</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27570549','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27570549"><span>Targeting Amino Acid Metabolism for <span class="hlt">Molecular</span> Imaging of Inflammation <span class="hlt">Early</span> After Myocardial Infarction.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Thackeray, James T; Bankstahl, Jens P; Wang, Yong; Wollert, Kai C; Bengel, Frank M</p> <p>2016-01-01</p> <p>Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. <span class="hlt">Molecular</span> imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001). C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery. Serial (11)C-methionine PET was performed 3, 5 and 7d later. MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV). PET detected increased (11)C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/g vs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy). Increased (11)C-methionine uptake was associated with macrophage infiltration of damaged myocardium. Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and (11)C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and <span class="hlt">early</span> reperfusion confirmed elevated (11)C-methionine uptake in the hypoperfused myocardial region. Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. (11)C-methionine-based <span class="hlt">molecular</span> imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4997235','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4997235"><span>Targeting Amino Acid Metabolism for <span class="hlt">Molecular</span> Imaging of Inflammation <span class="hlt">Early</span> After Myocardial Infarction</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Thackeray, James T.; Bankstahl, Jens P.; Wang, Yong; Wollert, Kai C.; Bengel, Frank M.</p> <p>2016-01-01</p> <p>Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. <span class="hlt">Molecular</span> imaging holds promise for guidance of such therapies. The amino acid 11C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with 11C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher 11C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001). C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery. Serial 11C-methionine PET was performed 3, 5 and 7d later. MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV). PET detected increased 11C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/g vs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy). Increased 11C-methionine uptake was associated with macrophage infiltration of damaged myocardium. Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and 11C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and <span class="hlt">early</span> reperfusion confirmed elevated 11C-methionine uptake in the hypoperfused myocardial region. Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. 11C-methionine-based <span class="hlt">molecular</span> imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15835268','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15835268"><span><span class="hlt">Molecular</span>, anatomical, and biochemical <span class="hlt">events</span> associated with neurodegeneration in mice with Niemann-Pick type C disease.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Hao; Repa, Joyce J; Valasek, Mark A; Beltroy, Eduardo P; Turley, Stephen D; German, Dwight C; Dietschy, John M</p> <p>2005-04-01</p> <p>In Niemann-Pick type C (NPC) disease, cholesterol associated with either apoE or apoB100 is taken up by cells in all tissues, including the central nervous system, through clathrin-coated pits and becomes trapped in late endosomes and lysosomes. This study defines the functional, biochemical, and <span class="hlt">molecular</span> <span class="hlt">events</span> that ensue as nerve cell death occurs. In mice homozygous for a mutation in NPC1, neuromuscular dysfunction begins at 5 weeks and death occurs at 13 weeks of age. Cholesterol accumulates in every tissue in the body. Purkinje cell loss in the cerebellum begins at 3 to 4 weeks of age and is nearly complete by 11 weeks. This neurodegeneration in the cerebellum is associated with increases in the levels of mRNA for caspase 1, caspase 3, NPC2, LipA, apoE, apoD, glial fibrillary acidic protein, and tumor necrosis factor-alpha, but not for most target genes of the LXR nuclear receptors. The level for apoER2 is significantly reduced. These studies show there is a compensatory increase in NPC2 and LipA in an attempt to overcome the physiological defect caused by the mutation. Nevertheless, neurodegeneration proceeds utilizing apoptosis with activation of glial cells, increased apoE and apoD synthesis, and increased cholesterol turnover across the CNS.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27422411','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27422411"><span>Transcriptomic Profiling Discloses <span class="hlt">Molecular</span> and Cellular <span class="hlt">Events</span> Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pezzini, Francesco; Bettinetti, Laura; Di Leva, Francesca; Bianchi, Marzia; Zoratti, Elisa; Carrozzo, Rosalba; Santorelli, Filippo M; Delledonne, Massimo; Lalowski, Maciej; Simonati, Alessandro</p> <p>2017-05-01</p> <p>Human SH-SY5Y neuroblastoma cells are widely utilized in in vitro studies to dissect out pathogenetic mechanisms of neurodegenerative disorders. These cells are considered as neuronal precursors and differentiate into more mature neuronal phenotypes under selected growth conditions. In this study, in order to decipher the pathways and cellular processes underlying neuroblastoma cell differentiation in vitro, we performed systematic transcriptomic (RNA-seq) and bioinformatic analysis of SH-SY5Y cells differentiated according to a two-step paradigm: retinoic acid treatment followed by enriched neurobasal medium. Categorization of 1989 differentially expressed genes (DEGs) identified in differentiated cells functionally linked them to changes in cell morphology including remodelling of plasma membrane and cytoskeleton, and neuritogenesis. Seventy-three DEGs were assigned to axonal guidance signalling pathway, and the expression of selected gene products such as neurotrophin receptors, the functionally related SLITRK6, and semaphorins, was validated by immunoblotting. Along with these findings, the differentiated cells exhibited an ability to elongate longer axonal process as assessed by the neuronal cytoskeletal markers biochemical characterization and morphometric evaluation. Recognition of <span class="hlt">molecular</span> <span class="hlt">events</span> occurring in differentiated SH-SY5Y cells is critical to accurately interpret the cellular responses to specific stimuli in studies on disease pathogenesis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1265767-ab-initio-molecular-dynamics-investigations-low-energy-recoil-events-ni-nico','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1265767-ab-initio-molecular-dynamics-investigations-low-energy-recoil-events-ni-nico"><span>Ab initio <span class="hlt">molecular</span> dynamics investigations of low-energy recoil <span class="hlt">events</span> in Ni and NiCo</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Liu, Bin; Yuan, Fenglin; Jin, Ke; ...</p> <p>2015-10-06</p> <p>Low-energy recoil <span class="hlt">events</span> in pure Ni and the equiatomic NiCo alloy are studied using ab initio <span class="hlt">molecular</span> dynamics simulations. We found that the threshold displacement energies are strongly dependent on orientation and weakly dependent on composition. The minimum threshold displacement energies are along the [1 1 0] direction in both pure Ni and the NiCo alloy. Compared to pure Ni, the threshold displacement energies increase slightly in the NiCo alloy due to stronger bonds in the alloy, irrespective of the element type of the PKA. A single Ni interstitial occupying the center of a tetrahedron formed by four Ni atomsmore » and a <1 0 0> split interstitial is produced in pure Ni by the recoils, while only the <1 0 0> split interstitial is formed in the NiCo alloy. Compared to the replacement sequences in pure Ni, anti-site defect sequences are observed in the alloy, which have high efficiency for both producing defects and transporting energy outside of the cascade core. These results provide insights into energy transfer processes occurring in equiatomic alloys under irradiation.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016QSRv..136...23F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016QSRv..136...23F"><span>Evidence of resilience to past climate change in Southwest Asia: <span class="hlt">Early</span> farming communities and the 9.2 and 8.2 ka <span class="hlt">events</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Flohr, Pascal; Fleitmann, Dominik; Matthews, Roger; Matthews, Wendy; Black, Stuart</p> <p>2016-03-01</p> <p>Climate change is often cited as a major factor in social change. The so-called 8.2 ka <span class="hlt">event</span> was one of the most pronounced and abrupt Holocene cold and arid <span class="hlt">events</span>. The 9.2 ka <span class="hlt">event</span> was similar, albeit of a smaller magnitude. Both <span class="hlt">events</span> affected the Northern Hemisphere climate and caused cooling and aridification in Southwest Asia. Yet, the impacts of the 8.2 and 9.2 ka <span class="hlt">events</span> on <span class="hlt">early</span> farming communities in this region are not well understood. Current hypotheses for an effect of the 8.2 ka <span class="hlt">event</span> vary from large-scale site abandonment and migration (including the Neolithisation of Europe) to continuation of occupation and local adaptation, while impacts of the 9.2 ka have not previously been systematically studied. In this paper, we present a thorough assessment of available, quality-checked radiocarbon (14C) dates for sites from Southwest Asia covering the time interval between 9500 and 7500 cal BP, which we interpret in combination with archaeological evidence. In this way, the synchronicity between changes observed in the archaeological record and the rapid climate <span class="hlt">events</span> is tested. It is shown that there is no evidence for a simultaneous and widespread collapse, large-scale site abandonment, or migration at the time of the <span class="hlt">events</span>. However, there are indications for local adaptation. We conclude that <span class="hlt">early</span> farming communities were resilient to the abrupt, severe climate changes at 9250 and 8200 cal BP.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25106045','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25106045"><span>Size-resolved aerosol chemical analysis of extreme haze pollution <span class="hlt">events</span> during <span class="hlt">early</span> 2013 in urban Beijing, China.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tian, Shili; Pan, Yuepeng; Liu, Zirui; Wen, Tianxue; Wang, Yuesi</p> <p>2014-08-30</p> <p>Using size-resolved filter sampling and chemical characterization, high concentrations of water-soluble ions, carbonaceous species and heavy metals were found in both fine (PM2.1) and coarse (PM2.1-9) particles in Beijing during haze <span class="hlt">events</span> in <span class="hlt">early</span> 2013. Even on clear days, average mass concentration of submicron particles (PM1.1) was several times higher than that previously measured in most of abroad urban areas. A high concentration of particulate matter on haze days weakens the incident solar radiation, which reduces the generation rate of secondary organic carbon in PM1.1. We show that the peak mass concentration of particles shifted from 0.43-0.65μm on clear days to 0.65-1.1μm on lightly polluted days and to 1.1-2.1μm on heavily polluted days. The peak shifts were also found for the following species: organic carbon, elemental carbon, NH4(+), SO4(2-), NO3(-), K, Cu, Zn, Cd and Pb. Our findings demonstrate that secondary inorganic aerosols (36%) and organic matter (26%) dominated the fine particle mass on heavily polluted days, while their contribution reduced to 29% and 18%, respectively, on clear days. Besides fine particles, anthropogenic chemical species also substantially accumulated in the coarse mode, which suggests that particles with aerodynamic diameter larger than 2.1μm cannot be neglected during severe haze <span class="hlt">events</span>. Copyright © 2014 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4495521','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4495521"><span><span class="hlt">Early</span> Results of Three-Year Monitoring of Red Wood Ants’ Behavioral Changes and Their Possible Correlation with Earthquake <span class="hlt">Events</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Berberich, Gabriele; Berberich, Martin; Grumpe, Arne; Wöhler, Christian; Schreiber, Ulrich</p> <p>2013-01-01</p> <p>Simple Summary For three years (2009–2012), two red wood ant mounds (Formica rufa-group), located at the seismically active Neuwied Basin (Eifel, Germany), have been monitored 24/7 by high-resolution cameras. <span class="hlt">Early</span> results show that ants have a well-identifiable standard daily routine. Correlation with local seismic <span class="hlt">events</span> suggests changes in the ants’ behavior hours before the earthquake: the nocturnal rest phase and daily activity are suppressed, and standard daily routine does not resume until the next day. At present, an automated image evaluation routine is being applied to the video streams. Based on this automated approach, a statistical analysis of the ant behavior will be carried out. Abstract Short-term earthquake predictions with an advance warning of several hours or days are currently not possible due to both incomplete understanding of the complex tectonic processes and inadequate observations. Abnormal animal behaviors before earthquakes have been reported previously, but create problems in monitoring and reliability. The situation is different with red wood ants (RWA; Formica rufa-group (Hymenoptera: Formicidae)). They have stationary mounds on tectonically active, gas-bearing fault systems. These faults may be potential earthquake areas. For three years (2009–2012), two red wood ant mounds (Formica rufa-group), located at the seismically active Neuwied Basin (Eifel, Germany), have been monitored 24/7 by high-resolution cameras with both a color and an infrared sensor. <span class="hlt">Early</span> results show that ants have a well-identifiable standard daily routine. Correlation with local seismic <span class="hlt">events</span> suggests changes in the ants’ behavior hours before the earthquake: the nocturnal rest phase and daily activity are suppressed, and standard daily routine does not resume until the next day. At present, an automated image evaluation routine is being applied to the more than 45,000 hours of video streams. Based on this automated approach, a statistical analysis of</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27440999','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27440999"><span>Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving <span class="hlt">early</span> <span class="hlt">molecular</span> diagnosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ben-Rebeh, Imen; Grati, Mhamed; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber</p> <p>2016-01-01</p> <p>Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient <span class="hlt">molecular</span> diagnosis of USH in a patient's <span class="hlt">early</span> childhood is of utmost importance, allowing better educational and therapeutic management.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4950652','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4950652"><span>Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving <span class="hlt">early</span> <span class="hlt">molecular</span> diagnosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ben-Rebeh, Imen; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber</p> <p>2016-01-01</p> <p>Purpose Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. Methods In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Results Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. Conclusions We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient <span class="hlt">molecular</span> diagnosis of USH in a patient’s <span class="hlt">early</span> childhood is of utmost importance, allowing better educational and therapeutic management. PMID:27440999</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015JSAES..63..293P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015JSAES..63..293P"><span>A late eocene-<span class="hlt">early</span> Oligocene transgressive <span class="hlt">event</span> in the Golfo San Jorge basin: Palynological results and stratigraphic implications</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Paredes, José M.; Foix, Nicolás; Guerstein, G. Raquel; Guler, María V.; Irigoyen, Martín; Moscoso, Pablo; Giordano, Sergio</p> <p>2015-11-01</p> <p>A new Cenozoic dataset in the subsurface of the South Flank of the Golfo San Jorge Basin (Santa Cruz province) allowed to identify a non-previously recognized transgressive <span class="hlt">event</span> of late Eocene to <span class="hlt">early</span> Oligocene age. Below of a marine succession containing a dinoflagellate cyst assemblage that characterizes the C/G palynological zone of the Chenque Formation (<span class="hlt">early</span> Miocene), a 80-110 m thick marine succession contains a palynological assemblage integrated by Gelatia inflata, Diphyes colligerum and Reticulatosphaera actinocoronata supporting the occurrence of a marine incursion in the basin during the Eocene-Oligocene transition (EOT). The new lithostratigraphic unit - here defined as El Huemul Formation - covers in sharp contact to the Sarmiento Formation, and become thinner from East to West; the unit has been identified in about 1800 well logs covering up to 3500 km2, and its subsurface distribution exceed the boundaries of the study area. The El Huemul Formation consists of a thin lag of glauconitic sandstones with fining-upward log motif, followed by a mudstone-dominated succession that coarsening-upward to sandstones, evidencing a full T-R cycle. Preservation of the El Huemul Formation in the subsurface of the South Flank has been favored by the reactivation of WNW-ESE late Cretaceous normal faults, and by the generation of N-S striking normal faults of Paleocene-Eocene age. Flexural loading associated to igneous intrusions of Paleocene?- middle Eocene age also promoted the increase of subsidence in the South Flank of the basin prior to the transgression.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24898513','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24898513"><span>TERT promoter mutation as an <span class="hlt">early</span> genetic <span class="hlt">event</span> activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei</p> <p>2014-10-01</p> <p>The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how <span class="hlt">early</span> these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an <span class="hlt">early</span> genetic <span class="hlt">event</span> in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_17 --> <div id="page_18" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="341"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28847475','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28847475"><span>Outcomes of Chronic Myeloid Leukemia Patients With <span class="hlt">Early</span> <span class="hlt">Molecular</span> Response at 3 and 6 Months: A Comparative Analysis of Generic Imatinib and Glivec.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Eskazan, Ahmet Emre; Sadri, Sevil; Keskin, Dilek; Ayer, Mesut; Kantarcioglu, Bulent; Demirel, Naciye; Aydin, Demet; Aydinli, Fuat; Yokus, Osman; Ozunal, Isil Erdogan; Berk, Selin; Yalniz, Fevzi Firat; Elverdi, Tugrul; Salihoglu, Ayse; Ar, Muhlis Cem; Ongoren, Seniz; Baslar, Zafer; Aydin, Yildiz; Tuzuner, Nukhet; Ozbek, Ugur; Soysal, Teoman</p> <p>2017-12-01</p> <p>The <span class="hlt">molecular</span> response at 3 months of the original imatinib (OI) in patients with chronic myeloid leukemia has prognostic significance; however, this has never been tested for generic imatinib (GI). We evaluated the BCR-ABL1 [international reporting scale (IS)] transcript levels at 3 and 6 months to determine whether an <span class="hlt">early</span> <span class="hlt">molecular</span> response (EMR) had a prognostic effect on the outcome among chronic myeloid leukemia patients receiving GI. Ninety patients were divided into 2 groups, according to the imatinib they received, as OI (group A) and GI (group B). Two groups were equally balanced for age, gender, Sokal risk score, and optimal response. The 2 groups did not differ in achieving an EMR at 3 months, and patients with EMR at 3 months had significantly superior complete cytogenetic response and major <span class="hlt">molecular</span> response rates compared with patients who did not achieve an EMR in both groups. The percentage of an optimal response [BCR-ABL1 (IS), < 1%] and a warning response [BCR-ABL1 (IS), 1%-10%] at 6 months was 93% and 95% for groups A and B, respectively (P = .553). Patients with an optimal response (OR) at both 3 and 6 months had significantly superior <span class="hlt">event</span>-free survival rates compared with patients without an OR in groups A and B. The results of the present study have demonstrated most probably for the first time that an OR at 3 and 6 months in patients receiving either first-line GI and OI is clearly associated with greater response and <span class="hlt">event</span>-free survival rates. Prospective randomized trials with larger numbers of patients and longer follow-up periods are needed to address the effect of EMR in patients receiving GI. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27029807','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27029807"><span>The predictive value of <span class="hlt">early</span> <span class="hlt">molecular</span> response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bee, Ping Chong; Sekaran, Veera; Ng, Richard Rui Jie; Kweh, Ting Yi; Gan, Gin Gin</p> <p>2017-03-01</p> <p>The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major <span class="hlt">molecular</span> response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that <span class="hlt">early</span> and deeper cytogenetic and <span class="hlt">molecular</span> responses predict a better long-term outcome. This study aimed to analyse the relationship between <span class="hlt">early</span> <span class="hlt">molecular</span> response and clinical outcome in a real-life setting. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and <span class="hlt">event</span>-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients. Copyright: © Singapore Medical Association</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22416938-ritonavir-binds-downregulates-estrogen-receptors-molecular-mechanism-promoting-early-atherosclerosis','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22416938-ritonavir-binds-downregulates-estrogen-receptors-molecular-mechanism-promoting-early-atherosclerosis"><span>Ritonavir binds to and downregulates estrogen receptors: <span class="hlt">Molecular</span> mechanism of promoting <span class="hlt">early</span> atherosclerosis</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Xiang, Jin; Wang, Ying; Su, Ke</p> <p></p> <p>Estrogenic actions are closely related to cardiovascular disease. Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes through estrogen pathway remains unclear. In this study, we found that RTV increases thickness of coronary artery walls of Sprague Dawley rats and plasma free fatty acids (FFA) levels. In addition, RTV could induce foam cell formation, downregulate both estrogen receptor α (ERα) and ERβ expression, upregulate G protein-coupled estrogen receptor (GPER) expression, and all of them could be partially blocked by 17β-estradiol (E2), suggesting RTV acts as an antagonist formore » E2. Computational modeling shows a similar interaction with ERα between RTV and 2-aryl indoles, which are highly subtype-selective ligands for ERα. We also found that RTV directly bound to ERα and selectively inhibited the nuclear localization of ERα, and residue Leu536 in the hydrophobic core of ligand binding domain (LBD) was essential for the interaction with RTV. In addition, RTV did not change the secondary structure of ERα-LBD like E2, which explained how ERα lost the capacity of nuclear translocation under the treatment of RTV. All of the evidences suggest that ritonavir acts as an antagonist for 17β-estradiol in regulating α subtype estrogen receptor function and <span class="hlt">early</span> <span class="hlt">events</span> of atherosclerosis. - Graphical abstract: RTV directly binds to ERα and Leu536 in the hydrophobic core of ligand binding domain is essential for the interaction. - Highlights: • RTV increases the thickness of rat coronary artery wall and foam cell formation. • RTV downregulates the expression of ERα and ERβ. • RTV inhibits ERα promoter activity. • RTV directly binds to ERα and the key amino acid is Leu536. • RTV inhibits the nuclear translocation of ERα and GPER.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22285261-perturbation-bile-acid-homeostasis-early-pathogenesis-event-drug-induced-liver-injury-rats','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22285261-perturbation-bile-acid-homeostasis-early-pathogenesis-event-drug-induced-liver-injury-rats"><span>Perturbation of bile acid homeostasis is an <span class="hlt">early</span> pathogenesis <span class="hlt">event</span> of drug induced liver injury in rats</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko</p> <p>2013-04-01</p> <p>Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolitesmore » profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the <span class="hlt">early</span> time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an <span class="hlt">early</span> <span class="hlt">event</span> of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and <span class="hlt">early</span> DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015CliPa..11..687H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015CliPa..11..687H"><span>Subsurface North Atlantic warming as a trigger of rapid cooling <span class="hlt">events</span>: evidence from the <span class="hlt">early</span> Pleistocene (MIS 31-19)</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hernández-Almeida, I.; Sierro, F.-J.; Cacho, I.; Flores, J.-A.</p> <p>2015-04-01</p> <p>Subsurface water column dynamics in the subpolar North Atlantic were reconstructed in order to improve the understanding of the cause of abrupt ice-rafted detritus (IRD) <span class="hlt">events</span> during cold periods of the <span class="hlt">early</span> Pleistocene. We used paired Mg / Ca and δ18O measurements of Neogloboquadrina pachyderma (sinistral - sin.), deep-dwelling planktonic foraminifera, to estimate the subsurface temperatures and seawater δ18O from a sediment core from Gardar Drift, in the subpolar North Atlantic. Carbon isotopes of benthic and planktonic foraminifera from the same site provide information about the ventilation and water column nutrient gradient. Mg / Ca-based temperatures and seawater δ18O suggest increased subsurface temperatures and salinities during ice-rafting, likely due to northward subsurface transport of subtropical waters during periods of weaker Atlantic Meridional Overturning Circulation (AMOC). Planktonic carbon isotopes support this suggestion, showing coincident increased subsurface ventilation during deposition of IRD. Subsurface accumulation of warm waters would have resulted in basal warming and break-up of ice-shelves, leading to massive iceberg discharges in the North Atlantic. The release of heat stored at the subsurface to the atmosphere would have helped to restart the AMOC. This mechanism is in agreement with modelling and proxy studies that observe a subsurface warming in the North Atlantic in response to AMOC slowdown during Marine Isotope Stage (MIS) 3.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2014CliPD..10.4033H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2014CliPD..10.4033H"><span>Subsurface North Atlantic warming as a trigger of rapid cooling <span class="hlt">events</span>: evidences from the <span class="hlt">Early</span> Pleistocene (MIS 31-19)</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hernández-Almeida, I.; Sierro, F.-J.; Cacho, I.; Flores, J.-A.</p> <p>2014-10-01</p> <p>Subsurface water column dynamics in the subpolar North Atlantic were reconstructed in order to improve the understanding of the cause of abrupt IRD <span class="hlt">events</span> during cold periods of the <span class="hlt">Early</span> Pleistocene. We used Mg / Ca-based temperatures of deep-dwelling (Neogloboquadrina pachyderma sinistral) planktonic foraminifera and paired Mg / Ca-δ18O measurements to estimate the subsurface temperatures and δ18O of seawater at Site U1314. Carbon isotopes on benthic and planktonic foraminifera from the same site provide information about the ventilation and water column nutrient gradient. Mg / Ca-based temperatures and δ18O of seawater suggest increased temperatures and salinities during ice-rafting, likely due to enhanced northward subsurface transport of subtropical waters during periods of AMOC reduction. Planktonic carbon isotopes support this suggestion, showing coincident increased subsurface ventilation during deposition of ice-rafted detritus (IRD). Warm waters accumulated at subsurface would result in basal warming and break-up of ice-shelves, leading to massive iceberg discharges in the North Atlantic. Release of heat and salt stored at subsurface would help to restart the AMOC. This mechanism is in agreement with modelling and proxy studies that observe a subsurface warming in the North Atlantic in response to AMOC slowdown during the MIS3.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25683140','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25683140"><span>The dimerization of the yeast cytochrome bc1 complex is an <span class="hlt">early</span> <span class="hlt">event</span> and is independent of Rip1.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Conte, Annalea; Papa, Benedetta; Ferramosca, Alessandra; Zara, Vincenzo</p> <p>2015-05-01</p> <p>In Saccharomyces cerevisiae the mature cytochrome bc1 complex exists as an obligate homo-dimer in which each monomer consists of ten distinct protein subunits inserted into or bound to the inner mitochondrial membrane. Among them, the Rieske iron-sulfur protein (Rip1), besides its catalytic role in electron transfer, may be implicated in the bc1 complex dimerization. Indeed, Rip1 has the globular domain containing the catalytic center in one monomer while the transmembrane helix interacts with the adjacent monomer. In addition, the lack of Rip1 leads to the accumulation of an immature bc1 intermediate, only loosely associated with cytochrome c oxidase. In this study we have investigated the biogenesis of the yeast cytochrome bc1 complex using epitope tagged proteins to purify native assembly intermediates. We showed that the dimerization process is an <span class="hlt">early</span> <span class="hlt">event</span> during bc1 complex biogenesis and that the presence of Rip1, differently from previous proposals, is not essential for this process. We also investigated the multi-step model of bc1 assembly thereby lending further support to the existence of bona fide subcomplexes during bc1 maturation in the inner mitochondrial membrane. Finally, a new model of cytochrome bc1 complex assembly, in which distinct intermediates sequentially interact during bc1 maturation, has been proposed. Copyright © 2015 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013ESASP.706E..21S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013ESASP.706E..21S"><span>Microgravity Effects on the <span class="hlt">Early</span> <span class="hlt">Events</span> of Biological Nitrogen Fixation in Medicago Truncatula: Results from the SyNRGE Experiment</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Stutte, Gary W.; Roberts, Michael S.</p> <p>2013-02-01</p> <p>SyNRGE (Symbiotic Nodulation in a Reduced Gravity Environment) was a sortie mission on STS-135 in the Biological Research in Canisters (BRIC) hardware to study the effect of μg on a plant-microbe symbiosis resulting in biological nitrogen fixation. Medicago truncatula, a model species for the legume family, was inoculated with its bacterial symbiont, Sinorhizobium meliloti, to observe <span class="hlt">early</span> biomolecular <span class="hlt">events</span> associated with infection and nodulation in Petri Dish Fixation Units (PDFU’s). Two sets of experiments were conducted in orbit and in 24-hour delayed ground controls. Experiments were designed to determine if S. meliloti would infect M. truncatula and initiate biomolecular changes associated with nodule formation and if the μg environment altered the host plant and/or bacteria to induce nodule formation upon return to 1g. Initial analysis results demonstrate that the legumes and bacteria cultivated in μg have potential to develop a symbiotic interaction, but suggest that μg alters their ability to form nodules upon return to 1g. (Research supported by NASA ESMD/ Advance Capabilities Division grant NNX10AR09A)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4414406','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4414406"><span>Microhemorrhage is an <span class="hlt">Early</span> <span class="hlt">Event</span> in the Pulmonary Fibrotic Disease of PECAM-1 Deficient FVB/n Mice</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Young, Lena C.; Woods, Steven J.; Groshong, Steven D.; Basaraba, Randall J.; Gilchrist, John M.; Higgins, David M.; Gonzalez-Juarrero, Mercedes; Bass, Todd A.; Muller, William A.; Schenkel, Alan R.</p> <p>2014-01-01</p> <p>Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory <span class="hlt">event</span>. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by <span class="hlt">early</span> loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment. PMID:24972347</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24766462','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24766462"><span><span class="hlt">Early</span> and late HIV-1 membrane fusion <span class="hlt">events</span> are impaired by sphinganine lipidated peptides that target the fusion site.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel</p> <p>2014-07-15</p> <p>Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired <span class="hlt">early</span> membrane fusion <span class="hlt">events</span> by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016DSRI..115....1M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016DSRI..115....1M"><span><span class="hlt">Molecular</span> characterization of benthic foraminifera communities from the Northeastern Gulf of Mexico shelf and slope following the Deepwater Horizon <span class="hlt">event</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Moss, Joseph A.; McCurry, Chelsea; Schwing, Patrick; Jeffrey, Wade H.; Romero, Isabel C.; Hollander, David J.; Snyder, Richard A.</p> <p>2016-09-01</p> <p>Benthic foraminifera are globally distributed protozoa in the world's oceans, which have been used as ecological indicators in both current and palaeo oceanography. The ecological properties and distribution of these organisms in various regions of the Gulf of Mexico (GOM) have been evaluated using microscopy; however <span class="hlt">molecular</span> approaches for these purposes have been limited, especially in deeper regions. The BP Deepwater Horizon oil well failure in the northern Gulf of Mexico highlighted the need to better understand the distribution and abundance of these organisms relative to environmental factors and ecosystem perturbations such as the oil spill. Sediment samples were collected using a Shipek grab along transects on the northwest Florida GOM shelf (18-270 m depth). Clone libraries were developed from PCR amplified 18S rDNA genes for sequence analysis. Analysis of random clones from libraries were used as a proxy for community structure (presence and relative abundance) to document the spatial and temporal dynamics of benthic foraminifera on the Northwest Florida Shelf in the NE GOM shelf. Additional continental slope samples (200-1600 m depth) were obtained by a multicorer and treated in similar fashion. Mean species diversity in this study (H=2.49-3.36), agreed with pre-DWH <span class="hlt">event</span> estimates, however the dominant agglutinated species in the deep-water samples did not match previous studies. Additionally, the dominant calcareous taxa from this study such as Allogromida sp. and Psammophaga sp., were inconsistent with previous reports. The dominant taxa in both coastal and deep-water sites include Glabratellina sp., Trochammina hadai, and Trochammina sp., and Textularia sagittula and Bathysiphon argenteus as well as members of genera Astrammina, Bolivina, Cibicides and Cibicidoides.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28655090','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28655090"><span>[<span class="hlt">Molecular</span> mechanisms and relationship of M2-polarized macrophages with <span class="hlt">early</span> response in multiple myeloma].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chen, X Y; Sun, R X; Zhang, W Y; Liu, T; Zheng, Y H; Wu, Y</p> <p>2017-06-14</p> <p>Objective: To investigate the relationship between M2-polarized macrophages and <span class="hlt">early</span> response in multiple myeloma and its <span class="hlt">molecular</span> mechanism. Methods: Two hundred and forty bone marrow biopsy tissue were collected and M2-polarized macrophages were stained by anti-CD163 monoclonal antibody. In vitro M2-polarized macrophages were derived from human peripheral blood mononuclear cell or THP-1 cells and identified by flow cytometry. Two myeloma cell lines RPMI 8226 and U266 were co-cultured with M2 macrophages using a transwell system. We measured myeloma cells proliferation through CCK-8 method and the pro-inflammatory cytokines expression (TNF-α and IL-6) by ELISA. Real time PCR was applied to measure chemokines (CCL2 and CCL3) , chemokine receptors (CCR2, CCR5) , VEGF and their receptors. In addition, flow cytometry was used to analyze the apoptosis of myeloma cells induced by dexamethasone. Results: ①Patients with high percentage of M2 macrophage involvement in bone marrow showed poorer response (23.9% versus 73.0%, χ (2)=60.31, P <0.001). ② In vitro the proliferation of RPMI 8226 cells ( P =0.005 at 24 h, P =0.020 at 36 h) or U266 myeloma cells ( P = 0.030 at 24h, P =0.020 at 36h) co-cultured with M2-polarized macrophages was higher than control group. ③In vitro the apoptotic rate of RPMI 8226 cells (29.0% versus 71.0%, t =4.97, P =0.008) or U266 myeloma cells (24.9% versus 67.7%, t =6.99, P =0.002) co-cultured with M2-polarized macrophages was lower than control group. ④ In vitro M2-polarized macrophages promoted myeloma cells secreting higher level of IL-6, TNF-α and higher expression of CCL2, CCL3, CCR2, CCR5, VEGFA, VEGFR-1,-2 compared with the non-macrophage co-culture system. Conclusion: M2-polarized macrophages promote myeloma cells proliferation and inhibit apoptosis through a very complex mechanism involving pro-inflammatory cytokines IL-6 and TNF-α, chemokines and related receptors such as CCL2, CCL3, CCR2, CCR3, and VEGF as well as related</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1136122','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1136122"><span>Non-Invasive <span class="hlt">Early</span> Detection and <span class="hlt">Molecular</span> Analysis of Low X-ray Dose Effects in the Lens</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Goldstein, Lee</p> <p></p> <p>This is the Final Progress Report for DOE-funded research project DE-PS02-08ER08-01 titled “Non-Invasive <span class="hlt">Early</span> Detection and <span class="hlt">Molecular</span> Analysis of Low X-ray Dose Effects in the Lens”. The project focuses on the effects of low-linear energy transfer (LET) radiation on the ocular lens. The lens is an exquisitely radiosensitive tissue with a highly-ordered <span class="hlt">molecular</span> structure that is amenable to non-invasive optical study from the periphery. These merits point to the lens as an ideal target for laser-based <span class="hlt">molecular</span> biodosimetry (MBD). Following exposure to different types of ionizing radiations, the lens demonstrates <span class="hlt">molecular</span> changes (e.g., oxidation, racemization, crosslinkage, truncation, aggregation, etc.) thatmore » impact the structure and function of the long-lived proteins in the cytosol of lens fiber cells. The vast majority of proteins in the lens comprise the highly-ordered crystallins. These highly conserved lens proteins are amongst the most concentrated and stable in the body. Once synthesized, the crystallins are retained in the fiber cell cytoplasm for life. Taken together, these properties point to the lens as an ideal system for quantitative in vivo MBD assessment using quasi-elastic light scattering (QLS) analysis. In this project, we deploy a purpose-designed non-invasive infrared laser QLS instrument as a quantitative tool for longitudinal assessment of pre-cataractous <span class="hlt">molecular</span> changes in the lenses of living mice exposed to low-dose low-LET radiation compared to non-irradiated sham controls. We hypothesize that radiation exposure will induce dose-dependent changes in the <span class="hlt">molecular</span> structure of matrix proteins in the lens. Mechanistic assays to ascertain radiation-induced <span class="hlt">molecular</span> changes in the lens focus on protein aggregation and gene/protein expression patterns. We anticipate that this study will contribute to our understanding of <span class="hlt">early</span> <span class="hlt">molecular</span> changes associated with radiation-induced tissue pathology. This study also affords</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18686996','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18686996"><span>Ab initio <span class="hlt">molecular</span> dynamics study on the initial chemical <span class="hlt">events</span> in nitramines: thermal decomposition of CL-20.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Isayev, Olexandr; Gorb, Leonid; Qasim, Mo; Leszczynski, Jerzy</p> <p>2008-09-04</p> <p>CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane or HNIW) is a high-energy nitramine explosive. To improve atomistic understanding of the thermal decomposition of CL-20 gas and solid phases, we performed a series of ab initio <span class="hlt">molecular</span> dynamics simulations. We found that during unimolecular decomposition, unlike other nitramines (e.g., RDX, HMX), CL-20 has only one distinct initial reaction channelhomolysis of the N-NO2 bond. We did not observe any HONO elimination reaction during unimolecular decomposition, whereas the ring-breaking reaction was followed by NO 2 fission. Therefore, in spite of limited sampling, that provides a mostly qualitative picture, we proposed here a scheme of unimolecular decomposition of CL-20. The averaged product population over all trajectories was estimated at four HCN, two to four NO2, two to four NO, one CO, and one OH molecule per one CL-20 molecule. Our simulations provide a detailed description of the chemical processes in the initial stages of thermal decomposition of condensed CL-20, allowing elucidation of key features of such processes as composition of primary reaction products, reaction timing, and Arrhenius behavior of the system. The primary reactions leading to NO2, NO, N 2O, and N2 occur at very <span class="hlt">early</span> stages. We also estimated potential activation barriers for the formation of NO2, which essentially determines overall decomposition kinetics and effective rate constants for NO2 and N2. The calculated solid-phase decomposition pathways correlate with available condensed-phase experimental data.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=307784&Lab=NHEERL&keyword=herbicide&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=307784&Lab=NHEERL&keyword=herbicide&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>Transcriptomic dose-and-time-course indicators of <span class="hlt">early</span> key <span class="hlt">events</span> in a cytotoxicity-mediated mode of action for rodent urinary bladder tumorigenesis</span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>TRANSCRIPTOMIC DOSE- AND TIME-COURSE INDICATORS OF <span class="hlt">EARLY</span> KEY <span class="hlt">EVENTS</span> IN A CYTOTOXICITY-MEDIATED MODE OF ACTION FOR RODENT URINARY BLADDER TUMORIGENESISDiuron is a substituted urea compound used globally as an herbicide. Urinary bladder tumors were induced in rats after chronic die...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10556055','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10556055"><span>Identification of tissues and patterning <span class="hlt">events</span> required for distinct steps in <span class="hlt">early</span> migration of zebrafish primordial germ cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Weidinger, G; Wolke, U; Köprunner, M; Klinger, M; Raz, E</p> <p>1999-12-01</p> <p>In many organisms, the primordial germ cells have to migrate from the position where they are specified towards the developing gonad where they generate gametes. Extensive studies of the migration of primordial germ cells in Drosophila, mouse, chick and Xenopus have identified somatic tissues important for this process and demonstrated a role for specific molecules in directing the cells towards their target. In zebrafish, a unique situation is found in that the primordial germ cells, as marked by expression of vasa mRNA, are specified in random positions relative to the future embryonic axis. Hence, the migrating cells have to navigate towards their destination from various starting positions that differ among individual embryos. Here, we present a detailed description of the migration of the primordial germ cells during the first 24 hours of wild-type zebrafish embryonic development. We define six distinct steps of migration bringing the primordial germ cells from their random positions before gastrulation to form two cell clusters on either side of the midline by the end of the first day of development. To obtain information on the origin of the positional cues provided to the germ cells by somatic tissues during their migration, we analyzed the migration pattern in mutants, including spadetail, swirl, chordino, floating head, cloche, knypek and no isthmus. In mutants with defects in axial structures, paraxial mesoderm or dorsoventral patterning, we find that certain steps of the migration process are specifically affected. We show that the paraxial mesoderm is important for providing proper anteroposterior information to the migrating primordial germ cells and that these cells can respond to changes in the global dorsoventral coordinates. In certain mutants, we observe accumulation of ectopic cells in different regions of the embryo. These ectopic cells can retain both morphological and <span class="hlt">molecular</span> characteristics of primordial germ cells, suggesting that, in</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27446149','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27446149"><span>Exogenous γ-aminobutyric Acid (GABA) Application Improved <span class="hlt">Early</span> Growth, Net Photosynthesis, and Associated Physio-Biochemical <span class="hlt">Events</span> in Maize.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Wu; Liu, Jianhua; Ashraf, Umair; Li, Gaoke; Li, Yuliang; Lu, Wenjia; Gao, Lei; Han, Fuguang; Hu, Jianguang</p> <p>2016-01-01</p> <p>γ-aminobutyric acid (GABA) is an endogenous signaling molecule and involved in growth regulations and plant development, however, a little information is available on the consequences of exogenous GABA application on growth, development, and associated physio-biochemical processes in maize. The present study examined the GABA-induced regulations in <span class="hlt">early</span> growth, net photosynthetic rate, gas exchange, osmoregulation, and enzymatic activities in three maize cultivars, i.e., Yuecainuo 6, Zhengtian 68, and Yuecainuo 2. Two levels of GABA, i.e., 0 mg L(-1) and 50 mg L(-1), in solution form, with total application volume of 100 ml per pot containing 15 maize seedlings were exogenously applied. Results revealed that exogenous GABA application improved seedling growth in terms of seedling length and biomass accumulation in all maize cultivars at both 3 and 7 days after treatment (DAT). It also promoted net photosynthesis and variably affected gas exchange attributes, i.e., stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr), as well as leaves SPAD value. Furthermore, lipid peroxidation [in terms of malondialdehyde (MDA)] under GABA treated maize seedlings were also remained variable; however, osmolyte accumulation (protein and proline) and activities of anti-oxidants enzymes, i.e., super-oxide dismutase and peroxidase were also affected differently at both 3 and 7 DAT in all maize cultivars. Furthermore, enzymes involved in nitrogen metabolism, e.g., nitrate reductase and glutamine synthetase were improved. These results suggest the involvement of GABA in various physio-metablical mechanisms which might lead to improvement in morphological growth of maize. In future, research is still needed at <span class="hlt">molecular</span> and genetic levels to unravel the involvement of GABA-mediated regulations in growth and its associated physio-biochemical mechanisms.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29232704','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29232704"><span>Do <span class="hlt">early</span> neural correlates of visual consciousness show the oblique effect? A binocular rivalry and <span class="hlt">event</span>-related potential study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jack, Bradley N; Roeber, Urte; O'Shea, Robert P</p> <p>2017-01-01</p> <p>When dissimilar images are presented one to each eye, we do not see both images; rather, we see one at a time, alternating unpredictably. This is called binocular rivalry, and it has recently been used to study brain processes that correlate with visual consciousness, because perception changes without any change in the sensory input. Such studies have used various types of images, but the most popular have been gratings: sets of bright and dark lines of orthogonal orientations presented one to each eye. We studied whether using cardinal rival gratings (vertical, 0°, and horizontal, 90°) versus oblique rival gratings (left-oblique, -45°, and right-oblique, 45°) influences <span class="hlt">early</span> neural correlates of visual consciousness, because of the oblique effect: the tendency for visual performance to be greater for cardinal gratings than for oblique gratings. Participants viewed rival gratings and pressed keys indicating which of the two gratings they perceived, was dominant. Next, we changed one of the gratings to match the grating shown to the other eye, yielding binocular fusion. Participants perceived the rivalry-to-fusion change to the dominant grating and not to the other, suppressed grating. Using <span class="hlt">event</span>-related potentials (ERPs), we found neural correlates of visual consciousness at the P1 for both sets of gratings, as well as at the P1-N1 for oblique gratings, and we found a neural correlate of the oblique effect at the N1, but only for perceived changes. These results show that the P1 is the earliest neural activity associated with visual consciousness and that visual consciousness might be necessary to elicit the oblique effect.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2013JGRE..118..278I','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2013JGRE..118..278I"><span>Distribution of <span class="hlt">Early</span>, Middle, and Late Noachian cratered surfaces in the Martian highlands: Implications for resurfacing <span class="hlt">events</span> and processes</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Irwin, Rossman P.; Tanaka, Kenneth L.; Robbins, Stuart J.</p> <p>2013-02-01</p> <p>Most of the geomorphic changes on Mars occurred during the Noachian Period, when the rates of impact crater degradation and valley network incision were highest. Fluvial erosion around the Noachian/Hesperian transition is better constrained than the longer-term landscape evolution throughout the Noachian Period, when the highland intercrater geomorphic surfaces developed. We interpret highland resurfacing <span class="hlt">events</span> and processes using a new global geologic map of Mars (at 1:20,000,000 scale), a crater data set that is complete down to 1 km in diameter, and Mars Orbiter Laser Altimeter topography. The <span class="hlt">Early</span> Noachian highland (eNh) unit is nearly saturated with craters of 32-128 km diameter, the Middle Noachian highland (mNh) unit has a resurfacing age of ~4 Ga, and the Late Noachian highland unit (lNh) includes younger composite surfaces of basin fill and partially buried cratered terrain. These units have statistically distinct ages, and their distribution varies with elevation. The eNh unit is concentrated in the high-standing Hellas basin annulus and in highland terrain that was thinly mantled by basin ejecta near 180° longitude. The mNh unit includes most of Arabia Terra, the Argyre vicinity, highland plateau areas between eNh outcrops, and the Thaumasia range. The lNh unit mostly occurs within highland basins. Crater depth/diameter ratios do not vary strongly between the eNh and mNh units, although crater losses to Noachian resurfacing appear greater in lower lying areas. Noachian resurfacing was spatially non-uniform, long-lived, and gravity-driven, more consistent with arid-zone fluvial and aeolian erosion and volcanism than with air fall mantling or mass wasting.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26810452','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26810452"><span><span class="hlt">Molecular</span> candidates for <span class="hlt">early</span>-stage flower-to-fruit transition in stenospermocarpic table grape (Vitis vinifera L.) inflorescences ascribed by differential transcriptome and metabolome profiles.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Domingos, Sara; Fino, Joana; Paulo, Octávio S; Oliveira, Cristina M; Goulao, Luis F</p> <p>2016-03-01</p> <p>Flower-to-fruit transition depends of nutrient availability and regulation at the <span class="hlt">molecular</span> level by sugar and hormone signalling crosstalk. However, in most species, the identities of fruit initiation regulators and their targets are largely unknown. To ascertain the main pathways involved in stenospermocarpic table grape fruit set, comprehensive transcriptional and metabolomic analyses were conducted specifically targeting the <span class="hlt">early</span> phase of this developmental stage in 'Thompson Seedless'. The high-throughput analyses performed disclosed the involvement of 496 differentially expressed genes and 28 differently accumulated metabolites in the sampled inflorescences. Our data show broad transcriptome reprogramming of molecule transporters, globally down-regulating gene expression, and suggest that regulation of sugar- and hormone-mediated pathways determines the downstream activation of berry development. The most affected gene was the SWEET14 sugar transporter. Hormone-related transcription changes were observed associated with increased indole-3-acetic acid, stimulation of ethylene and gibberellin metabolisms and cytokinin degradation, and regulation of MADS-box and AP2-like ethylene-responsive transcription factor expression. Secondary metabolism, the most representative biological process at transcriptome level, was predominantly repressed. The results add to the knowledge of <span class="hlt">molecular</span> <span class="hlt">events</span> occurring in grapevine inflorescence fruit set and provide a list of candidates, paving the way for genetic manipulation aimed at model research and plant breeding. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_18 --> <div id="page_19" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="361"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27182789','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27182789"><span>Cluster Evolution at <span class="hlt">Early</span> Stages of 1,3,5-Triamino-2,4,6-trinitrobenzene under Various Heating Conditions: A <span class="hlt">Molecular</span> Reactive Force Field Study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wen, Yushi; Xue, Xianggui; Long, Xinping; Zhang, Chaoyang</p> <p>2016-06-09</p> <p>We carried out reactive <span class="hlt">molecular</span> dynamics simulations by ReaxFF to study the initial <span class="hlt">events</span> of an insensitive high explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) against various thermal stimuli including constant-temperature heating, programmed heating, and adiabatic heating to simulate TATB suffering from accidental heating in reality. Cluster evolution at the <span class="hlt">early</span> stage of the thermal decomposition of condensed TATB was the main focus as cluster formation primarily occurs when TATB is heated. The results show that cluster formation is the balance of the competition of intermolecular collision and <span class="hlt">molecular</span> decomposition of TATB, that is, an appropriate temperature and certain duration are required for cluster formation and preservation. The temperature in the range of 2000-3000 K was found to be optimum for fast formation and a period of preservation. Besides, the intra- and intermolecular H transfers are always favorable, whereas the C-NO2 partition was favorable at high temperature. The simulation results are helpful to deepen the insight into the thermal properties of condensed TATB.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25086079','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25086079"><span>Tumor necrosis factor-α inhibitor treatment and the risk of incident cardiovascular <span class="hlt">events</span> in patients with <span class="hlt">early</span> rheumatoid arthritis: a nested case-control study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Desai, Rishi J; Rao, Jaya K; Hansen, Richard A; Fang, Gang; Maciejewski, Matthew; Farley, Joel</p> <p>2014-11-01</p> <p>To compare the risk of cardiovascular (CV) <span class="hlt">events</span> between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with <span class="hlt">early</span> rheumatoid arthritis (RA). A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with <span class="hlt">early</span> RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV <span class="hlt">event</span> diagnosis for cases was defined as the <span class="hlt">event</span> date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the <span class="hlt">event</span> date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). From the cohort of patients with <span class="hlt">early</span> RA, 279 cases of incident CV <span class="hlt">events</span> and 3348 matched controls were identified. The adjusted risk of CV <span class="hlt">events</span> was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with <span class="hlt">early</span> RA.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28701166','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28701166"><span>Which <span class="hlt">early</span> life <span class="hlt">events</span> or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Luzak, Agnes; Fuertes, Elaine; Flexeder, Claudia; Standl, Marie; von Berg, Andrea; Berdel, Dietrich; Koletzko, Sibylle; Heinrich, Joachim; Nowak, Dennis; Schulz, Holger</p> <p>2017-07-12</p> <p>Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of <span class="hlt">early</span> life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. Best subset selection was performed for linear regression models to investigate associations between 21 diverse <span class="hlt">early</span> life <span class="hlt">events</span> and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF 25-75 )) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. A higher peak weight velocity and <span class="hlt">early</span> lung infections were the <span class="hlt">early</span> life <span class="hlt">events</span> prevalently associated with airflow limitation and FEF 25-75 . Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by <span class="hlt">early</span> life <span class="hlt">events</span> was comparatively low (median: 4.8%; range: 0.2-22.4%), but these <span class="hlt">events</span> were consistently negatively associated with airway function. Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate <span class="hlt">early</span> life and current factors that should be considered in studies on lung health among adolescents.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26137297','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26137297"><span>Combining simple patient-oriented tests with state-of-the-art <span class="hlt">molecular</span> diagnostics for <span class="hlt">early</span> diagnosis of cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fitzgerald, Rebecca C</p> <p>2015-06-01</p> <p><span class="hlt">Early</span> diagnosis is an important strategy to improve outcomes from cancer. Oesophageal adenocarcinoma is an example of a cancer that presents late, with very poor outcomes, and for which the presence of the precursor lesion Barrett's oesophagus provides the opportunity to intervene at an <span class="hlt">early</span> stage. In this review, I describe the challenges in the field and the work that we have done to devise a conceptually novel approach to <span class="hlt">early</span> diagnosis, using a cell collection device (Cytosponge), coupled with <span class="hlt">molecular</span> assays. This is a personal perspective in which I also describe the career pathway that led me into academic gastroenterology, and the rewards and challenges of translational research in <span class="hlt">molecular</span> diagnostics. There are fantastic opportunities for clinicians wishing to pursue academic medicine, because it is a time when massive strides are being made in a whole number of areas; for example: imaging, sequencing technology and targeted therapies. Clinicians who can straddle the laboratory and the clinic are essential, to maximise the progress that can be made for the benefit of patients.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27228435','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27228435"><span><span class="hlt">Early</span> blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular <span class="hlt">events</span> in the Scandinavian Candesartan Acute Stroke Trial (SCAST).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M; Berge, Eivind</p> <p>2016-08-01</p> <p><span class="hlt">Early</span> blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular <span class="hlt">events</span> in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was dependent on the timing of treatment. Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular <span class="hlt">event</span> (vascular death, nonfatal stroke or nonfatal myocardial infarction) during the first 6 months. The modified Rankin Scale (mRS) score following a vascular <span class="hlt">event</span> was used to categorize vascular <span class="hlt">events</span> in order of severity: no <span class="hlt">event</span> (n = 1798), minor (mRS 0-2, n = 59), moderately severe (mRS 3-4, n = 57) and major <span class="hlt">event</span> (mRS 5-6, n = 115). We used ordinal logistic regression for analysis and adjusted for predefined prognostic variables. Candesartan had no overall effect on vascular <span class="hlt">events</span> (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among the patients treated within 6 h, the adjusted common odds ratio for vascular <span class="hlt">events</span> was 0.37, 95% confidence interval 0.16-0.84, P = 0.02, and there was no heterogeneity of effect between ischaemic and haemorrhagic strokes. Ordinal analysis of vascular <span class="hlt">events</span> showed no overall effect of candesartan in the subacute phase of stroke. The effect of treatment given within 6 h of stroke onset appears promising, and will be addressed in ongoing trials. Ordinal analysis of vascular <span class="hlt">events</span> is feasible and can be used in future trials.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20030977','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20030977"><span><span class="hlt">Molecular</span> spectral imaging system for quantitative immunohistochemical analysis of <span class="hlt">early</span> diabetic retinopathy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng</p> <p>2009-12-01</p> <p>A <span class="hlt">molecular</span> spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring <span class="hlt">molecular</span> spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some <span class="hlt">molecular</span> spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from <span class="hlt">molecular</span> spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of <span class="hlt">molecular</span> spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017APS..MARK26010H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017APS..MARK26010H"><span><span class="hlt">Molecular</span> insights into <span class="hlt">early</span> stage aggregation of di-Fmoc-L-lysine in binary mixture of organic solvent and water</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Huda, Md Masrul; Rai, Neeraj</p> <p></p> <p><span class="hlt">Molecular</span> gels are relatively new class of soft materials, which are formed by the supramolecular aggregation of low <span class="hlt">molecular</span> weight gelators (LMWGs) in organic solvents and/or water. Hierarchical self-assembly of small gelator molecules lead to three-dimensional complex fibrillar networks, which restricts the flow of solvents and results in viscous solid like materials or gels. These gels have drawn significant attentions for their potential applications for drug delivery, tissue engineering, materials for sensors etc. As of now, self-assembly of gelator molecules into one-dimensional fibers is not well understood, although that is very important to design new gelators for desired applications. Here, we present <span class="hlt">molecular</span> dynamics study that provides <span class="hlt">molecular</span> level insight into <span class="hlt">early</span> stage aggregation of selected gelator, di-Fmoc-L-lysine in binary mixture of organic solvent and water. We will present the role of different functional groups of gelator molecule such as aromatic ring, amide, and carboxylic group on aggregation. We will also present the effect of concentrations of gelator and solvent on self-assembly of gelators. This study has captured helical fiber growth and branching of fiber, which is in good agreement with experimental observations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24599585','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24599585"><span>Impact of COX2 genotype, ER status and body constitution on risk of <span class="hlt">early</span> <span class="hlt">events</span> in different treatment groups of breast cancer patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Markkula, Andrea; Simonsson, Maria; Rosendahl, Ann H; Gaber, Alexander; Ingvar, Christian; Rose, Carsten; Jernström, Helena</p> <p>2014-10-15</p> <p>The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers. In breast cancer, tumor COX-2 expression has been associated with increased estrogen levels in estrogen receptor (ER)-positive and activated Akt-pathway in ER-negative tumors. Our study investigated the impact of COX2 genotypes on <span class="hlt">early</span> breast cancer <span class="hlt">events</span> and treatment response in relation to tumor ER status and body constitution. In Sweden, between 2002 and 2008, 634 primary breast cancer patients, aged 25-99 years, were included. Disease-free survival was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained preoperatively. Clinical data, patient- and tumor-characteristics were obtained from questionnaires, patients' charts, population registries and pathology reports. Minor allele(C) frequency was 16.1%. Genotype was not linked to COX-2 tumor expression. Median follow-up was 5.1 years. G/G genotype was not associated with <span class="hlt">early</span> <span class="hlt">events</span> in patients with ER-positive tumors, adjusted HR 0.77 (0.46-1.29), but conferred an over 4-fold increased risk in patients with ER-negative tumors, adjusted HR 4.41 (1.21-16.02)(p(interaction) = 0.015). Chemotherapy-treated G/G-carriers with a breast volume ≥ 850 ml had an increased risk of <span class="hlt">early</span> <span class="hlt">events</span> irrespective of ER status, adjusted HR 8.99 (1.14-70.89). Endocrine-treated C-allele carriers with ER-positive tumors and a breast volume ≥ 850 ml had increased risk of <span class="hlt">early</span> <span class="hlt">events</span>, adjusted HR 2.30 (1.12-4.75). COX2 genotype, body constitution and ER status had a combined effect on the risk of <span class="hlt">early</span> <span class="hlt">events</span> and treatment response. The high risk for <span class="hlt">early</span> <span class="hlt">events</span> in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may identify patients in need of more personalized treatment. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18980666','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18980666"><span>Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an <span class="hlt">early</span> domain shuffling <span class="hlt">event</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kyndt, Tina; Haegeman, Annelies; Gheysen, Godelieve</p> <p>2008-11-03</p> <p> the whole gene cassette, i.e. the GHF5 catalytic domain and the CBM2, rather than that it evolved by domain shuffling. Our evolutionary model for the gene structure in PPN GHF5 endoglucanases implies the occurrence of an <span class="hlt">early</span> duplication <span class="hlt">event</span>, and more recent gene duplications at genus or species level.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4139900','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4139900"><span><span class="hlt">Molecular</span> imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for <span class="hlt">early</span> diagnosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali</p> <p>2014-01-01</p> <p>Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for <span class="hlt">early</span> diagnosis of DR are urgently needed. Using a new <span class="hlt">molecular</span> imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for <span class="hlt">early</span> diagnosis of DR and VEGFR-2 as a <span class="hlt">molecular</span> marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients.—Sun, D., Nakao, S., Xie, F., Zandi, S., Bagheri, A., Kanavi, M. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. <span class="hlt">Molecular</span> imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for <span class="hlt">early</span> diagnosis. PMID:24903276</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24368387','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24368387"><span><span class="hlt">Early</span> sex-specific modulation of the <span class="hlt">molecular</span> clock in trauma.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mehraj, Vikram; Wiramus, Sandrine; Capo, Christian; Leone, Marc; Mege, Jean-Louis; Textoris, Julien</p> <p>2014-01-01</p> <p>Immune system biology and most physiologic functions are tightly linked to circadian rhythms. Time of day-dependent variations in many biologic parameters also play a fundamental role in the disease process. We previously showed that the genes encoding the peripheral <span class="hlt">molecular</span> clock were modulated in a sex-dependent manner in Q fever. Here, we examined severe trauma patients at admission to the intensive care unit. Using quantitative real-time polymerase chain reaction, the whole-blood expression of the <span class="hlt">molecular</span> clock components ARNTL, CLOCK, and PER2 was assessed in male and female trauma patients. Healthy volunteers of both sexes were used as controls. We observed a significant overexpression of both ARNTL and CLOCK in male trauma patients. We report, for the first time, the sex-related modulation of the <span class="hlt">molecular</span> clock genes in the blood following severe trauma. These results emphasize the role of circadian rhythms in the immune response in trauma patients. Epidemiologic study, level IV.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2011MNRAS.417..882D','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2011MNRAS.417..882D"><span>The ATLAS3D project - X. On the origin of the <span class="hlt">molecular</span> and ionized gas in <span class="hlt">early</span>-type galaxies</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Davis, Timothy A.; Alatalo, Katherine; Sarzi, Marc; Bureau, Martin; Young, Lisa M.; Blitz, Leo; Serra, Paolo; Crocker, Alison F.; Krajnović, Davor; McDermid, Richard M.; Bois, Maxime; Bournaud, Frédéric; Cappellari, Michele; Davies, Roger L.; Duc, Pierre-Alain; de Zeeuw, P. Tim; Emsellem, Eric; Khochfar, Sadegh; Kuntschner, Harald; Lablanche, Pierre-Yves; Morganti, Raffaella; Naab, Thorsten; Oosterloo, Tom; Scott, Nicholas; Weijmans, Anne-Marie</p> <p>2011-10-01</p> <p>We make use of interferometric CO and H I observations, and optical integral-field spectroscopy from the ATLAS3D survey, to probe the origin of the <span class="hlt">molecular</span> and ionized interstellar medium (ISM) in local <span class="hlt">early</span>-type galaxies. We find that 36 ± 5 per cent of our sample of fast-rotating <span class="hlt">early</span>-type galaxies have their ionized gas kinematically misaligned with respect to the stars, setting a strong lower limit on the importance of externally acquired gas (e.g. from mergers and cold accretion). Slow rotators have a flat distribution of misalignments, indicating that the dominant source of gas is external. The <span class="hlt">molecular</span>, ionized and atomic gas in all the detected galaxies are always kinematically aligned, even when they are misaligned from the stars, suggesting that all these three phases of the ISM share a common origin. In addition, we find that the origin of the cold and warm gas in fast-rotating <span class="hlt">early</span>-type galaxies is strongly affected by environment, despite the <span class="hlt">molecular</span> gas detection rate and mass fractions being fairly independent of group/cluster membership. Galaxies in dense groups and the Virgo cluster nearly always have their <span class="hlt">molecular</span> gas kinematically aligned with the stellar kinematics, consistent with a purely internal origin (presumably stellar mass loss). In the field, however, kinematic misalignments between the stellar and gaseous components indicate that at least 42 ± 5 per cent of local fast-rotating <span class="hlt">early</span>-type galaxies have their gas supplied from external sources. When one also considers evidence of accretion present in the galaxies' atomic gas distributions, ≳46 per cent of fast-rotating field ETGs are likely to have acquired a detectable amount of ISM from accretion and mergers. We discuss several scenarios which could explain the environmental dichotomy, including preprocessing in galaxy groups/cluster outskirts and the morphological transformation of spiral galaxies, but we find it difficult to simultaneously explain the kinematic</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=event&pg=7&id=EJ1157100','ERIC'); return false;" href="https://eric.ed.gov/?q=event&pg=7&id=EJ1157100"><span><span class="hlt">Early</span> Preservice Teachers' Experiences of the Environment: A Case Study of Participation in a Community Outdoor <span class="hlt">Event</span></span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>van Rooy, Wilhelmina</p> <p>2017-01-01</p> <p>Clean Up Australia Day is the country's largest community-based environmental annual <span class="hlt">event</span> when participants work in teams to remove rubbish from their local environment. This article describes an interpretive study in which a sample of preservice primary teachers' (n = 30) responses to questions about their involvement in the <span class="hlt">event</span> were evaluated…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26089009','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26089009"><span>Relation of Cardiac Complications in the <span class="hlt">Early</span> Phase of Community-Acquired Pneumonia to Long-Term Mortality and Cardiovascular <span class="hlt">Events</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cangemi, Roberto; Calvieri, Camilla; Falcone, Marco; Bucci, Tommaso; Bertazzoni, Giuliano; Scarpellini, Maria G; Barillà, Francesco; Taliani, Gloria; Violi, Francesco</p> <p>2015-08-15</p> <p>Community-acquired pneumonia (CAP) is complicated by cardiac <span class="hlt">events</span> in the <span class="hlt">early</span> phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular <span class="hlt">events</span> occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular <span class="hlt">events</span> (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive <span class="hlt">events</span>). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p <0.001) and 73 experienced a cardiovascular <span class="hlt">event</span> (47% of patients with and 19% of patients without an intrahospital cardiac complication, p <0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular <span class="hlt">events</span> during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the <span class="hlt">early</span> phase of pneumonia are associated with an enhanced risk of death and cardiovascular <span class="hlt">events</span> during long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3835057','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3835057"><span><span class="hlt">Molecular</span> Profiling of Glatiramer Acetate <span class="hlt">Early</span> Treatment Effects in Multiple Sclerosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Achiron, Anat; Feldman, Anna; Gurevich, Michael</p> <p>2009-01-01</p> <p>Background: Glatiramer acetate (GA, Copaxone®) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact <span class="hlt">molecular</span> mechanisms of GA effects are only partially understood. Objective: To characterized GA <span class="hlt">molecular</span> effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC). Methods: Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS. Results: GA induced a specific gene expression <span class="hlt">molecular</span> signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation. Conclusions: Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as <span class="hlt">molecular</span> markers of GA activity. PMID:19893201</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA591911','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA591911"><span>Targeting Cell Surface Proteins in <span class="hlt">Molecular</span> Photoacoustic Imaging to Detect Ovarian Cancer <span class="hlt">Early</span></span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2013-07-01</p> <p>biology, nanotechnology, and imaging technology, <span class="hlt">molecular</span> imaging utilizes specific probes as contrast agents to visualize cellular processes at the...This reagent was covalently coupled to the oligosaccharides attached to polypeptide side-chains of extracellular membrane proteins on living cells...website. The normal tissue gene expression profile dataset was modified and processed as described by Fang (8) and mean intensities and standard</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26275839','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26275839"><span><span class="hlt">Molecular</span>-level insights of <span class="hlt">early</span>-stage prion protein aggregation on mica and gold surface determined by AFM imaging and <span class="hlt">molecular</span> simulation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lou, Zhichao; Wang, Bin; Guo, Cunlan; Wang, Kun; Zhang, Haiqian; Xu, Bingqian</p> <p>2015-11-01</p> <p>By in situ time-lapse AFM, we investigated <span class="hlt">early</span>-stage aggregates of PrP formed at low concentration (100 ng/mL) on mica and Au(111) surfaces in acetate buffer (pH 4.5). Remarkably different PrP assemblies were observed. Oligomeric structures of PrP aggregates were observed on mica surface, which was in sharp contrast to the multi-layer PrP aggregates yielding parallel linear patterns observed Au(111) surface. Combining <span class="hlt">molecular</span> dynamics and docking simulations, PrP monomers, dimers and trimers were revealed as the basic units of the observed aggregates. Besides, the mechanisms of the observed PrP aggregations and the corresponding <span class="hlt">molecular</span>-substrate and intermolecular interactions were suggested. These interactions involved gold-sulfur interaction, electrostatic interaction, hydrophobic interaction, and hydrogen binding interaction. In contrast, the PrP aggregates observed in pH 7.2 PBS buffer demonstrated similar large ball-like structures on both mica and Au(111) surfaces. The results indicate that the pH of a solution and the surface of the system can have strong effects on supramolecular assemblies of prion proteins. This study provides in-depth understanding on the structural and mechanistic nature of PrP aggregation, and can be used to study the aggregation mechanisms of other proteins with similar misfolding properties. Copyright © 2015 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22522478-reanalyses-anomalous-gravitational-microlensing-events-ogle-iii-early-warning-system-database-combined-data','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22522478-reanalyses-anomalous-gravitational-microlensing-events-ogle-iii-early-warning-system-database-combined-data"><span>REANALYSES OF ANOMALOUS GRAVITATIONAL MICROLENSING <span class="hlt">EVENTS</span> IN THE OGLE-III <span class="hlt">EARLY</span> WARNING SYSTEM DATABASE WITH COMBINED DATA</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Jeong, J.; Park, H.; Han, C.</p> <p>2015-05-01</p> <p>We reanalyze microlensing <span class="hlt">events</span> in the published list of anomalous <span class="hlt">events</span> that were observed from the Optical Gravitational Lensing Experiment (OGLE) lensing survey conducted during the 2004–2008 period. In order to check the existence of possible degenerate solutions and extract extra information, we conduct analyses based on combined data from other survey and follow-up observation and consider higher-order effects. Among the analyzed <span class="hlt">events</span>, we present analyses of eight <span class="hlt">events</span> for which either new solutions are identified or additional information is obtained. We find that the previous binary-source interpretations of five <span class="hlt">events</span> are better interpreted by binary-lens models. These <span class="hlt">events</span> includemore » OGLE-2006-BLG-238, OGLE-2007-BLG-159, OGLE-2007-BLG-491, OGLE-2008-BLG-143, and OGLE-2008-BLG-210. With additional data covering caustic crossings, we detect finite-source effects for six <span class="hlt">events</span> including OGLE-2006-BLG-215, OGLE-2006-BLG-238, OGLE-2006-BLG-450, OGLE-2008-BLG-143, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. Among them, we are able to measure the Einstein radii of three <span class="hlt">events</span> for which multi-band data are available. These <span class="hlt">events</span> are OGLE-2006-BLG-238, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. For OGLE-2008-BLG-143, we detect higher-order effects induced by the changes of the observer’s position caused by the orbital motion of the Earth around the Sun. In addition, we present degenerate solutions resulting from the known close/wide or ecliptic degeneracy. Finally, we note that the masses of the binary companions of the lenses of OGLE-2006-BLG-450 and OGLE-2008-BLG-210 are in the brown-dwarf regime.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17574686','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17574686"><span>Stressful life <span class="hlt">events</span> and depressive problems in <span class="hlt">early</span> adolescent boys and girls: the influence of parental depression, temperament and family environment.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bouma, Esther M C; Ormel, Johan; Verhulst, Frank C; Oldehinkel, Albertine J</p> <p>2008-01-01</p> <p>Stressful life <span class="hlt">events</span> increase the probability of depressive problems in <span class="hlt">early</span> adolescence. Several genetic and environmental risk factors may change individual sensitivity to the depressogenic effect of these <span class="hlt">events</span>. We examined modification by parental depression and gender, and mediation of the former by temperament and family environment. Data were collected as part of a longitudinal cohort study of (pre)adolescents (n = 2127). During the first assessment wave at approximately age 11, we assessed parental depression, family functioning, perceived parenting behaviours, and temperamental frustration and fearfulness. At the second wave, about two and a half years later, stressful life <span class="hlt">events</span> between the first and second assessment were assessed. Depressive problems were measured at both waves. Adolescents with parents who had a (lifetime) depressive episode were more sensitive to the depressogenic effect of stressful <span class="hlt">events</span> than adolescents without depressed parents. Furthermore, girls are more sensitive to these effects than boys. The modifying effect of parental depression was not mediated by temperament, family functioning and perceived parenting. Life <span class="hlt">events</span> were assessed without consideration of contextual information. Depressive problems were measured by questionnaires that did not directly represent DSM-IV criteria. The measure of parental depression was unspecific regarding severity and timing of depressive episodes. The results suggest that gender and parental depression are associated with increased sensitivity to depression after experiencing stressful life <span class="hlt">events</span> during adolescence.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ClinicalTrials.gov/ct2/show/study/NCT02269592','CLINICALTRIALS'); return false;" href="https://ClinicalTrials.gov/ct2/show/study/NCT02269592"><span>Study of MGUS, Smoldering Myeloma, <span class="hlt">Early</span> MDS and CLL to Assess <span class="hlt">Molecular</span> <span class="hlt">Events</span> of Progression and Clinical Outcome</span></a></p> <p><a target="_blank" href="http://www.clinicaltrials.gov/ct/screen/SimpleSearch">ClinicalTrials.gov</a></p> <p></p> <p>2017-08-25</p> <p>Monoclonal Gammopathy of Undetermined Significance (MGUS); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic-Myeloproliferative Diseases; Hematological Malignancies; B-cell Malignancy, Low-grade; Myelodysplastic Syndrome With Low-grade Lesions; IgG Monoclonal Gammopathy of Uncertain Significance; Smoldering Multiple Myeloma; Waldenstrom Macroglobulinemia</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_19 --> <div id="page_20" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="381"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5646184','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5646184"><span><span class="hlt">Early</span> Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction <span class="hlt">event</span>: evidence from a new genus and species, Grimmenodon aureum</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Stumpf, Sebastian; Ansorge, Jörg; Pfaff, Cathrin; Kriwet, Jürgen</p> <p>2017-01-01</p> <p>ABSTRACT A new genus and species of pycnodontiform fishes, Grimmenodon aureum, from marginal marine, marine-brackish lower Toarcian (Harpoceras exaratum ammonite subzone) clay deposits of Grimmen in northeastern Germany is described. The single specimen represents a diagnostic left prearticular dentition characterized by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum, gen. et sp. nov., is the second unambiguously identified pycnodontiform species from the <span class="hlt">Early</span> Jurassic, in addition to Eomesodon liassicus from the <span class="hlt">early</span> Lower Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth crown from the upper Pliensbachian (Pleuroceras apyrenum ammonite subzone) of the same site. The material expands the <span class="hlt">Early</span> Jurassic range of pycnodontiforms significantly northwards and confirms their presence before and immediately following the onset of the Toarcian Oceanic Anoxic <span class="hlt">Event</span> (T-OAE) in the marginal marine ecosystems south of the Fennoscandian Shield. Moreover, the new records indicate that the <span class="hlt">Early</span> Jurassic diversity of pycnodontiform fishes was greater than previously assumed and probably equaled that of the Late Triassic. Therefore, it is hypothesized that the Triassic-Jurassic mass extinction <span class="hlt">event</span> did not affect pycnodontiform fishes significantly. Micro-computed tomography was used to study the internal anatomy of the prearticular of Grimmenodon aureum, gen. et sp. nov. Our results show that no replacement teeth were formed within the tooth-bearing bone but rather were added posteriorly to functional teeth. http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2 Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017. <span class="hlt">Early</span> Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction <span class="hlt">event</span>: Evidence from a new genus and species, Grimmenodon aureum. Journal of Vertebrate Paleontology. DOI: 10</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2863820','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2863820"><span><span class="hlt">Early</span> Spatial and Temporal <span class="hlt">Events</span> of Human T-Lymphotropic Virus Type 1 Spread following Blood-Borne Transmission in a Rabbit Model of Infection ▿</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Haynes, Rashade A. H.; Zimmerman, Bevin; Millward, Laurie; Ware, Evan; Premanandan, Christopher; Yu, Lianbo; Phipps, Andrew J.; Lairmore, Michael D.</p> <p>2010-01-01</p> <p>Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and <span class="hlt">early</span> virus replication <span class="hlt">events</span> are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of <span class="hlt">early</span> <span class="hlt">events</span> of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study <span class="hlt">early</span> spatial and temporal <span class="hlt">events</span> of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the <span class="hlt">early</span> spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding <span class="hlt">early</span> viral spread in lymphoid compartments to establish and maintain persistent infection. PMID:20219918</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29170576','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29170576"><span><span class="hlt">Early</span> Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction <span class="hlt">event</span>: evidence from a new genus and species, Grimmenodon aureum.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Stumpf, Sebastian; Ansorge, Jörg; Pfaff, Cathrin; Kriwet, Jürgen</p> <p>2017-07-04</p> <p>A new genus and species of pycnodontiform fishes, Grimmenodon aureum , from marginal marine, marine-brackish lower Toarcian ( Harpoceras exaratum ammonite subzone) clay deposits of Grimmen in northeastern Germany is described. The single specimen represents a diagnostic left prearticular dentition characterized by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum , gen. et sp. nov., is the second unambiguously identified pycnodontiform species from the <span class="hlt">Early</span> Jurassic, in addition to Eomesodon liassicus from the <span class="hlt">early</span> Lower Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth crown from the upper Pliensbachian ( Pleuroceras apyrenum ammonite subzone) of the same site. The material expands the <span class="hlt">Early</span> Jurassic range of pycnodontiforms significantly northwards and confirms their presence before and immediately following the onset of the Toarcian Oceanic Anoxic <span class="hlt">Event</span> (T-OAE) in the marginal marine ecosystems south of the Fennoscandian Shield. Moreover, the new records indicate that the <span class="hlt">Early</span> Jurassic diversity of pycnodontiform fishes was greater than previously assumed and probably equaled that of the Late Triassic. Therefore, it is hypothesized that the Triassic-Jurassic mass extinction <span class="hlt">event</span> did not affect pycnodontiform fishes significantly. Micro-computed tomography was used to study the internal anatomy of the prearticular of Grimmenodon aureum , gen. et sp. nov. Our results show that no replacement teeth were formed within the tooth-bearing bone but rather were added posteriorly to functional teeth. http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2 Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017. <span class="hlt">Early</span> Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction <span class="hlt">event</span>: Evidence from a new genus and species, Grimmenodon aureum . Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2017.1344679.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24903276','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24903276"><span><span class="hlt">Molecular</span> imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for <span class="hlt">early</span> diagnosis.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali</p> <p>2014-09-01</p> <p>Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for <span class="hlt">early</span> diagnosis of DR are urgently needed. Using a new <span class="hlt">molecular</span> imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for <span class="hlt">early</span> diagnosis of DR and VEGFR-2 as a <span class="hlt">molecular</span> marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20869460','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20869460"><span><span class="hlt">Molecular</span> mechanisms involved in the <span class="hlt">early</span> steps of flavivirus cell entry.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kaufmann, Bärbel; Rossmann, Michael G</p> <p>2011-01-01</p> <p>Flaviviruses enter their host cells by receptor-mediated endocytosis, a well-orchestrated process of receptor recognition, penetration and uncoating. Recent findings on these <span class="hlt">early</span> steps in the life cycle of flaviviruses are the focus of this review. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22325703','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22325703"><span>The relation of <span class="hlt">early</span> experienced negative life <span class="hlt">events</span> and current itch. A longitudinal study among adolescents in Oslo, Norway.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lien, Lars; Halvorsen, Jon Anders; Haavet, Ole Rikard; Dalgard, Florence</p> <p>2012-03-01</p> <p>Negative life <span class="hlt">events</span> have impact on mental health and skin diseases among adults. Itch is a common, disabling skin symptom. The aim was to describe negative life <span class="hlt">events</span> associated with current itch and to analyze the impact of number of negative life <span class="hlt">events</span> on symptoms of itch, controlling for possible confounders. This school-based longitudinal survey was conducted among 15 and 18 years old high-school students in Oslo, Norway. From a baseline cohort of 3811 students, 2489 (65%) participants were followed-up after three years later. They completed questionnaires at baseline and follow-up. Current itch was measured with a validated instrument asking for symptoms on a four point Likert scale at follow-up. More girls than boys reported itch. There were no gender differences in number of negative life <span class="hlt">events</span>. Death among close relative/friend was the most common negative life <span class="hlt">event</span> among boys and girls. All negative life experiences before 15 years of age were statistically significantly associated with itch, but after 15 years only half of the negative life <span class="hlt">events</span> were associated with itch. The bivariate association between number of negative life <span class="hlt">events</span> and itch was statistically significant, and only when adjusting for mental distress at baseline there was a considerable drop in the Odds Ratio. There is a clear association between number of negative life <span class="hlt">events</span> at baseline and itch at follow-up three years later among adolescents. It is therefore important to discuss possible adverse experiences with adolescents presenting with severe symptoms of itch. Copyright © 2011 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017JPhD...50V5201F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017JPhD...50V5201F"><span>A model of <span class="hlt">early</span> formation of uranium <span class="hlt">molecular</span> oxides in laser-ablated plasmas</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Finko, Mikhail S.; Curreli, Davide; Weisz, David G.; Crowhurst, Jonathan C.; Rose, Timothy P.; Koroglu, Batikan; Radousky, Harry B.; Armstrong, Michael R.</p> <p>2017-12-01</p> <p>In this work, we present a newly constructed U x O y reaction mechanism that consists of 30 reaction channels (21 of which are reversible channels) for 11 uranium <span class="hlt">molecular</span> species (including ions). Both the selection of reaction channels and calculation of corresponding rate coefficients is accomplished via a comprehensive literature review and application of basic reaction rate theory. The reaction mechanism is supplemented by a detailed description of oxygen plasma chemistry (19 species and 142 reaction channels) and is used to model an atmospheric laser ablated uranium plume via a 0D (global) model. The global model is used to analyze the evolution of key uranium <span class="hlt">molecular</span> species predicted by the reaction mechanism, and the initial stage of formation of uranium oxide species.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1426094-model-early-formation-uranium-molecular-oxides-laser-ablated-plasmas','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1426094-model-early-formation-uranium-molecular-oxides-laser-ablated-plasmas"><span>A model of <span class="hlt">early</span> formation of uranium <span class="hlt">molecular</span> oxides in laser-ablated plasmas</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Finko, Mikhail S.; Curreli, Davide; Weisz, David G.; ...</p> <p>2017-10-12</p> <p>Here, in this work, we present a newly constructed U xO y reaction mechanism that consists of 30 reaction channels (21 of which are reversible channels) for 11 uranium <span class="hlt">molecular</span> species (including ions). Both the selection of reaction channels and calculation of corresponding rate coefficients is accomplished via a comprehensive literature review and application of basic reaction rate theory. The reaction mechanism is supplemented by a detailed description of oxygen plasma chemistry (19 species and 142 reaction channels) and is used to model an atmospheric laser ablated uranium plume via a 0D (global) model. Finally, the global model is usedmore » to analyze the evolution of key uranium <span class="hlt">molecular</span> species predicted by the reaction mechanism, and the initial stage of formation of uranium oxide species.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/1426094-model-early-formation-uranium-molecular-oxides-laser-ablated-plasmas','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/1426094-model-early-formation-uranium-molecular-oxides-laser-ablated-plasmas"><span>A model of <span class="hlt">early</span> formation of uranium <span class="hlt">molecular</span> oxides in laser-ablated plasmas</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Finko, Mikhail S.; Curreli, Davide; Weisz, David G.</p> <p></p> <p>Here, in this work, we present a newly constructed U xO y reaction mechanism that consists of 30 reaction channels (21 of which are reversible channels) for 11 uranium <span class="hlt">molecular</span> species (including ions). Both the selection of reaction channels and calculation of corresponding rate coefficients is accomplished via a comprehensive literature review and application of basic reaction rate theory. The reaction mechanism is supplemented by a detailed description of oxygen plasma chemistry (19 species and 142 reaction channels) and is used to model an atmospheric laser ablated uranium plume via a 0D (global) model. Finally, the global model is usedmore » to analyze the evolution of key uranium <span class="hlt">molecular</span> species predicted by the reaction mechanism, and the initial stage of formation of uranium oxide species.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28665188','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28665188"><span><span class="hlt">Molecular</span> dynamics simulations of lysozyme-lipid systems: probing the <span class="hlt">early</span> steps of protein aggregation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Trusova, Valeriya M; Gorbenko, Galyna P</p> <p>2017-07-10</p> <p>Using the <span class="hlt">molecular</span> dynamics simulation, the role of lipids in the lysozyme transition into the aggregation-competent conformation has been clarified. Analysis of the changes of lysozyme secondary structure upon its interactions with the model bilayer membranes composed of phosphatidylcholine and its mixtures with phosphatidylglycerol (10, 40, and 80 mol%) within the time interval of 100 ns showed that lipid-bound protein is characterized by the increased content of β-structures. Along with this, the formation of protein-lipid complexes was accompanied by the increase in the gyration radius and the decrease in RMSD of polypeptide chain. The results obtained were interpreted in terms of the partial unfolding of lysozyme molecule on the lipid matrix, with the magnitude of this effect being increased with increasing the fraction of anionic lipids. Based on the results of <span class="hlt">molecular</span> dynamics simulation, a hypothetical model of the nucleation of lysozyme amyloid fibrils in a membrane environment was suggested.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23025838','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23025838"><span><span class="hlt">Early</span> traumatic life <span class="hlt">events</span>, parental attitudes, family history, and birth risk factors in patients with depressive disorder and healthy controls.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bandelow, Borwin; Gutermann, Julia; Peter, Helmut; Wedekind, Dirk</p> <p>2013-02-01</p> <p>Only few studies have compared the frequency of traumatic life <span class="hlt">events</span> during childhood in inpatients with depression with a healthy control group. Consecutively admitted inpatients with depression (n = 79), most of whom belonged to the melancholic subtype (n = 73; 92.4%), and healthy controls (n = 110) were investigated using a comprehensive retrospective interview with 203 questions regarding childhood traumatic life <span class="hlt">events</span>, parental attitudes, family history of psychiatric disorders and birth risk factors. Depressed patients had significantly more severe traumatic <span class="hlt">events</span> (mean score 1.33; SD 1.4) than control subjects (0.85; SD 1.2) on a 0-10 point "severe trauma scale". 70.9% (n = 56) of the depressed patients, but only 48.2% (n = 53) of the controls reported at least one severe traumatic <span class="hlt">event</span>. When looking at single <span class="hlt">events</span>, only few differences were found between patients and controls. Compared to controls, patients described significantly higher rates of psychiatric disorders in their families, in particular depression. Parental rearing styles were rated as more unfavorable in the patient group. In a logistic regression model, of all possible etiological factors examined, only a family history of psychiatric disorders showed a significant influence (OR = 3.6). Melancholic depression seems to be less associated with traumatic <span class="hlt">events</span> than other psychiatric disorders.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5930114-early-diagenesis-organic-matter-preservation-molecular-stable-isotope-perspective','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5930114-early-diagenesis-organic-matter-preservation-molecular-stable-isotope-perspective"><span><span class="hlt">Early</span> diagenesis and organic matter preservation--A <span class="hlt">molecular</span> stable isotope perspective</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Macko, S.A.; Engel, M.H.; Qian, Y.</p> <p>1992-01-01</p> <p>Through new developments in stable isotope capability, gas chromatography coupled to a stable isotope ratio mass spectrometer (GC/IRMS), the <span class="hlt">molecular</span> pathways of the diagenetic reactions can be observed on the components themselves. The authors report the results of laboratory-controlled degradation experiments of fresh organic substrates. Isotopically resolvable materials were used. Seagrass showed slight enrichments in [delta]N-15 with little change in [delta]C-13 following four weeks of decomposition. During that period the identifiable amino acid content decreased by approx. 50% for each amino acid. Mixtures of marine sediment with the same seagrass showed enrichments in nitrogen with associated depletions in carbon isotopicmore » compositions over the same time span. Control experiments on the sediments without added fresh seagrass showed no change in isotopic content. These changes are attributed to hydrolysis, deamination and decarboxylation reactions. Isotopic fractionations of similar size and direction have been observed in laboratory studies on peptide hydrolysis and natural samples of particulate organic materials. At the <span class="hlt">molecular</span> level, using GC/IRMS, certain amino acids are seen to decrease in C-13 content while others become increasingly enriched in C-13. Similar reactions are seen in carbohydrates. The <span class="hlt">molecular</span> isotope approach indicates that the process of diagenesis and preservation is significantly more complex than simple breakdown and loss. A large portion of the organic matter eventually preserved in organic-rich deposits can be attributed to new production in the deposit.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=427566','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=427566"><span><span class="hlt">Early</span> Estrogen Action: Stimulation of the Metabolism of High <span class="hlt">Molecular</span> Weight and Ribosomal RNAs</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Luck, Dennis N.; Hamilton, Terrell H.</p> <p>1972-01-01</p> <p>Samples of RNA, isolated from uteri of ovariectomized adult rats treated with estrogen, have been analyzed on sucrose gradients. Treatment with estrogen either for 20 min or 2 hr increased the specific activity of all classes of uterine RNA, but produced no significant alteration in the distribution of radioactivity in the gradients, when animals received [3H]uridine intraperitoneally 15 min before they were killed. After labeling periods of 30 min, 1 hr, or 2 hr, however, the RNAs isolated from animals treated with estrogen had a smaller percentage of rapidly sedimenting (faster than 28S) species of RNA than did RNA from animals not treated with the hormone. The decreased percentage of high <span class="hlt">molecular</span> weight RNA correlated with increases in both the specific activity of 28S and 18S RNA and the concentration of RNA in the whole organ. The labeled RNA of high <span class="hlt">molecular</span> weight was also demonstrated, by the use of actinomycin D in vivo, to have a more rapid turnover rate in the estrogen-stimulated uterus. Our results indicate that estrogen increases not only the rate of synthesis of ribosomal RNA in the uterus of the ovariectomized adult rat, but also the rate or efficiency of processing of precursor RNA species of high <span class="hlt">molecular</span> weight. PMID:4500546</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/1990JGR....9517605A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/1990JGR....9517605A"><span>A major 2.1 Ga <span class="hlt">event</span> of mafic magmatism in west Africa: An <span class="hlt">Early</span> stage of crustal accretion</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Abouchami, Wafa; Boher, Muriel; Michard, Annie; Albarede, Francis</p> <p>1990-10-01</p> <p> environments. Back-arc or low-Ti continental flood basalts provide a marginally good agreement but still face some difficulties. Oceanic flood basalts similar to those which form oceanic plateaus (e.g. in the Nauru basin) and later accreted to continents as allochtonous terranes represent the most acceptable modern analogue of many Proterozoic basalts. It is suggested that deep plumes piercing young lithosphere can generate huge amounts of tholeiites in a short time. Birimian basalts, like many <span class="hlt">Early</span> Proterozoic basalts, may also be viewed as recent equivalents of the Archean greenstone belts. The modern komatiite of Gorgona Island is suggested to fit this model of intraplate volcanism. Although the 2.1 Ga magmatic <span class="hlt">event</span> in West Africa has gone virtually unnoticed in the literature, it extends over several thousand kilometers and compares with the distribution of mantle-derived magmatic activity in other major orogenic provinces (e.g. Superior). It shows that the growth rate of continents cannot be extrapolated from the data obtained solely from the best studied continents (North America, Europe, Australia). If such large crustal segments were overlooked, a spurious pattern of episodic activity of the mantle could arise.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20962406','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20962406"><span>The spectral absorption coefficient at 254 nm as a real-time <span class="hlt">early</span> warning proxy for detecting faecal pollution <span class="hlt">events</span> at alpine karst water resources.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Stadler, H; Klock, E; Skritek, P; Mach, R L; Zerobin, W; Farnleitner, A H</p> <p>2010-01-01</p> <p>Because spring water quality from alpine karst aquifers can change very rapidly during <span class="hlt">event</span> situations, water abstraction management has to be performed in near real-time. Four summer <span class="hlt">events</span> (2005-2008) at alpine karst springs were investigated in detail in order to evaluate the spectral absorption coefficient at 254 nm (SAC254) as a real-time <span class="hlt">early</span> warning proxy for faecal pollution. For the investigation Low-Earth-Orbit (LEO) Satellite-based data communication between portable hydrometeorological measuring stations and an automated microbiological sampling device was used. The method for <span class="hlt">event</span> triggered microbial sampling and analyzing was already established and described in a previous paper. Data analysis including on-line <span class="hlt">event</span> characterisation (i.e. precipitation, discharge, turbidity, SAC254) and comprehensive E. coli determination (n>800) indicated that SAC254 is a useful <span class="hlt">early</span> warning proxy. Irrespective of the studied <span class="hlt">event</span> situations SAC254 always increased 3 to 6 hours earlier than the onset of faecal pollution, featuring different correlation phases. Furthermore, it seems also possible to use SAC254 as a real-time proxy parameter for estimating the extent of faecal pollution after establishing specific spring and <span class="hlt">event</span>-type calibrations that take into consideration the variability of the occurrence and the transferability of faecal material It should be highlighted that diffuse faecal pollution from wildlife and live stock sources was responsible for spring water contamination at the investigated catchments. In this respect, the SAC254 can also provide useful information to support microbial source tracking efforts where different situations of infiltration have to be investigated.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2011AtmEn..45.2473W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2011AtmEn..45.2473W"><span><span class="hlt">Molecular</span> composition and size distribution of sugars, sugar-alcohols and carboxylic acids in airborne particles during a severe urban haze <span class="hlt">event</span> caused by wheat straw burning</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wang, Gehui; Chen, Chunlei; Li, Jianjun; Zhou, Bianhong; Xie, Mingjie; Hu, Shuyuan; Kawamura, Kimitaka; Chen, Yan</p> <p>2011-05-01</p> <p><span class="hlt">Molecular</span> compositions and size distributions of water-soluble organic compounds (WSOC, i.e., sugars, sugar-alcohols and carboxylic acids) in particles from urban air of Nanjing, China during a severe haze <span class="hlt">event</span> caused by field burning of wheat straw were characterized and compared with those in the summer and autumn non-haze periods. During the haze <span class="hlt">event</span> levoglucosan (4030 ng m -3) was the most abundant compound among the measured WSOC, followed by succinic acid, malic acid, glycerol, arabitol and glucose, being different from those in the non-haze samples, in which sucrose or azelaic acid showed a second highest concentration, although levoglucosan was the highest. The measured WSOC in the haze <span class="hlt">event</span> were 2-20 times more than those in the non-hazy days. Size distribution results showed that there was no significant change in the compound peaks in coarse mode (>2.1 μm) with respect to the haze and non-haze samples, but a large difference in the fine fraction (<2.1 μm) was found with a sharp increase during the hazy days mostly due to the increased emissions of wheat straw burning. <span class="hlt">Molecular</span> compositions of organic compounds in the fresh smoke particles from wheat straw burning demonstrate that sharply increased concentrations of glycerol and succinic and malic acids in the fine particles during the haze <span class="hlt">event</span> were mainly derived from the field burning of wheat straw, although the sources of glucose and related sugar-alcohols whose concentrations significantly increased in the fine haze samples are unclear. Compared to that in the fresh smoke particles of wheat straw burning an increase in relative abundance of succinic acid to levoglucosan during the haze <span class="hlt">event</span> suggests a significant production of secondary organic aerosols during transport of the smoke plumes.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27457982','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27457982"><span>Identification and characterization of contrasting sunflower genotypes to <span class="hlt">early</span> leaf senescence process combining <span class="hlt">molecular</span> and physiological studies (Helianthus annuus L.).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>López Gialdi, A I; Moschen, S; Villán, C S; López Fernández, M P; Maldonado, S; Paniego, N; Heinz, R A; Fernandez, P</p> <p>2016-09-01</p> <p>Leaf senescence is a complex mechanism ruled by multiple genetic and environmental variables that affect crop yields. It is the last stage in leaf development, is characterized by an active decline in photosynthetic rate, nutrients recycling and cell death. The aim of this work was to identify contrasting sunflower inbred lines differing in leaf senescence and to deepen the study of this process in sunflower. Ten sunflower genotypes, previously selected by physiological analysis from 150 inbred genotypes, were evaluated under field conditions through physiological, cytological and <span class="hlt">molecular</span> analysis. The physiological measurement allowed the identification of two contrasting senescence inbred lines, R453 and B481-6, with an increase in yield in the senescence delayed genotype. These findings were confirmed by cytological and <span class="hlt">molecular</span> analysis using TUNEL, genomic DNA gel electrophoresis, flow sorting and gene expression analysis by qPCR. These results allowed the selection of the two most promising contrasting genotypes, which enables future studies and the identification of new biomarkers associated to <span class="hlt">early</span> senescence in sunflower. In addition, they allowed the tuning of cytological techniques for a non-model species and its integration with <span class="hlt">molecular</span> variables. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5743559','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5743559"><span>Identification of type IV collagen exposure as a <span class="hlt">molecular</span> imaging target for <span class="hlt">early</span> detection of thoracic aortic dissection</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Xu, Ke; Xu, Chen; Zhang, Yanzhenzi; Qi, Feiran; Yu, Bingran; Li, Ping; Jia, Lixin; Li, Yulin; Xu, Fu-jian; Du, Jie</p> <p>2018-01-01</p> <p>Thoracic aortic dissection (TAD) is an aggressive and life-threatening vascular disease and there is no effective means of <span class="hlt">early</span> diagnosis of dissection. Type IV collagen (Col-IV) is a major component of the sub-endothelial basement membrane, which is initially exposed followed by endothelial injury as <span class="hlt">early</span>-stage <span class="hlt">event</span> of TAD. So, we want to build a noninvasive diagnostic method to detect <span class="hlt">early</span> dissection by identifying the exposed Col-IV via MRI. Methods: Col-IV-targeted magnetic resonance/ fluorescence dual probe (Col-IV-DOTA-Gd-rhodamine B; CDR) was synthesized by amide reaction and coordination reaction. Flow cytometry analysis was used to evaluate the cell viability of SMC treated with CDR and fluorescence assays were used to assess the Col-IV targeting ability of CDR in vitro. We then examined the sensitivity and specificity of CDR at different stages of TAD via MRI and bioluminescence imaging in vivo. Results: The localization of Col-IV (under the intima) was observed by histology images. CDR bound specifically to Col-IV-expressing vascular smooth muscle cells and BAPN-induced dissected aorta. The CDR signal was co-detected by magnetic resonance imaging (MRI) and bioluminescence imaging as <span class="hlt">early</span> as 2 weeks after BAPN administration (pre-dissection stage). The ability to detect rupture of dissected aorta was indicated by a strong normalized signal enhancement (NSE) in vivo. Moreover, NSE was negatively correlated with the time of dissection rupture after BAPN administration (r2 = 0.8482). Conclusion: As confirmed by in vivo studies, the CDR can identify the exposed Col-IV in degenerated aorta to monitor the progress of aortic dissection from the <span class="hlt">early</span> stage to the rupture via MRI. Thus, CDR-enhanced MRI proposes a potential method for dissection screening, and for monitoring disease progression and therapeutic response. PMID:29290819</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3348129','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3348129"><span>Direct <span class="hlt">Molecular</span> Detection and Genotyping of Borrelia burgdorferi from Whole Blood of Patients with <span class="hlt">Early</span> Lyme Disease</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Eshoo, Mark W.; Crowder, Christopher C.; Rebman, Alison W.; Rounds, Megan A.; Matthews, Heather E.; Picuri, John M.; Soloski, Mark J.; Ecker, David J.; Schutzer, Steven E.; Aucott, John N.</p> <p>2012-01-01</p> <p>Direct <span class="hlt">molecular</span> tests in blood for <span class="hlt">early</span> Lyme disease can be insensitive due to low amount of circulating Borrelia burgdorferi DNA. To address this challenge, we have developed a sensitive strategy to both detect and genotype B. burgdorferi directly from whole blood collected during the initial patient visit. This strategy improved sensitivity by employing 1.25 mL of whole blood, a novel pre-enrichment of the entire specimen extract for Borrelia DNA prior to a multi-locus PCR and electrospray ionization mass spectrometry detection assay. We evaluated the assay on blood collected at the initial presentation from 21 endemic area patients who had both physician-diagnosed erythema migrans (EM) and positive two-tiered serology either at the initial visit or at a follow-up visit after three weeks of antibiotic therapy. Results of this DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%). In most cases the new assay also provided the B. burgdorferi genotype. The combined results of our direct detection assay with initial physician visit serology resulted in the detection of <span class="hlt">early</span> Lyme disease in 19 of 21 (90%) of patients at the initial visit. In 5 of 21 cases we demonstrate the ability to detect B. burgdorferi in <span class="hlt">early</span> Lyme disease directly from whole blood specimens prior to seroconversion. PMID:22590620</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22661424-ultraviolet-escape-fractions-from-giant-molecular-clouds-during-early-cluster-formation','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22661424-ultraviolet-escape-fractions-from-giant-molecular-clouds-during-early-cluster-formation"><span>ULTRAVIOLET ESCAPE FRACTIONS FROM GIANT <span class="hlt">MOLECULAR</span> CLOUDS DURING <span class="hlt">EARLY</span> CLUSTER FORMATION</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Howard, Corey; Pudritz, Ralph; Klessen, Ralf</p> <p>2017-01-01</p> <p>The UV photon escape fraction from <span class="hlt">molecular</span> clouds is a key parameter for understanding the ionization of the interstellar medium and extragalactic processes such as cosmic reionization. We present the ionizing photon flux and the corresponding photon escape fraction ( f {sub esc}) arising as a consequence of star cluster formation in a turbulent, 10{sup 6} M {sub ⊙} giant <span class="hlt">molecular</span> cloud, simulated using the code FLASH. We make use of sink particles to represent young, star-forming clusters coupled with a radiative transfer scheme to calculate the emergent UV flux. We find that the ionizing photon flux across the cloudmore » boundary is highly variable in time and space due to the turbulent nature of the intervening gas. The escaping photon fraction remains at ∼5% for the first 2.5 Myr, followed by two pronounced peaks at 3.25 and 3.8 Myr with a maximum f {sub esc} of 30% and 37%, respectively. These peaks are due to the formation of large H ii regions that expand into regions of lower density, some of which reaching the cloud surface. However, these phases are short-lived, and f {sub esc} drops sharply as the H ii regions are quenched by the central cluster passing through high-density material due to the turbulent nature of the cloud. We find an average f {sub esc} of 15% with factor of two variations over 1 Myr timescales. Our results suggest that assuming a single value for f {sub esc} from a <span class="hlt">molecular</span> cloud is in general a poor approximation, and that the dynamical evolution of the system leads to large temporal variation.« less</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_20 --> <div id="page_21" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="401"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018JSAES..82..329M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018JSAES..82..329M"><span>High-resolution carbonate isotopic study of the Mural Formation (Cerro Pimas section), Sonora, México: Implications for <span class="hlt">early</span> Albian oceanic anoxic <span class="hlt">events</span></span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Madhavaraju, J.; Lee, Yong Il; Scott, R. W.; González-León, C. M.; Jenkyns, H. C.; Saucedo-Samaniego, J. C.; Ramasamy, S.</p> <p>2018-03-01</p> <p>The 420-m thick stratigraphic section of the Mural Formation that is exposed in the Cerro Pimas area of northern Sonora, Mexico, is composed of limestone lithofacies ranging from bioclastic wackestone to boundstone, whose biota is characterized by low diversity. Prominent age-diagnostic fossils are benthic foraminifera and long-ranging calcareous algae that indicate the Aptian/Albian boundary is close to the base of the Los Coyotes Member. The carbonates of this formation have negative to positive δ13C values (-4.63 to +2.6‰) and highly depleted δ18O values that range from -12.74 to -8.34‰. The absence of correlation between δ13C and δ18O values supports a primary marine origin for the δ13C values of these limestones. The carbon-isotopic curve of the Cerro Pimas stratigraphic section has well-defined δ13C segments (C8 - C15) that compare with published curves of similar age. In the lower part of the <span class="hlt">early</span> Albian Los Coyotes Member, the presence of OAE 1b is indicated by an increase followed by a decrease in δ13C values, suggesting correlation with the Kilian <span class="hlt">Event</span>. The middle part of the Los Coyotes Member has a significant negative carbon-isotope excursion correlated with the globally recognizable <span class="hlt">early</span> Albian Paquier <span class="hlt">event</span>. Moreover, another significant negative carbon-isotope shift is observed in the upper part of the Los Coyotes Member, which can be correlated with the Leenhardt <span class="hlt">Event</span>. The occurrence of the Kilian, Paquier and Leenhardt <span class="hlt">Events</span> (OAE 1b cluster) in the Cerro Pimas stratigraphy confirms the global nature of these <span class="hlt">early</span> Albian disturbances of the carbon cycle.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.ars.usda.gov/research/publications/publication/?seqNo115=287783','TEKTRAN'); return false;" href="http://www.ars.usda.gov/research/publications/publication/?seqNo115=287783"><span>Infection of Brachypodium distachyon by formae speciales of Puccinia graminis: <span class="hlt">early</span> infection <span class="hlt">events</span> and host-pathogen incompatibility</span></a></p> <p><a target="_blank" href=""></a></p> <p></p> <p></p> <p>Brachypodium distachyon is an emerging model to study fungal disease resistance in cereals and grasses. We characterized the stem rust-Brachypodium pathosystem to evaluate its potential for investigating <span class="hlt">molecular</span> and genetic aspects of resistance to P. graminis, the pathogen that causes stem rust. ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3539680','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3539680"><span><span class="hlt">Molecular</span> signaling along the anterior–posterior axis of <span class="hlt">early</span> palate development</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Smith, Tara M.; Lozanoff, Scott; Iyyanar, Paul P.; Nazarali, Adil J.</p> <p>2013-01-01</p> <p>Cleft palate is a common congenital birth defect in humans. In mammals, the palatal tissue can be distinguished into anterior bony hard palate and posterior muscular soft palate that have specialized functions in occlusion, speech or swallowing. Regulation of palate development appears to be the result of distinct signaling and genetic networks in the anterior and posterior regions of the palate. Development and maintenance of expression of these region-specific genes is crucial for normal palate development. Numerous transcription factors and signaling pathways are now recognized as either anterior- (e.g., Msx1, Bmp4, Bmp2, Shh, Spry2, Fgf10, Fgf7, and Shox2) or posterior-specific (e.g., Meox2, Tbx22, and Barx1). Localized expression and function clearly highlight the importance of regional patterning and differentiation within the palate at the <span class="hlt">molecular</span> level. Here, we review how these <span class="hlt">molecular</span> pathways and networks regulate the anterior–posterior patterning and development of secondary palate. We hypothesize that the anterior palate acts as a signaling center in setting up development of the secondary palate. PMID:23316168</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28183856','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28183856"><span>Prediction of <span class="hlt">Early</span> Recurrent Thromboembolic <span class="hlt">Event</span> and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi</p> <p>2017-03-01</p> <p>This study was designed to derive and validate a score to predict <span class="hlt">early</span> ischemic <span class="hlt">events</span> and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome <span class="hlt">events</span> (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome <span class="hlt">events</span> (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome <span class="hlt">events</span> and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome <span class="hlt">events</span> and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome <span class="hlt">events</span>. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic <span class="hlt">events</span> but not of major bleedings. © 2017 American Heart Association, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24046514','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24046514"><span>Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular <span class="hlt">events</span> in <span class="hlt">early</span> stages of chronic kidney disease.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon</p> <p>2013-01-01</p> <p>In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular <span class="hlt">events</span> in the <span class="hlt">early</span> stages of chronic kidney disease (CKD). Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m(2), eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m(2) (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular <span class="hlt">events</span>. baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular <span class="hlt">events</span> (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV <span class="hlt">events</span> in the eGFR < 90 group (area under curve=0.691, p=0.03) CONCLUSIONS: In patients with <span class="hlt">early</span> stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular <span class="hlt">events</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28249226','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28249226"><span><span class="hlt">Molecular</span> effectors in the chronic exposure to arsenic as <span class="hlt">early</span> and sensitive biomarkers in developing Rhinella arenarum toads.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mardirosian, Mariana Noelia; Ceschin, Danilo Guillermo; Lascano, Cecilia Inés; Venturino, Andrés</p> <p>2017-05-01</p> <p>Arsenic, a natural element of ecological relevance, is one of the most toxic elements present in various regions of the world. It can be found in natural water sources throughout Argentina in concentrations between 0.01 and 15mgL -1 . The Argentinean autochthonous toad Rhinella arenarum was selected to study the <span class="hlt">molecular</span> mechanisms involved in the effects and response to the chronic As exposure along its embryonic and larval development. We evaluated the effects on MAPK signal transduction pathway and transcription factors c-FOS and c-JUN, and the regulation of the expression at protein levels of different antioxidant enzymes. Our results indicated that As is modulating the MAPK pathway, increasing MEK and ERK levels both in the nuclear and post-nuclear fraction along the embryonic development and mainly at the beginning of the larval stage. Through this pathway, As can upregulate transcription factors like c-FOS and c-JUN, impacting the antioxidant response of the exposed embryos and larvae through antioxidant enzymes and recycling of GSH. Arsenic triggered specifically the synthesis of antioxidant enzymes in exposed R. arenarum embryo and larvae. In particular, the expression levels of SOD, CAT and GST enzymes analyzed by Western blot showed a similar behavior to their enzymatic activities in our previous work. This fact suggests that not only the synthesis of these antioxidant enzymes but also their rapid degradation after inactivation would be regulated in response to ROS levels. Antioxidant enzymes may show dual responses of induction and inactivation followed by degradation depending on the levels of oxidative stress and impact on ROS targets when the exposure is sustained in time and intensity. We also performed a probability of exceedence analysis including our previous results to visualize a progression of the response in time and also established the best <span class="hlt">early</span>-responding biomarkers at the lowest As concentrations. As a conclusion, the <span class="hlt">molecular</span></p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.fs.usda.gov/treesearch/pubs/34958','TREESEARCH'); return false;" href="https://www.fs.usda.gov/treesearch/pubs/34958"><span>Patch dynamics and the timing of colonization-abandonment <span class="hlt">events</span> by male Kirtland's Warblers in an <span class="hlt">early</span> succession habitat</span></a></p> <p><a target="_blank" href=""></a></p> <p>Deahn M. Donner; Christine A. Ribic; John R. Probst</p> <p>2010-01-01</p> <p>Habitat colonization and abandonment affects the distribution of a species in space and time, ultimately influencing the duration of time habitat is used and the total area of habitat occupied in any given year. Both aspects have important implications to long-term conservation planning. The importance of patch isolation and area to colonization-extinction <span class="hlt">events</span> is...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/21077853-gene-expression-profiling-reveals-underlying-molecular-mechanisms-early-stages-tamoxifen-induced-rat-hepatocarcinogenesis','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/21077853-gene-expression-profiling-reveals-underlying-molecular-mechanisms-early-stages-tamoxifen-induced-rat-hepatocarcinogenesis"><span>Gene expression profiling reveals underlying <span class="hlt">molecular</span> mechanisms of the <span class="hlt">early</span> stages of tamoxifen-induced rat hepatocarcinogenesis</span></a></p> <p><a target="_blank" href="http://www.osti.gov/scitech">SciT</a></p> <p>Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.</p> <p>2007-11-15</p> <p>Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the <span class="hlt">molecular</span> mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. Inmore » the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during <span class="hlt">early</span> stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that <span class="hlt">early</span> stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during <span class="hlt">early</span> stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G{sub 1} to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The <span class="hlt">early</span> appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3375772','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3375772"><span><span class="hlt">Molecular</span> characteristics and alterations during <span class="hlt">early</span> development of the human vagina</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Fritsch, Helga; Richter, Elisabeth; Adam, Nadia</p> <p>2012-01-01</p> <p>Unresolved questions remain concerning the derivation of the vagina with respect to the relative contributions from the Müllerian ducts, the urogenital sinus, and the Wolffian ducts. Recent <span class="hlt">molecular</span> and cellular studies in rodents have opened up a large gap between the level of understanding of vaginal development in mice and understanding of human vaginal development, which is based on histology. To compare the findings in mice with human vaginal development and to address this gap, we analysed <span class="hlt">molecular</span> characteristics of the urogenital sinus, Wolffian ducts, and Müllerian ducts in 8–14-week-old human specimens using immunohistochemical methods. The monoclonal antibodies used were directed against cytokeratin (CK) 14, CK19, vimentin, laminin, p63, E-cadherin, caspase-3, Ki67, HOX A13, and BMP-4. The immunohistochemical analysis revealed that, during weeks 8–9, the epithelium of the Müllerian ducts became positive for p63 as p63-positive cells that originated from the sinus epithelium reached the caudal tip of the fused Müllerian ducts via the Wolffian ducts. The lumen of the fused Müllerian ducts was closed by an epithelial plug that contained both vimentin-positive and vimentin-negative cells. Subsequently, the resulting epithelial tube enlarged by proliferation of basal p63-positive cells. The first signs of squamous differentiation were detected during week 14, with the appearance of CK14-positive cells. According to our results, all three components, namely, the urogenital sinus, Wolffian ducts, and Müllerian ducts, interacted during the formation of the human vagina. The sinus epithelium provided p63-positive cells, the Wollfian ducts acted as a ‘transporter’, and the Müllerian ducts contributed the guiding structure for the vaginal anlagen. Epithelial differentiation began at the end of the period studied and extended in a caudo-cranial direction. The present study is one of the first to provide up-to-date <span class="hlt">molecular</span> correlates for human</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24035318','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24035318"><span>Technical Performance Scores are strongly associated with <span class="hlt">early</span> mortality, postoperative adverse <span class="hlt">events</span>, and intensive care unit length of stay-analysis of consecutive discharges for 2 years.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nathan, Meena; Karamichalis, John; Liu, Hua; Gauvreau, Kimberley; Colan, Steven; Saia, Matthew; Pigula, Frank; Fynn-Thompson, Francis; Emani, Sitaram; Baird, Christopher; Mayer, John E; del Nido, Pedro J</p> <p>2014-01-01</p> <p>Previous work in our institution has indicated that the Technical Performance Score (TPS) is highly associated with <span class="hlt">early</span> outcomes in select subsets of procedures and age groups. We hypothesized that the TPS could predict <span class="hlt">early</span> outcomes in a wide range of diagnoses and age groups. Consecutive patients discharged from January 2011 to March 2013 were prospectively evaluated. The TPS was assigned according to the discharge echocardiographic findings and the need for reinterventions in the anatomic area of interest. Case complexity was determined using Risk Adjustment for Congenital Heart Surgery (RACHS-1) categories. <span class="hlt">Early</span> mortality and postoperative adverse <span class="hlt">events</span> were recorded. Relationships between the TPS and outcomes were assessed after adjusting for the baseline patient characteristics. The median age of the 1926 patients was 1.8 years (range, 0 days to 68 years). Bypass was used in 1740 (90%); 322 (17%) were neonates, 520 (27%) infants, 873 (45%) children, 211 (11%) adults. TPS was class 1 (optimal) in 956 (50%), class 2 (adequate) in 584 (30%), and class 3 (inadequate) in 226 (12%); 160 patients (8%) could not be scored. A total of 51 <span class="hlt">early</span> deaths (2.6%) and 111 adverse <span class="hlt">events</span> (5.7%) occurred. On univariate analysis, age, RACHS-1 category, and TPS were significantly associated with mortality and the occurrence of adverse <span class="hlt">events</span>. On multivariate modeling, class 3 (inadequate) TPS was strongly associated with mortality (odds ratio, 16.9; 95% confidence interval, 6.7-42.9; P < .001), adverse <span class="hlt">events</span> (odds ratio, 6.9; 95% confidence interval, 4.1-11.6; P < .001), and postoperative intensive care unit length of stay (coefficient, 2.3; 95% confidence interval, 2.0-2.6; P < .001) after adjusting for other covariates. The TPS is strongly associated with <span class="hlt">early</span> outcomes across a wide range of ages and disease complexity and can serve as important tool for self-assessment and quality improvement. Copyright © 2014 The American Association for Thoracic Surgery</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28689169','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28689169"><span>Leber congenital amaurosis/<span class="hlt">early</span>-onset severe retinal dystrophy: clinical features, <span class="hlt">molecular</span> genetics and therapeutic interventions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel</p> <p>2017-09-01</p> <p>Leber congenital amaurosis (LCA) and <span class="hlt">early</span>-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/<span class="hlt">early</span> infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1440995-early-stage-oxidation-titanium-surface-reactive-molecular-dynamics-simulation','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1440995-early-stage-oxidation-titanium-surface-reactive-molecular-dynamics-simulation"><span><span class="hlt">Early</span> Stage of Oxidation on Titanium Surface by Reactive <span class="hlt">Molecular</span> Dynamics Simulation</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Yang, Liang; Wang, C. Z.; Lin, Shiwei; ...</p> <p>2018-01-01</p> <p>Understanding of metal oxidation is very critical to corrosion control, catalysis synthesis, and advanced materials engineering. Metal oxidation is a very complex phenomenon, with many different processes which are coupled and involved from the onset of reaction. In this work, the initial stage of oxidation on titanium surface was investigated in atomic scale by <span class="hlt">molecular</span> dynamics (MD) simulations using a reactive force field (ReaxFF). We show that oxygen transport is the dominant process during the initial oxidation. Our simulation also demonstrate that a compressive stress was generated in the oxide layer which blocked the oxygen transport perpendicular to the Titaniummore » (0001) surface and further prevented oxidation in the deeper layers. As a result, the mechanism of initial oxidation observed in this work can be also applicable to other self-limiting oxidation.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017acs..conf..176M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017acs..conf..176M"><span>The <span class="hlt">Early</span> Years of <span class="hlt">Molecular</span> Dynamics and Computers at UCRL, LRL, LLL, and LLNL</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Mansigh Karlsen, Mary Ann</p> <p></p> <p>I'm the young woman in the picture shown in Fig. 12.1 that appeared with the invitation to the Symposium to celebrate Berni Alder's ninetieth birthday. I worked with Berni for over 25 years on the computer programs that provided the data he needed to write the fifteen papers published in scientific journals on Studies in <span class="hlt">Molecular</span> Dynamics. My name appears at the end of each one thanking me for computer support. It has been interesting to look on the Internet to find my name in the middle of many foreign languages, including Japanese characters and Russian Cyrillic script. It shows how Berni's work has been of interest to many scientists all over the world from the earliest years. Figure 12.1 was also included with articles written when he received the National Medal of Science from President Obama in 2009…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010EGUGA..12.4185L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010EGUGA..12.4185L"><span>Impacts of a water stress followed by an <span class="hlt">early</span> frost <span class="hlt">event</span> on beech (Fagus sylvatica L.) susceptibility to Scolytine ambrosia beetles - Research strategy and first results</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>La Spina, Sylvie; de Cannière, Charles; Molenberg, Jean-Marc; Vincke, Caroline; Deman, Déborah; Grégoire, Jean-Claude</p> <p>2010-05-01</p> <p>Climate change tends to induce more frequent abiotic and biotic extreme <span class="hlt">events</span>, having large impacts on tree vitality. Weakened trees are then more susceptible to secondary insect outbreaks, as it happened in Belgium in the <span class="hlt">early</span> 2000s: after an <span class="hlt">early</span> frost <span class="hlt">event</span>, secondary Scolytine ambrosia beetles attacks were observed on beech trees. In this study, we test if a combination of stress, i.e. a soil water deficit preceding an <span class="hlt">early</span> frost, could render trees more attractive to beetles. An experimental study was set in autumn 2008. Two parcels of a beech forest were covered with plastic tents to induce a water stress by rain interception. The parcels were surrounded by 2-meters depth trenches to avoid water supply by streaming. Soil water content and different indicators of tree water use (sap flow, predawn leaf water potential, tree radial growth) were followed. In autumn 2010, artificial frost injuries will be inflicted to trees using dry ice. Trees attractivity for Scolytine insects, and the success of insect colonization will then be studied. The poster will focus on experiment setting and first results (impacts of soil water deficit on trees).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=children+AND+personality+AND+development&pg=5&id=EJ1025752','ERIC'); return false;" href="https://eric.ed.gov/?q=children+AND+personality+AND+development&pg=5&id=EJ1025752"><span>Associations of Mother-Child Reminiscing about Negative Past <span class="hlt">Events</span>, Coping, and Self-Concept in <span class="hlt">Early</span> Childhood</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Goodvin, Rebecca; Romdall, Lisa</p> <p>2013-01-01</p> <p>Parent-child reminiscing conversations in <span class="hlt">early</span> childhood have received theoretical attention as a forum for children's self-concept development, but this has been little addressed in empirical work. This study examines associations between emotion reminiscing and children's self-concepts and, building from the reminiscing and…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12384566','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12384566"><span>Genome-wide allelotyping of a new in vitro model system reveals <span class="hlt">early</span> <span class="hlt">events</span> in breast cancer progression.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H</p> <p>2002-10-15</p> <p>Toward the goal of identifying <span class="hlt">early</span> genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of <span class="hlt">early</span> passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for <span class="hlt">early</span> immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an <span class="hlt">early</span> occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that <span class="hlt">early</span> allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28817802','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28817802"><span><span class="hlt">Molecular</span> Memory of Morphologies by Septins during Neuron Generation Allows <span class="hlt">Early</span> Polarity Inheritance.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Boubakar, Leila; Falk, Julien; Ducuing, Hugo; Thoinet, Karine; Reynaud, Florie; Derrington, Edmund; Castellani, Valérie</p> <p>2017-08-16</p> <p>Transmission of polarity established <span class="hlt">early</span> during cell lineage history is emerging as a key process guiding cell differentiation. Highly polarized neurons provide a fascinating model to study inheritance of polarity over cell generations and across morphological transitions. Neural crest cells (NCCs) migrate to the dorsal root ganglia to generate neurons directly or after cell divisions in situ. Using live imaging of vertebrate embryo slices, we found that bipolar NCC progenitors lose their polarity, retracting their processes to round for division, but generate neurons with bipolar morphology by emitting processes from the same locations as the progenitor. Monitoring the dynamics of Septins, which play key roles in yeast polarity, indicates that Septin 7 tags process sites for re-initiation of process growth following mitosis. Interfering with Septins blocks this mechanism. Thus, Septins store polarity features during mitotic rounding so that daughters can reconstitute the initial progenitor polarity. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16231210','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16231210"><span>Production of low <span class="hlt">molecular</span> weight hydrocarbons by volcanic eruptions on <span class="hlt">early</span> Mars.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Segura, Antígona; Navarro-González, Rafael</p> <p>2005-10-01</p> <p>Methane and other larger hydrocarbons have been proposed as possible greenhouse gases on <span class="hlt">early</span> Mars. In this work we explore if volcanic processes may have been a source for such molecules based on theoretical and experimental considerations. Geologic evidence and numerical simulations indicate that explosive volcanism was widely distributed throughout Mars. Volcanic lightning is typically produced in such explosive volcanism. Therefore this geologic setting was studied to determine if lightning could be a source for hydrocarbons in volcanic plumes. Volcanic lightning was simulated by focusing a high-energy infrared laser beam inside of a Pyrex reactor that contained the proposed volcanic gas mixture composed of 64% CH(4), 24% H(2), 10% H(2)O and 2% N(2), according to an accretion model and the nitrogen content measured in Martian meteorites. The analysis of products was performed by gas chromatography coupled to infrared and mass spectroscopy. Eleven hydrocarbons were identified among the products, of which acetylene (C(2)H(2)) was the most abundant. A thermochemical model was used to determine which hydrocarbons could arise only from volcanic heat. In this case, acetylene and ethylene are formed at magmatic temperatures. Our results indicate that explosive volcanism may have injected into the atmosphere of <span class="hlt">early</span> Mars approximately 6 x 10(12) g yr(-1) of acetylene, and approximately 2 x 10(12) g yr(-1) of 1,3-butadiyne, both produced by volcanic lightning, approximately 5 x 10(11) g yr(-1) of ethylene produced by volcanic heat, and 10(13) g yr(-1) of methane.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=363405','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=363405"><span>Decreased expression of the stress protein HSP70 is an <span class="hlt">early</span> <span class="hlt">event</span> in murine erythroleukemic cell differentiation.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Hensold, J O; Housman, D E</p> <p>1988-01-01</p> <p>Two-dimensional protein gels were used to systematically assess changes in gene expression in Friend erythroleukemia cells after exposure to inducers of differentiation. A rapid decrease in expression of the stress protein HSP70 was observed after exposure to inducers. The kinetics of this change suggest that it may be related to the cellular <span class="hlt">events</span> that regulate the onset of differentiation. Images PMID:3164440</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AGUFMNH51B0129U','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AGUFMNH51B0129U"><span>Anomalous Ionospheric signatures observed at low-mid latitude Indian station Delhi prior to earthquake <span class="hlt">events</span> during the year 2015 to <span class="hlt">early</span> 2016.</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Upadhayaya, A. K.; Gupta, S.; Kotnala, R. K.</p> <p>2017-12-01</p> <p>Five major earthquake <span class="hlt">events</span> measuring greater than six on Richter scale (M>6) that occurred during the year 2015 to <span class="hlt">early</span> 2016, affecting Indian region ionosphere, are analyzed using F2 layer critical parameters (foF2, hmF2) obtained using Digisonde from a low-mid latitude Indian station, Delhi (28.6°N, 77.2°E, 19.2°N Geomagnetic latitude, 42.4°N Dip). Normal day-to-day variability occurring in ionosphere is segregated by calculating F2 layer critical frequency and peak height variations (ΔfoF2, ΔhmF2) from the normal quiet time behavior. We find that the ionospheric F2 region across Delhi by and large shows some significant perturbations 3-4 days prior to these earthquake <span class="hlt">events</span>, resulting in a large peak electron density variation of 200%. These observed perturbations indicate towards a possibility of seismo-ionospheric coupling as the solar and geomagnetic indices were normally quiet and stable during the period of these <span class="hlt">events</span>. It was also observed that the precursory effect of earthquake was predominantly seen even outside the earthquake preparation zone, as given by Dobrovolsky et al. [1979]. The thermosphere neutral composition (O/N2) as observed by GUVI [Christensen et al., 2003], across Delhi, during these earthquake <span class="hlt">events</span> does not show any marked variation. Further, the effect of earthquake <span class="hlt">events</span> on ionospheric peak electron density is compared to the lower atmosphere meteorological phenomenon of 2015 Sudden Stratospheric Warming <span class="hlt">event</span> and are found to be comparable.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_21 --> <div id="page_22" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="421"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4974900','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4974900"><span>Correlating carbon and oxygen isotope <span class="hlt">events</span> in <span class="hlt">early</span> to middle Miocene shallow marine carbonates in the Mediterranean region using orbitally tuned chemostratigraphy and lithostratigraphy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Piller, Werner E.; Reuter, Markus; Harzhauser, Mathias</p> <p>2015-01-01</p> <p>Abstract During the Miocene prominent oxygen isotope <span class="hlt">events</span> (Mi‐<span class="hlt">events</span>) reflect major changes in glaciation, while carbonate isotope maxima (CM‐<span class="hlt">events</span>) reflect changes in organic carbon burial, particularly during the Monterey carbon isotope excursion. However, despite their importance to the global climate history they have never been recorded in shallow marine carbonate successions. The Decontra section on the Maiella Platform (central Apennines, Italy), however, allows to resolve them for the first time in such a setting during the <span class="hlt">early</span> to middle Miocene. The present study improves the stratigraphic resolution of parts of the Decontra section via orbital tuning of high‐resolution gamma ray (GR) and magnetic susceptibility data to the 405 kyr eccentricity metronome. The tuning allows, within the established biostratigraphic, sequence stratigraphic, and isotope stratigraphic frameworks, a precise correlation of the Decontra section with pelagic records of the Mediterranean region, as well as the global paleoclimatic record and the global sea level curve. Spectral series analyses of GR data further indicate that the 405 kyr orbital cycle is particularly well preserved during the Monterey <span class="hlt">Event</span>. Since GR is a direct proxy for authigenic uranium precipitation during increased burial of organic carbon in the Decontra section, it follows the same long‐term orbital pacing as observed in the carbon isotope records. The 405 kyr GR beat is thus correlated with the carbon isotope maxima observed during the Monterey <span class="hlt">Event</span>. Finally, the Mi‐<span class="hlt">events</span> can now be recognized in the δ18O record and coincide with plankton‐rich, siliceous, or phosphatic horizons in the lithology of the section. PMID:27546980</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015PalOc..30..332A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015PalOc..30..332A"><span>Correlating carbon and oxygen isotope <span class="hlt">events</span> in <span class="hlt">early</span> to middle Miocene shallow marine carbonates in the Mediterranean region using orbitally tuned chemostratigraphy and lithostratigraphy</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Auer, Gerald; Piller, Werner E.; Reuter, Markus; Harzhauser, Mathias</p> <p>2015-04-01</p> <p>During the Miocene prominent oxygen isotope <span class="hlt">events</span> (Mi-<span class="hlt">events</span>) reflect major changes in glaciation, while carbonate isotope maxima (CM-<span class="hlt">events</span>) reflect changes in organic carbon burial, particularly during the Monterey carbon isotope excursion. However, despite their importance to the global climate history they have never been recorded in shallow marine carbonate successions. The Decontra section on the Maiella Platform (central Apennines, Italy), however, allows to resolve them for the first time in such a setting during the <span class="hlt">early</span> to middle Miocene. The present study improves the stratigraphic resolution of parts of the Decontra section via orbital tuning of high-resolution gamma ray (GR) and magnetic susceptibility data to the 405 kyr eccentricity metronome. The tuning allows, within the established biostratigraphic, sequence stratigraphic, and isotope stratigraphic frameworks, a precise correlation of the Decontra section with pelagic records of the Mediterranean region, as well as the global paleoclimatic record and the global sea level curve. Spectral series analyses of GR data further indicate that the 405 kyr orbital cycle is particularly well preserved during the Monterey <span class="hlt">Event</span>. Since GR is a direct proxy for authigenic uranium precipitation during increased burial of organic carbon in the Decontra section, it follows the same long-term orbital pacing as observed in the carbon isotope records. The 405 kyr GR beat is thus correlated with the carbon isotope maxima observed during the Monterey <span class="hlt">Event</span>. Finally, the Mi-<span class="hlt">events</span> can now be recognized in the δ18O record and coincide with plankton-rich, siliceous, or phosphatic horizons in the lithology of the section.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4116082','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4116082"><span>Rumination as a Mechanism Linking Stressful Life <span class="hlt">Events</span> to Symptoms of Depression and Anxiety: Longitudinal Evidence in <span class="hlt">Early</span> Adolescents and Adults</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Michl, Louisa C.; McLaughlin, Katie A.; Shepherd, Kathrine; Nolen-Hoeksema, Susan</p> <p>2014-01-01</p> <p>Rumination is a well-established risk factor for the onset of major depression and anxiety symptomatology in both adolescents and adults. Despite the robust associations between rumination and internalizing psychopathology, there is a dearth of research examining factors that might lead to a ruminative response style. In the current study, we examined whether social environmental experiences were associated with rumination. Specifically, we evaluated whether self-reported exposure to stressful life <span class="hlt">events</span> predicted subsequent increases in rumination. We also investigated whether rumination served as a mechanism underlying the longitudinal association between self-reported stressful life <span class="hlt">events</span> and internalizing symptoms. Self-reported stressful life <span class="hlt">events</span>, rumination, and symptoms of depression and anxiety were assessed in 2 separate longitudinal samples. A sample of <span class="hlt">early</span> adolescents (N = 1,065) was assessed at 3 time points spanning 7 months. A sample of adults (N = 1,132) was assessed at 2 time points spanning 12 months. In both samples, self-reported exposure to stressful life <span class="hlt">events</span> was associated longitudinally with increased engagement in rumination. In addition, rumination mediated the longitudinal relationship between self-reported stressors and symptoms of anxiety in both samples and the relationship between self-reported life <span class="hlt">events</span> and symptoms of depression in the adult sample. Identifying the psychological and neurobiological mechanisms that explain a greater propensity for rumination following stressors remains an important goal for future research. This study provides novel evidence for the role of stressful life <span class="hlt">events</span> in shaping characteristic responses to distress, specifically engagement in rumination, highlighting potentially useful targets for interventions aimed at preventing the onset of depression and anxiety. PMID:23713497</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010A%26A...522A..40M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010A%26A...522A..40M"><span>Tracing <span class="hlt">early</span> evolutionary stages of high-mass star formation with <span class="hlt">molecular</span> lines</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Marseille, M. G.; van der Tak, F. F. S.; Herpin, F.; Jacq, T.</p> <p>2010-11-01</p> <p>Context. Despite its major role in the evolution of the interstellar medium, the formation of high-mass stars (M ≥ 10 M_⊙) remains poorly understood. Two types of massive star cluster precursors, the so-called massive dense cores (MDCs), have been observed, which differ in terms of their mid-infrared brightness. The origin of this difference has not yet been established and may be the result of evolution, density, geometry differences, or a combination of these. Aims: We compare several <span class="hlt">molecular</span> tracers of physical conditions (hot cores, shocks) observed in a sample of mid-IR weakly emitting MDCs with previous results obtained in a sample of exclusively mid-IR bright MDCs. We attempt to understand the differences between these two types of object. Methods: We present single-dish observations of HDO, H_218O, SO2, and CH3OH lines at λ = 1.3-3.5 mm. We study line profiles and estimate abundances of these molecules, and use a partial correlation method to search for trends in the results. Results: The detection rates of thermal emission lines are found to be very similar for both mid-IR quiet and bright objects. The abundances of H2O, HDO (10-13 to 10-9 in the cold outer envelopes), SO2 and CH3OH differ from source to source but independently of their mid-IR flux. In contrast, the methanol class I maser emission, a tracer of outflow shocks, is found to be strongly anti-correlated with the 12 μm source brightnesses. Conclusions: The enhancement of the methanol maser emission in mid-IR quiet MDCs may be indicative of a more embedded nature. Since total masses are similar between the two samples, we suggest that the matter distribution is spherical around mid-IR quiet sources but flattened around mid-IR bright ones. In contrast, water emission is associated with objects containing a hot <span class="hlt">molecular</span> core, irrespective of their mid-IR brightness. These results indicate that the mid-IR brightness of MDCs is an indicator of their evolutionary stage.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2011AGUFM.B51I0531W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2011AGUFM.B51I0531W"><span><span class="hlt">Early</span> stages of carbonate mineralization revealed from <span class="hlt">molecular</span> simulations: Implications for biomineral formation</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wallace, A. F.; DeYoreo, J.; Banfield, J. F.</p> <p>2011-12-01</p> <p>The carbonate mineral constituents of many biomineralized products, formed both in and ex vivo, grow by a multi-stage crystallization process that involves the nucleation and structural reorganization of transient amorphous phases. The existence of transient phases and cluster species has significant implications for carbonate nucleation and growth in natural and engineered environments, both modern and ancient. The structure of these intermediate phases remains elusive, as does the nature of the disorder to order transition, however, these process details may strongly influence the interpretation of elemental and isotopic climate proxy data obtained from authigenic and biogenic carbonates. While <span class="hlt">molecular</span> simulations have been applied to certain aspects of crystal growth, studies of metal carbonate nucleation are strongly inhibited by the presence of kinetic traps that prevent adequate sampling of the potential landscape upon which the growing clusters reside within timescales accessible by simulation. This research addresses this challenge by marrying the recent Kawska-Zahn (KZ) approach to simulation of crystal nucleation and growth from solution with replica-exchange <span class="hlt">molecular</span> dynamics (REMD) techniques. REMD has been used previously to enhance sampling of protein conformations that occupy energy wells that are separated by sizable thermodynamic and kinetic barriers, and is used here to probe the initial formation and onset of order within hydrated calcium and iron carbonate cluster species during nucleation. Results to date suggest that growing clusters initiate as short linear ion chains that evolve into two- and three-dimensional structures with continued growth. The planar structures exhibit an obvious 2d lattice, while establishment of a 3d lattice is hindered by incomplete ion desolvation. The formation of a dehydrated core consisting of a single carbonate ion is observed when the clusters are ~0.75 nm. At the same size a distorted, but discernible</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24894899','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24894899"><span>Different rates of DNA replication at <span class="hlt">early</span> versus late S-phase sections: multiscale modeling of stochastic <span class="hlt">events</span> related to DNA content/EdU (5-ethynyl-2'deoxyuridine) incorporation distributions.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Biao; Zhao, Hong; Rybak, Paulina; Dobrucki, Jurek W; Darzynkiewicz, Zbigniew; Kimmel, Marek</p> <p>2014-09-01</p> <p>Mathematical modeling allows relating <span class="hlt">molecular</span> <span class="hlt">events</span> to single-cell characteristics assessed by multiparameter cytometry. In the present study we labeled newly synthesized DNA in A549 human lung carcinoma cells with 15-120 min pulses of EdU. All DNA was stained with DAPI and cellular fluorescence was measured by laser scanning cytometry. The frequency of cells in the ascending (left) side of the "horseshoe"-shaped EdU/DAPI bivariate distributions reports the rate of DNA replication at the time of entrance to S phase while their frequency in the descending (right) side is a marker of DNA replication rate at the time of transition from S to G2 phase. To understand the connection between <span class="hlt">molecular</span>-scale <span class="hlt">events</span> and scatterplot asymmetry, we developed a multiscale stochastic model, which simulates DNA replication and cell cycle progression of individual cells and produces in silico EdU/DAPI scatterplots. For each S-phase cell the time points at which replication origins are fired are modeled by a non-homogeneous Poisson Process (NHPP). Shifted gamma distributions are assumed for durations of cell cycle phases (G1, S and G2 M), Depending on the rate of DNA synthesis being an increasing or decreasing function, simulated EdU/DAPI bivariate graphs show predominance of cells in left (<span class="hlt">early</span>-S) or right (late-S) side of the horseshoe distribution. Assuming NHPP rate estimated from independent experiments, simulated EdU/DAPI graphs are nearly indistinguishable from those experimentally observed. This finding proves consistency between the S-phase DNA-replication rate based on <span class="hlt">molecular</span>-scale analyses, and cell population kinetics ascertained from EdU/DAPI scatterplots and demonstrates that DNA replication rate at entrance to S is relatively slow compared with its rather abrupt termination during S to G2 transition. Our approach opens a possibility of similar modeling to study the effect of anticancer drugs on DNA replication/cell cycle progression and also to quantify other</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3758748','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3758748"><span>Homology and Potential Cellular and <span class="hlt">Molecular</span> Mechanisms for the Development of Unique Feather Morphologies in <span class="hlt">Early</span> Birds</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>O’Connor, Jingmai K.; Chiappe, Luis M.; Chuong, Cheng-ming; Bottjer, David J.; You, Hailu</p> <p>2013-01-01</p> <p>At least two lineages of Mesozoic birds are known to have possessed a distinct feather morphotype for which there is no neornithine (modern) equivalent. The <span class="hlt">early</span> stepwise evolution of apparently modern feathers occurred within Maniraptora, basal to the avian transition, with asymmetrical pennaceous feathers suited for flight present in the most basal recognized avian, Archaeopteryx lithographica. The number of extinct primitive feather morphotypes recognized among non-avian dinosaurs continues to increase with new discoveries; some of these resemble feathers present in basal birds. As a result, feathers between phylogenetically widely separated taxa have been described as homologous. Here we examine the extinct feather morphotypes recognized within Aves and compare these structures with those found in non-avian dinosaurs. We conclude that the “rachis dominated” tail feathers of Confuciusornis sanctus and some enantiornithines are not equivalent to the “proximally ribbon-like” pennaceous feathers of the juvenile oviraptorosaur Similicaudipteryx yixianensis. Close morphological analysis of these unusual rectrices in basal birds supports the interpretation that they are modified pennaceous feathers. Because this feather morphotype is not seen in living birds, we build on current understanding of modern feather <span class="hlt">molecular</span> morphogenesis to suggest a hypothetical <span class="hlt">molecular</span> developmental model for the formation of the rachis dominated feathers of extinct basal birds. PMID:24003379</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5226479','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5226479"><span><span class="hlt">Early</span> versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in <span class="hlt">molecular</span> apocrine breast cancer</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun</p> <p>2016-01-01</p> <p>As a new subtype of breast cancer, <span class="hlt">molecular</span> apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between <span class="hlt">early</span> and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to <span class="hlt">molecular</span> subtype. PMID:27340922</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27340922','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27340922"><span><span class="hlt">Early</span> versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in <span class="hlt">molecular</span> apocrine breast cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun</p> <p>2016-08-02</p> <p>As a new subtype of breast cancer, <span class="hlt">molecular</span> apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between <span class="hlt">early</span> and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to <span class="hlt">molecular</span> subtype.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3888901','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3888901"><span><span class="hlt">MOLECULAR</span> IMAGING REVEALS RAPID REDUCTION OF ENDOTHELIAL ACTIVATION IN <span class="hlt">EARLY</span> ATHEROSCLEROSIS WITH APOCYNIN INDEPENDENT OF ANTI-OXIDATIVE PROPERTIES</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Khanicheh, Elham; Qi, Yue; Xie, Aris; Mitterhuber, Martina; Xu, Lifen; Mochizuki, Michika; Daali, Youssef; Jaquet, Vincent; Krause, Karl-Heinz; Ruggeri, Zaverio M.; Kuster, Gabriela M.; Lindner, Jonathan R.; Kaufmann, Beat A.</p> <p>2013-01-01</p> <p>OBJECTIVE Anti-oxidative drugs continue to be developed for the treatment of atherosclerosis. Apocynin is an NADPH-oxidase-inhibitor with anti-inflammatory properties. We used contrast enhanced ultrasound (CEU) <span class="hlt">molecular</span> imaging to assess whether short-term apocynin therapy in atherosclerosis reduces vascular oxidative stress and endothelial activation APPROACH AND RESULTS Genetically-modified mice with <span class="hlt">early</span> atherosclerosis were studied at baseline and after 7 days of therapy with apocynin (4mg/kg/d I.P.) or saline. CEU <span class="hlt">molecular</span> imaging of the aorta was performed with microbubbles targeted to vascular cell adhesion molecule 1 (VCAM-1; MBV), to platelet GPIbα (MBPl), and control microbubbles (MBCtr). Aortic VCAM-1 was measured using Western Blot. Aortic ROS generation was measured using a lucigenin assay. Hydroethidine (HE) oxidation was used to assess aortic superoxide generation. Baseline signal for MBV (1.3±0.3 A.U.) and MBPl (1.5±0.5 A.U.) was higher than for MBCtr (0.5±0.2 A.U., p<0.01). In saline-treated animals, signal did not significantly change for any microbubble agent whereas short-term apocynin significantly (p<0.05) reduced VCAM-1 and platelet signal (MBV: 0.3±0.1, MBPl: 0.4±0.1 MBCtr: 0.3±0.2 A.U., p=0.6 between agents). Apocynin reduced aortic VCAM-1 expression by 50% (p<0.05). However, apocynin therapy did not reduce either ROS content, superoxide generation, or macrophage content. CONCLUSIONS Short-term treatment with apocynin in atherosclerosis reduces endothelial cell adhesion molecule expression. This change in endothelial phenotype can be detected by <span class="hlt">molecular</span> imaging before any measurable decrease in macrophage content, and is not associated with a detectable change in oxidative burden. PMID:23908248</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3231835','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3231835"><span><span class="hlt">Early</span> Life Exposure to Endocrine-Disrupting Chemicals Causes Lifelong <span class="hlt">Molecular</span> Reprogramming of the Hypothalamus and Premature Reproductive Aging</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Walker, Deena M.; Zama, Aparna M.; Armenti, AnnMarie E.; Uzumcu, Mehmet</p> <p>2011-01-01</p> <p>Gestational exposure to the estrogenic endocrine disruptor methoxychlor (MXC) disrupts the female reproductive system at the <span class="hlt">molecular</span>, physiological, and behavioral levels in adulthood. The current study addressed whether perinatal exposure to endocrine disruptors reprograms expression of a suite of genes expressed in the hypothalamus that control reproductive function and related these <span class="hlt">molecular</span> changes to premature reproductive aging. Fischer rats were exposed daily for 12 consecutive days to vehicle (dimethylsulfoxide), estradiol benzoate (EB) (1 mg/kg), and MXC (low dose, 20 μg/kg or high dose, 100 mg/kg), beginning on embryonic d 19 through postnatal d 7. The perinatally exposed females were aged to 16–17 months and monitored for reproductive senescence. After euthanasia, hypothalamic regions [preoptic area (POA) and medial basal hypothalamus] were dissected for real-time PCR of gene expression or pyrosequencing to assess DNA methylation of the Esr1 gene. Using a 48-gene PCR platform, two genes (Kiss1 and Esr1) were significantly different in the POA of endocrine-disrupting chemical-exposed rats compared with vehicle-exposed rats after Bonferroni correction. Fifteen POA genes were up-regulated by at least 50% in EB or high-dose MXC compared with vehicle. To understand the epigenetic basis of the increased Esr1 gene expression, we performed bisulfite conversion and pyrosequencing of the Esr1 promoter. EB-treated rats had significantly higher percentage of methylation at three CpG sites in the Esr1 promoter compared with control rats. Together with these <span class="hlt">molecular</span> effects, perinatal MXC and EB altered estrous cyclicity and advanced reproductive senescence. Thus, <span class="hlt">early</span> life exposure to endocrine disruptors has lifelong effects on neuroendocrine gene expression and DNA methylation, together with causing the advancement of reproductive senescence. PMID:22016562</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27086330','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27086330"><span>Pain and tactile dissociation, derealization and depersonalization symptoms in women and recalled traumatic <span class="hlt">events</span> in childhood, adolescence and <span class="hlt">early</span> adulthood.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Smiatek-Mazgaj, Bogna; Sobański, Jerzy A; Rutkowski, Krzysztof; Klasa, Katarzyna; Dembińska, Edyta; Müldner-Nieckowski, Łukasz; Cyranka, Katarzyna; Mielimąka, Michał</p> <p>2016-01-01</p> <p>The symptoms of dissociation, depersonalization and derealization are often associated with exposure of patients to mental and physical injuries, usually occurring in childhood. Most of these observations were carried out in populations of patients with various disorders (posttraumatic, conversion-dissociation, personality disorders - especially borderline), who reported their exposure to adverse life circumstances through questionnaire interviews. Assessment of the risk associated with various traumatic <span class="hlt">events</span> in childhood and adolescence concerning the symptoms of pain and tactile dissociation, depersonalization and derealization. The coexistence of the earlier life circumstances and the currently existing symptoms was examined on the basis of KO "0" Symptom Checklist and Life Inventory, completed prior to treatment in a day hospital for neurotic disorders. In the group of 2582 women, patients of a day hospital for neurotic and personality disorders, the symptoms of pain and tactile dissociation, depersonalization and derealization were present in 24-36 % of patients, while the maximum severity of these symptoms reported approximately 4-8 % of patients. The studied patients reported the exposure during childhood and adolescence (before 18yo) to numerous traumatic <span class="hlt">events</span> of varying severity and frequency, including hostility of one parent (approximately 5% of respondents), the sexual initiation before 13yo (1%), worse than peers material conditions (23%), harassment of the family of origin (2%), reluctance of their peers (9%). Conducted regression analysis showed illustrated by the coefficients OR (odds ratios) a statistically significant relationship between the majority of the analyzed symptoms and many of the listed <span class="hlt">events</span>, such as being regarded as worse than siblings, mother's anger in the situation of the patient's disease in childhood, lack of support, indifference of parent, poverty and worseness of the family of origin, inferior position in the classroom</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3302645','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3302645"><span><span class="hlt">Early</span> stages of the recovery stroke in myosin II studied by <span class="hlt">molecular</span> dynamics simulations</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Baumketner, Andrij; Nesmelov, Yuri</p> <p>2011-01-01</p> <p>The recovery stroke is a key step in the functional cycle of muscle motor protein myosin, during which pre-recovery conformation of the protein is changed into the active post-recovery conformation, ready to exersice force. We study the microscopic details of this transition using <span class="hlt">molecular</span> dynamics simulations of atomistic models in implicit and explicit solvent. In more than 2 μs of aggregate simulation time, we uncover evidence that the recovery stroke is a two-step process consisting of two stages separated by a time delay. In our simulations, we directly observe the first stage at which switch II loop closes in the presence of adenosine triphosphate at the nucleotide binding site. The resulting configuration of the nucleotide binding site is identical to that detected experimentally. Distribution of inter-residue distances measured in the force generating region of myosin is in good agreement with the experimental data. The second stage of the recovery stroke structural transition, rotation of the converter domain, was not observed in our simulations. Apparently it occurs on a longer time scale. We suggest that the two parts of the recovery stroke need to be studied using separate computational models. PMID:21922589</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27657133','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27657133"><span><span class="hlt">Molecular</span> Inconsistencies in a Fragile X Male with <span class="hlt">Early</span> Onset Ataxia.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hwang, Yun Tae; Dudding, Tracy; Aliaga, Solange Mabel; Arpone, Marta; Francis, David; Li, Xin; Slater, Howard Robert; Rogers, Carolyn; Bretherton, Lesley; du Sart, Desirée; Heard, Robert; Godler, David Eugeny</p> <p>2016-09-21</p> <p>Mosaicism for FMR1 premutation (PM: 55-199 CGG)/full mutation (FM: >200 CGG) alleles or the presence of unmethylated FM (UFM) have been associated with a less severe fragile X syndrome (FXS) phenotype and fragile X associated tremor/ataxia syndrome (FXTAS)-a late onset neurodegenerative disorder. We describe a 38 year old male carrying a 100% methylated FM detected with Southern blot (SB), which is consistent with complete silencing of FMR1 and a diagnosis of fragile X syndrome. However, his formal cognitive scores were not at the most severe end of the FXS phenotype and he displayed tremor and ataxic gait. With the association of UFM with FXTAS, we speculated that his ataxia might be related to an undetected proportion of UFM alleles. Such UFM alleles were confirmed by more sensitive PCR based methylation testing showing FM methylation between 60% and 70% in blood, buccal, and saliva samples and real-time PCR analysis showing incomplete silencing of FMR1. While he did not meet diagnostic criteria for FXTAS based on MRI findings, the underlying cause of his ataxia may be related to UFM alleles not detected by SB, and follow-up clinical and <span class="hlt">molecular</span> assessment are justified if his symptoms worsen.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5042398','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5042398"><span><span class="hlt">Molecular</span> Inconsistencies in a Fragile X Male with <span class="hlt">Early</span> Onset Ataxia</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Hwang, Yun Tae; Dudding, Tracy; Aliaga, Solange Mabel; Arpone, Marta; Francis, David; Li, Xin; Slater, Howard Robert; Rogers, Carolyn; Bretherton, Lesley; du Sart, Desirée; Heard, Robert; Godler, David Eugeny</p> <p>2016-01-01</p> <p>Mosaicism for FMR1 premutation (PM: 55–199 CGG)/full mutation (FM: >200 CGG) alleles or the presence of unmethylated FM (UFM) have been associated with a less severe fragile X syndrome (FXS) phenotype and fragile X associated tremor/ataxia syndrome (FXTAS)—a late onset neurodegenerative disorder. We describe a 38 year old male carrying a 100% methylated FM detected with Southern blot (SB), which is consistent with complete silencing of FMR1 and a diagnosis of fragile X syndrome. However, his formal cognitive scores were not at the most severe end of the FXS phenotype and he displayed tremor and ataxic gait. With the association of UFM with FXTAS, we speculated that his ataxia might be related to an undetected proportion of UFM alleles. Such UFM alleles were confirmed by more sensitive PCR based methylation testing showing FM methylation between 60% and 70% in blood, buccal, and saliva samples and real-time PCR analysis showing incomplete silencing of FMR1. While he did not meet diagnostic criteria for FXTAS based on MRI findings, the underlying cause of his ataxia may be related to UFM alleles not detected by SB, and follow-up clinical and <span class="hlt">molecular</span> assessment are justified if his symptoms worsen. PMID:27657133</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19203011','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19203011"><span>Different methods and metaphysics in <span class="hlt">early</span> <span class="hlt">molecular</span> genetics--a case of disparity of research?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Deichmann, Ute</p> <p>2008-01-01</p> <p>The encounter between two fundamentally different approaches in seminal research in <span class="hlt">molecular</span> biology--the problems, aims, methods and metaphysics--is delineated and analyzed. They are exemplified by the microbiologist Oswald T. Avery who, in line with the reductionist mechanistic metaphysics of Jacques Loeb, attempted to explain basic life phenomena through chemistry; and the theoretical physicist Max Delbrück who, influenced by Bohr's antimechanistic views, preferred to explain these phenomena without chemistry. Avery's and Delbrück's most important studies took place concurrently. Thus analysis of their contrasting approaches lends itself to examination of the Weltanschauungen view concerning the role of fundamental (metaphysical) assumptions in scientific change, that is, the view that empirical research cannot be neutral in regard to the worldviews of the researchers. This study shows that the initial ostensible disparity (non-integratibility) of the two approaches lasted for just a short time. Ironically it was a student of Delbrück's school, James Watson, who (with Crick) proposed a chemical model, the DNA double helix, as a solution to Delbrück's problem. The structure of DNA has not been seriously challenged over the past half century Moreover, Watson's and Crick's work did not call into question the validity of Delbrück's research, but opened it up to entirely new approaches. The case of Avery and Delbrück demonstrates that after initial obstacles were overcome the different fundamental attitudes and the resulting research practices were capable of integration.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19890011957','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19890011957"><span>High resolution chronology of late Cretaceous-<span class="hlt">early</span> Tertiary <span class="hlt">events</span> determined from 21,000 yr orbital-climatic cycles in marine sediments</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Herbert, Timothy D.; Dhondt, Steven</p> <p>1988-01-01</p> <p>A number of South Atlantic sites cored by the Deep Sea Drilling Project (DSDP) recovered late Cretaceous and <span class="hlt">early</span> Tertiary sediments with alternating light-dark, high-low carbonate content. The sedimentary oscillations were turned into time series by digitizing color photographs of core segments at a resolution of about 5 points/cm. Spectral analysis of these records indicates prominent periodicity at 25 to 35 cm in the Cretaceous intervals, and about 15 cm in the <span class="hlt">early</span> Tertiary sediments. The absolute period of the cycles that is determined from paleomagnetic calibration at two sites is 20,000 to 25,000 yr, and almost certainly corresponds to the period of the earth's precessional cycle. These sequences therefore contain an internal chronometer to measure <span class="hlt">events</span> across the K/T extinction boundary at this scale of resolution. The orbital metronome was used to address several related questions: the position of the K/T boundary within magnetic chron 29R, the fluxes of biogenic and detrital material to the deep sea immediately before and after the K/T <span class="hlt">event</span>, the duration of the Sr anomaly, and the level of background climatic variability in the latest Cretaceous time. The carbonate/color cycles that were analyzed contain primary records of ocean carbonate productivity and chemistry, as evidenced by bioturbational mixing of adjacent beds and the weak lithification of the rhythmic sequences. It was concluded that sedimentary sequences that contain orbital cyclicity are capable of providing resolution of dramatic <span class="hlt">events</span> in earth history with much greater precision than obtainable through radiometric methods. The data show no evidence for a gradual climatic deterioration prior to the K/T extinction <span class="hlt">event</span>, and argue for a geologically rapid revolution at this horizon.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20150001940','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20150001940"><span><span class="hlt">Early</span> Solar System Alkali Fractionation <span class="hlt">Events</span> Recorded by K-Ca Isotopes in the Yamato-74442 LL-Chondritic Breccia</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Tatsunori, T.; Misawa, K.; Okano, O.; Shih, C.-Y.; Nyquist, L. E.; Simon, J. I.; Tappa, M. J.; Yoneda, S.</p> <p>2015-01-01</p> <p>Radiogenic ingrowth of Ca-40 due to decay of K-40 occurred <span class="hlt">early</span> in the solar system history causing the Ca-40 abundance to vary within different <span class="hlt">early</span>-former reservoirs. Marshall and DePaolo ] demonstrated that the K-40/Ca-40 decay system could be a useful radiogenic tracer for studies of terrestrial rocks. Shih et al. [3,4] determined 40K/40Ca ages of lunar granitic rock fragments and discussed the chemical characteristics of their source materials. Recently, Yokoyama et al. [5] showed the application of the K-40/Ca-40 chronometer for high K/Ca materials in ordinary chondrites (OCs). High-precision calcium isotopic data are needed to constrain mixing processes among <span class="hlt">early</span> solar system materials and the time of planetesimal formation. To better constrain the solar system calcium isotopic compositions among astromaterials, we have determined the calcium isotopic compositions of OCs and an angrite. We further estimated a source K/Ca ratio for alkali-rich fragments in a chondritic breccia using the estimated solar system initial Ca-40/Ca-44.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24420571','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24420571"><span>Deciphering <span class="hlt">early</span> <span class="hlt">events</span> involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François</p> <p>2014-03-01</p> <p>Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on <span class="hlt">early</span> responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an <span class="hlt">early</span> influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared <span class="hlt">early</span> responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3969528','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3969528"><span>Deciphering <span class="hlt">early</span> <span class="hlt">events</span> involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Monetti, Emanuela; Kadono, Takashi; Bouteau, François</p> <p>2014-01-01</p> <p>Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on <span class="hlt">early</span> responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca2+ concentration ([Ca2+]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·–) generation by NADPH-oxidase. In the case of NaCl, an <span class="hlt">early</span> influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·– generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared <span class="hlt">early</span> responses, such as [Ca2+]cyt increase and singlet oxygen production, do not seem to be involved in PCD. PMID:24420571</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_22 --> <div id="page_23" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="441"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23606220','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23606220"><span>Sweet preference modified by <span class="hlt">early</span> experience in mice and the related <span class="hlt">molecular</span> modulations on the peripheral pathway.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Wei-Li; Chen, Meng-Ling; Liu, Si-Si; Li, Guo-Liang; Gu, Tian-Yuan; Liang, Pei; Qin, Yu-Mei; Zhan, Yue-Hua; Quan, Ying; Zhang, Gen-Hua</p> <p>2013-09-01</p> <p>The sweet taste is of immense interest to scientists and has been intensively studied during the last two decades. However, the sweet preference modification and the related mechanisms are still unclear. In this study, we try to establish a mice model with manipulated sweet taste preference and explore the involved possible <span class="hlt">molecular</span> mechanisms. The animals were exposed to acesulfame-K via maternal milk during lactation and the sweet preference tests were carried out when they grew to adulthood. Our results showed that the preference thresholds for sweet taste were increased in adults by <span class="hlt">early</span> acesulfame-K exposure and the preference ratios for sweet tastants at low or pref