Comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone
Moody, Laura R; Herbst, Allen J; Yoo, Han Sang; Vanderloo, Joshua P
2009-01-01
Identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets. Although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified. Cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, resulting in both spongiform change and astrocytosis. The use of cuprizone-treated animals as an experimental control during comparative expression profiling allows for the identification of transcripts whose expression increases during prion disease and remains unchanged during cuprizone-triggered neuropathology. In this study, expression profiles from the brains of mice preclinically and clinically infected with Rocky Mountain Laboratory (RML) mouse-adapted scrapie agent and age-matched controls were profiled using Affymetrix gene arrays. In total, 164 genes were differentially regulated during prion infection. Eighty-three of these transcripts have been previously undescribed as differentially regulated during prion disease. A 0.4% cuprizone diet was utilized as a control for comparative expression profiling. Cuprizone treatment induced spongiosis and astrocyte proliferation as indicated by glial fibrillary acidic protein (Gfap) transcriptional activation and immunohistochemistry. Gene expression profiles from brain tissue obtained from cuprizone-treated mice identified 307 differentially regulated transcript changes. After comparative analysis, 17 transcripts unaffected by cuprizone treatment but increasing in expression from preclinical to clinical prion infection were identified. Here we describe the novel use of the prion disease mimetic, cuprizone, to control for cell population changes in the brain during prion infection. PMID:19535908
Allami, Youssef; Vitaro, Frank; Brendgen, Mara; Carbonneau, René; Tremblay, Richard E
2018-05-01
Past studies have identified various risk and protective factors for problem gambling (PG). However, no study has examined the interplay between these factors using a combination of person-centered and variable-centered approaches embedded within a longitudinal design. The present study aimed to (a) identify distinct profiles in early adolescence based on a set of risk factors commonly associated with PG (impulsivity, depression, anxiety, drug-alcohol use, aggressiveness, and antisociality), (b) explore the difference in reported gambling problems between these profiles during midadolescence and early adulthood, and (c) identify family- and peer-related variables that could operate as protective or compensatory factors in this context. Two samples were used: (a) a population sample (N = 1,033) living in low socioeconomic-status neighborhoods and (b) a population sample (N = 3,017) representative of students attending Quebec schools. Latent profile analyses were conducted to identify at-risk profiles based on individual risk factors measured at age 12 years. Negative binomial regression models were estimated to compare profiles in terms of their reported gambling problems at ages 16 and 23. Finally, family- and peer-related variables measured at age 14 were included to test their protective or compensatory role with respect to the link between at-risk profiles and gambling problems. Four profiles were identified: well-adjusted, internalizing, externalizing, and comorbid. Compared to the well-adjusted profile, the externalizing and comorbid profiles reported more gambling problems at ages 16 and 23, but the internalizing profile did not differ significantly. Various protective and compensatory factors emerged for each profile at both time points. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
ERIC Educational Resources Information Center
Moore, Paula Hearn; Griffin, Richard B.
2017-01-01
This paper describes and compares the profiles of the top accounting programs in the United States as identified by "U.S. News and World Report" in 2004 with the profiles of the top accounting programs in the United States as identified by the "Accounting Degree Review" in 2014. The "Accounting Degree Review"'s list…
ERIC Educational Resources Information Center
Lin, Tzung-Jin; Liang, Jyh-Chong; Tsai, Chin-Chung
2015-01-01
The main purposes of this study were to identify Taiwanese university students' physics learning profiles in terms of their critical conceptions of learning physics and to compare their physics learning self-efficacy with the different learning profiles. A total of 250 Taiwanese undergraduates who were majoring in physics participated in this…
Effectively identifying user profiles in network and host metrics
NASA Astrophysics Data System (ADS)
Murphy, John P.; Berk, Vincent H.; Gregorio-de Souza, Ian
2010-04-01
This work presents a collection of methods that is used to effectively identify users of computers systems based on their particular usage of the software and the network. Not only are we able to identify individual computer users by their behavioral patterns, we are also able to detect significant deviations in their typical computer usage over time, or compared to a group of their peers. For instance, most people have a small, and relatively unique selection of regularly visited websites, certain email services, daily work hours, and typical preferred applications for mandated tasks. We argue that these habitual patterns are sufficiently specific to identify fully anonymized network users. We demonstrate that with only a modest data collection capability, profiles of individual computer users can be constructed so as to uniquely identify a profiled user from among their peers. As time progresses and habits or circumstances change, the methods presented update each profile so that changes in user behavior can be reliably detected over both abrupt and gradual time frames, without losing the ability to identify the profiled user. The primary benefit of our methodology allows one to efficiently detect deviant behaviors, such as subverted user accounts, or organizational policy violations. Thanks to the relative robustness, these techniques can be used in scenarios with very diverse data collection capabilities, and data privacy requirements. In addition to behavioral change detection, the generated profiles can also be compared against pre-defined examples of known adversarial patterns.
Symptom-Hemodynamic Mismatch and Heart Failure Event Risk
Lee, Christopher S.; Hiatt, Shirin O.; Denfeld, Quin E.; Mudd, James O.; Chien, Christopher; Gelow, Jill M.
2014-01-01
Background Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. Objective The goal of this study was to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics, and quantify differences in 180-day event-risk among observed profiles. Methods A secondary analysis of data collected during two prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event-risk (HF emergency visit, hospitalization or death) among profiles. Results The mean age (n=291) was 57±13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified. 17.9% of patients had concordant symptoms and hemodynamics (i.e. moderate physical and psychological symptoms matched the comparatively hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared to those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event-risk (severe symptoms hazards ratio = 3.38, p=0.033; poor hemodynamics hazards ratio = 3.48, p=0.016). Conclusions A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death. PMID:24988323
Three subgroups of pain profiles identified in 227 women with arthritis: a latent class analysis.
de Luca, Katie; Parkinson, Lynne; Downie, Aron; Blyth, Fiona; Byles, Julie
2017-03-01
The objectives were to identify subgroups of women with arthritis based upon the multi-dimensional nature of their pain experience and to compare health and socio-demographic variables between subgroups. A latent class analysis of 227 women with self-reported arthritis was used to identify clusters of women based upon the sensory, affective, and cognitive dimensions of the pain experience. Multivariate multinomial logistic regression analysis was used to determine the relationship between cluster membership and health and sociodemographic characteristics. A three-class cluster model was most parsimonious. 39.5 % of women had a unidimensional pain profile; 38.6 % of women had moderate multidimensional pain profile that included additional pain symptomatology such as sensory qualities and pain catastrophizing; and 21.9 % of women had severe multidimensional pain profile that included prominent pain symptomatology such as sensory and affective qualities of pain, pain catastrophizing, and neuropathic pain. Women with severe multidimensional pain profile have a 30.5 % higher risk of poorer quality of life and a 7.3 % higher risk of suffering depression, and women with moderate multidimensional pain profile have a 6.4 % higher risk of poorer quality of life when compared to women with unidimensional pain. This study identified three distinct subgroups of pain profiles in older women with arthritis. Women had very different experiences of pain, and cluster membership impacted significantly on health-related quality of life. These preliminary findings provide a stronger understanding of profiles of pain and may contribute to the development of tailored treatment options in arthritis.
Walker, Lynn S.; Sherman, Amanda L.; Bruehl, Stephen; Garber, Judy; Smith, Craig A.
2012-01-01
Although pediatric functional abdominal pain (FAP) has been linked to abdominal pain later in life, childhood predictors of long-term outcomes have not been identified. This study evaluated whether distinct FAP profiles based on patterns of pain and adaptation in childhood could be identified and whether these profiles predicted differences in clinical outcomes and central sensitization (wind-up) on average 9 years later. In 843 pediatric FAP patients, cluster analysis was used to identify subgroups at initial FAP evaluation based on profiles of pain severity, gastrointestinal (GI) and non-GI symptoms, pain threat appraisal, pain coping efficacy, catastrophizing, negative affect, and activity impairment. Three profiles were identified: High Pain Dysfunctional, High Pain Adaptive, and Low Pain Adaptive. Logistic regression analyses controlling for age and sex showed that, compared to pediatric patients with the Low Pain Adaptive profile, those with the High Pain Dysfunctional profile were significantly more likely at long-term follow-up to meet criteria for pain-related functional gastrointestinal disorder (FGID) (OR: 3.45; CI: 1.95–6.11), FGID with comorbid non-abdominal chronic pain (OR: 2.6; CI:1.45–4.66), and FGID with comorbid anxiety or depressive psychiatric disorder (OR: 2.84; CI: 1.35–6.00). Pediatric patients with the High Pain Adaptive profile had baseline pain severity comparable to the High Pain Dysfunctional profile, but had outcomes as favorable as the Low Pain Adaptive profile. In laboratory pain testing at follow-up, High Pain Dysfunctional patients exhibited significantly greater thermal wind-up than Low Pain Adaptive patients, suggesting that a subgroup of FAP patients has outcomes consistent with widespread effects of heightened central sensitization. PMID:22721910
Burro, Roberto; Raccanello, Daniela; Pasini, Margherita; Brondino, Margherita
2018-01-01
Conceptualizing affect as a complex nonlinear dynamic process, we used latent class extended mixed models (LCMM) to understand whether there were unobserved groupings in a dataset including longitudinal measures. Our aim was to identify affect profiles over time in people vicariously exposed to terrorism, studying their relations with personality traits. The participants were 193 university students who completed online measures of affect during the seven days following two terrorist attacks (Paris, November 13, 2015; Brussels, March 22, 2016); Big Five personality traits; and antecedents of affect. After selecting students whose negative affect was influenced by the two attacks (33%), we analysed the data with the LCMM package of R. We identified two affect profiles, characterized by different trends over time: The first profile comprised students with lower positive affect and higher negative affect compared to the second profile. Concerning personality traits, conscientious-ness was lower for the first profile compared to the second profile, and vice versa for neuroticism. Findings are discussed for both their theoretical and applied relevance.
Kimmel, Allison L.; Cheng, Yao Iris; Wang, Jichuan
2016-01-01
The purpose of this study was to determine whether distinct latent profiles of religiousness/spirituality exist for ALWH, and if so, are latent profile memberships associated with health-related quality of life (HRQoL). Latent profile analysis of religiosity identified four profiles/groups. Compared to the other three groups, higher levels of emotional well-being were found among young perinatally infected adolescents who attended religious services, but who did not pray privately, feel God's presence or identify as religious or spiritual. Social HRQoL was significantly higher among the highest overall religious/spiritual group. Understanding adolescent profiles of religiousness/spirituality on HRQoL could inform faith-based interventions. PMID:27071797
Lyon, Maureen E; Kimmel, Allison L; Cheng, Yao Iris; Wang, Jichuan
2016-10-01
The purpose of this study was to determine whether distinct latent profiles of religiousness/spirituality exist for ALWH, and if so, are latent profile memberships associated with health-related quality of life (HRQoL). Latent profile analysis of religiosity identified four profiles/groups. Compared to the other three groups, higher levels of emotional well-being were found among young perinatally infected adolescents who attended religious services, but who did not pray privately, feel God's presence or identify as religious or spiritual. Social HRQoL was significantly higher among the highest overall religious/spiritual group. Understanding adolescent profiles of religiousness/spirituality on HRQoL could inform faith-based interventions. Trial registration NCT01289444.
Tambyraja, Sherine R; Schmitt, Mary Beth; Farquharson, Kelly; Justice, Laura M
2015-08-01
The present study focused on the identification and stability of language and literacy profiles of primary school children receiving school-based language therapy over the course of one academic year. Participants included 272 early elementary school-age children (144 boys, 128 girls) who had been clinically identified as having a language impairment. A latent profile analysis was used to identify distinct profiles on the basis of a battery of language and literacy assessments in the fall and spring of the academic year. Four profiles were identified in both fall and spring that could be best described as representing high, average, and low overall abilities. Two average groups were identified that differentiated according to phonological awareness abilities. Children's profile membership was variable from fall to spring with nearly 60% of children shifting into a higher profile. The results of t tests comparing children who shifted into higher profiles from those who remained stable in profile membership revealed group differences regarding language severity, socio-economic status, and proportion of therapy sessions received in the classroom. These results provide further evidence regarding the heterogeneity of children with language impairment served in the public schools, indicating that differences may be best conceptualized along a continuum of severity.
Bray, Mark-Anthony; Singh, Shantanu; Han, Han; Davis, Chadwick T.; Borgeson, Blake; Hartland, Cathy; Kost-Alimova, Maria; Gustafsdottir, Sigrun M.; Gibson, Christopher C.; Carpenter, Anne E.
2016-01-01
In morphological profiling, quantitative data are extracted from microscopy images of cells to identify biologically relevant similarities and differences among samples based on these profiles. This protocol describes the design and execution of experiments using Cell Painting, a morphological profiling assay multiplexing six fluorescent dyes imaged in five channels, to reveal eight broadly relevant cellular components or organelles. Cells are plated in multi-well plates, perturbed with the treatments to be tested, stained, fixed, and imaged on a high-throughput microscope. Then, automated image analysis software identifies individual cells and measures ~1,500 morphological features (various measures of size, shape, texture, intensity, etc.) to produce a rich profile suitable for detecting subtle phenotypes. Profiles of cell populations treated with different experimental perturbations can be compared to suit many goals, such as identifying the phenotypic impact of chemical or genetic perturbations, grouping compounds and/or genes into functional pathways, and identifying signatures of disease. Cell culture and image acquisition takes two weeks; feature extraction and data analysis take an additional 1-2 weeks. PMID:27560178
Stanford, Sarah; Jones, Michael P; Hudson, Jennifer L
2018-05-01
Past research identifies a number of risk factors for adolescent self-harm, but often fails to account for overlap between these factors. This study investigated the underlying, broader concepts by identifying different psychological profiles among adolescents. We then compared new self-harm rates over a six-month period across different psychological profiles. Australian high school students (n = 326, 68.1% female) completed a questionnaire including a broad range of psychological and socioenvironmental risk and protective factors. Non-hierarchical cluster analysis produced six groups with different psychological profiles at baseline and rate of new self-harm at follow-up. The lowest rate was 1.4% in a group that appeared psychologically healthy; the highest rate was 37.5% in a group that displayed numerous psychological difficulties. Four groups with average self-harm had varied psychological profiles including low impulsivity, anxiety, impulsivity, and poor use of positive coping strategies. Identifying multiple profiles with distinct psychological characteristics can improve detection, guide prevention, and tailor treatment.
Proteomic Analyses of Corneal Tissue Subjected to Alkali Exposure
Parikh, Toral; Eisner, Natalie; Venugopalan, Praseeda; Yang, Qin; Lam, Byron L.
2011-01-01
Purpose. To determine whether exposure to alkaline chemicals results in predictable changes in corneal protein profile. To determine whether protein profile changes are indicative of severity and duration of alkali exposure. Methods. Enucleated bovine and porcine (n = 59 each) eyes were used for exposure to sodium, ammonium, and calcium hydroxide, respectively. Eyes were subjected to fluorescein staining, 5-bromo-2′-deoxy-uridine (BrdU) labeling. Excised cornea was subjected to protein extraction, spectrophotometric determination of protein amount, dynamic light scattering and SDS-PAGE profiling, mass spectrometric protein identification, and iTRAQ-labeled quantification. Select identified proteins were subjected to Western blot and immunohistochemical analyses. Results. Alkali exposure resulted in lower protein extractability from corneal tissue. Elevated aggregate formation was found with strong alkali exposure (sodium hydroxide>ammonium, calcium hydroxide), even with a short duration of exposure compared with controls. The protein yield after exposure varied as a function of postexposure time. Protein profiles changed because of alkali exposure. Concentration and strength of the alkali affected the profile change significantly. Mass spectrometry identified 15 proteins from different bands with relative quantification. Plexin D1 was identified for the first time in the cornea at a protein level that was further confirmed by Western blot and immunohistochemical analyses. Conclusions. Exposure to alkaline chemicals results in predictable and reproducible changes in corneal protein profile. Stronger alkali, longer durations, or both, of exposure resulted in lower yields and significant protein profile changes compared with controls. PMID:20861482
Comparative Time Course Profiles of Phthalate Stereoisomers in Mice
ABSTRACT More efficient models are needed to assess potential carcinogenicity hazard of environmental chemicals. Here we evaluated time course profiles for two reference phthalates, di(2-ethylhexyl) phthalate (DEHP) and its stereoisomer di-n-octyl phthalate (DNOP), to identify...
Newman, Mackenzie S; Nguyen, Tina; Watson, Michael J; Hull, Robert W; Yu, Han-Gang
2017-07-01
How obesity or sex may affect the gene expression profiles of human cardiac hypertrophy is unknown. We hypothesized that body-mass index (BMI) and sex can affect gene expression profiles of cardiac hypertrophy. Human heart tissues were grouped according to sex (male, female), BMI (lean<25 kg/m 2 , obese>30 kg/m 2 ), or left ventricular hypertrophy (LVH) and non-LVH nonfailed controls (NF). We identified 24 differentially expressed (DE) genes comparing female with male samples. In obese subgroup, there were 236 DE genes comparing LVH with NF; in lean subgroup, there were seven DE genes comparing LVH with NF. In female subgroup, we identified 1,320 significant genes comparing LVH with NF; in male subgroup, there were 1,383 significant genes comparing LVH with NF. There were seven significant genes comparing obese LVH with lean NF; comparing male obese LVH with male lean NF samples we found 106 significant genes; comparing female obese LVH with male lean NF, we found no significant genes. Using absolute value of log 2 fold-change > 2 or extremely small P value (10 -20 ) as a criterion, we identified nine significant genes (HBA1, HBB, HIST1H2AC, GSTT1, MYL7, NPPA, NPPB, PDK4, PLA2G2A) in LVH, also found in published data set for ischemic and dilated cardiomyopathy in heart failure. We identified a potential gene expression signature that distinguishes between patients with high BMI or between men and women with cardiac hypertrophy. Expression of established biomarkers atrial natriuretic peptide A (NPPA) and B (NPPB) were already significantly increased in hypertrophy compared with controls. Copyright © 2017 the American Physiological Society.
Profiles of internalizing and externalizing symptoms associated with bullying victimization.
Eastman, Meridith; Foshee, Vangie; Ennett, Susan; Sotres-Alvarez, Daniela; Reyes, H Luz McNaughton; Faris, Robert; North, Kari
2018-06-01
This study identified profiles of internalizing (anxiety and depression) and externalizing (delinquency and violence against peers) symptoms among bullying victims and examined associations between bullying victimization characteristics and profile membership. The sample consisted of 1196 bullying victims in grades 8-10 (M age = 14.4, SD = 1.01) who participated in The Context Study in three North Carolina counties in Fall 2003. Five profiles were identified using latent profile analysis: an asymptomatic profile and four profiles capturing combinations of internalizing and externalizing symptoms. Associations between bullying characteristics and membership in symptom profiles were tested using multinomial logistic regression. More frequent victimization increased odds of membership in the two high internalizing profiles compared to the asymptomatic profile. Across all multinomial logistic regression models, when the high internalizing, high externalizing profile was the reference category, adolescents who received any type of bullying (direct, indirect, or dual) were more likely to be in this category than any others. Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.
Toka Özer, Türkan; Yula, Erkan; Doğan, Metin; Baskın, Hüseyin
2018-04-27
Incidence of mycobacterial infections has been increasing. However, diagnosis and treatment of mycobacterial infections can be difficult. The aim of this study was to investigate high-performance liquid chromatography (HPLC) analysis of the mycolic acids for rapid identification and dendrogram cluster analysis of mycobacterium species. Clinical specimens received for mycobacterial culture and antimicrobial susceptibility test were processed by standard laboratory protocols. Positive cultures were analyzed with HPLC method. Mycolic acid analysis with HPLC was used for diagnosis of tuberculosis and other mycobacterial infections. These reports were compared with Sherlock Library mycobacterial species, and the similarity index was analyzed. This value was formed by a software in multidimensional space that was the calculation of the average distance between the nearest library profile and unknown profile. The ninety-two samples were identified as M. tuberculosis. (similarity index between 0.593 and 0.994). One of the other strains was identified as M. avium intracellulare (strain No. 82) (SI = 0.906); one of them was identified as M. interjectum (strain no. 89) (SI = 0.644). Total 94 samples were identified, and dendrogram was applied to these samples. Profile A (10.6%), profile B (59.6%), profile C (11.7%), profile D (3.2%), and other profiles as single different profiles were identified. Rates for each as 1% (89, 94, 1, 82, 26, 42, 32, 41, 100, 43, 47, 44, 40, 35). High-performance liquid chromatography is a useful, rapid, reliable, and practical method for diagnosis of mycobacterium species. © 2018 Wiley Periodicals, Inc.
2016-12-01
VARIABILITY OF THE ACOUSTIC PROPAGATION IN THE MEDITERRANEAN SEA IDENTIFIED FROM A SYNOPTIC MONTHLY GRIDDED DATABASE AS COMPARED WITH GDEM by...ANNUAL VARIABILITY OF THE ACOUSTIC PROPAGATION IN THE MEDITERRANEAN SEA IDENTIFIED FROM A SYNOPTIC MONTHLY GRIDDED DATABASE AS COMPARED WITH GDEM 5...profiles obtained from the synoptic monthly gridded World Ocean Database (SMD-WOD) and Generalized Digital Environmental Model (GDEM) temperature (T
Goga, Haruhisa
2012-09-01
It is crucial to identify the owner of unattended footwear left at a crime scene. However, retrieving enough DNA for DNA profiling from the owner's foot skin (plantar skin) cells from inside the footwear is often unsuccessful. This is sometimes because footwear that is used on a daily basis contains an abundance of bacteria that degrade DNA. Further, numerous other factors related to the inside of the shoe, such as high humidity and temperature, can encourage bacterial growth inside the footwear and enhance DNA degradation. This project sought to determine if bacteria from inside footwear could be used for footwear trace evidence. The plantar skins and insoles of shoes of volunteers were swabbed for bacteria, and their bacterial community profiles were compared using bacterial 16S rRNA terminal restriction fragment length polymorphism analysis. Sufficient bacteria were recovered from both footwear insoles and the plantar skins of the volunteers. The profiling identified that each volunteer's plantar skins harbored unique bacterial communities, as did the individuals' footwear insoles. In most cases, a significant similarity in the bacterial community was identified for the matched foot/insole swabs from each volunteer, as compared with those profiles from different volunteers. These observations indicate the probability to discriminate the owner of footwear by comparing the microbial DNA fingerprint from inside footwear with that of the skin from the soles of the feet of the suspected owner. This novel strategy will offer auxiliary forensic footwear evidence for human DNA identification, although further investigations into this technique are required.
Wang, Wenyu; Liu, Yang; Hao, Jingcan; Zheng, Shuyu; Wen, Yan; Xiao, Xiao; He, Awen; Fan, Qianrui; Zhang, Feng; Liu, Ruiyu
2016-10-10
Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA. Copyright © 2016 Elsevier B.V. All rights reserved.
Eley, Diann S; Leung, Janni; Hong, Barry A; Cloninger, Kevin M; Cloninger, C Robert
2016-01-01
There is a high prevalence of stress, depression, and burn-out in medical students. Medical students differ widely in personality traits, self-perceptions, and values that may have an impact on their well-being. This study aimed to investigate variability in their personality profiles in relation to their potential for well-being and resilience. Participants were 808 medical students from The University of Queensland. An online questionnaire collected socio-demographics and the Temperament and Character Inventory to assess personality traits. Latent profile analyses identified students' trait profiles. Two distinct personality profiles were identified. Profile 1 ("Resilient") characterized 60% of the sample and was distinguished by low Harm Avoidance combined with very high Persistence, Self-Directedness and Cooperativeness compared to Profile 2 ("Conscientious"). Both Profiles had average levels of Reward Dependence and Novelty Seeking and low levels of Self-Transcendence. Profiles did not differ by age, gender, or country of birth, but rural background students were more likely to have Profile 1. While both Profiles indicate mature and healthy personalities, the combination of traits in Profile 1 is more strongly indicative of well-being and resilience. Finding two distinct profiles of personality highlights the importance of considering combinations of traits and how they may interact with medical students' potential for well-being. Although both profiles of students show healthy personalities, many may lack the resilience to maintain well-being over years of medical training. Programs that develop character and personality self-awareness would enhance their well-being and prepare them to promote the health of their patients.
Leung, Janni; Hong, Barry A.; Cloninger, Kevin M.; Cloninger, C. Robert
2016-01-01
Purpose There is a high prevalence of stress, depression, and burn-out in medical students. Medical students differ widely in personality traits, self-perceptions, and values that may have an impact on their well-being. This study aimed to investigate variability in their personality profiles in relation to their potential for well-being and resilience. Method Participants were 808 medical students from The University of Queensland. An online questionnaire collected socio-demographics and the Temperament and Character Inventory to assess personality traits. Latent profile analyses identified students’ trait profiles. Results Two distinct personality profiles were identified. Profile 1 (“Resilient”) characterized 60% of the sample and was distinguished by low Harm Avoidance combined with very high Persistence, Self-Directedness and Cooperativeness compared to Profile 2 ("Conscientious"). Both Profiles had average levels of Reward Dependence and Novelty Seeking and low levels of Self-Transcendence. Profiles did not differ by age, gender, or country of birth, but rural background students were more likely to have Profile 1. While both Profiles indicate mature and healthy personalities, the combination of traits in Profile 1 is more strongly indicative of well-being and resilience. Conclusions Finding two distinct profiles of personality highlights the importance of considering combinations of traits and how they may interact with medical students’ potential for well-being. Although both profiles of students show healthy personalities, many may lack the resilience to maintain well-being over years of medical training. Programs that develop character and personality self-awareness would enhance their well-being and prepare them to promote the health of their patients. PMID:27494401
Aerodynamic profiles of women with muscle tension dysphonia/aphonia.
Gillespie, Amanda I; Gartner-Schmidt, Jackie; Rubinstein, Elaine N; Abbott, Katherine Verdolini
2013-04-01
In this study, the authors aimed to (a) determine whether phonatory airflows and estimated subglottal pressures (est-Psub) for women with primary muscle tension dysphonia/aphonia (MTD/A) differ from those for healthy speakers; (b) identify different aerodynamic profile patterns within the MTD/A subject group; and (c) determine whether results suggest new understanding of pathogenesis in MTD/A. Retrospective review of aerodynamic data collected from 90 women at the time of primary MTD/A diagnosis. Aerodynamic profiles were significantly different for women with MTD/A as compared with healthy speakers. Five distinct profiles were identified: (a) normal flow, normal est-Psub; (b) high flow, high est-Psub; (c) low flow, normal est-Psub; (d) normal flow, high est-Psub; and (e) high flow, normal est-Psub. This study is the first to identify distinct subgroups of aerodynamic profiles in women with MTD/A and to quantitatively identify a clinical phenomenon sometimes described in association with it-"breath holding"-that is shown by low airflow with normal est-Psub. Results were consistent with clinical claims that diverse respiratory and laryngeal functions may underlie phonatory patterns associated with MTD/A. One potential mechanism, based in psychobiological theory, is introduced to explain some of the variability in aerodynamic profiles of women with MTD/A.
Cognitive Profiles of Chinese Adolescents with Dyslexia
ERIC Educational Resources Information Center
Chung, Kevin K. H.; Ho, Connie Suk-Han; Chan, David W.; Tsang, Suk-Man; Lee, Suk-Han
2010-01-01
The present study sought to identify cognitive abilities that might distinguish Hong Kong Chinese adolescents with and without dyslexia and examined the cognitive profile of dyslexic adolescents in order to better understand this important problem. The performance of 27 Chinese adolescents with childhood diagnoses of dyslexia was compared with 27…
The Fecal Microbiota Profile and Bronchiolitis in Infants
Linnemann, Rachel W.; Mansbach, Jonathan M.; Ajami, Nadim J.; Espinola, Janice A.; Petrosino, Joseph F.; Piedra, Pedro A.; Stevenson, Michelle D.; Sullivan, Ashley F.; Thompson, Amy D.; Camargo, Carlos A.
2016-01-01
BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case–control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichia-dominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonella-dominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58–15.5; P = .008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56–12.0; P = .005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case–control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis. PMID:27354456
PCoM-DB Update: A Protein Co-Migration Database for Photosynthetic Organisms.
Takabayashi, Atsushi; Takabayashi, Saeka; Takahashi, Kaori; Watanabe, Mai; Uchida, Hiroko; Murakami, Akio; Fujita, Tomomichi; Ikeuchi, Masahiko; Tanaka, Ayumi
2017-01-01
The identification of protein complexes is important for the understanding of protein structure and function and the regulation of cellular processes. We used blue-native PAGE and tandem mass spectrometry to identify protein complexes systematically, and built a web database, the protein co-migration database (PCoM-DB, http://pcomdb.lowtem.hokudai.ac.jp/proteins/top), to provide prediction tools for protein complexes. PCoM-DB provides migration profiles for any given protein of interest, and allows users to compare them with migration profiles of other proteins, showing the oligomeric states of proteins and thus identifying potential interaction partners. The initial version of PCoM-DB (launched in January 2013) included protein complex data for Synechocystis whole cells and Arabidopsis thaliana thylakoid membranes. Here we report PCoM-DB version 2.0, which includes new data sets and analytical tools. Additional data are included from whole cells of the pelagic marine picocyanobacterium Prochlorococcus marinus, the thermophilic cyanobacterium Thermosynechococcus elongatus, the unicellular green alga Chlamydomonas reinhardtii and the bryophyte Physcomitrella patens. The Arabidopsis protein data now include data for intact mitochondria, intact chloroplasts, chloroplast stroma and chloroplast envelopes. The new tools comprise a multiple-protein search form and a heat map viewer for protein migration profiles. Users can compare migration profiles of a protein of interest among different organelles or compare migration profiles among different proteins within the same sample. For Arabidopsis proteins, users can compare migration profiles of a protein of interest with putative homologous proteins from non-Arabidopsis organisms. The updated PCoM-DB will help researchers find novel protein complexes and estimate their evolutionary changes in the green lineage. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Method and apparatus for detecting flaws and defects in heat seals
NASA Technical Reports Server (NTRS)
Rai, Kula R. (Inventor); Lew, Thomas M. (Inventor); Sinclair, Robert B. (Inventor)
1993-01-01
Flaws and defects in heat seals formed between sheets of translucent film are identified by optically examining consecutive lateral sections of the seal along the seal length. Each lateral seal section is illuminated and an optical sensor array detects the intensity of light transmitted through the seal section for the purpose of detecting and locating edges in the heat seal. A line profile for each consecutive seal section is derived having an amplitude proportional to the change in light intensity across the seal section. Instances in the derived line profile where the amplitude is greater than a threshold level indicate the detection of a seal edge. The detected edges in each derived line profile are then compared to a preset profile edge standard to identify the existence of a flaw or defect.
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
2009-01-01
Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular 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 molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early 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 early, 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, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular 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
Multidimensional profiles of health locus of control in Hispanic Americans
Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L
2016-01-01
Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables. PMID:25855212
Widerström-Noga, Eva G; Duncan, Robert; Turk, Dennis C
2004-01-01
The objectives of the study were to: (1) identify psychosocial profiles of people with pain associated with spinal cord injuries (SCI), and (2) compare the psychosocial profiles with other chronic pain syndromes. History questionnaires and the Multidimensional Pain Inventory (MPI) were mailed to 159 persons with chronic pain and SCIs (SCICP) and 120 (75.5%) agreed to participate. Cluster analysis of MPI scores identified 2 subgroups of SCICP. One (42.5%) was characterized by high Pain Severity (PS), Affective Distress (AD), Life Interference (LI), and low Life Control (LC) similar to a previously identified cluster labeled Dysfunctional. The second (57.5%) was characterized by low PS, AD, LI, and high levels of LC and activity (GA), similar to the Adaptive Copers (AC) cluster identified in previous studies with the exception that the scores were lower on Support (S), Solicitous Responses (SR), and Negative Responses (NR) and higher on Distracting Responses (DR). Both subgroups were similar to those observed in other chronic pain syndromes (CPSs). People with SCIs differed significantly from heterogeneous chronic pain and chronic headaches in that they indicated less inference of pain with activities. They also scored lower on S. SCICP reported comparable levels of LI, LC, AD, S, SR, but greater levels of PS compared with a group of people with post-polio syndrome. The similarities and differences between SCI and other CPSs suggest that although a general measure assessing psychosocial impact can be used across pain syndromes, it is important to use different norms for comparison of particular pain syndromes. The failure to identify a subgroup of patients characterized by low levels of S and high levels of NR, and the low SR and DR for SCICP compared with other CPSs warrants examination.
Comparative transcriptional profiling identifies takeout as a gene that regulates life span
Bauer, Johannes; Antosh, Michael; Chang, Chengyi; Schorl, Christoph; Kolli, Santharam; Neretti, Nicola; Helfand, Stephen L.
2010-01-01
A major challenge in translating the positive effects of dietary restriction (DR) for the improvement of human health is the development of therapeutic mimics. One approach to finding DR mimics is based upon identification of the proximal effectors of DR life span extension. Whole genome profiling of DR in Drosophila shows a large number of changes in gene expression, making it difficult to establish which changes are involved in life span determination as opposed to other unrelated physiological changes. We used comparative whole genome expression profiling to discover genes whose change in expression is shared between DR and two molecular genetic life span extending interventions related to DR, increased dSir2 and decreased Dmp53 activity. We find twenty-one genes shared among the three related life span extending interventions. One of these genes, takeout, thought to be involved in circadian rhythms, feeding behavior and juvenile hormone binding is also increased in four other life span extending conditions: Rpd3, Indy, chico and methuselah. We demonstrate takeout is involved in longevity determination by specifically increasing adult takeout expression and extending life span. These studies demonstrate the power of comparative whole genome transcriptional profiling for identifying specific downstream elements of the DR life span extending pathway. PMID:20519778
Sargent, Rachel; Jones, Dan; Abruzzo, Lynne V.; Yao, Hui; Bonderover, Jaime; Cisneros, Marissa; Wierda, William G.; Keating, Michael J.; Luthra, Rajyalakshmi
2009-01-01
Chromosome gains and losses used for risk stratification in chronic lymphocytic leukemia (CLL) are commonly assessed by multiprobe fluorescence in situ hybridization (FISH) studies. We designed and validated a customized array-comparative genomic hybridization (aCGH) platform as a clinical assay for CLL genomic profiling. A 60-mer, 44,000-probe oligonucleotide array with a 50-kb average spatial resolution was augmented with high-density probe tiling at loci that are frequently aberrant in CLL. Aberrations identified by aCGH were compared with those identified by a FISH panel, including locus-specific probes to ATM (11q22.3), the centromeric region of chromosome 12 (12p11.1–q11), D13S319 (13q14.3), LAMP1 (13q34), and TP53 (17p13.1). In 100 CLL samples, aCGH/FISH concordance was seen for 89% of FISH-called aberrations at the ATM (n = 18), D13S319 (n = 42), LAMP (n = 12), and TP53 (n = 22) loci and for chromosome 12 (n = 14). Eighty-four percentage of FISH/aCGH discordant calls were in samples either at or below the limit of aCGH sensitivity (10% to 25% FISH aberration-containing cells). Therefore, aCGH profiling is a feasible routine clinical test with comparable results to multiprobe FISH studies; however, it may be less sensitive than FISH in cases with low-level aberrations. Further, a customized array design can provide comprehensive genomic profiling with additional accuracy in both identifying and defining the extent of small aberrations at target loci. PMID:19074592
Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan; Mora-Jensen, Helena; Krogh, Anders; Kohlmann, Alexander; Thiede, Christian; Borregaard, Niels; Bullinger, Lars; Winther, Ole; Theilgaard-Mönch, Kim; Porse, Bo T
2014-02-06
Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.
Jang, Jae-Wook; Yun, Jaesung; Mohaisen, Aziz; Woo, Jiyoung; Kim, Huy Kang
2016-01-01
Mass-market mobile security threats have increased recently due to the growth of mobile technologies and the popularity of mobile devices. Accordingly, techniques have been introduced for identifying, classifying, and defending against mobile threats utilizing static, dynamic, on-device, and off-device techniques. Static techniques are easy to evade, while dynamic techniques are expensive. On-device techniques are evasion, while off-device techniques need being always online. To address some of those shortcomings, we introduce Andro-profiler, a hybrid behavior based analysis and classification system for mobile malware. Andro-profiler main goals are efficiency, scalability, and accuracy. For that, Andro-profiler classifies malware by exploiting the behavior profiling extracted from the integrated system logs including system calls. Andro-profiler executes a malicious application on an emulator in order to generate the integrated system logs, and creates human-readable behavior profiles by analyzing the integrated system logs. By comparing the behavior profile of malicious application with representative behavior profile for each malware family using a weighted similarity matching technique, Andro-profiler detects and classifies it into malware families. The experiment results demonstrate that Andro-profiler is scalable, performs well in detecting and classifying malware with accuracy greater than 98 %, outperforms the existing state-of-the-art work, and is capable of identifying 0-day mobile malware samples.
Profiling depression in childhood and adolescence: the role of conduct problems.
Riglin, Lucy; Thapar, Anita; Shelton, Katherine H; Langley, Kate; Frederickson, Norah; Rice, Frances
2016-04-01
Depression is typically more common in females and rates rise around puberty. However, studies of children and adolescents suggest that depression accompanied by conduct problems may represent a different subtype not characterised by a female preponderance, with differing risk factors and genetic architecture compared to pure-depression. This study aimed to identify aetiologically distinct profiles of depressive symptoms, distinguished by the presence or absence of co-occurring conduct problems. Latent profile analysis was conducted on a school sample of 1648 children (11-12 years) and replicated in a sample of 2006 twins (8-17 years). In both samples pure-depressive and conduct-depressive profiles were identified. The pure-depressive profile was associated with female gender, while the conduct-depressive profile was associated with lower cognitive ability but not with gender. Twin analyses indicated possible differences in genetic aetiology. There was evidence for aetiologically heterogeneous depression symptom profiles based on the presence or absence of co-occurring conduct problems. © 2015 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.
A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia
Perrot, Aurore; Pionneau, Cédric; Nadaud, Sophie; Davi, Frédéric; Leblond, Véronique; Jacob, Frédéric; Merle-Béral, Hélène; Herbrecht, Raoul; Béné, Marie-Christine; Gribben, John G.; Vallat, Laurent
2011-01-01
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course with 2 extreme subsets: indolent, ZAP70− and mutated immunoglobulin heavy chain gene (M-CLL); and aggressive, ZAP70+ and unmutated immunoglobulin heavy chain (UM-CLL). Given the long-term suspicion of antigenic stimulation as a primum movens in the disease, the role of the B-cell receptor has been extensively studied in various experimental settings; albeit scarcely in a comparative dynamic proteomic approach. Here we use a quantitative 2-dimensional fluorescence difference gel electrophoresis technology to compare 48 proteomic profiles of the 2 CLL subsets before and after anti-IgM ligation. Differentially expressed proteins were subsequently identified by mass spectrometry. We show that unstimulated M- and UM-CLL cells display distinct proteomic profiles. Furthermore, anti-IgM stimulation induces a specific proteomic response, more pronounced in the more aggressive CLL. Statistical analyses demonstrate several significant protein variations according to stimulation conditions. Finally, we identify an intermediate form of M-CLL cells, with an indolent profile (ZAP70−) but sharing aggressive proteomic profiles alike UM-CLL cells. Collectively, this first quantitative and dynamic proteome analysis of CLL further dissects the complex molecular pathway after B-cell receptor stimulation and depicts distinct proteomic profiles, which could lead to novel molecular stratification of the disease. PMID:21602524
Exploitation of molecular profiling techniques for GM food safety assessment.
Kuiper, Harry A; Kok, Esther J; Engel, Karl-Heinz
2003-04-01
Several strategies have been developed to identify unintended alterations in the composition of genetically modified (GM) food crops that may occur as a result of the genetic modification process. These include comparative chemical analysis of single compounds in GM food crops and their conventional non-GM counterparts, and profiling methods such as DNA/RNA microarray technologies, proteomics and metabolite profiling. The potential of profiling methods is obvious, but further exploration of specificity, sensitivity and validation is needed. Moreover, the successful application of profiling techniques to the safety evaluation of GM foods will require linked databases to be built that contain information on variations in profiles associated with differences in developmental stages and environmental conditions.
USDA-ARS?s Scientific Manuscript database
Overlaps in transcriptome profiles between different phases of bud and seed dormancy have not been determined. Thus, we compared various phases of dormancy between seeds and buds to identify common genes and molecular processes. Cluster analysis of expression profiles for 201 selected genes indicate...
A New Look at Multiple Goal Pursuit: The Promise of a Person-Centered Approach
ERIC Educational Resources Information Center
Wormington, Stephanie Virgine; Linnenbrink-Garcia, Lisa
2017-01-01
The current study reviewed and synthesized studies employing a person-centered approach to studying achievement goals. Towards this end, a common labeling scheme was developed for goal profiles. Ten profile types were identified across studies and compared via meta-analytic techniques in terms of academic motivation, social/emotional well-being,…
Multidimensional profiles of health locus of control in Hispanic Americans.
Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L
2016-10-01
Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables. © The Author(s) 2015.
Hewett, Timothy E; Ford, Kevin R; Xu, Yingying Y; Khoury, Jane; Myer, Gregory D
2016-12-01
The widespread use of anterior cruciate ligament (ACL) injury prevention interventions has not been effective in reducing the injury incidence among female athletes who participate in high-risk sports. The purpose of this study was to determine if biomechanical and neuromuscular factors that contribute to the knee abduction moment (KAM), a predictor of future ACL injuries, could be used to characterize athletes by a distinct factor. Specifically, we hypothesized that a priori selected biomechanical and neuromuscular factors would characterize participants into distinct at-risk profiles. Controlled laboratory study. A total of 624 female athletes who participated in jumping, cutting, and pivoting sports underwent testing before their competitive season. During testing, athletes performed drop-jump tasks from which biomechanical measures were captured. Using data from these tasks, latent profile analysis (LPA) was conducted to identify distinct profiles based on preintervention biomechanical and neuromuscular measures. As a validation, we examined whether the profile membership was a significant predictor of the KAM. LPA using 6 preintervention biomechanical measures selected a priori resulted in 3 distinct profiles, including a low (profile 1), moderate (profile 2), and high (profile 3) risk for ACL injuries. Athletes with profiles 2 and 3 had a significantly higher KAM compared with those with profile 1 (P < .05). This is the first study to use LPA of biomechanical landing data to create ACL injury risk profiles. Three distinct risk groups were identified based on differences in the peak KAM. These findings demonstrate the existence of discernable groups of athletes that may benefit from injury prevention interventions. ClinicalTrials.gov NCT identifier: NCT01034527. © 2016 The Author(s).
Ketterer, Caroline; Zeiger, Ulrike; Budak, Murat T.; Rubinstein, Neal A.; Khurana, Tejvir S.
2010-01-01
Purpose. To examine and characterize the profile of genes expressed at the synapses or neuromuscular junctions (NMJs) of extraocular muscles (EOMs) compared with those expressed at the tibialis anterior (TA). Methods. Adult rat eyeballs with rectus EOMs attached and TAs were dissected, snap frozen, serially sectioned, and stained for acetylcholinesterase (AChE) to identify the NMJs. Approximately 6000 NMJs for rectus EOM (EOMsyn), 6000 NMJs for TA (TAsyn), equal amounts of NMJ-free fiber regions (EOMfib, TAfib), and underlying myonuclei and RNAs were captured by laser capture microdissection (LCM). RNA was processed for microarray-based expression profiling. Expression profiles and interaction lists were generated for genes differentially expressed at synaptic and nonsynaptic regions of EOM (EOMsyn versus EOMfib) and TA (TAsyn versus TAfib). Profiles were validated by using real-time quantitative polymerase chain reaction (qPCR). Results. The regional transcriptomes associated with NMJs of EOMs and TAs were identified. Two hundred seventy-five genes were preferentially expressed in EOMsyn (compared with EOMfib), 230 in TAsyn (compared with TAfib), and 288 additional transcripts expressed in both synapses. Identified genes included novel genes as well as well-known, evolutionarily conserved synaptic markers (e.g., nicotinic acetylcholine receptor (AChR) alpha (Chrna) and epsilon (Chrne) subunits and nestin (Nes). Conclusions. Transcriptome level differences exist between EOM synaptic regions and TA synaptic regions. The definition of the synaptic transcriptome provides insight into the mechanism of formation and functioning of the unique synapses of EOM and their differential involvement in diseases noted in the EOM allotype. PMID:20393109
Lau, Susanna K P; Lee, Kim-Chung; Lo, George C S; Ding, Vanessa S Y; Chow, Wang-Ngai; Ke, Tony Y H; Curreem, Shirly O T; To, Kelvin K W; Ho, Deborah T Y; Sridhar, Siddharth; Wong, Sally C Y; Chan, Jasper F W; Hung, Ivan F N; Sze, Kong-Hung; Lam, Ching-Wan; Yuen, Kwok-Yung; Woo, Patrick C Y
2016-02-27
To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.
Lau, Susanna K. P.; Lee, Kim-Chung; Lo, George C. S.; Ding, Vanessa S. Y.; Chow, Wang-Ngai; Ke, Tony Y. H.; Curreem, Shirly O. T.; To, Kelvin K. W.; Ho, Deborah T. Y.; Sridhar, Siddharth; Wong, Sally C. Y.; Chan, Jasper F. W.; Hung, Ivan F. N.; Sze, Kong-Hung; Lam, Ching-Wan; Yuen, Kwok-Yung; Woo, Patrick C. Y.
2016-01-01
To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis. PMID:26927094
Moreno-Ortega, Beatriz; Fort, Guillaume; Muller, Bertrand; Guédon, Yann
2017-01-01
The identification of the limits between the cell division, elongation and mature zones in the root apex is still a matter of controversy when methods based on cellular features, molecular markers or kinematics are compared while methods based on cell length profiles have been comparatively underexplored. Segmentation models were developed to identify developmental zones within a root apex on the basis of epidermal cell length profiles. Heteroscedastic piecewise linear models were estimated for maize lateral roots of various lengths of both wild type and two mutants affected in auxin signaling (rtcs and rum-1). The outputs of these individual root analyses combined with morphological features (first root hair position and root diameter) were then globally analyzed using principal component analysis. Three zones corresponding to the division zone, the elongation zone and the mature zone were identified in most lateral roots while division zone and sometimes elongation zone were missing in arrested roots. Our results are consistent with an auxin-dependent coordination between cell flux, cell elongation and cell differentiation. The proposed segmentation models could extend our knowledge of developmental regulations in longitudinally organized plant organs such as roots, monocot leaves or internodes. PMID:29123533
Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults
USDA-ARS?s Scientific Manuscript database
In this study we used stool profiling to identify intestinal bacteria and metabolites that are differentially represented in humans with colorectal cancer (CRC) compared to healthy controls to identify how microbial functions may influence CRC development. Stool samples were collected from healthy a...
NASA Astrophysics Data System (ADS)
Lin, Tzung-Jin; Liang, Jyh-Chong; Tsai, Chin-Chung
2015-08-01
The main purposes of this study were to identify Taiwanese university students' physics learning profiles in terms of their critical conceptions of learning physics and to compare their physics learning self-efficacy with the different learning profiles. A total of 250 Taiwanese undergraduates who were majoring in physics participated in this study and were invited to complete two instruments, physics learning profile and physics learning self-efficacy (PLSE). The main results indicated that, first, the two instruments developed in this study had satisfactory validity and reliability. Second, three fundamental physics learning profiles, the reproductive, transitional, and constructive profiles, were characterized based on the cluster analysis. It is also evident that the three learning profiles demonstrated different levels of self-efficacy for the five PLSE dimensions. The students with a reproductive profile tended to possess the lowest PLSE across the five dimensions. The students with a transitional profile may possess higher confidence in higher-order cognitive skills and laboratory activities than those with a reproductive profile. However, only those with a constructive profile, highlighting a comprehensive understanding of physics knowledge/concepts as well as de-emphasizing physics learning as preparing for tests and calculating and practising tutorial problems, possessed stronger PLSE in applying what they learned to real-world contexts as well as in scientifically communicating with others.
Target biomarker profile for the clinical management of paracetamol overdose
Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W
2015-01-01
Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366
Comparing Pearson, Spearman and Hoeffding's D measure for gene expression association analysis.
Fujita, André; Sato, João Ricardo; Demasi, Marcos Angelo Almeida; Sogayar, Mari Cleide; Ferreira, Carlos Eduardo; Miyano, Satoru
2009-08-01
DNA microarrays have become a powerful tool to describe gene expression profiles associated with different cellular states, various phenotypes and responses to drugs and other extra- or intra-cellular perturbations. In order to cluster co-expressed genes and/or to construct regulatory networks, definition of distance or similarity between measured gene expression data is usually required, the most common choices being Pearson's and Spearman's correlations. Here, we evaluate these two methods and also compare them with a third one, namely Hoeffding's D measure, which is used to infer nonlinear and non-monotonic associations, i.e. independence in a general sense. By comparing three different variable association approaches, namely Pearson's correlation, Spearman's correlation and Hoeffding's D measure, we aimed at assessing the most appropriate one for each purpose. Using simulations, we demonstrate that the Hoeffding's D measure outperforms Pearson's and Spearman's approaches in identifying nonlinear associations. Our results demonstrate that Hoeffding's D measure is less sensitive to outliers and is a more powerful tool to identify nonlinear and non-monotonic associations. We have also applied Hoeffding's D measure in order to identify new putative genes associated with tp53. Therefore, we propose the Hoeffding's D measure to identify nonlinear associations between gene expression profiles.
Stress amplifies sex differences in primate prefrontal profiles of gene expression.
Lee, Alex G; Hagenauer, Megan; Absher, Devin; Morrison, Kathleen E; Bale, Tracy L; Myers, Richard M; Watson, Stanley J; Akil, Huda; Schatzberg, Alan F; Lyons, David M
2017-11-02
Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults. Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys. Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex. Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.
Liu, Yuesheng; Ji, Yuqiang; Li, Min; Wang, Min; Yi, Xiaoqing; Yin, Chunyan; Wang, Sisi; Zhang, Meizhen; Zhao, Zhao; Xiao, Yanfeng
2018-06-08
Long noncoding RNAs (lncRNAs) have an important role in adipose tissue function and energy metabolism homeostasis, and abnormalities may lead to obesity. To investigate whether lncRNAs are involved in childhood obesity, we investigated the differential expression profile of lncRNAs in obese children compared with non-obese children. A total number of 1268 differentially expressed lncRNAs and 1085 differentially expressed mRNAs were identified. Gene Ontology (GO) and pathway analysis revealed that these lncRNAs were involved in varied biological processes, including the inflammatory response, lipid metabolic process, osteoclast differentiation and fatty acid metabolism. In addition, the lncRNA-mRNA co-expression network and the protein-protein interaction (PPI) network were constructed to identify hub regulatory lncRNAs and genes based on the microarray expression profiles. This study for the first time identifies an expression profile of differentially expressed lncRNAs in obese children and indicated hub lncRNA RP11-20G13.3 attenuated adipogenesis of preadipocytes, which is conducive to the search for new diagnostic and therapeutic strategies of childhood obesity.
Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice.
Jackson, Kathryn C; Wohlers, Lindsay M; Lovering, Richard M; Schuh, Rosemary A; Maher, Amy C; Bonen, Arend; Koves, Timothy R; Ilkayeva, Olga; Thomson, David M; Muoio, Deborah M; Spangenburg, Espen E
2013-02-01
Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) female mice compared with age-matched ovary-intact adult female mice (sham). The OVX mice exhibited significant increases in body weight, visceral, and inguinal fat mass compared with sham mice. OVX mice also had significant increases in skeletal muscle intramyocellular lipids (IMCL) compared with the sham animals, which corresponded to significant increases in the protein content of the fatty acid transporters CD36/FAT and FABPpm. A targeted metabolic profiling approach identified significantly lower levels of specific acyl carnitine species and various amino acids in skeletal muscle from OVX mice compared with the sham animals, suggesting a potential dysfunction in lipid and amino acid metabolism, respectively. Basal and maximal mitochondrial oxygen consumption rates were significantly impaired in skeletal muscle fibers from OVX mice compared with sham animals. Collectively, these data indicate that loss of ovarian function results in increased IMCL storage that is coupled with alterations in mitochondrial function and changes in the skeletal muscle metabolic profile.
Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice
Jackson, Kathryn C.; Wohlers, Lindsay M.; Lovering, Richard M.; Schuh, Rosemary A.; Maher, Amy C.; Bonen, Arend; Koves, Timothy R.; Ilkayeva, Olga; Thomson, David M.; Muoio, Deborah M.
2013-01-01
Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) female mice compared with age-matched ovary-intact adult female mice (sham). The OVX mice exhibited significant increases in body weight, visceral, and inguinal fat mass compared with sham mice. OVX mice also had significant increases in skeletal muscle intramyocellular lipids (IMCL) compared with the sham animals, which corresponded to significant increases in the protein content of the fatty acid transporters CD36/FAT and FABPpm. A targeted metabolic profiling approach identified significantly lower levels of specific acyl carnitine species and various amino acids in skeletal muscle from OVX mice compared with the sham animals, suggesting a potential dysfunction in lipid and amino acid metabolism, respectively. Basal and maximal mitochondrial oxygen consumption rates were significantly impaired in skeletal muscle fibers from OVX mice compared with sham animals. Collectively, these data indicate that loss of ovarian function results in increased IMCL storage that is coupled with alterations in mitochondrial function and changes in the skeletal muscle metabolic profile. PMID:23193112
NICU Network Neurobehavioral Profiles Predict Developmental Outcomes in a Low Risk Sample
Sucharew, Heidi; Khoury, Jane C.; Xu, Yingying; Succop, Paul; Yolton, Kimberly
2012-01-01
Summary Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants. NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined. Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles. In conclusion, three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations. PMID:22686386
Mahamad Maifiah, Mohd Hafidz; Cheah, Soon-Ee; Johnson, Matthew D.; Han, Mei-Ling; Boyce, John D.; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S.; Hertzog, Paul; Purcell, Anthony W.; Song, Jiangning; Velkov, Tony; Creek, Darren J.; Li, Jian
2016-01-01
Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii. PMID:26924392
Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian
2016-02-29
Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.
Worrell, Frank C; Andretta, James R; Woodland, Malcolm H
2014-10-01
In this study, we examined the internal consistency and structural validity of Cross Racial Identity Scale (CRIS) scores in a sample of 477 African American adolescents who had been arrested in a city in the mid-Atlantic. Using cluster analysis, we also identified profiles of CRIS scores and compared adolescents with different profiles on Major Depressive Episode, Manic Episode, Generalized Anxiety Disorder, and Obsessive-Compulsive Disorder scores. Results indicated that CRIS subscale scores were reliable, and the 6-factor structure of the CRIS was supported. Five nigrescence profiles were identified: Miseducation-Pro-Black, Conflicted-Self-Hatred, Multiculturalist, Low Race Salience, and Conflicted-Anti-White. Individuals with Conflicted-Self-Hatred profiles reported significantly and meaningfully higher scores on the 4 syndromes than did their peers, and individuals with the Multiculturalist and Low Race Salience profiles reported the lowest scores. A greater percentage of individuals with Conflicted racial identity profiles had syndrome scores in the clinically significant range. The results of this study demonstrate that some of the nigrescence profiles found in college-age students generalize to adolescents. The implications of the findings for theory, research, and practice are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Testing job typologies and identifying at-risk subpopulations using factor mixture models.
Keller, Anita C; Igic, Ivana; Meier, Laurenz L; Semmer, Norbert K; Schaubroeck, John M; Brunner, Beatrice; Elfering, Achim
2017-10-01
Research in occupational health psychology has tended to focus on the effects of single job characteristics or various job characteristics combined into 1 factor. However, such a variable-centered approach does not account for the clustering of job attributes among groups of employees. We addressed this issue by using a person-centered approach to (a) investigate the occurrence of different empirical constellations of perceived job stressors and resources and (b) validate the meaningfulness of profiles by analyzing their association with employee well-being and performance. We applied factor mixture modeling to identify profiles in 4 large samples consisting of employees in Switzerland (Studies 1 and 2) and the United States (Studies 3 and 4). We identified 2 profiles that spanned the 4 samples, with 1 reflecting a combination of relatively low stressors and high resources (P1) and the other relatively high stressors and low resources (P3). The profiles differed mainly in terms of their organizational and social aspects. Employees in P1 reported significantly higher mean levels of job satisfaction, performance, and general health, and lower means in exhaustion compared with P3. Additional analyses showed differential relationships between job attributes and outcomes depending on profile membership. These findings may benefit organizational interventions as they show that perceived work stressors and resources more strongly influence satisfaction and well-being in particular profiles. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Liver microRNA profile of induced allograft tolerance
Vitalone, Matthew James; Wai, Liang; Fujiki, Masato; Lau, Audrey H.; Littau, Erik; Esquivel, Carlos; Martinez, Olivia M.; Krams, Sheri M.
2016-01-01
Introduction Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total Lymphoid Irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance. Methods To identify the miRNAs associated with TLI-induced tolerance we examined syngeneic recipients (Lewis→Lewis) and allogeneic recipients (DA→Lewis) of orthotropic liver transplants that received post-transplant TLI, allogeneic recipients that were not treated post-transplantation and experienced acute rejection, and native DA livers. QPCR miRNA array cards were used to profile liver grafts. Results We identified 12 miRNAs that were specifically and significantly increased during acute rejection. In early tolerance, 33 miRNAs were altered compared to syngeneic livers, with 80% of the miRNAs increased. In established tolerance 42 miRNAs were altered. In addition, miR-142-5p and miR-181a demonstrated increased expression in tolerant livers (both early and established tolerance) as compared to syngeneic livers. A principal component analysis of all miRNAs assayed, demonstrated a profile in established tolerance that was closely related to that seen in syngeneic livers. Conclusions The miRNA profile of established tolerant allografts is very similar to syngeneic grafts suggesting tolerance may be a return to an immunological state of quiescence. PMID:26950716
2010-01-01
Background Accurate identification is necessary to discriminate harmless environmental Yersinia species from the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis and from the group A bioterrorism plague agent Yersinia pestis. In order to circumvent the limitations of current phenotypic and PCR-based identification methods, we aimed to assess the usefulness of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) protein profiling for accurate and rapid identification of Yersinia species. As a first step, we built a database of 39 different Yersinia strains representing 12 different Yersinia species, including 13 Y. pestis isolates representative of the Antiqua, Medievalis and Orientalis biotypes. The organisms were deposited on the MALDI-TOF plate after appropriate ethanol-based inactivation, and a protein profile was obtained within 6 minutes for each of the Yersinia species. Results When compared with a 3,025-profile database, every Yersinia species yielded a unique protein profile and was unambiguously identified. In the second step of analysis, environmental and clinical isolates of Y. pestis (n = 2) and Y. enterocolitica (n = 11) were compared to the database and correctly identified. In particular, Y. pestis was unambiguously identified at the species level, and MALDI-TOF was able to successfully differentiate the three biotypes. Conclusion These data indicate that MALDI-TOF can be used as a rapid and accurate first-line method for the identification of Yersinia isolates. PMID:21073689
Wimmer, Helge; Gundacker, Nina C; Griss, Johannes; Haudek, Verena J; Stättner, Stefan; Mohr, Thomas; Zwickl, Hannes; Paulitschke, Verena; Baron, David M; Trittner, Wolfgang; Kubicek, Markus; Bayer, Editha; Slany, Astrid; Gerner, Christopher
2009-06-01
Interpretation of proteome data with a focus on biomarker discovery largely relies on comparative proteome analyses. Here, we introduce a database-assisted interpretation strategy based on proteome profiles of primary cells. Both 2-D-PAGE and shotgun proteomics are applied. We obtain high data concordance with these two different techniques. When applying mass analysis of tryptic spot digests from 2-D gels of cytoplasmic fractions, we typically identify several hundred proteins. Using the same protein fractions, we usually identify more than thousand proteins by shotgun proteomics. The data consistency obtained when comparing these independent data sets exceeds 99% of the proteins identified in the 2-D gels. Many characteristic differences in protein expression of different cells can thus be independently confirmed. Our self-designed SQL database (CPL/MUW - database of the Clinical Proteomics Laboratories at the Medical University of Vienna accessible via www.meduniwien.ac.at/proteomics/database) facilitates (i) quality management of protein identification data, which are based on MS, (ii) the detection of cell type-specific proteins and (iii) of molecular signatures of specific functional cell states. Here, we demonstrate, how the interpretation of proteome profiles obtained from human liver tissue and hepatocellular carcinoma tissue is assisted by the Clinical Proteomics Laboratories at the Medical University of Vienna-database. Therefore, we suggest that the use of reference experiments supported by a tailored database may substantially facilitate data interpretation of proteome profiling experiments.
Ayyadurai, Saravanan; Flaudrops, Christophe; Raoult, Didier; Drancourt, Michel
2010-11-12
Accurate identification is necessary to discriminate harmless environmental Yersinia species from the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis and from the group A bioterrorism plague agent Yersinia pestis. In order to circumvent the limitations of current phenotypic and PCR-based identification methods, we aimed to assess the usefulness of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) protein profiling for accurate and rapid identification of Yersinia species. As a first step, we built a database of 39 different Yersinia strains representing 12 different Yersinia species, including 13 Y. pestis isolates representative of the Antiqua, Medievalis and Orientalis biotypes. The organisms were deposited on the MALDI-TOF plate after appropriate ethanol-based inactivation, and a protein profile was obtained within 6 minutes for each of the Yersinia species. When compared with a 3,025-profile database, every Yersinia species yielded a unique protein profile and was unambiguously identified. In the second step of analysis, environmental and clinical isolates of Y. pestis (n = 2) and Y. enterocolitica (n = 11) were compared to the database and correctly identified. In particular, Y. pestis was unambiguously identified at the species level, and MALDI-TOF was able to successfully differentiate the three biotypes. These data indicate that MALDI-TOF can be used as a rapid and accurate first-line method for the identification of Yersinia isolates.
Killoren, Sarah E.; De Jesús, Sue A. Rodríguez; Updegraff, Kimberly A.; Wheeler, Lorey A.
2015-01-01
We examined profiles of sibling relationship qualities in 246 Mexican-origin families living in the United States using latent profile analyses. Three profiles were identified: Positive, Negative and Affect-Intense. Links between profiles and youths’ familism values and adjustment were assessed using longitudinal data. Siblings in the Positive profile reported the highest familism values, followed by siblings in the Affect-Intense profile and, finally, siblings in the Negative profile. Older siblings in the Positive and Affect-Intense profiles reported fewer depressive symptoms than siblings in the Negative profile. Further, in the Positive and Negative profiles, older siblings reported less involvement in risky behaviors than younger siblings. In the Negative profile, younger siblings reported greater sexual risk behaviors in late adolescence than older siblings; siblings in opposite-sex dyads, as compared to same-sex dyads, engaged in riskier sexual behaviors. Our findings highlight sibling relationship quality as promotive and risky, depending on sibling characteristics and adjustment outcomes. PMID:28239217
Killoren, Sarah E; De Jesús, Sue A Rodríguez; Updegraff, Kimberly A; Wheeler, Lorey A
2017-03-01
We examined profiles of sibling relationship qualities in 246 Mexican-origin families living in the United States using latent profile analyses. Three profiles were identified: Positive , Negative and Affect-Intense . Links between profiles and youths' familism values and adjustment were assessed using longitudinal data. Siblings in the Positive profile reported the highest familism values, followed by siblings in the Affect-Intense profile and, finally, siblings in the Negative profile. Older siblings in the Positive and Affect-Intense profiles reported fewer depressive symptoms than siblings in the Negative profile. Further, in the Positive and Negative profiles, older siblings reported less involvement in risky behaviors than younger siblings. In the Negative profile, younger siblings reported greater sexual risk behaviors in late adolescence than older siblings; siblings in opposite-sex dyads, as compared to same-sex dyads, engaged in riskier sexual behaviors. Our findings highlight sibling relationship quality as promotive and risky, depending on sibling characteristics and adjustment outcomes.
Quality Control of Wind Data from 50-MHz Doppler Radar Wind Profiler
NASA Technical Reports Server (NTRS)
Vacek, Austin
2016-01-01
Upper-level wind profiles obtained from a 50-MHz Doppler Radar Wind Profiler (DRWP) instrument at Kennedy Space Center are incorporated in space launch vehicle design and day-of-launch operations to assess wind effects on the vehicle during ascent. Automated and manual quality control (QC) techniques are implemented to remove spurious data in the upper-level wind profiles caused from atmospheric and non-atmospheric artifacts over the 2010-2012 period of record (POR). By adding the new quality controlled profiles with older profiles from 1997-2009, a robust database will be constructed of upper-level wind characteristics. Statistical analysis will determine the maximum, minimum, and 95th percentile of the wind components from the DRWP profiles over recent POR and compare against the older database. Additionally, this study identifies specific QC flags triggered during the QC process to understand how much data is retained and removed from the profiles.
Quality Control of Wind Data from 50-MHz Doppler Radar Wind Profiler
NASA Technical Reports Server (NTRS)
Vacek, Austin
2015-01-01
Upper-level wind profiles obtained from a 50-MHz Doppler Radar Wind Profiler (DRWP) instrument at Kennedy Space Center are incorporated in space launch vehicle design and day-of-launch operations to assess wind effects on the vehicle during ascent. Automated and manual quality control (QC) techniques are implemented to remove spurious data in the upper-level wind profiles caused from atmospheric and non-atmospheric artifacts over the 2010-2012 period of record (POR). By adding the new quality controlled profiles with older profiles from 1997-2009, a robust database will be constructed of upper-level wind characteristics. Statistical analysis will determine the maximum, minimum, and 95th percentile of the wind components from the DRWP profiles over recent POR and compare against the older database. Additionally, this study identifies specific QC flags triggered during the QC process to understand how much data is retained and removed from the profiles.
Flåm, Siri Tennebø; Gunnarsson, Ragnar; Garen, Torhild; Lie, Benedicte Alexandra; Molberg, Øyvind
2015-03-01
The Norwegian nationwide MCTD cohort was established to obtain unbiased data on key disease issues, and thereby reappraise the concept of MCTD. In the current study, the aims were to obtain detailed HLA profile data on the large Norwegian MCTD cohort and compare these with the HLA profiles of ethnically matched healthy controls and related CTD controls. HLA profiles, determined by sequence-based typing of HLA-B* and DRB1*, were compared between four control groups of Norwegian ancestry, SLE (n = 96), SSc (n = 95), PM/DM (n = 84), healthy individuals (n = 282), the complete MCTD cohort (n = 155) and MCTD subsets defined by key clinical parameters. HLA-B*08 [odds ratio (OR) 2.05, P = 1.31 × 10(-4)) and DRB1*04:01 (OR 2.82, P = 3.64 × 10(-8)) were identified as risk alleles for MCTD, while DRB1*04:04, DRB1*13:01 and DRB1*13:02 were protective. Risk alleles for SLE and PM/DM were B*08 and DRB1*03:01. SSc risk was associated with DRB1*08:01. Analyses of MCTD subsets identified B*18 [OR 3.32 (95% CI 1.38, 8.01)] and DRB1*03:01 [OR 1.83 (95% CI 1.03, 3.25)] as independent risk factors for lung fibrosis. Novel HLA alleles associated with MCTD and disease subsets were identified and DRB1*04:01 was confirmed as a major risk allele. Altogether, the data reinforce the notion of MCTD as a disease entity distinct from SLE, SSc and PM/DM. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Janssen, Eveline P C J; de Vugt, Marjolein; Köhler, Sebastian; Wolfs, Claire; Kerpershoek, Liselot; Handels, Ron L H; Orrell, Martin; Woods, Bob; Jelley, Hannah; Stephan, Astrid; Bieber, Anja; Meyer, Gabriele; Engedal, Knut; Selbaek, Geir; Wimo, Anders; Irving, Kate; Hopper, Louise; Gonçalves-Pereira, Manuel; Portolani, Elisa; Zanetti, Orazio; Verhey, Frans R
2017-01-01
To identify caregiver profiles of persons with mild to moderate dementia and to investigate differences between identified caregiver profiles, using baseline data of the international prospective cohort study Actifcare. A latent class analysis was used to discover different caregiver profiles based on disease related characteristics of 453 persons with dementia and their 453 informal caregivers. These profiles were compared with regard to quality of life (CarerQoL score), depressive symptoms (HADS-D score) and perseverance time. A 5-class model was identified, with the best Bayesian Information Criterion value, significant likelihood ratio test (p < 0.001), high entropy score (0.88) and substantive interpretability. The classes could be differentiated on two axes: (i) caregivers' age, relationship with persons with dementia, severity of dementia, and (ii) tendency towards stress and difficulty adapting to stress. Classes showed significant differences with all dependent variables, and were labelled 'older low strain', 'older intermediate strain', 'older high strain', 'younger low strain' and 'younger high strain'. Differences exist between types of caregivers that explain variability in quality of life, depressive symptoms and perseverance time. Our findings may give direction for tailored interventions for caregivers of persons with dementia, which may improve social health and reduce health care costs.
Bader, Sabine; Zajac, Magdalena; Friess, Thomas; Ruge, Elisabeth; Rieder, Natascha; Gierke, Berthold; Heubach, Yvonne; Thomas, Marlene; Pawlak, Michael
2015-01-01
Reverse phase protein arrays (RPPA) are an established tool for measuring the expression and activation status of multiple proteins in parallel using only very small amounts of tissue. Several studies have demonstrated the value of this technique for signaling pathway analysis using proteins extracted from fresh frozen (FF) tissue in line with validated antibodies for this tissue type; however, formalin fixation and paraffin embedding (FFPE) is the standard method for tissue preservation in the clinical setting. Hence, we performed RPPA to measure profiles for a set of 300 protein markers using matched FF and FFPE tissue specimens to identify which markers performed similarly using the RPPA technique in fixed and unfixed tissues. Protein lysates were prepared from matched FF and FFPE tissue specimens of individual tumors taken from three different xenograft models of human cancer. Materials from both untreated mice and mice treated with either anti-HER3 or bispecific anti-IGF-1R/EGFR monoclonal antibodies were analyzed. Correlations between signals from FF and FFPE tissue samples were investigated. Overall, 60 markers were identified that produced comparable profiles between FF and FFPE tissues, demonstrating significant correlation between the two sample types. The top 25 markers also showed significance after correction for multiple testing. The panel of markers covered several clinically relevant tumor signaling pathways and both phosphorylated and nonphosphorylated proteins were represented. Biologically relevant changes in marker expression were noted when RPPA profiles from treated and untreated xenografts were compared. These data demonstrate that, using appropriately selected antibodies, RPPA analysis from FFPE tissue is well feasible and generates biologically meaningful information. The identified panel of markers that generate similar profiles in matched fixed and unfixed tissue samples may be clinically useful for pharmacodynamic studies of drug effect using FFPE tissues. PMID:26106084
Kumar, Sanjay; Shankar, Binoy; Arya, Sugandha; Deb, Manorma; Chellani, Harish
Healthcare-associated infections (HAI) are frequent complications in neonatal intensive care units (NICU) with varying risk factors and bacteriological profile. There is paucity of literature comparing the bacteriological profile of organisms causing HAI with the environmental surveillance isolates. Therefore, this study aimed to evaluate demographic profile, risk factors and outcome of HAI in NICU and correlate with environmental surveillance. Three hundred newborns with signs and symptoms of sepsis were enrolled in the study group and their profile, risk factors and outcome were compared with the control group. Univariate analysis and multivariable logistic regression were performed. Environmental surveillance results were compared to the bacteriological profile of HAIs. We identified lower gestational age, male gender and apgar score less than 7 at 5min, use of peripheral vascular catheter & ventilator along with their duration as significant risk factors. Mortality rate was 29% in the study group (p<0.05). The HAI site distribution showed blood-stream infections (73%) to be the most common followed by pneumonia (12%) and meningitis (10%). Gram positive cocci were the most common isolates in HAI as well as environmental surveillance. The bacteriological profile of HAI correlates with the environmental surveillance report thus insisting for periodic surveillance and thereby avoiding irrational antibiotic usage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Bucci, Sandra; Emsley, Richard; Berry, Katherine
2017-01-01
Attachment has been identified as one of various possible mechanisms involved in understanding models of psychosis, but measures that reliably and validly assess attachment styles in psychosis are limited. The aim of this study was to identify attachment patterns in psychosis and examine demographic and clinical correlates across attachment groups. Latent profile analysis on attachment data from 588 participants who met criteria for non-affective psychosis was used to classify people into attachment classes. Four latent classes of attachment were identified: secure, insecure-anxious, insecure-avoidant and disorganised. Secure attachment was the most common attachment style, suggesting that a significant number of clients with psychosis are inherently resilient. Disorganised attachment was associated with a higher proportion of sexual and physical abuse and more severe positive symptoms compared to other attachment classes. This is not only the largest study to examine attachment styles, their demographic and clinical profile, and the clinical profile of disorganised attachment more specifically, in psychosis, but also the first study to use a validated self-report measure of attachment in psychosis to identify four classes of attachment style. Findings advance developmental models of attachment and psychosis; participants with disorganised attachment report more frequent trauma history and more severe psychotic symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Jing, Jin; Ma, Jun; Chen, Yajun; Li, Xiuhong; Yang, Wenhan; Guo, Li; Jin, Yu
2016-01-01
Background Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) are used in screening and predicting obesity in adults. However, the best identifier of metabolic complications in children with obesity remains unclear. This study evaluated lipid profile distribution and investigated the best anthropometric parameter in association with lipid disorders in children with obesity. Methods A total of 2243 school children aged 7–17 years were enrolled in Guangzhou, China, in 2014. The anthropometric indices and lipid profiles were measured. Dyslipidemia was defined according to the US Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. The association between anthropometry (BMI, WC, and WHR) and lipid profile values was examined using chi-square analysis and discriminant function analysis. Information about demography, physical activity, and dietary intake was provided by the participant children and their parents. Results Children aged 10–14 and 15–17 years old generally had higher triglyceride values but lower median concentration of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol compared with children aged 7–9 years old (all P < 0.001). These lipid parameters fluctuated in children aged 10–14 years old. The combination of age groups, BMI, WC and WHR achieved 65.1% accuracy in determining dyslipidemic disorders. BMI correctly identified 77% of the total dyslipidemic disorders in obese children, which was higher than that by WHR (70.8%) (P< 0.05). Conclusion The distribution of lipid profiles in Chinese children differed between younger and older age groups, and the tendency of these lipid levels remarkably fluctuated during 10 to 14 years old. BMI had better practical utility in identifying dyslipidemia among school-aged children with obesity compared with other anthropometric measures. PMID:26963377
Alevizos, Ilias; Alexander, Stefanie; Turner, R. James; Illei, Gabor G.
2013-01-01
Objective MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjögren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction. Methods MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA. MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA. Results MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes. Conclusion Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers. PMID:21280008
Zhu, Yanna; Shao, Zixian; Jing, Jin; Ma, Jun; Chen, Yajun; Li, Xiuhong; Yang, Wenhan; Guo, Li; Jin, Yu
2016-01-01
Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) are used in screening and predicting obesity in adults. However, the best identifier of metabolic complications in children with obesity remains unclear. This study evaluated lipid profile distribution and investigated the best anthropometric parameter in association with lipid disorders in children with obesity. A total of 2243 school children aged 7-17 years were enrolled in Guangzhou, China, in 2014. The anthropometric indices and lipid profiles were measured. Dyslipidemia was defined according to the US Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. The association between anthropometry (BMI, WC, and WHR) and lipid profile values was examined using chi-square analysis and discriminant function analysis. Information about demography, physical activity, and dietary intake was provided by the participant children and their parents. Children aged 10-14 and 15-17 years old generally had higher triglyceride values but lower median concentration of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol compared with children aged 7-9 years old (all P < 0.001). These lipid parameters fluctuated in children aged 10-14 years old. The combination of age groups, BMI, WC and WHR achieved 65.1% accuracy in determining dyslipidemic disorders. BMI correctly identified 77% of the total dyslipidemic disorders in obese children, which was higher than that by WHR (70.8%) (P< 0.05). The distribution of lipid profiles in Chinese children differed between younger and older age groups, and the tendency of these lipid levels remarkably fluctuated during 10 to 14 years old. BMI had better practical utility in identifying dyslipidemia among school-aged children with obesity compared with other anthropometric measures.
Severgnini, Marco; Bicciato, Silvio; Mangano, Eleonora; Scarlatti, Francesca; Mezzelani, Alessandra; Mattioli, Michela; Ghidoni, Riccardo; Peano, Clelia; Bonnal, Raoul; Viti, Federica; Milanesi, Luciano; De Bellis, Gianluca; Battaglia, Cristina
2006-06-01
Meta-analysis of microarray data is increasingly important, considering both the availability of multiple platforms using disparate technologies and the accumulation in public repositories of data sets from different laboratories. We addressed the issue of comparing gene expression profiles from two microarray platforms by devising a standardized investigative strategy. We tested this procedure by studying MDA-MB-231 cells, which undergo apoptosis on treatment with resveratrol. Gene expression profiles were obtained using high-density, short-oligonucleotide, single-color microarray platforms: GeneChip (Affymetrix) and CodeLink (Amersham). Interplatform analyses were carried out on 8414 common transcripts represented on both platforms, as identified by LocusLink ID, representing 70.8% and 88.6% of annotated GeneChip and CodeLink features, respectively. We identified 105 differentially expressed genes (DEGs) on CodeLink and 42 DEGs on GeneChip. Among them, only 9 DEGs were commonly identified by both platforms. Multiple analyses (BLAST alignment of probes with target sequences, gene ontology, literature mining, and quantitative real-time PCR) permitted us to investigate the factors contributing to the generation of platform-dependent results in single-color microarray experiments. An effective approach to cross-platform comparison involves microarrays of similar technologies, samples prepared by identical methods, and a standardized battery of bioinformatic and statistical analyses.
Zhao, Lihua; He, Jiangman; Cai, Hanyang; Lin, Haiyan; Li, Yanqiang; Liu, Renyi; Yang, Zhenbiao; Qin, Yuan
2014-11-01
Megasporogenesis is essential for female fertility, and requires the accomplishment of meiosis and the formation of functional megaspores. The inaccessibility and low abundance of female meiocytes make it particularly difficult to elucidate the molecular basis underlying megasporogenesis. We used high-throughput tag-sequencing analysis to identify genes expressed in female meiocytes (FMs) by comparing gene expression profiles from wild-type ovules undergoing megasporogenesis with those from the spl mutant ovules, which lack megasporogenesis. A total of 862 genes were identified as FMs, with levels that are consistently reduced in spl ovules in two biological replicates. Fluorescence-assisted cell sorting followed by RNA-seq analysis of DMC1:GFP-labeled female meiocytes confirmed that 90% of the FMs are indeed detected in the female meiocyte protoplast profiling. We performed reverse genetic analysis of 120 candidate genes and identified four FM genes with a function in female meiosis progression in Arabidopsis. We further revealed that KLU, a putative cytochrome P450 monooxygenase, is involved in chromosome pairing during female meiosis, most likely by affecting the normal expression pattern of DMC1 in ovules during female meiosis. Our studies provide valuable information for functional genomic analyses of plant germline development as well as insights into meiosis. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.
Tai, Helen H; Worrall, Kraig; Pelletier, Yvan; De Koeyer, David; Calhoun, Larry A
2014-09-10
The Colorado potato beetle Leptinotarsa decemlineata (Say) (CPB) is a coleopteran herbivore that feeds on the foliage on Solanum species, in particular, potato. Six resistant wild Solanum species were identified, and two of these species had low levels of glycoalkaloids. Comparative analysis of the untargeted metabolite profiles of the foliage using UPLC-qTOF-MS was done to find metabolites shared between the wild species but not with Solanum tuberosum (L.) to identify resistance-related metabolites. It was found that only S. tuberosum produced the triose glycoalkaloids solanine and chaconine. Instead, the six wild species produced glycoalkaloids that shared in common tetrose sugar side chains. Additionally, there were non-glycoalkaloid metabolites associated with resistance including hydroxycoumarin and a phenylpropanoid, which were produced in all wild species but not in S. tuberosum.
Serum Biochemical Phenotypes in the Domestic Dog
Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.
2016-01-01
The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479
2011-01-01
Background Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms of pain generation. The aims were (1) to compare epidemiological features and co-morbidities and (2) to identify similarities and differences of sensory symptoms in both entities. Methods The present multi-center study compares epidemiological data and sensory symptoms of a large cohort of 1434 fibromyalgia patients and 1623 patients with painful diabetic neuropathy. Data acquisition included standard demographic questions and self-report questionnaires (MOS sleep scale, PHQ-9, PainDETECT). To identify subgroups of patients with characteristic combinations of symptoms (sensory profiles) a cluster analysis was performed using all patients in both cohorts. Results Significant differences in co-morbidities (depression, sleep disturbance) were found between both disorders. Patients of both aetiologies chose very similar descriptors to characterize their sensory perceptions. Burning pain, prickling and touch-evoked allodynia were present in the same frequency. Five subgroups with distinct symptom profiles could be detected. Two of the subgroups were characteristic for fibromyalgia whereas one profile occurred predominantly in DPN patients. Two profiles were found frequently in patients of both entities (20-35%). Conclusions DPN and fibromyalgia patients experience very similar sensory phenomena. The combination of sensory symptoms - the sensory profile - is in most cases distinct and almost unique for each one of the two entities indicating aetiology-specific mechanisms of symptom generation. Beside the unique aetiology-specific sensory profiles an overlap of sensory profiles can be found in 20-35% of patients of both aetiologies. PMID:21612589
The Subglacial Drainage Patterns of Devon Island, Canada
NASA Astrophysics Data System (ADS)
Grau Galofre, A.; Jellinek, M.; Osinski, G. R.
2016-12-01
Meltwater drainage patterns incised underneath ice masses can appear strikingly similar to fluvially dissected landscapes. We introduce a landscape evolution model to describe the longitudinal profiles of subglacial meltwater channels (tunnel valleys).We propose a way to identify them from topography data and imagery on the basis of the vertical scale of undulations compared to the total elevation gain. We test the model with field data from tunnel valleys exposed in Devon Island, NU, Canada. We use field measurements of longitudinal profiles, photogrammetry and 3D LIDAR to establish a quantitative comparison of tunnel valleys and fluvial channels. Tunnel valleys are oriented parallel to former ice flow lines and are characterized by undulating longitudinal profiles. We use these features to identify quantitatively tunnel valleys in central Devon Island (figure 1). We ground truth our observations with imagery of tunnel valleys appearing at the edges of the actively retreating ice cap. Longitudinal profiles show undulations with amplitudes up to 14m over a total elevation gain of 20m and with wavelengths comparable to the channel width. These "overdeepenings" are not observed in any fluvial channels in the area and are consistent with expectations of flow driven by variations in ice thickness. Our identification scheme rigorously distinguishes fluvial and subglacial dissected landscapes.
Nahum, Amit; Brener, Avivit; Granot, Ettie
2015-11-01
Severe allergic reaction to food following liver transplantation is a well-known phenomenon. However, the mechanisms underlying this phenomenon are not yet elucidated. This study aimed to reveal the nature of the immune response in post-transplanted allergic patients and compare them to non-allergic transplanted as well as allergic and non-allergic control subjects, with focus on cytokine milieu. Post-liver transplant patients with and without allergic reactions as well as food-allergic but otherwise healthy and healthy non-allergic control patients were recruited. We reviewed patient records and routine laboratory tests and assayed subjects' PBMCs, studying cytokine secretion profile in response to different stimuli. Post-transplant patients with food allergy showed a unique cytokine profile in response to various stimuli, with extremely elevated IL-5, low IL-10 secretion, and somewhat higher IFN-γ. T regulatory cell number was not significantly different among the groups of patients and controls. Immune response of food-allergic post-liver transplant patients is identified by a unique cytokine profile when compared to allergic but otherwise healthy individuals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Gu, Fenglin; Chen, Yonggan; Fang, Yiming; Wu, Guiping; Tan, Lehe
2015-10-09
Colonizing Bacillus in vanilla (Vanilla planifolia Andrews) beans is involved in glucovanillin hydrolysis and vanillin formation during conventional curing. The flavor profiles of vanilla beans under Bacillus-assisted curing were analyzed through gas chromatography-mass spectrometry, electronic nose, and quantitative sensory analysis. The flavor profiles were analytically compared among the vanilla beans under Bacillus-assisted curing, conventional curing, and non-microorganism-assisted curing. Vanilla beans added with Bacillus vanillea XY18 and Bacillus subtilis XY20 contained higher vanillin (3.58%±0.05% and 3.48%±0.10%, respectively) than vanilla beans that underwent non-microorganism-assisted curing and conventional curing (3.09%±0.14% and 3.21%±0.15%, respectively). Forty-two volatiles were identified from endogenous vanilla metabolism. Five other compounds were identified from exogenous Bacillus metabolism. Electronic nose data confirmed that vanilla flavors produced through the different curing processes were easily distinguished. Quantitative sensory analysis confirmed that Bacillus-assisted curing increased vanillin production without generating any unpleasant sensory attribute. Partial least squares regression further provided a correlation model of different measurements. Overall, we comparatively analyzed the flavor profiles of vanilla beans under Bacillus-assisted curing, indirectly demonstrated the mechanism of vanilla flavor formation by microbes.
The psychosocial profile of adolescent risk of homelessness.
Bearsley-Smith, Cate A; Bond, Lyndal M; Littlefield, Lyn; Thomas, Lyndal R
2008-06-01
To contrast the psychosocial profile of adolescents with risk factors for homelessness, identified using Chamberlain and MacKenzie's self-report scale, compared to the profiles of homeless adolescents. Multinomial logistic regression analyses were conducted contrasting profiles for (a) 137 homeless adolescents, (b) 766 secondary students reporting risk factors for homelessness, and (c) 4,844 students not reporting risks for homelessness. Fourteen percent of a representative population of at-school adolescents, from Victoria, Australia, showed elevated risk of homelessness. These adolescents showed depressive symptoms at least equivalent to homeless adolescents (RR 6.0, 95% CI: 4.9, 7.3, and RR 3.5, 95% CI: 2.1, 5.8, respectively). In multivariate analyses, homeless and at risk adolescents reported equivalent levels of family conflict, early problem behaviour and low opportunities and rewards for family involvement. Compared to adolescents not at risk, at risk adolescents were more likely to be female and to show poorer social skills/assertiveness and depressive symptoms. Compared to at risk adolescents, homeless adolescents showed additional family, school, peer and individual risks, but lower depressive symptomatology. The findings highlight the potential we have to quickly and simply detect adolescents showing significant risk of homelessness. This sizable minority of adolescents report risks often equivalent to homeless adolescents. It is hoped that stakeholders working with young people will utilise this screening potential to identify and intervene effectively with this significant subpopulation of youth, and their families, while they are still at home and school.
Geisner, Irene M; Mallett, Kimberly; Varvil-Weld, Lindsey; Ackerman, Sarah; Trager, Bradley M; Turrisi, Rob
2018-03-01
Research has identified college students who experience depressed mood and consume alcohol are at an increased risk for experiencing alcohol problems. The present study identified profiles of differential alcohol use, depression, key psychosocial indicators of drinking (e.g., normative perceptions) and examined the relationship between these profiles and alcohol-related consequences. Students with a history of risky drinking and elevated depressed mood (n=311; 62.4% female) completed a web-based survey assessing typical and peak drinking, depressive symptoms, descriptive norms, drinking to cope motives, protective behavioral strategies, and alcohol-related consequences. Latent profile analysis was used to classify participants into distinct profiles focusing on alcohol use patterns and level of depressed mood and drinking related constructs. Profiles were then compared based on their association with reported rates of alcohol-related consequences. Four profiles emerged: 1) Mild Depression, Heavy Drinkers; 2) Mild Depression, Severe Drinkers; 3) Moderate Depression, Heavy Drinkers; and 4) Moderate Depression, Severe Drinkers. Findings revealed significant differences between the four profiles on both risky drinking and alcohol-related consequences. These findings suggest the importance of assessing and addressing depressive symptoms among college students in order to reduce rates of risky drinking and alcohol-related consequences. Copyright © 2017 Elsevier Ltd. All rights reserved.
Ahmad, Tariq; Desai, Nihar; Wilson, Francis; Schulte, Phillip; Dunning, Allison; Jacoby, Daniel; Allen, Larry; Fiuzat, Mona; Rogers, Joseph; Felker, G Michael; O'Connor, Christopher; Patel, Chetan B
2016-01-01
Classification of acute decompensated heart failure (ADHF) is based on subjective criteria that crudely capture disease heterogeneity. Improved phenotyping of the syndrome may help improve therapeutic strategies. To derive cluster analysis-based groupings for patients hospitalized with ADHF, and compare their prognostic performance to hemodynamic classifications derived at the bedside. We performed a cluster analysis on baseline clinical variables and PAC measurements of 172 ADHF patients from the ESCAPE trial. Employing regression techniques, we examined associations between clusters and clinically determined hemodynamic profiles (warm/cold/wet/dry). We assessed association with clinical outcomes using Cox proportional hazards models. Likelihood ratio tests were used to compare the prognostic value of cluster data to that of hemodynamic data. We identified four advanced HF clusters: 1) male Caucasians with ischemic cardiomyopathy, multiple comorbidities, lowest B-type natriuretic peptide (BNP) levels; 2) females with non-ischemic cardiomyopathy, few comorbidities, most favorable hemodynamics; 3) young African American males with non-ischemic cardiomyopathy, most adverse hemodynamics, advanced disease; and 4) older Caucasians with ischemic cardiomyopathy, concomitant renal insufficiency, highest BNP levels. There was no association between clusters and bedside-derived hemodynamic profiles (p = 0.70). For all adverse clinical outcomes, Cluster 4 had the highest risk, and Cluster 2, the lowest. Compared to Cluster 4, Clusters 1-3 had 45-70% lower risk of all-cause mortality. Clusters were significantly associated with clinical outcomes, whereas hemodynamic profiles were not. By clustering patients with similar objective variables, we identified four clinically relevant phenotypes of ADHF patients, with no discernable relationship to hemodynamic profiles, but distinct associations with adverse outcomes. Our analysis suggests that ADHF classification using simultaneous considerations of etiology, comorbid conditions, and biomarker levels, may be superior to bedside classifications.
Kim, Jaehee; Ogden, Robert Todd; Kim, Haseong
2013-10-18
Time course gene expression experiments are an increasingly popular method for exploring biological processes. Temporal gene expression profiles provide an important characterization of gene function, as biological systems are both developmental and dynamic. With such data it is possible to study gene expression changes over time and thereby to detect differential genes. Much of the early work on analyzing time series expression data relied on methods developed originally for static data and thus there is a need for improved methodology. Since time series expression is a temporal process, its unique features such as autocorrelation between successive points should be incorporated into the analysis. This work aims to identify genes that show different gene expression profiles across time. We propose a statistical procedure to discover gene groups with similar profiles using a nonparametric representation that accounts for the autocorrelation in the data. In particular, we first represent each profile in terms of a Fourier basis, and then we screen out genes that are not differentially expressed based on the Fourier coefficients. Finally, we cluster the remaining gene profiles using a model-based approach in the Fourier domain. We evaluate the screening results in terms of sensitivity, specificity, FDR and FNR, compare with the Gaussian process regression screening in a simulation study and illustrate the results by application to yeast cell-cycle microarray expression data with alpha-factor synchronization.The key elements of the proposed methodology: (i) representation of gene profiles in the Fourier domain; (ii) automatic screening of genes based on the Fourier coefficients and taking into account autocorrelation in the data, while controlling the false discovery rate (FDR); (iii) model-based clustering of the remaining gene profiles. Using this method, we identified a set of cell-cycle-regulated time-course yeast genes. The proposed method is general and can be potentially used to identify genes which have the same patterns or biological processes, and help facing the present and forthcoming challenges of data analysis in functional genomics.
Bresolin, Silvia; Marconato, Laura; Comazzi, Stefano; Te Kronnie, Geertruy; Aresu, Luca
2014-01-01
Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs) by high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL. PMID:25372838
Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Muir, Kenneth; Schleutker, Johanna; Henderson, Brian E; Haiman, Christopher A; Schumacher, Fredrick R; Pashayan, Nora; Pharoah, Paul D P; Ostrander, Elaine A; Stanford, Janet L; Batra, Jyotsna; Clements, Judith A; Chambers, Suzanne K; Weischer, Maren; Nordestgaard, Børge G; Ingles, Sue A; Sorensen, Karina D; Orntoft, Torben F; Park, Jong Y; Cybulski, Cezary; Maier, Christiane; Doerk, Thilo; Dickinson, Joanne L; Cannon-Albright, Lisa; Brenner, Hermann; Rebbeck, Timothy R; Zeigler-Johnson, Charnita; Habuchi, Tomonori; Thibodeau, Stephen N; Cooney, Kathleen A; Chappuis, Pierre O; Hutter, Pierre; Kaneva, Radka P; Foulkes, William D; Zeegers, Maurice P; Lu, Yong-Jie; Zhang, Hong-Wei; Stephenson, Robert; Cox, Angela; Southey, Melissa C; Spurdle, Amanda B; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L; Lophatonanon, Aritaya; Rinckleb, Antje E; Kote-Jarai, Zsofia; Eeles, Rosalind A; Easton, Douglas F
2015-07-01
Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. ©2015 American Association for Cancer Research.
Amin Al Olama, Ali; Benlloch, Sara; Antoniou, Antonis C.; Zeigler-Johnson, Charnita; Stephenson, Robert; Cox, Angela; Southey, Melissa C.; Spurdle, Amanda B.; FitzGerald, Liesel; Leongamornlert, Daniel; Saunders, Edward; Tymrakiewicz, Malgorzata; Guy, Michelle; Dadaev, Tokhir; Little, Sarah J.; Govindasami, Koveela; Sawyer, Emma; Wilkinson, Rosemary; Herkommer, Kathleen; Hopper, John L.; Lophatonanon, Aritaya; Rinckleb, Antje E.; Kote-Jarai, Zsofia; Eeles, Rosalind A.; Easton, Douglas F.
2015-01-01
Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer (PrCa) risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of PrCa. Methods We genotyped 25 PrCa susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical Odds Ratios for PrCa associated with different risk strata defined by PRS and derived age-specific absolute risks of developing PrCa by PRS stratum and family history. Results The PrCa risk for men in the top 1% of the PRS distribution was 30.6 (95% CI 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI 3.2-5.5) fold compared with the median risk. The absolute risk of PrCa by age 85 was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation=0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of PrCa. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of PrCa. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs. PMID:25837820
McLean, Duncan; Barrett, Robert; Loa, Peter; Thara, Rangaswamy; John, Sujit; McGrath, John; Gratten, Jake; Mowry, Bryan
2015-03-01
The symptom profile of schizophrenia can vary between ethnic groups. We explored selected symptom variables previously reported to be characteristic of schizophrenia in the Iban of Sarawak in transethnic populations from Australia, India, and Sarawak, Malaysia. We tested site differences to confirm previous research, and to explore implications of differences across populations for future investigations. We recruited schizophrenia samples in Australia (n = 609), India (n = 310) and Sarawak (n = 205) primarily for the purposes of genetic studies. We analyzed seven identified variables and their relationship to site using logistic regression, including: global delusions, bizarre delusions, thought broadcast/insertion/withdrawal delusions, global hallucinations, auditory hallucinations, disorganized behavior, and prodromal duration. We identified a distinct symptom profile in our Sarawak sample. Specifically, the Iban exhibit: low frequency of thought broadcast/insertion/withdrawal delusions, high frequency of auditory hallucinations and disorganized behavior, with a comparatively short prodrome when compared with Australian and Indian populations. Understanding between-site variation in symptom profile may complement future transethnic genetic studies, and provide important clues as to the nature of differing schizophrenia expression across ethnically distinct groups. A comprehensive approach to subtyping schizophrenia is warranted, utilizing comprehensively ascertained transethnic samples to inform both schizophrenia genetics and nosology. Copyright © 2013 Wiley Publishing Asia Pty Ltd.
A Comparison of Multiple Facets of Self-Concept in Gifted vs. Non-Identified Israeli Students
ERIC Educational Resources Information Center
Zeidner, Moshe; Shani-Zinovich, Inbal
2015-01-01
This study compares facets of self-concept in gifted and non-identified Israeli adolescent students. The self-concept mean score profile of gifted vs. non-selected Israeli students was significantly different, with gifted students reporting higher mean levels of academic self-concept, but lower mean levels of social, personal, and physical…
Differentially Expressed Proteins Associated with Fusarium Head Blight Resistance in Wheat
Zhang, Xianghui; Fu, Jianming; Hiromasa, Yasuaki; Pan, Hongyu; Bai, Guihua
2013-01-01
Background Fusarium head blight (FHB), mainly caused by Fusarium graminearum, substantially reduces wheat grain yield and quality worldwide. Proteins play important roles in defense against the fungal infection. This study characterized differentially expressed proteins between near-isogenic lines (NILs) contrasting in alleles of Fhb1, a major FHB resistance gene in wheat, to identify proteins underlining FHB resistance of Fhb1. Methods The two-dimensional protein profiles were compared between the Fusarium-inoculated spikes of the two NILs collected 72 h after inoculation. The protein profiles of mock- and Fusarium-inoculated Fhb1+NIL were also compared to identify pathogen-responsive proteins. Results Eight proteins were either induced or upregulated in inoculated Fhb1+NIL when compared with mock-inoculated Fhb1+NIL; nine proteins were either induced or upregulated in the Fusarium-inoculated Fhb1+NIL when compared with Fusarium-inoculated Fhb1−NIL. Proteins that were differentially expressed in the Fhb1+NIL, not in the Fhb1−NIL, after Fusarium inoculation included wheat proteins for defending fungal penetration, photosynthesis, energy metabolism, and detoxification. Conclusions Coordinated expression of the identified proteins resulted in FHB resistance in Fhb1+NIL. The results provide insight into the pathway of Fhb1-mediated FHB resistance. PMID:24376514
O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik
2015-01-01
To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329
Identification of cancer-specific motifs in mimotope profiles of serum antibody repertoire.
Gerasimov, Ekaterina; Zelikovsky, Alex; Măndoiu, Ion; Ionov, Yurij
2017-06-07
For fighting cancer, earlier detection is crucial. Circulating auto-antibodies produced by the patient's own immune system after exposure to cancer proteins are promising bio-markers for the early detection of cancer. Since an antibody recognizes not the whole antigen but 4-7 critical amino acids within the antigenic determinant (epitope), the whole proteome can be represented by a random peptide phage display library. This opens the possibility to develop an early cancer detection test based on a set of peptide sequences identified by comparing cancer patients' and healthy donors' global peptide profiles of antibody specificities. Due to the enormously large number of peptide sequences contained in global peptide profiles generated by next generation sequencing, the large number of cancer and control sera is required to identify cancer-specific peptides with high degree of statistical significance. To decrease the number of peptides in profiles generated by nextgen sequencing without losing cancer-specific sequences we used for generation of profiles the phage library enriched by panning on the pool of cancer sera. To further decrease the complexity of profiles we used computational methods for transforming a list of peptides constituting the mimotope profiles to the list motifs formed by similar peptide sequences. We have shown that the amino-acid order is meaningful in mimotope motifs since they contain significantly more peptides than motifs among peptides where amino-acids are randomly permuted. Also the single sample motifs significantly differ from motifs in peptides drawn from multiple samples. Finally, multiple cancer-specific motifs have been identified.
Bushman, B Shaun; Amundsen, Keenan L; Warnke, Scott E; Robins, Joseph G; Johnson, Paul G
2016-01-13
Kentucky bluegrass (Poa pratensis L.) is a prominent turfgrass in the cool-season regions, but it is sensitive to salt stress. Previously, a relatively salt tolerant Kentucky bluegrass accession was identified that maintained green colour under consistent salt applications. In this study, a transcriptome study between the tolerant (PI 372742) accession and a salt susceptible (PI 368233) accession was conducted, under control and salt treatments, and in shoot and root tissues. Sample replicates grouped tightly by tissue and treatment, and fewer differentially expressed transcripts were detected in the tolerant PI 372742 samples compared to the susceptible PI 368233 samples, and in root tissues compared to shoot tissues. A de novo assembly resulted in 388,764 transcripts, with 36,587 detected as differentially expressed. Approximately 75 % of transcripts had homology based annotations, with several differences in GO terms enriched between the PI 368233 and PI 372742 samples. Gene expression profiling identified salt-responsive gene families that were consistently down-regulated in PI 372742 and unlikely to contribute to salt tolerance in Kentucky bluegrass. Gene expression profiling also identified sets of transcripts relating to transcription factors, ion and water transport genes, and oxidation-reduction process genes with likely roles in salt tolerance. The transcript assembly represents the first such assembly in the highly polyploidy, facultative apomictic Kentucky bluegrass. The transcripts identified provide genetic information on how this plant responds to and tolerates salt stress in both shoot and root tissues, and can be used for further genetic testing and introgression.
OP17MICRORNA PROFILING USING SMALL RNA-SEQ IN PAEDIATRIC LOW GRADE GLIOMAS
Jeyapalan, Jennie N.; Jones, Tania A.; Tatevossian, Ruth G.; Qaddoumi, Ibrahim; Ellison, David W.; Sheer, Denise
2014-01-01
INTRODUCTION: MicroRNAs regulate gene expression by targeting mRNAs for translational repression or degradation at the post-transcriptional level. In paediatric low-grade gliomas a few key genetic mutations have been identified, including BRAF fusions, FGFR1 duplications and MYB rearrangements. Our aim in the current study is to profile aberrant microRNA expression in paediatric low-grade gliomas and determine the role of epigenetic changes in the aetiology and behaviour of these tumours. METHOD: MicroRNA profiling of tumour samples (6 pilocytic, 2 diffuse, 2 pilomyxoid astrocytomas) and normal brain controls (4 adult normal brain samples and a primary glial progenitor cell-line) was performed using small RNA sequencing. Bioinformatic analysis included sequence alignment, analysis of the number of reads (CPM, counts per million) and differential expression. RESULTS: Sequence alignment identified 695 microRNAs, whose expression was compared in tumours v. normal brain. PCA and hierarchical clustering showed separate groups for tumours and normal brain. Computational analysis identified approximately 400 differentially expressed microRNAs in the tumours compared to matched location controls. Our findings will then be validated and integrated with extensive genetic and epigenetic information we have previously obtained for the full tumour cohort. CONCLUSION: We have identified microRNAs that are differentially expressed in paediatric low-grade gliomas. As microRNAs are known to target genes involved in the initiation and progression of cancer, they provide critical information on tumour pathogenesis and are an important class of biomarkers.
Aroonsri, Aiyada; Akinola, Olugbenga; Posayapisit, Navaporn; Songsungthong, Warangkhana; Uthaipibull, Chairat; Kamchonwongpaisan, Sumalee; Gbotosho, Grace O; Yuthavong, Yongyuth; Shaw, Philip J
2016-07-01
The mode of action of many antimalarial drugs is unknown. Chemogenomic profiling is a powerful method to address this issue. This experimental approach entails disruption of gene function and phenotypic screening for changes in sensitivity to bioactive compounds. Here, we describe the application of reverse genetics for chemogenomic profiling in Plasmodium. Plasmodium falciparum parasites harbouring a transgenic insertion of the glmS ribozyme downstream of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene were used for chemogenomic profiling of antimalarial compounds to identify those which target DHFR-TS. DHFR-TS expression can be attenuated by exposing parasites to glucosamine. Parasites with attenuated DHFR-TS expression were significantly more sensitive to antifolate drugs known to target DHFR-TS. In contrast, no change in sensitivity to other antimalarial drugs with different modes of action was observed. Chemogenomic profiling was performed using the Medicines for Malaria Venture (Switzerland) Malaria Box compound library, and two compounds were identified as novel DHFR-TS inhibitors. We also tested the glmS ribozyme in Plasmodium berghei, a rodent malaria parasite. The expression of reporter genes with downstream glmS ribozyme could be attenuated in transgenic parasites comparable with that obtained in P. falciparum. The chemogenomic profiling method was applied in a P. berghei line expressing a pyrimethamine-resistant Toxoplasma gondii DHFR-TS reporter gene under glmS ribozyme control. Parasites with attenuated expression of this gene were significantly sensitised to antifolates targeting DHFR-TS, but not other drugs with different modes of action. In conclusion, these data show that the glmS ribozyme reverse genetic tool can be applied for identifying primary targets of antimalarial compounds in human and rodent malaria parasites. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.
Fatty acid methyl ester analysis to identify sources of soil in surface water.
Banowetz, Gary M; Whittaker, Gerald W; Dierksen, Karen P; Azevedo, Mark D; Kennedy, Ann C; Griffith, Stephen M; Steiner, Jeffrey J
2006-01-01
Efforts to improve land-use practices to prevent contamination of surface waters with soil are limited by an inability to identify the primary sources of soil present in these waters. We evaluated the utility of fatty acid methyl ester (FAME) profiles of dry reference soils for multivariate statistical classification of soils collected from surface waters adjacent to agricultural production fields and a wooded riparian zone. Trials that compared approaches to concentrate soil from surface water showed that aluminum sulfate precipitation provided comparable yields to that obtained by vacuum filtration and was more suitable for handling large numbers of samples. Fatty acid methyl ester profiles were developed from reference soils collected from contrasting land uses in different seasons to determine whether specific fatty acids would consistently serve as variables in multivariate statistical analyses to permit reliable classification of soils. We used a Bayesian method and an independent iterative process to select appropriate fatty acids and found that variable selection was strongly impacted by the season during which soil was collected. The apparent seasonal variation in the occurrence of marker fatty acids in FAME profiles from reference soils prevented preparation of a standardized set of variables. Nevertheless, accurate classification of soil in surface water was achieved utilizing fatty acid variables identified in seasonally matched reference soils. Correlation analysis of entire chromatograms and subsequent discriminant analyses utilizing a restricted number of fatty acid variables showed that FAME profiles of soils exposed to the aquatic environment still had utility for classification at least 1 wk after submersion.
Wang, Chee Keng John; Liu, Woon Chia; Nie, Youyan; Chye, Yen Leng Stefanie; Lim, Boon San Coral; Liem, Gregory Arief; Tay, Eng Guan; Hong, Ying-Yi; Chiu, Chi-Yue
2017-05-01
The purpose of the current study was to identify the motivation profiles at the intraindividual level using a latent profile analyses (LPA) approach. A total of 1151 secondary school students aged 13 to 17 years old from Singapore took part in the study. Using LPA, four distinct motivational profiles were identified based on four motivation regulations. Profile 1 has very low introjected and low autonomous motivation (6% of sample). Profile 2 had high external and identified regulations and very low intrinsic regulation (10%). Profile 3 consisted of students with high identified and intrinsic regulations (51%). Profile 4 had moderately low identified and intrinsic regulations (33%). The results showed that the four profiles differed significantly in terms of effort, competence, value, and time spent on math beyond homework. The best profile (Profile 3) reported highest scores in effort, value, competence and time spent on Math beyond homework. The worst profile (Profile 1) reported lowest scores in all the four outcome variables.
Identifying at-risk children at school entry: the usefulness of multibehavioral problem profiles.
Flanagan, Kelly S; Bierman, Karen L; Kam, Chi-Ming
2003-09-01
Found that 1st-grade teacher ratings of aggressive, hyperactive-inattentive, and low levels of prosocial behaviors made unique contributions to the prediction of school outcomes (measured 2 years later) for 755 children. Person-oriented analyses compared the predictive utility of 5 screening strategies based on child problem profiles to identify children at risk for school problems. A broad screening strategy, in which children with elevations in any 1 of the 3 behavior problem dimensions were identified as "at-risk," showed lower specificity but superior sensitivity, odds ratios, and overall accuracy in the prediction of school outcomes than the other screening strategies that were more narrowly focused or were based on a total problem score. Results are discussed in terms of implications for the screening and design of preventive interventions.
Gene Expression Profiling in Pachyonychia Congenita Skin
Cao, Yu-An; Hickerson, Robyn P.; Seegmiller, Brandon L.; Grapov, Dmitry; Gross, Maren M.; Bessette, Marc R.; Phinney, Brett S.; Flores, Manuel A.; Speaker, Tycho J.; Vermeulen, Annaleen; Bravo, Albert A.; Bruckner, Anna L.; Milstone, Leonard M.; Schwartz, Mary E.; Rice, Robert H.; Kaspar, Roger L.
2015-01-01
Background Pachyonychia congenita (PC) is a skin disorder resulting from mutations in keratin (K) proteins including K6a, K6b, K16, and K17. One of the major symptoms is painful plantar keratoderma. The pathogenic sequelae resulting from the keratin mutations remain unclear. Objective To better understand PC pathogenesis. Methods RNA profiling was performed on biopsies taken from PC-involved and uninvolved plantar skin of seven genotyped PC patients (two K6a, one K6b, three K16, and one K17) as well as from control volunteers. Protein profiling was generated from tape-stripping samples. Results A comparison of PC-involved skin biopsies to adjacent uninvolved plantar skin identified 112 differentially-expressed mRNAs common to patient groups harboring K6 (i.e., both K6a and K6b) and K16 mutations. Among these mRNAs, 25 encode structural proteins including keratins, small proline-rich and late cornified envelope proteins, 20 are related to metabolism and 16 encode proteases, peptidases, and their inhibitors including kallikrein-related peptidases (KLKs), and serine protease inhibitors (SERPINs). mRNAs were also identified to be differentially expressed only in K6 (81) or K16 (141) patient samples. Furthermore, 13 mRNAs were identified that may be involved in pain including nociception and neuropathy. Protein profiling, comparing three K6a plantar tape-stripping samples to non-PC controls, showed changes in the PC corneocytes similar, but not identical, to the mRNA analysis. Conclusion Many differentially-expressed genes identified in PC-involved skin encode components critical for skin barrier homeostasis including keratinocyte proliferation, differentiation, cornification, and desquamation. The profiling data provide a foundation for unraveling the pathogenesis of PC and identifying targets for developing effective PC therapeutics. PMID:25656049
Comparative analysis of human milk and infant formula derived peptides following in vitro digestion.
Su, M-Y; Broadhurst, M; Liu, C-P; Gathercole, J; Cheng, W-L; Qi, X-Y; Clerens, S; Dyer, J M; Day, L; Haigh, B
2017-04-15
It has long been recognised that there are differences between human milk and infant formulas which lead to differences in health and nutrition for the neonate. In this study we examine and compare the peptide profile of human milk and an exemplar infant formula. The study identifies both similarities and differences in the endogenous and postdigestion peptide profiles of human milk and infant formula. This includes differences in the protein source of these peptides but also with the region within the protein producing the dominant proteins. Clustering of similar peptides around regions of high sequence identity and known bioactivity was also observed. Together the data may explain some of the functional differences between human milk and infant formula, while identifying some aspects of conserved function between bovine and human milks which contribute to the effectiveness of modern infant formula as a substitute for human milk. Copyright © 2016 Elsevier Ltd. All rights reserved.
Profiles of Resilience and Psychosocial Outcomes among Young Black Gay and Bisexual Men.
Wilson, Patrick A; Meyer, Ilan H; Antebi-Gruszka, Nadav; Boone, Melissa R; Cook, Stephanie H; Cherenack, Emily M
2016-03-01
Young Black gay/bisexual men (YBGBM) are affected by contextual stressors-namely syndemic conditions and minority stress-that threaten their health and well-being. Resilience is a process through which YBGBM achieve positive psychosocial outcomes in the face of adverse conditions. Self-efficacy, hardiness and adaptive coping, and social support may be important resilience factors for YBGBM. This study explores different profiles of these resilience factors in 228 YBGBM in New York City and compares profiles on psychological distress, mental health, and other psychosocial factors. Four profiles of resilience were identified: (a) Low self-efficacy and hardiness/adaptive coping (23.5%); (b) Low peer and parental support (21.2%); (c) High peer support, low father support (34.5%); and (d) High father and mother support, self-efficacy, and hardiness/adaptive coping (20.8%). YBGBM in profile 1 scored markedly higher on distress (d = .74) and lower on mental health functioning (d = .93) compared to men in the other profiles. Results suggest that self-efficacy and hardiness/adaptive coping may play a more important role in protecting YBGBM from risks compared to social support and should be targeted in interventions. The findings show that resilience is a multidimensional construct and support the notion that there are different patterns of resilience among YBGBM. © Society for Community Research and Action 2016.
Butch-Femme Identity and Visuospatial Performance Among Lesbian and Bisexual Women in China.
Zheng, Lijun; Wen, Guangju; Zheng, Yong
2018-05-01
Lesbian and bisexual women who self-identify as "butch" show a masculine profile with regard to gender roles, gender nonconformity, and systemizing cognitive style, whereas lesbian and bisexual women who self-identify as "femme" show a corresponding feminine profile and those who self-identify as "androgynes" show an intermediate profile. This study examined the association between butch or femme lesbian or bisexual identity and visuospatial ability among 323 lesbian and bisexual women, compared to heterosexual women (n = 207) and men (n = 125), from multiple cities in China. Visuospatial ability was assessed using a Shepard and Metzler-type mental rotation task and Judgment of Line Angle and Position (JLAP) test on the Internet. Heterosexual men outperformed heterosexual women on both mental rotation and JLAP tasks. Lesbian and bisexual women outperformed heterosexual women on mental rotation, but not on JLAP. There were significant differences in mental rotation performance among women, with butch- and androgyne-identified lesbian/bisexual women outperforming femme-identified and heterosexual women. There were also significant differences in JLAP performance among women, with butch- and androgyne-identified lesbian/bisexual women and heterosexual women outperforming femme-identified lesbian/bisexual women. The butch-femme differences in visuospatial ability indicated an association between cognitive ability and butch-femme identity and suggest that neurobiological underpinnings may contribute to butch-femme identity although alternative explanations exist.
Mupfasoni, Denise; Karibushi, Blaise; Koukounari, Artemis; Ruberanziza, Eugene; Kaberuka, Teddy; Kramer, Michael H.; Mukabayire, Odette; Kabera, Michee; Nizeyimana, Vianney; Deville, Marie-Alice; Ruxin, Josh; Webster, Joanne P.; Fenwick, Alan
2009-01-01
Background Intestinal schistosomiasis and soil-transmitted helminth (STH) infections constitute major public health problems in many parts of sub-Saharan Africa. In this study we examined the functional significance of such polyparasite infections in anemia and undernutrition in Rwandan individuals. Methods Three polyparasite infection profiles were defined, in addition to a reference profile that consisted of either no infections or low-intensity infection with only one of the focal parasite species. Logistic regression models were applied to data of 1,605 individuals from 6 schools in 2 districts of the Northern Province before chemotherapeutic treatment in order to correctly identify individuals who were at higher odds of being anaemic and/or undernourished. Findings Stunted relative to nonstunted, and males compared to females, were found to be at higher odds of being anaemic independently of polyparasite infection profile. The odds of being wasted were 2-fold greater for children with concurrent infection of at least 2 parasites at M+ intensity compared to those children with the reference profile. Males compared to females and anaemic compared to nonanaemic children were significantly more likely to be stunted. None of the three polyparasite infection profiles were found to have significant effects on stunting. Conclusion The present data suggest that the levels of polyparasitism, and infection intensities in the Rwandan individuals examined here may be lower as compared to other recent similar epidemiological studies in different regions across sub-Saharan Africa. Neither the odds of anaemia nor the odds of stunting were found to be significantly different in the three-polyparasite infection profiles. However, the odds of wasting were higher in those children with at least two parasites at M+ intensity compared to those children with the reference profile. Nevertheless, despite the low morbidity levels indicated in the population under study here, we recommend sustainable efforts for the deworming of affected populations to be continued in order to support the economic development of the country. PMID:19753110
Liesenfeld, David B; Grapov, Dmitry; Fahrmann, Johannes F; Salou, Mariam; Scherer, Dominique; Toth, Reka; Habermann, Nina; Böhm, Jürgen; Schrotz-King, Petra; Gigic, Biljana; Schneider, Martin; Ulrich, Alexis; Herpel, Esther; Schirmacher, Peter; Fiehn, Oliver; Lampe, Johanna W; Ulrich, Cornelia M
2015-01-01
Background: Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions. Objectives: Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients’ tumor stage and metabolic profiles was assessed. Design: Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I–IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina’s HumanHT-12 Expression BeadChips. Results: Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis–related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients’ adipose tissues, which were associated with CRC tumor stage. Conclusions: As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer. This trial was registered at clinicaltrials.gov as NCT02328677. PMID:26156741
Liesenfeld, David B; Grapov, Dmitry; Fahrmann, Johannes F; Salou, Mariam; Scherer, Dominique; Toth, Reka; Habermann, Nina; Böhm, Jürgen; Schrotz-King, Petra; Gigic, Biljana; Schneider, Martin; Ulrich, Alexis; Herpel, Esther; Schirmacher, Peter; Fiehn, Oliver; Lampe, Johanna W; Ulrich, Cornelia M
2015-08-01
Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions. Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed. Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips. Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage. As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer. © 2015 American Society for Nutrition.
Hayashi, Ken-Go; Hosoe, Misa; Kizaki, Keiichiro; Fujii, Shiori; Kanahara, Hiroko; Takahashi, Toru; Sakumoto, Ryosuke
2017-03-23
Repeat breeding directly affects reproductive efficiency in cattle due to an increase in services per conception and calving interval. This study aimed to investigate whether changes in endometrial gene expression profile are involved in repeat breeding in cows. Differential gene expression profiles of the endometrium were investigated during the mid-luteal phase of the estrous cycle between repeat breeder (RB) and non-RB cows using microarray analysis. The caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and non-RB cows on Day 15 of the estrous cycle (4 cows/group). Global gene expression profiles of these endometrial samples were analyzed with a 15 K custom-made oligo-microarray for cattle. Immunohistochemistry was performed to investigate the cellular localization of proteins of three identified transcripts in the endometrium. Microarray analysis revealed that 405 and 397 genes were differentially expressed in the CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with non-RB cows. In the contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with non-RB cows. Gene ontology analysis revealed that genes involved in development and morphogenesis were mainly up-regulated in the CAR of RB cows. In the ICAR of both the ipsilateral and contralateral uterine horns, genes related to the metabolic process were predominantly enriched in the RB cows when compared with non-RB cows. In the analysis of the whole uterus (combining the data above four endometrial compartments), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3 and PIPOX and down-regulation of 39 genes including CHGA, KRT35 and THBS4 when compared with non-RB cows. Immunohistochemistry revealed that CHGA, GSTA3 and PRSS2 proteins were localized in luminal and glandular epithelial cells and stroma of the endometrium. The present study showed that endometrial gene expression profiles are different between RB and non-RB cows. The identified candidate endometrial genes and functions in each endometrial compartment may contribute to bovine reproductive performance.
Tanaka, Rika; Nolan, Robert P
2018-05-11
Practice guidelines advocate combining pharmacotherapy with lifestyle counseling for patients with hypertension. To allow for appropriate tailoring of interventions to meet individual patient needs, a comprehensive understanding of baseline patient characteristics is essential. However, few studies have empirically assessed behavioral profiles of hypertensive patients in Web-based lifestyle counseling programs. The objectives of this study were to (1) specify baseline psychobehavioral profiles of patients with hypertension who were enrolled in a Web-based lifestyle counseling trial, and (2) examine mean differences among the identified profile groups in demographics, psychological distress, self-reported self-care behaviors, physiological outcomes, and program engagement to determine prognostic implications. Participants (N=264; mean age 57.5 years; 154/264, 58.3% female; 193/264, 73.1% white) were recruited into a longitudinal, double-blind, randomized controlled trial, designed to evaluate an online lifestyle intervention for hypertensive patients. A series of latent profile analyses identified psychobehavioral profiles, indicated by baseline measures of mood, motivation, and health behaviors. Mean differences between profile groups were then explored. A 2-class solution provided the best model fit (the Bayesian information criterion (BIC) is 10,133.11; sample-size adjusted BIC is 10,006.54; Lo-Mendell-Rubin likelihood ratio test is 65.56, P=.001). The 2 profile groups were (1) adaptive adjustment, marked by low distress, high motivation, and somewhat satisfactory engagement in health behaviors and (2) affectively distressed, marked by clinically significant distress. At baseline, on average, affectively distressed patients had lower income, higher body mass index, and endorsed higher stress compared with their adaptive adjustment counterparts. At 12-months post intervention, treatment effects were sustained for systolic blood pressure and Framingham risk index in the adaptive adjustment group, and those in the adaptive adjustment group were 2.4 times more likely to complete the 12-month intervention study, compared with their affectively distressed counterparts. Interventions for patients who are adaptively adjusted may differ in focus from those designed for the affectively distressed patients. As such, this study underscores the importance of identifying psychobehavioral profiles, as they allow for evidence-based tailoring of lifestyle counseling programs for patients with hypertension. ClinicalTrials.gov NCT01541540; https://clinicaltrials.gov/ct2/show/NCT01541540 (Archived by WebCite at http://www.webcitation.org/6yzZYZcWF). ©Rika Tanaka, Robert P Nolan. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.05.2018.
An in-vitro investigation of the accuracy of fit of Procera and Empress crowns.
Fleming, Garry J R; Dobinson, Marie M; Landini, Gabriel; Harris, Jonathan J
2005-09-01
The current study aimed to investigate the accuracy of fit and the reproducibility of inner crown profile for two types of high strength ceramics, IPS Empress and Procera. Procera and Empress crowns with four different morphologies were cemented to dies using zinc phosphate dental cement. Vertical and horizontal sections were made through each of the crown/die preparations and images of the vertical sections were compared for curvature reproduction by alignment using image processing. Measurements were made on horizontal sections to determine cement layer thickness. Alignment of the crowns using image analysis identified quantifiable variations in the inner surface profile compared with the outer surface of the die. The largest differences occurred from the cusp tips to the occlusal adaptation area and differences in surface profile were less pronounced for Procera than Empress crowns. Marginal gap varied independently of ceramic or internal crown shape from 7-529 microm for Procera and 26-548 microm for Empress. IPS Empress has a superior ability to reproduce the inner surface profile of the crown morphologies investigated compared with Procera. The reduced reproduction of surface profile was associated with an increased cement thickness at the occlusal contact area that may inadvertently lead to failure of the crowns functional characteristics.
Comparison of gene expression and fatty acid profiles in concentrate and forage finished beef.
Buchanan, J W; Garmyn, A J; Hilton, G G; VanOverbeke, D L; Duan, Q; Beitz, D C; Mateescu, R G
2013-01-01
Fatty acid profiles and intramuscular expression of genes involved in fatty acid metabolism were characterized in concentrate- (CO) and forage- (FO) based finishing systems. Intramuscular samples from the adductor were taken at slaughter from 99 heifers finished on a CO diet and 58 heifers finished on a FO diet. Strip loins were obtained at fabrication to evaluate fatty acid profiles of LM muscle for all 157 heifers by using gas chromatography fatty acid methyl ester analysis. Composition was analyzed for differences by using the General Linear Model (GLM) procedure in SAS. Differences in fatty acid profile included a greater atherogenic index, greater percentage total MUFA, decreased omega-3 to omega-6 ratio, decreased percentage total PUFA, and decreased percentage omega-3 fatty acids in CO- compared with FO-finished heifers (P<0.05). Fatty acid profiles from intramuscular samples were ranked by the atherogenic index, and 20 heifers with either a high (HAI; n=10) or low (LAI; n=10) atherogenic index were selected for gene expression analysis using real-time PCR (RT-PCR). Gene expression data for the 20 individuals were analyzed as a 2 by 2 factorial arrangement of treatments using the GLM procedure in SAS. There was no significant diet × atherogenic index interaction identified for any gene (P>0.05). Upregulation was observed for PPARγ, fatty acid synthase (FASN), and fatty acid binding protein 4 (FABP4) in FO-finished compared with CO-finished heifers in both atherogenic index categories (P<0.05). Upregulation of diglyceride acyl transferase 2 (DGAT2) was observed in FO-finished heifers with a HAI (P<0.05). Expression of steroyl Co-A desaturase (SCD) was upregulated in CO-finished heifers with a LAI, and downregulated in FO-finished heifers with a HAI (P<0.05). Expression of adiponectin (ADIPOQ) was significantly downregulated in CO-finished heifers with a HAI compared with all other categories (P<0.05). The genes identified in this study which exhibit differential regulation in response to diet or in animals with extreme fatty acid profiles may provide genetic markers for selecting desirable fatty acid profiles in future selection programs.
Bravo, Adrian J; Pearson, Matthew R; Kelley, Michelle L
2018-02-01
Previous research on trait mindfulness facets using person-centered analyses (e.g., latent profile analysis [LPA]) has identified four distinct mindfulness profiles among college students: a high mindfulness group (high on all facets of the Five-Factor Mindfulness Questionnaire [FFMQ]), a judgmentally observing group (highest on observing, but low on non-judging of inner experience and acting with awareness), a non-judgmentally aware group (high on non-judging of inner experience and acting with awareness, but very low on observing), and a low mindfulness group (low on all facets of the FFMQ). In the present study, we used LPA to identify distinct mindfulness profiles in a community based sample of U.S. military personnel (majority veterans; n = 407) and non-military college students ( n = 310) and compare these profiles on symptoms of psychological health outcomes (e.g., suicidality, PTSD, anxiety, rumination) and percentage of participants exceeding clinically significant cut-offs for depressive symptoms, substance use, and alcohol use. In the subsample of college students, we replicated previous research and found four distinct mindfulness profiles; however, in the military subsample we found three distinct mindfulness profiles (a combined low mindfulness/judgmentally observing class). In both subsamples, we found that the most adaptive profile was the "high mindfulness" profile (i.e., demonstrated the lowest scores on all psychological symptoms and the lowest probability of exceeding clinical cut-offs). Based on these findings, we purport that the comprehensive examination of an individual's mindfulness profile could help clinicians tailor interventions/treatments that capitalize on individual's specific strengths and work to address their specific deficits.
Objective Classification of Radar Profile Types, and Their Relationship to Lightning Occurrence
NASA Technical Reports Server (NTRS)
Boccippio, Dennis
2003-01-01
A cluster analysis technique is used to identify 16 "archetypal" vertical radar profile types from a large, globally representative sample of profiles from the TRMM Precipitation Radar. These include nine convective types (7 of these deep convective) and seven stratiform types (5 of these clearly glaciated). Radar profile classification provides an alternative to conventional deep convective storm metrics, such as 30 dBZ echo height, maximum reflectivity or VIL. As expected, the global frequency of occurrence of deep convective profile types matches satellite-observed total lightning production, including to very small scall local features. Each location's "mix" of profile types provides an objective description of the local convective spectrum, and in turn, is a first step in objectively classifying convective regimes. These classifiers are tested as inputs to a neural network which attempts to predict lightning occurrence based on radar-only storm observations, and performance is compared with networks using traditional radar metrics as inputs.
Boyette, Lindy-Lou; van Dam, Daniëlla; Meijer, Carin; Velthorst, Eva; Cahn, Wiepke; de Haan, Lieuwe; Kahn, René; de Haan, Lieuwe; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; Meijer, Carin; Myin-Germeys, Inez
2014-11-01
Patients with psychotic disorders who experienced childhood trauma show more social dysfunction than patients without traumatic experiences. However, this may not hold for all patients with traumatic experiences. Little is known about the potential compensating role of Five-Factor Model personality traits within this group, despite their strong predictive value for social functioning and well-being in the general population. Our sample consisted of 195 patients with psychotic disorders (74% diagnosed with schizophrenia) and 132 controls. Cluster analyses were conducted to identify and validate distinct personality profiles. General linear model analyses were conducted to examine whether patients with different profiles differed in social functioning and quality of life (QoL), while controlling for possible confounders. Mediation models were tested to assess potential causal links. In general, patients with higher levels of self-reported traumatic experiences (PT+) showed lower QoL and more social withdrawal compared with patients with lower traumatic experiences (PT-). Two clusters reflecting personality profiles were identified. PT+ with the first profile (lower neuroticism and higher extraversion, openness, agreeableness, and conscientiousness) presented higher levels of QoL and better social functioning in several areas, including less withdrawal, compared with both PT+ and PT- with the second profile. PT+ and PT- with the first personality profile did not differ in QoL and social functioning. Mediation analyses suggested that personality traits mediate the relation between traumatic experiences and QoL and social withdrawal. Our findings indicate that personality may "buffer" the impact of childhood traumatic experiences on functional outcome in patients with psychotic disorders. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
ERIC Educational Resources Information Center
Van den Broeck, Anja; Lens, Willy; De Witte, Hans; Van Coillie, Hermina
2013-01-01
The current study compares the quantitative and the qualitative viewpoints on work motivation by relying on Self-Determination Theory's differentiation between autonomous and controlled motivation. Specifically, we employed a person-centered approach to identify workers' naturally occurring motivational profiles and compared them in terms of…
Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Karger, David R.; Lindquist, Susan; Fraenkel, Ernest
2009-01-01
Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens, yet the functional roles of the genes identified by these assays often remain enigmatic. By comparing the results of these two assays across various cellular responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify response regulators, while mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We harnessed this approach to reveal cellular pathways related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative disorders including Parkinson disease. For this we screened an established yeast model for alpha-synuclein toxicity to identify genes that when overexpressed alter cellular survival. Application of our algorithm to these data and data from mRNA profiling provided functional explanations for many of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470
Knapp, Dunja; Schulz, Herbert; Rascon, Cynthia Alexander; Volkmer, Michael; Scholz, Juliane; Nacu, Eugen; Le, Mu; Novozhilov, Sergey; Tazaki, Akira; Protze, Stephanie; Jacob, Tina; Hubner, Norbert; Habermann, Bianca; Tanaka, Elly M.
2013-01-01
Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression – early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation. PMID:23658691
Ji, Dong Yoon; Park, Se Hee; Park, Soo Jin; Kim, Kyoung Heon; Ku, Cheol Ryong; Shin, Dong Yeob; Yoon, Jin Sook; Lee, Do Yup; Lee, Eun Jig
2018-06-18
Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.
Widlund, Anna; Tuominen, Heta; Korhonen, Johan
2018-01-01
It has been suggested that both performance and academic well-being play a role in adolescent students’ educational attainment and school dropout. In this study, we therefore examined, first, what kinds of academic well-being (i.e., school burnout, schoolwork engagement, and mathematics self-concept) and mathematics performance profiles can be identified among lower secondary school students (Ngrade 7 = 583, Ngrade 9 = 497); second, how stable these profiles are across one school year during the seventh and ninth grades; and, third, how students with different academic well-being and mathematics performance profiles differ with respect to their educational aspirations. By means of latent profile analyses, three groups of students in seventh grade: thriving (34%), average (51%), and negative academic well-being (15%) and four groups of students in ninth grade: thriving (25%), average (50%), negative academic well-being (18%), and low-performing (7%) with distinct well-being and mathematics performance profiles were identified. Configural frequency analyses revealed that the profiles were relatively stable across one school year; 60% of the students displayed identical profiles over time. The thriving students reported the highest educational aspirations compared to the other groups. In addition, the low-performing students in the ninth grade had the lowest educational aspirations just before the transition to upper secondary school. Practical implications as well as directions for future research are discussed. PMID:29593603
Widlund, Anna; Tuominen, Heta; Korhonen, Johan
2018-01-01
It has been suggested that both performance and academic well-being play a role in adolescent students' educational attainment and school dropout. In this study, we therefore examined, first, what kinds of academic well-being (i.e., school burnout, schoolwork engagement, and mathematics self-concept) and mathematics performance profiles can be identified among lower secondary school students ( N grade 7 = 583, N grade 9 = 497); second, how stable these profiles are across one school year during the seventh and ninth grades; and, third, how students with different academic well-being and mathematics performance profiles differ with respect to their educational aspirations. By means of latent profile analyses, three groups of students in seventh grade: thriving (34%), average (51%), and negative academic well-being (15%) and four groups of students in ninth grade: thriving (25%), average (50%), negative academic well-being (18%), and low-performing (7%) with distinct well-being and mathematics performance profiles were identified. Configural frequency analyses revealed that the profiles were relatively stable across one school year; 60% of the students displayed identical profiles over time. The thriving students reported the highest educational aspirations compared to the other groups. In addition, the low-performing students in the ninth grade had the lowest educational aspirations just before the transition to upper secondary school. Practical implications as well as directions for future research are discussed.
Anderson, K J; Henneberg, M; Norris, R M
2008-01-01
There is a lack in the understanding of the variation within the thickness of the soft tissue structures (muscle, skin and fat) overlying the cartilaginous skeleton of the nose and their relationship to the dorsum shape. We examined such relationships by dissecting noses of six adult female and six adult male cadavers, comparing the internal anatomical structures to the external nasal profile. We found that the soft tissue structures differ in thickness along the dorsum and that these differences are individualized. Specifically, continuous presence of subcutaneous fat from root to tip was found in half the sample, one nose had fat only on the tip, another one only on the root, the four others at both positions. The nasalis muscle was identifiable in nine of the 12 noses, transversing the nose in half the sample, and in the remaining three, only the lateral section of the muscle was identified. The superior border of the septal cartilage does not form a linear extension of the profile contour of the nasal bones but angles downwards. The actual profile contour of the dorsum does not follow the profile of the nasal bones or the septal cartilage. These results may influence the current use of nasal guidelines in forensic facial approximation. PMID:19172735
Zhou, Zhan; Zou, Yangyun; Liu, Gangbiao; Zhou, Jingqi; Wu, Jingcheng; Zhao, Shimin; Su, Zhixi; Gu, Xun
2017-08-29
Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes ( C N / C S ) and normal populations ( p N / p S ). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels. Both the relaxation of purifying selection on passenger mutations and the positive selection of driver mutations may contribute to the increased C N / C S values of human genes in cancer genomes compared with the p N / p S values in human populations. The C N / C S values also contribute to the improved classification of cancer genes and a better understanding of the onco-functionalization of cancer genes during oncogenesis. The use of our computational pipeline to identify cancer-specific positively and negatively selected genes may provide useful information for understanding the evolution of cancers and identifying possible targets for therapeutic intervention.
2014-01-01
Background Definitions and assessment methods of fussy/picky eating are heterogeneous and remain unclear. We aimed to identify an eating behavior profile reflecting fussy/picky eating in children and to describe characteristics of fussy eaters. Methods Eating behavior was assessed with the Child Eating Behavior Questionnaire (CEBQ) in 4914 4-year olds in a population-based birth cohort study. Latent Profile Analysis (LPA) was used to identify eating behavior profiles based on CEBQ subscales. Results and discussion We found a “fussy” eating behavior profile (5.6% of children) characterized by high food fussiness, slowness in eating, and satiety responsiveness in combination with low enjoyment of food and food responsiveness. Fussy eaters were more often from families with low household income than non-fussy eaters (42% vs. 31.8% respectively; Χ 2 (1) = 9.97, p < .01). When they were 14 months old, fussy eaters had a lower intake of vegetables (t [3008] = 2.42, p < .05) and fish (t [169.77] = 2.40, p < .05) but higher intake of savory snacks (t [153.69] = -2.03, p < .05) and sweets (t [3008] = -2.30, p < .05) compared to non-fussy eaters. Also, fussy eaters were more likely to be underweight at 4 years of age (19.3%) than non-fussy eaters (12.3%; Χ 2 (1) = 7.71, p < .01). Conclusions A distinct fussy eating behavior profile was identified by LPA, which was related to family and child characteristics, food intake, and BMI. This behavior profile might be used in future research and the development of interventions. PMID:24512388
Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-yu; Zhang, Xiao-mei; Song, Da-feng; Zhang, Chen
2016-01-01
Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate. PMID:27487802
Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-Yu; Zhang, Xiao-Mei; Song, Da-Feng; Zhang, Chen
2016-08-01
In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate.
Multivariate proteomic profiling identifies novel accessory proteins of coated vesicles
Antrobus, Robin; Hirst, Jennifer; Bhumbra, Gary S.; Kozik, Patrycja; Jackson, Lauren P.; Sahlender, Daniela A.
2012-01-01
Despite recent advances in mass spectrometry, proteomic characterization of transport vesicles remains challenging. Here, we describe a multivariate proteomics approach to analyzing clathrin-coated vesicles (CCVs) from HeLa cells. siRNA knockdown of coat components and different fractionation protocols were used to obtain modified coated vesicle-enriched fractions, which were compared by stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative mass spectrometry. 10 datasets were combined through principal component analysis into a “profiling” cluster analysis. Overall, 136 CCV-associated proteins were predicted, including 36 new proteins. The method identified >93% of established CCV coat proteins and assigned >91% correctly to intracellular or endocytic CCVs. Furthermore, the profiling analysis extends to less well characterized types of coated vesicles, and we identify and characterize the first AP-4 accessory protein, which we have named tepsin. Finally, our data explain how sequestration of TACC3 in cytosolic clathrin cages causes the severe mitotic defects observed in auxilin-depleted cells. The profiling approach can be adapted to address related cell and systems biological questions. PMID:22472443
Evidence for the importance of personalized molecular profiling in pancreatic cancer.
Lili, Loukia N; Matyunina, Lilya V; Walker, L DeEtte; Daneker, George W; McDonald, John F
2014-03-01
There is a growing body of evidence that targeted gene therapy holds great promise for the future treatment of cancer. A crucial step in this therapy is the accurate identification of appropriate candidate genes/pathways for targeted treatment. One approach is to identify variant genes/pathways that are significantly enriched in groups of afflicted individuals relative to control subjects. However, if there are multiple molecular pathways to the same cancer, the molecular determinants of the disease may be heterogeneous among individuals and possibly go undetected by group analyses. In an effort to explore this question in pancreatic cancer, we compared the most significantly differentially expressed genes/pathways between cancer and control patient samples as determined by group versus personalized analyses. We found little to no overlap between genes/pathways identified by gene expression profiling using group analyses relative to those identified by personalized analyses. Our results indicate that personalized and not group molecular profiling is the most appropriate approach for the identification of putative candidates for targeted gene therapy of pancreatic and perhaps other cancers with heterogeneous molecular etiology.
An artificial neural network system to identify alleles in reference electropherograms.
Taylor, Duncan; Harrison, Ash; Powers, David
2017-09-01
Electropherograms are produced in great numbers in forensic DNA laboratories as part of everyday criminal casework. Before the results of these electropherograms can be used they must be scrutinised by analysts to determine what the identified data tells them about the underlying DNA sequences and what is purely an artefact of the DNA profiling process. This process of interpreting the electropherograms can be time consuming and is prone to subjective differences between analysts. Recently it was demonstrated that artificial neural networks could be used to classify information within an electropherogram as allelic (i.e. representative of a DNA fragment present in the DNA extract) or as one of several different categories of artefactual fluorescence that arise as a result of generating an electropherogram. We extend that work here to demonstrate a series of algorithms and artificial neural networks that can be used to identify peaks on an electropherogram and classify them. We demonstrate the functioning of the system on several profiles and compare the results to a leading commercial DNA profile reading system. Copyright © 2017 Elsevier B.V. All rights reserved.
Gene expression profiling in whole blood of patients with coronary artery disease
Taurino, Chiara; Miller, William H.; McBride, Martin W.; McClure, John D.; Khanin, Raya; Moreno, María U.; Dymott, Jane A.; Delles, Christian; Dominiczak, Anna F.
2010-01-01
Owing to the dynamic nature of the transcriptome, gene expression profiling is a promising tool for discovery of disease-related genes and biological pathways. In the present study, we examined gene expression in whole blood of 12 patients with CAD (coronary artery disease) and 12 healthy control subjects. Furthermore, ten patients with CAD underwent whole-blood gene expression analysis before and after the completion of a cardiac rehabilitation programme following surgical coronary revascularization. mRNA and miRNA (microRNA) were isolated for expression profiling. Gene expression analysis identified 365 differentially expressed genes in patients with CAD compared with healthy controls (175 up- and 190 down-regulated in CAD), and 645 in CAD rehabilitation patients (196 up- and 449 down-regulated post-rehabilitation). Biological pathway analysis identified a number of canonical pathways, including oxidative phosphorylation and mitochondrial function, as being significantly and consistently modulated across the groups. Analysis of miRNA expression revealed a number of differentially expressed miRNAs, including hsa-miR-140-3p (control compared with CAD, P=0.017), hsa-miR-182 (control compared with CAD, P=0.093), hsa-miR-92a and hsa-miR-92b (post- compared with pre-exercise, P<0.01). Global analysis of predicted miRNA targets found significantly reduced expression of genes with target regions compared with those without: hsa-miR-140-3p (P=0.002), hsa-miR-182 (P=0.001), hsa-miR-92a and hsa-miR-92b (P=2.2×10−16). In conclusion, using whole blood as a ‘surrogate tissue’ in patients with CAD, we have identified differentially expressed miRNAs, differentially regulated genes and modulated pathways which warrant further investigation in the setting of cardiovascular function. This approach may represent a novel non-invasive strategy to unravel potentially modifiable pathways and possible therapeutic targets in cardiovascular disease. PMID:20528768
Distinct Evening Fatigue Profiles in Oncology Outpatients Receiving Chemotherapy
Wright, Fay; Cooper, Bruce A.; Conley, Yvette P.; Hammer, Marilyn J.; Chen, Lee-May; Paul, Steven M.; Levine, Jon D.; Miaskowski, Christine; Kober, Kord M.
2018-01-01
Background Fatigue is the most common and debilitating symptom experienced by oncology patients during chemotherapy (CTX). Fatigue severity demonstrates a large amount of inter-individual and diurnal variability. Purpose Study purposes were to evaluate for subgroups of patients with distinct evening fatigue profiles and evaluate how these subgroups differed on demographic, clinical, and symptom characteristics. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=1332) completed questionnaires six times over two cycles of CTX. Lee Fatigue Scale (LFS) evaluated evening fatigue severity. Latent profile analysis was used to identify distinct evening fatigue profiles. Results Four distinct evening fatigue classes (i.e., Low (14.0%), Moderate (17.2%), High (36.0%), Very High (32.8%)) were identified. Compared to the Low class, patients in the Very High evening fatigue class were: younger, female, had childcare responsibilities, had more years of education, had a lower functional status, had a higher comorbidity burden, and were diagnosed with breast cancer. Patients in the Very High class reported higher levels of depressive symptoms, sleep disturbance, and evening fatigue at enrollment. Conclusions Findings provide new insights into modifiable risk factors for higher levels of evening fatigue. Clinicians can use this information to identify higher risk patients and plan appropriate interventions. PMID:29725554
Schäfer, Lisa; Hübner, Claudia; Carus, Thomas; Herbig, Beate; Seyfried, Florian; Kaiser, Stefan; Schütz, Tatjana; Dietrich, Arne; Hilbert, Anja
2017-10-01
The efficacy of bariatric surgery has been proven; however, a subset of patients fails to achieve expected long-term weight loss postoperatively. As differences in surgery outcome may be influenced by heterogeneous psychological profiles in prebariatric patients, previous subtyping models differentiated patients based on temperament traits. The objective of this study was to expand these models by additionally considering emotion dysregulation and disinhibited eating behaviors for subtyping, as these factors were associated with maladaptive eating behaviors and poor postbariatric weight loss outcome. Within a prospective multicenter registry, N = 370 prebariatric patients were examined using interview and self-report questionnaires. A latent profile analysis was performed to identify subtypes based on temperament traits, emotion dysregulation, and disinhibited eating behaviors. Five prebariatric subtypes were identified with specific profiles regarding self-control, emotion dysregulation, and disinhibited eating behaviors. Subtypes were associated with different levels of eating disorder psychopathology, depression, and quality of life. The expanded model increased variance explanation compared to temperament-based models. By adding emotion dysregulation and disinhibited eating behaviors to previous subtyping models, specific prebariatric subtypes emerged with distinct psychological deficit patterns. Future investigations should test the predictive value of these subtypes for postbariatric weight loss and health-related outcomes. © 2017 Wiley Periodicals, Inc.
Silva, Anderson Tadeu; Ligterink, Wilco; Hilhorst, Henk W M
2017-11-01
Metabolic and transcriptomic correlation analysis identified two distinctive profiles involved in the metabolic preparation for seed germination and seedling establishment, respectively. Transcripts were identified that may control metabolic fluxes. The transition from a quiescent metabolic state (dry seed) to the active state of a vigorous seedling is crucial in the plant's life cycle. We analysed this complex physiological trait by measuring the changes in primary metabolism that occur during the transition in order to determine which metabolic networks are operational. The transition involves several developmental stages from seed germination to seedling establishment, i.e. between imbibition of the mature dry seed and opening of the cotyledons, the final stage of seedling establishment. We hypothesized that the advancement of growth is associated with certain signature metabolite profiles. Metabolite-metabolite correlation analysis underlined two specific profiles which appear to be involved in the metabolic preparation for seed germination and efficient seedling establishment, respectively. Metabolite profiles were also compared to transcript profiles and although transcriptional changes did not always equate to a proportional metabolic response, in depth correlation analysis identified several transcripts that may directly influence the flux through metabolic pathways during the seed-to-seedling transition. This correlation analysis also pinpointed metabolic pathways which are significant for the seed-to-seedling transition, and metabolite contents that appeared to be controlled directly by transcript abundance. This global view of the transcriptional and metabolic changes during the seed-to-seedling transition in Arabidopsis opens up new perspectives for understanding the complex regulatory mechanism underlying this transition.
Doi, Ryoichi
2012-09-01
Observation of leaf colour (spectral profiles) through remote sensing is an effective method of identifying the spatial distribution patterns of abnormalities in leaf colour, which enables appropriate plant management measures to be taken. However, because the brightness of remote sensing images varies with acquisition time, in the observation of leaf spectral profiles in multi-temporally acquired remote sensing images, changes in brightness must be taken into account. This study identified a simple luminosity normalization technique that enables leaf colours to be compared in remote sensing images over time. The intensity values of green and yellow (green+red) exhibited strong linear relationships with luminosity (R2 greater than 0.926) when various invariant rooftops in Bangkok or Tokyo were spectralprofiled using remote sensing images acquired at different time points. The values of the coefficient and constant or the coefficient of the formulae describing the intensity of green or yellow were comparable among the single Bangkok site and the two Tokyo sites, indicating the technique's general applicability. For single rooftops, the values of the coefficient of variation for green, yellow, and red/green were 16% or less (n=6-11), indicating an accuracy not less than those of well-established remote sensing measures such as the normalized difference vegetation index. After obtaining the above linear relationships, raw intensity values were normalized and a temporal comparison of the spectral profiles of the canopies of evergreen and deciduous tree species in Tokyo was made to highlight the changes in the canopies' spectral profiles. Future aspects of this technique are discussed herein.
Moorkanikkara, Srinivas Nageswaran; Blankschtein, Daniel
2010-12-21
How does one design a surfactant mixture using a set of available surfactants such that it exhibits a desired adsorption kinetics behavior? The traditional approach used to address this design problem involves conducting trial-and-error experiments with specific surfactant mixtures. This approach is typically time-consuming and resource-intensive and becomes increasingly challenging when the number of surfactants that can be mixed increases. In this article, we propose a new theoretical framework to identify a surfactant mixture that most closely meets a desired adsorption kinetics behavior. Specifically, the new theoretical framework involves (a) formulating the surfactant mixture design problem as an optimization problem using an adsorption kinetics model and (b) solving the optimization problem using a commercial optimization package. The proposed framework aims to identify the surfactant mixture that most closely satisfies the desired adsorption kinetics behavior subject to the predictive capabilities of the chosen adsorption kinetics model. Experiments can then be conducted at the identified surfactant mixture condition to validate the predictions. We demonstrate the reliability and effectiveness of the proposed theoretical framework through a realistic case study by identifying a nonionic surfactant mixture consisting of up to four alkyl poly(ethylene oxide) surfactants (C(10)E(4), C(12)E(5), C(12)E(6), and C(10)E(8)) such that it most closely exhibits a desired dynamic surface tension (DST) profile. Specifically, we use the Mulqueen-Stebe-Blankschtein (MSB) adsorption kinetics model (Mulqueen, M.; Stebe, K. J.; Blankschtein, D. Langmuir 2001, 17, 5196-5207) to formulate the optimization problem as well as the SNOPT commercial optimization solver to identify a surfactant mixture consisting of these four surfactants that most closely exhibits the desired DST profile. Finally, we compare the experimental DST profile measured at the surfactant mixture condition identified by the new theoretical framework with the desired DST profile and find good agreement between the two profiles.
Healthcare managers' leadership profiles in relation to perceptions of work stressors and stress.
Lornudd, Caroline; Bergman, David; Sandahl, Christer; von Thiele Schwarz, Ulrica
2016-05-03
Purpose The purpose of this study is to investigate the relationship between leadership profiles and differences in managers' own levels of work stress symptoms and perceptions of work stressors causing stress. Design/methodology/approach Cross-sectional data were used. Healthcare managers ( n = 188) rated three dimensions of their leadership behavior and levels of work stressors and stress. Hierarchical cluster analysis was performed to identify leadership profiles based on leadership behaviors. Differences in stress-related outcomes between profiles were assessed using one-way analysis of variance. Findings Four distinct clusters of leadership profiles were found. They discriminated in perception of work stressors and stress: the profile distinguished by the lowest mean in all behavior dimensions, exhibited a pattern with significantly more negative ratings compared to the other profiles. Practical implications This paper proposes that leadership profile is an individual factor involved in the stress process, including work stressors and stress, which may inform targeted health promoting interventions for healthcare managers. Originality/value This is the first study to investigate the relationship between leadership profiles and work stressors and stress in healthcare managers.
Behavioural Profiles of Brown and Sloth Bears in Captivity
Quintavalle Pastorino, Giovanni; Christodoulides, Yiannis; Curone, Giulio; Pearce-Kelly, Paul; Faustini, Massimo; Albertini, Mariangela; Preziosi, Richard; Mazzola, Silvia Michela
2017-01-01
Simple Summary Animal personality research is a growing field, since understanding animal personalities has notable implications in ecology and the evolution of animal behaviours. In the current study, we tested different methods described in the literature to obtain robust individual behavioural profiles. Data collected through behavioral observations were categorised into activity budgets, space usage, and social interactions for each individual. In addition, behavioural profile questionnaires were completed by the three zoo keepers who had regular interactions with the bears. The questionnaires included 22 adjectives, which were rated on a scale of 1–12 depending on how well they described each individual bear. The mean ratings of the keepers were used to create the behavioural profiles by adding the adjectives to the appropriate domains, according to the NEO Five Factor Inventory of personality model (NEO-FFI). The data gathered was used to produce behavioural profiles for all animals, in order to clarify the personality characteristics of each subject. Testing and improving existing methodologies to determine animal personality is important for providing optimal welfare and management of captive animals, since it can help to develop more effective management regimes in zoos by remodelling husbandry according to each animal’s personality type. Abstract Three brown bear (Ursus arctos arctos) individuals and two sloth bear (Melursus ursinus inornatus) individuals were observed in captivity to produce behavioural profiles for each individual. Data collected through behavioural observations were used to produce activity budgets, and to identify space usage and certain aspects of social behavior. Behaviour monitoring allowed the researchers to evaluate the welfare of the animals by identifying the occurrence of stereotypic behaviours, which are sometimes associated with stress. Behavioural profiles were created using data obtained through behavioural observations (coding) and keeper questionnaires (rating). The behavioural observations indicated a number of stereotypic behaviours in sloth bears but not in brown bears. The uniformity of zone usage was calculated to investigate if the enclosure size and features were adequate for use, and a social aspect of otherwise solitary animals was also identified. The behavioural profiles generated through coding and rating were compared to determine the reliability between these two methods in Ursids. Profiles were not compared between individuals since this study is not a comparison between different personality types but rather an effort (one of the few ones existing in literature) to select a valid and reproducible methodology capable of assessing personality in bears. PMID:28505095
Weernink, Marieke G M; Groothuis-Oudshoorn, Catharina G M; IJzerman, Maarten J; van Til, Janine A
2016-01-01
The objective of this study was to compare treatment profiles including both health outcomes and process characteristics in Parkinson disease using best-worst scaling (BWS), time trade-off (TTO), and visual analogue scales (VAS). From the model comprising of seven attributes with three levels, six unique profiles were selected representing process-related factors and health outcomes in Parkinson disease. A Web-based survey (N = 613) was conducted in a general population to estimate process-related utilities using profile-based BWS (case 2), multiprofile-based BWS (case 3), TTO, and VAS. The rank order of the six profiles was compared, convergent validity among methods was assessed, and individual analysis focused on the differentiation between pairs of profiles with methods used. The aggregated health-state utilities for the six treatment profiles were highly comparable for all methods and no rank reversals were identified. On the individual level, the convergent validity between all methods was strong; however, respondents differentiated less in the utility of closely related treatment profiles with a VAS or TTO than with BWS. For TTO and VAS, this resulted in nonsignificant differences in mean utilities for closely related treatment profiles. This study suggests that all methods are equally able to measure process-related utility when the aim is to estimate the overall value of treatments. On an individual level, such as in shared decision making, BWS allows for better prioritization of treatment alternatives, especially if they are closely related. The decision-making problem and the need for explicit trade-off between attributes should determine the choice for a method. Copyright © 2016. Published by Elsevier Inc.
2013-01-01
Background Time course gene expression experiments are an increasingly popular method for exploring biological processes. Temporal gene expression profiles provide an important characterization of gene function, as biological systems are both developmental and dynamic. With such data it is possible to study gene expression changes over time and thereby to detect differential genes. Much of the early work on analyzing time series expression data relied on methods developed originally for static data and thus there is a need for improved methodology. Since time series expression is a temporal process, its unique features such as autocorrelation between successive points should be incorporated into the analysis. Results This work aims to identify genes that show different gene expression profiles across time. We propose a statistical procedure to discover gene groups with similar profiles using a nonparametric representation that accounts for the autocorrelation in the data. In particular, we first represent each profile in terms of a Fourier basis, and then we screen out genes that are not differentially expressed based on the Fourier coefficients. Finally, we cluster the remaining gene profiles using a model-based approach in the Fourier domain. We evaluate the screening results in terms of sensitivity, specificity, FDR and FNR, compare with the Gaussian process regression screening in a simulation study and illustrate the results by application to yeast cell-cycle microarray expression data with alpha-factor synchronization. The key elements of the proposed methodology: (i) representation of gene profiles in the Fourier domain; (ii) automatic screening of genes based on the Fourier coefficients and taking into account autocorrelation in the data, while controlling the false discovery rate (FDR); (iii) model-based clustering of the remaining gene profiles. Conclusions Using this method, we identified a set of cell-cycle-regulated time-course yeast genes. The proposed method is general and can be potentially used to identify genes which have the same patterns or biological processes, and help facing the present and forthcoming challenges of data analysis in functional genomics. PMID:24134721
2014-01-01
Background Cis-regulatory modules (CRMs), or the DNA sequences required for regulating gene expression, play the central role in biological researches on transcriptional regulation in metazoan species. Nowadays, the systematic understanding of CRMs still mainly resorts to computational methods due to the time-consuming and small-scale nature of experimental methods. But the accuracy and reliability of different CRM prediction tools are still unclear. Without comparative cross-analysis of the results and combinatorial consideration with extra experimental information, there is no easy way to assess the confidence of the predicted CRMs. This limits the genome-wide understanding of CRMs. Description It is known that transcription factor binding and epigenetic profiles tend to determine functions of CRMs in gene transcriptional regulation. Thus integration of the genome-wide epigenetic profiles with systematically predicted CRMs can greatly help researchers evaluate and decipher the prediction confidence and possible transcriptional regulatory functions of these potential CRMs. However, these data are still fragmentary in the literatures. Here we performed the computational genome-wide screening for potential CRMs using different prediction tools and constructed the pioneer database, cisMEP (cis-regulatory module epigenetic profile database), to integrate these computationally identified CRMs with genomic epigenetic profile data. cisMEP collects the literature-curated TFBS location data and nine genres of epigenetic data for assessing the confidence of these potential CRMs and deciphering the possible CRM functionality. Conclusions cisMEP aims to provide a user-friendly interface for researchers to assess the confidence of different potential CRMs and to understand the functions of CRMs through experimentally-identified epigenetic profiles. The deposited potential CRMs and experimental epigenetic profiles for confidence assessment provide experimentally testable hypotheses for the molecular mechanisms of metazoan gene regulation. We believe that the information deposited in cisMEP will greatly facilitate the comparative usage of different CRM prediction tools and will help biologists to study the modular regulatory mechanisms between different TFs and their target genes. PMID:25521507
Revisiting Social Network Utilization by Physicians-in-Training.
Black, Erik W; Thompson, Lindsay A; Duff, W Patrick; Dawson, Kara; Saliba, Heidi; Black, Nicole M Paradise
2010-06-01
To measure and compare the frequency and content of online social networking among 2 cohorts of medical students and residents (2007 and 2009). Using the online social networking application Facebook, we evaluated social networking profiles for 2 cohorts of medical students (n = 528) and residents (n = 712) at the University of Florida in Gainesville. Objective measures included existence of a profile, whether it was made private, and whether any personally identifiable information was included. Subjective outcomes included photographic content, affiliated social groups, and personal information not generally disclosed in a doctor-patient encounter. We compared our results to our previously published and reported data from 2007. Social networking continues to be common amongst physicians-in-training, with 39.8% of residents and 69.5% of medical students maintaining Facebook accounts. Residents' participation significantly increased (P < .01) when compared to the 2007 data. Individuals in the 2009 cohort had significantly more "friends" (P < .01), belonged to more "groups" (P < .01), and were more likely to limit public access to their profiles through the use of privacy settings (P < .01) than the individuals in the 2007 cohort. Online social networking application use by physicians-in-training remains common. While most now limit access to their profiles, personal profiles that still allow public access exhibited a few instances of unprofessional behavior. Concerns remain related to the discovery of content in violation of patient privacy and the expansive and impersonal networks of online "friends" who may view profiles.
Sung, Ki-Chul; Reaven, Gerald; Kim, Sun
2014-07-01
The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) has identified increased cardio-metabolic risk and outcome in European populations. The goal of this study was to see if this ratio would also have clinical utility in identifying cardio-metabolic risk in an East Asian population. Measurements of various cardio-metabolic risk factors, including coronary calcium scores, were available on 12,166 apparently healthy Korean adults. Approximately 25% of men and women with the highest TG/HDL-C ratios were classified as being at high cardio-metabolic risk, and their risk factor profiles compared to the remainder of the population, as well as to individuals with the metabolic syndrome (MetS). High cardio-metabolic risk (upper 25%) was defined as a TG/HDL-C ratio ≥3.5 (men) or ≥2.0 (women), and all cardio-metabolic risk factors measured, including coronary calcium scores, were significantly more adverse when compared to individuals beneath these cut-points. Although cardio-metabolic risk profiles appeared reasonably comparable in subjects identified by either a high TG/HDL-C or a diagnosis of MetS, use of the TG/HDL-C increased the numbers at high risk. Evidence that determination of the plasma TG/HDL-C concentration ratio provides a simple way to identify individual at increased cardio-metabolic risk has been extended to an East Asian population. The ability of an elevated TG/HDL-C ratio to accomplish this goal is comparable to that achieved using the more complicated MetS criteria. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Fukuoka, Yoshimi; Lindgren, Teri G; Mintz, Yonatan Dov; Hooper, Julie; Aswani, Anil
2018-06-20
Regular physical activity is associated with reduced risk of chronic illnesses. Despite various types of successful physical activity interventions, maintenance of activity over the long term is extremely challenging. The aims of this original paper are to 1) describe physical activity engagement post intervention, 2) identify motivational profiles using natural language processing (NLP) and clustering techniques in a sample of women who completed the physical activity intervention, and 3) compare sociodemographic and clinical data among these identified cluster groups. In this cross-sectional analysis of 203 women completing a 12-month study exit (telephone) interview in the mobile phone-based physical activity education study were examined. The mobile phone-based physical activity education study was a randomized, controlled trial to test the efficacy of the app and accelerometer intervention and its sustainability over a 9-month period. All subjects returned the accelerometer and stopped accessing the app at the last 9-month research office visit. Physical engagement and motivational profiles were assessed by both closed and open-ended questions, such as "Since your 9-month study visit, has your physical activity been more, less, or about the same (compared to the first 9 months of the study)?" and, "What motivates you the most to be physically active?" NLP and cluster analysis were used to classify motivational profiles. Descriptive statistics were used to compare participants' baseline characteristics among identified groups. Approximately half of the 2 intervention groups (Regular and Plus) reported that they were still wearing an accelerometer and engaging in brisk walking as they were directed during the intervention phases. These numbers in the 2 intervention groups were much higher than the control group (overall P=.01 and P=.003, respectively). Three clusters were identified through NLP and named as the Weight Loss group (n=19), the Illness Prevention group (n=138), and the Health Promotion group (n=46). The Weight Loss group was significantly younger than the Illness Prevention and Health Promotion groups (overall P<.001). The Illness Prevention group had a larger number of Caucasians as compared to the Weight Loss group (P=.001), which was composed mostly of those who identified as African American, Hispanic, or mixed race. Additionally, the Health Promotion group tended to have lower BMI scores compared to the Illness Prevention group (overall P=.02). However, no difference was noted in the baseline moderate-to-vigorous intensity activity level among the 3 groups (overall P>.05). The findings could be relevant to tailoring a physical activity maintenance intervention. Furthermore, the findings from NLP and cluster analysis are useful methods to analyze short free text to differentiate motivational profiles. As more sophisticated NL tools are developed in the future, the potential of NLP application in behavioral research will broaden. ClinicalTrials.gov NCT01280812; https://clinicaltrials.gov/ct2/show/NCT01280812 (Archived by WebCite at http://www.webcitation.org/70IkGagAJ). ©Yoshimi Fukuoka, Teri G Lindgren, Yonatan Dov Mintz, Julie Hooper, Anil Aswani. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 20.06.2018.
Microdissection of Shoot Meristem Functional Domains
USDA-ARS?s Scientific Manuscript database
The shoot apical meristem (SAM) maintains a pool of indeterminate cells within the SAM proper, while lateral organs are initiated from the SAM periphery. Laser microdissection–microarray technology was used to compare transcriptional profiles within these SAM domains to identify novel maize genes th...
Common patterns and disease-related signatures in tuberculosis and sarcoidosis.
Maertzdorf, Jeroen; Weiner, January; Mollenkopf, Hans-Joachim; Bauer, Torsten; Prasse, Antje; Müller-Quernheim, Joachim; Kaufmann, Stefan H E
2012-05-15
In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.
Conroy, Melissa J; Galvin, Karen C; Doyle, Suzanne L; Kavanagh, Maria E; Mongan, Ann-Marie; Cannon, Aoife; Moore, Gillian Y; Reynolds, John V; Lysaght, Joanne
2016-10-01
In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum and liver of patients with the obesity-associated malignancy oesophageal adenocarcinoma (OAC). Furthermore, we assessed the secreted cytokine profile in OAC patient serum, omentum and liver to assess systemic and local inflammation. We observed parallel T cell cytokine profiles and phenotypes in the omentum and liver of OAC patients, in particular CD69(+) and inflammatory effector memory T cells. This study reflects similar processes of inflammation and T cell activation in the omentum and liver, and may suggest common targets to modulate pathological inflammation at these sites.
Panis, C; Binato, R; Correa, S; Victorino, V J; Dias-Alves, V; Herrera, A C S A; Cecchini, R; Simão, A N C; Barbosa, D S; Pizzatti, L; Abdelhay, E
2017-09-01
Although paclitaxel-based chemotherapy is widely used for treating breast cancer, paclitaxel therapy has been associated with several adverse effects. Such adverse effects have primarily been associated with long-term regimens, but some acute effects are being increasingly reported in the literature. In this context, the present study analyzed the systemic proteomic profiles of women diagnosed with breast cancer at the first cycle of short paclitaxel infusion (n = 30). Proteomic profiles thus obtained were compared with those of breast cancer patients without chemotherapy (n = 50), as well as with those of healthy controls (n = 40). Plasma samples were evaluated by label-free LC-MS to obtain systemic proteomic profiles. Putative dysregulated pathways were identified and validated by in silico analysis of proteomic profiles. Our results identified 188 proteins that were differentially expressed in patients who received a single short paclitaxel infusion when compared to patients who did not receive the infusion. Gene ontology analysis indicated that the cholesterol pathway may be dysregulated by paclitaxel in these patients. Validation analysis showed that paclitaxel treatment significantly reduced plasma high-density lipoprotein levels and increased plasma hydroperoxide levels when compared to breast cancer patients without chemotherapy. Furthermore, augmented C-reactive protein and creatine kinase fraction MB were found to be significantly higher in paclitaxel-treated patients in comparison with healthy controls. Taken together, these data suggest that a single dose of short paclitaxel infusion is sufficient to trigger significant alterations in lipid metabolism, which puts breast cancer patients at risk for increased incidence of cardiovascular disease.
Treatment Algorithms Based on Tumor Molecular Profiling: The Essence of Precision Medicine Trials.
Le Tourneau, Christophe; Kamal, Maud; Tsimberidou, Apostolia-Maria; Bedard, Philippe; Pierron, Gaëlle; Callens, Céline; Rouleau, Etienne; Vincent-Salomon, Anne; Servant, Nicolas; Alt, Marie; Rouzier, Roman; Paoletti, Xavier; Delattre, Olivier; Bièche, Ivan
2016-04-01
With the advent of high-throughput molecular technologies, several precision medicine (PM) studies are currently ongoing that include molecular screening programs and PM clinical trials. Molecular profiling programs establish the molecular profile of patients' tumors with the aim to guide therapy based on identified molecular alterations. The aim of prospective PM clinical trials is to assess the clinical utility of tumor molecular profiling and to determine whether treatment selection based on molecular alterations produces superior outcomes compared with unselected treatment. These trials use treatment algorithms to assign patients to specific targeted therapies based on tumor molecular alterations. These algorithms should be governed by fixed rules to ensure standardization and reproducibility. Here, we summarize key molecular, biological, and technical criteria that, in our view, should be addressed when establishing treatment algorithms based on tumor molecular profiling for PM trials. © The Author 2015. Published by Oxford University Press.
PCR array analysis of gene expression profiles in chronic active Epstein-Barr virus infection.
Murakami, Masanao; Hashida, Yumiko; Imajoh, Masayuki; Maeda, Akihiko; Kamioka, Mikio; Senda, Yasutaka; Sato, Tetsuya; Fujieda, Mikiya; Wakiguchi, Hiroshi; Daibata, Masanori
2014-07-01
To determine the host cellular gene expression profiles in chronic active Epstein-Barr virus infection (CAEBV), peripheral blood samples were obtained from three patients with CAEBV and investigated using a PCR array analysis that focused on T-cell/B-cell activation. We identified six genes with expression levels that were tenfold higher in CAEBV patients compared with those in healthy controls. These results were verified by quantitative reverse transcription-PCR. We identified four highly upregulated genes, i.e., IL-10, IL-2, IFNGR1, and INHBA. These genes may be involved in inflammatory responses and cell proliferation, and they may contribute to the development and progression of CAEBV. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Han, Sangjo; Lee, Minho; Chang, Hyeshik
Highlights: •The first compendium of chemical-genetic profiles form fission yeast was generated. •The first HTS of drug mode-of-action in fission yeast was performed. •The first comparative chemical genetic analysis between two yeasts was conducted. -- Abstract: Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defectmore » measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at (http://pombe.kaist.ac.kr/compendium)« less
Al-Khelaifi, Fatima; Diboun, Ilhame; Donati, Francesco; Botrè, Francesco; Alsayrafi, Mohammed; Georgakopoulos, Costas; Suhre, Karsten; Yousri, Noha A; Elrayess, Mohamed A
2018-01-05
The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes' elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications.
GEMINI: a computationally-efficient search engine for large gene expression datasets.
DeFreitas, Timothy; Saddiki, Hachem; Flaherty, Patrick
2016-02-24
Low-cost DNA sequencing allows organizations to accumulate massive amounts of genomic data and use that data to answer a diverse range of research questions. Presently, users must search for relevant genomic data using a keyword, accession number of meta-data tag. However, in this search paradigm the form of the query - a text-based string - is mismatched with the form of the target - a genomic profile. To improve access to massive genomic data resources, we have developed a fast search engine, GEMINI, that uses a genomic profile as a query to search for similar genomic profiles. GEMINI implements a nearest-neighbor search algorithm using a vantage-point tree to store a database of n profiles and in certain circumstances achieves an [Formula: see text] expected query time in the limit. We tested GEMINI on breast and ovarian cancer gene expression data from The Cancer Genome Atlas project and show that it achieves a query time that scales as the logarithm of the number of records in practice on genomic data. In a database with 10(5) samples, GEMINI identifies the nearest neighbor in 0.05 sec compared to a brute force search time of 0.6 sec. GEMINI is a fast search engine that uses a query genomic profile to search for similar profiles in a very large genomic database. It enables users to identify similar profiles independent of sample label, data origin or other meta-data information.
Bruderer, Roland; Bernhardt, Oliver M.; Gandhi, Tejas; Miladinović, Saša M.; Cheng, Lin-Yang; Messner, Simon; Ehrenberger, Tobias; Zanotelli, Vito; Butscheid, Yulia; Escher, Claudia; Vitek, Olga; Rinner, Oliver; Reiter, Lukas
2015-01-01
The data-independent acquisition (DIA) approach has recently been introduced as a novel mass spectrometric method that promises to combine the high content aspect of shotgun proteomics with the reproducibility and precision of selected reaction monitoring. Here, we evaluate, whether SWATH-MS type DIA effectively translates into a better protein profiling as compared with the established shotgun proteomics. We implemented a novel DIA method on the widely used Orbitrap platform and used retention-time-normalized (iRT) spectral libraries for targeted data extraction using Spectronaut. We call this combination hyper reaction monitoring (HRM). Using a controlled sample set, we show that HRM outperformed shotgun proteomics both in the number of consistently identified peptides across multiple measurements and quantification of differentially abundant proteins. The reproducibility of HRM in peptide detection was above 98%, resulting in quasi complete data sets compared with 49% of shotgun proteomics. Utilizing HRM, we profiled acetaminophen (APAP)1-treated three-dimensional human liver microtissues. An early onset of relevant proteome changes was revealed at subtoxic doses of APAP. Further, we detected and quantified for the first time human NAPQI-protein adducts that might be relevant for the toxicity of APAP. The adducts were identified on four mitochondrial oxidative stress related proteins (GATM, PARK7, PRDX6, and VDAC2) and two other proteins (ANXA2 and FTCD). Our findings imply that DIA should be the preferred method for quantitative protein profiling. PMID:25724911
Swindell, William R; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P; Voorhees, John J; Elder, James T; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P; DiGiovanni, John; Pittelkow, Mark R; Ward, Nicole L; Gudjonsson, Johann E
2011-04-04
Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.
GLOBAL PROPERTIES OF M31'S STELLAR HALO FROM THE SPLASH SURVEY. I. SURFACE BRIGHTNESS PROFILE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gilbert, Karoline M.; Guhathakurta, Puragra; Beaton, Rachael L.
2012-11-20
We present the surface brightness profile of M31's stellar halo out to a projected radius of 175 kpc. The surface brightness estimates are based on confirmed samples of M31 red giant branch stars derived from Keck/DEIMOS spectroscopic observations. A set of empirical spectroscopic and photometric M31 membership diagnostics is used to identify and reject foreground and background contaminants. This enables us to trace the stellar halo of M31 to larger projected distances and fainter surface brightnesses than previous photometric studies. The surface brightness profile of M31's halo follows a power law with index -2.2 {+-} 0.2 and extends to amore » projected distance of at least {approx}175 kpc ({approx}2/3 of M31's virial radius), with no evidence of a downward break at large radii. The best-fit elliptical isophotes have b/a = 0.94 with the major axis of the halo aligned along the minor axis of M31's disk, consistent with a prolate halo, although the data are also consistent with M31's halo having spherical symmetry. The fact that tidal debris features are kinematically cold is used to identify substructure in the spectroscopic fields out to projected radii of 90 kpc and investigate the effect of this substructure on the surface brightness profile. The scatter in the surface brightness profile is reduced when kinematically identified tidal debris features in M31 are statistically subtracted; the remaining profile indicates that a comparatively diffuse stellar component to M31's stellar halo exists to large distances. Beyond 90 kpc, kinematically cold tidal debris features cannot be identified due to small number statistics; nevertheless, the significant field-to-field variation in surface brightness beyond 90 kpc suggests that the outermost region of M31's halo is also comprised to a significant degree of stars stripped from accreted objects.« less
Filatov, Victor; Dowdle, John; Smirnoff, Nicholas; Ford-Lloyd, Brian; Newbury, H John; Macnair, Mark R
2006-09-01
One of the challenges of comparative genomics is to identify specific genetic changes associated with the evolution of a novel adaptation or trait. We need to be able to disassociate the genes involved with a particular character from all the other genetic changes that take place as lineages diverge. Here we show that by comparing the transcriptional profile of segregating families with that of parent species differing in a novel trait, it is possible to narrow down substantially the list of potential target genes. In addition, by assuming synteny with a related model organism for which the complete genome sequence is available, it is possible to use the cosegregation of markers differing in transcription level to identify regions of the genome which probably contain quantitative trait loci (QTLs) for the character. This novel combination of genomics and classical genetics provides a very powerful tool to identify candidate genes. We use this methodology to investigate zinc hyperaccumulation in Arabidopsis halleri, the sister species to the model plant, Arabidopsis thaliana. We compare the transcriptional profile of A. halleri with that of its sister nonaccumulator species, Arabidopsis petraea, and between accumulator and nonaccumulator F(3)s derived from the cross between the two species. We identify eight genes which consistently show greater expression in accumulator phenotypes in both roots and shoots, including two metal transporter genes (NRAMP3 and ZIP6), and cytoplasmic aconitase, a gene involved in iron homeostasis in mammals. We also show that there appear to be two QTLs for zinc accumulation, on chromosomes 3 and 7.
Zhang, Bin; Lin, Ting; He, Hong
2015-12-24
This study aimed to identify characteristic representative genes through a comparative analysis of gene expression profiles in the blood and saliva of chronic periodontitis (CP) and refractory periodontitis (RP) patients to provide new treatment strategies that may be helpful in the treatment of different forms of periodontitis. GSE43525 was downloaded from Gene Expression Omnibus. In the dataset, thirteen samples were from blood including 4 controls, 4 CP and 5 RP samples, and ten samples were from saliva including 3 controls, 4 CP and 3 RP samples. After comparing the CP and RP samples, differentially expressed genes (DEGs) between these two types of periodontitis in the blood and saliva samples were identified by an LIMMA package. Then, functional and pathway enrichment analyses were performed by DAVID and KOBAS, respectively. The significantly associated miRNAs in CP and RP were searched by WebGestalt. In total, 213 DEGs in CP and 45 DEGs in RP were identified. Functional enrichment showed that the DEGs of CP were mainly enriched in ribosome and regulation of apoptosis-related pathways in blood as well as saliva, while the DEGs of RP were significantly enriched in immune responses and response to organic substance-related pathways. Several miRNAs, such as miR-381 and miR-494, were identified as being closely associated with CP. In addition, CD24, EST1, MTSS1, ING3, CCND2 and SYNE2 might be potential targets for diagnosis and treatment of CP. The identified DEGs and miRNAs might be potential targets for the treatment of chronic and refractory periodontitis.
Chemical libraries paired with phenotypic screens can now readily identify compounds with therapeutic potential. A central limitation to exploiting these compounds, however, has been in identifying their relevant cellular targets. Here, we present a two-tiered CRISPR-mediated chemical-genetic strategy for target identification: combined genome-wide knockdown and overexpression screening as well as focused, comparative chemical-genetic profiling.
NASA Astrophysics Data System (ADS)
Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen
2016-05-01
We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347-356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205-214), and isoform 1 of fibrinogen α chain precursor (FGA 588-624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.
Sonuga-Barke, Edmund J S; Van Lier, Pol; Swanson, James M; Coghill, David; Wigal, Sharon; Vandenberghe, Mieke; Hatch, Simon
2008-06-01
To use growth mixture modelling (GMM) to identify subgroups of children with attention deficit hyperactive disorder (ADHD) who have different pharmacodynamic profiles in response to extended release methylphenidate as assessed in a laboratory classroom setting. GMM analysis was performed on data from the COMACS study (Comparison of Methylphenidates in the Analog Classroom Setting): a large (n = 184) placebo-controlled cross-over study comparing three treatment conditions in the Laboratory School Protocol (with a 1.5-h cycle of attention and deportment assessments). Two orally administered, once-daily methylphenidate (MPH) bioequivalent formulations [Metadate CD/Equasym XL (MCD-EQXL) and Concerta XL (CON)] were compared with placebo (PLA). Three classes of children with distinct severity profiles in the PLA condition were identified. For both MCD-EQXL and CON, the more severe their PLA symptoms the better, the children's response. However, the formulations produced different growth curves by class, with CON having essentially a flat profile for all three classes (i.e. no effect of PLA severity) and MCD-EQXL showing a marked decline in symptoms immediately post-dosing in the two most severe classes compared with the least severe. Comparison of daily doses matched for immediate-release (IR) components accounted for this difference. The results suggest considerable heterogeneity in the pharmacodynamics of MPH response by children with ADHD. When treatment response for near-equal, bioequivalent daily doses the two formulations was compared, marked differences were seen for children in the most severe classes with a strong curvilinear trajectory for MCD-EQXL related to the greater IR component.
NASA Astrophysics Data System (ADS)
Zhang, Hong
2016-07-01
We investigated potential mechanisms of acute injury in pubertal mice testes after exposure to carbon ion radiation (CIR). Serum testosterone was measured following whole-body irradiation with a 2Gy carbon ion beam. Comparative proteomic profiling and Western blotting were applied to identify potential biomarkers and measure protein expression, and terminal dUTP nick end-labeling (TUNEL) was performed to detect apoptotic cells. Immunohistochemistry and immunofluorescence were used to investigate protein localization. Serum testosterone was lowest at 24h after CIR, and 10 differentially expressed proteins were identified at this time point that included eIF4E, an important regulator of initiation that combines with mTOR and 4EBP1 to control protein synthesis via the mTOR signalling pathway during proliferation and apoptosis. Protein expression and localization studies confirmed their association with acute injury following exposure to CIR. These three proteins may be useful molecular markers for detecting abnormal spermatogenesis following exposure to environmental and cosmic radiation
Wang, Nani; Wang, Xuping; Zhang, Yang; Zhang, Qiaoyan; Xu, Pingcui; Xin, Hailiang; Wu, Renjie; Shou, Dan; Qin, Luping
2018-05-30
Osthole is a derivative of coumnarin, which has been used to treat several diseases, including osteoporosis. To investigate the metabolite profile of osthole in osteoporosis rats was utilized to understand its underlying mechanisms of its anti-osteoporosis effect. In this study, plasma samples were collected from normal and osteoporosis rats after oral administration of osthole and analyzed to identify the metabolites of osthole by high performance liquid chromatography quadrupole time-of-flight mass spectrometry. By comparing the molecular weight and MS fragmentation of the metabolites with those of parent drug and reference standards, a total of 36 metabolites in plasma were identified. Demethylation, hydroxylation, hydroxymethylene loss and reduction, and subsequent glucuronidation, methylation and sulfation were the major metabolic pathways of osthole in both normal and osteoporosis rats. A specific hydration metabolic pathway was found in osteoporosis rats. These results provided a meaningful basis for studying the underlying mechanism of the anti-osteoporosis effect of osthole. Copyright © 2018 Elsevier B.V. All rights reserved.
2012-01-01
Background Proteins that are associated with hypertension may be identified by comparing the 2-dimensional gel electrophoresis (2-DE) profiles of the sera of spontaneously hypertensive rats (SHR) with those generated from normotensive Spraque-Dawley rats (SDR). Results Five proteins of high abundance were found to be significantly altered when the 2-DE serum profiles of the SHR were compared to those that were similarly generated from the SDR. Analysis by mass spectrometry and database search identified the proteins as retinol binding protein 4, complement C3, albumin (19.9 kDa fragment), alpha1 macroglobulin and alpha1 antiproteinase, which are all known to be associated with hypertension. The altered expression of the two latter proteins was found to be abrogated when similar analysis was performed on sera of the SHR that were treated with captopril. Conclusion Our data suggests that serum alpha1 macroglobulin and alpha1 antiproteinase are potentially useful complementary biomolecular indicators for monitoring of hypertension. PMID:22416803
Maker, Garth L.; Trengove, Robert D.; O'Handley, Ryan M.
2015-01-01
The aim of this study was to utilize gas chromatography coupled with mass spectrometry (GC-MS) to compare and identify patterns of biochemical change between Salmonella cells grown in planktonic and biofilm phases and Salmonella biofilms of different ages. Our results showed a clear separation between planktonic and biofilm modes of growth. The majority of metabolites contributing to variance between planktonic and biofilm supernatants were identified as amino acids, including alanine, glutamic acid, glycine, and ornithine. Metabolites contributing to variance in intracellular profiles were identified as succinic acid, putrescine, pyroglutamic acid, and N-acetylglutamic acid. Principal-component analysis revealed no significant differences between the various ages of intracellular profiles, which would otherwise allow differentiation of biofilm cells on the basis of age. A shifting pattern across the score plot was illustrated when analyzing extracellular metabolites sampled from different days of biofilm growth, and amino acids were again identified as the metabolites contributing most to variance. An understanding of biofilm-specific metabolic responses to perturbations, especially antibiotics, can lead to the identification of novel drug targets and potential therapies for combating biofilm-associated diseases. We concluded that under the conditions of this study, GC-MS can be successfully applied as a high-throughput technique for “bottom-up” metabolomic biofilm research. PMID:25636852
Collins, Mahlon A; An, Jiyan; Hood, Brian L; Conrads, Thomas P; Bowser, Robert P
2015-11-06
Analysis of the cerebrospinal fluid (CSF) proteome has proven valuable to the study of neurodegenerative disorders. To identify new protein/pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis (ALS), we performed comparative proteomic profiling of CSF from sporadic ALS (sALS), healthy control (HC), and other neurological disease (OND) subjects using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1712 CSF proteins were detected and relatively quantified by spectral counting. Levels of several proteins with diverse biological functions were significantly altered in sALS samples. Enrichment analysis was used to link these alterations to biological pathways, which were predominantly related to inflammation, neuronal activity, and extracellular matrix regulation. We then used our CSF proteomic profiles to create a support vector machines classifier capable of discriminating training set ALS from non-ALS (HC and OND) samples. Four classifier proteins, WD repeat-containing protein 63, amyloid-like protein 1, SPARC-like protein 1, and cell adhesion molecule 3, were identified by feature selection and externally validated. The resultant classifier distinguished ALS from non-ALS samples with 83% sensitivity and 100% specificity in an independent test set. Collectively, our results illustrate the utility of CSF proteomic profiling for identifying ALS protein/pathway alterations and candidate disease biomarkers.
The recovery and analysis of mitochondrial DNA from exploded pipe bombs.
Foran, David R; Gehring, Michael E; Stallworth, Shawn E
2009-01-01
Improvised explosive devices (IEDs) represent one of the most common modes of arbitrarily injuring or killing human beings. Because of the heat generated by, and destruction to, an IED postconflagration, most methods for identifying who assembled the device are ineffective. In the research presented, steel pipe bombs were mock-assembled by volunteers, and the bombs detonated under controlled conditions. The resultant shrapnel was collected and swabbed for residual cellular material. Mitochondrial DNA profiles were generated and compared blind to the pool of individuals who assembled the bombs. Assemblers were correctly identified 50% of the time, while another 19% could be placed into a group of three individuals with shared haplotypes. Only one bomb was assigned incorrectly. In some instances a contaminating profile (mixture) was also observed. Taken together, the results speak to the extreme sensitivity the methods have for identifying those who assemble IEDs, along with precautions needed when collecting and processing such evidence.
Transcriptional programming during cell wall maturation in the expanding Arabidopsis stem.
Hall, Hardy; Ellis, Brian
2013-01-25
Plant cell walls are complex dynamic structures that play a vital role in coordinating the directional growth of plant tissues. The rapid elongation of the inflorescence stem in the model plant Arabidopsis thaliana is accompanied by radical changes in cell wall structure and chemistry, but analysis of the underlying mechanisms and identification of the genes that are involved has been hampered by difficulties in accurately sampling discrete developmental states along the developing stem. By creating stem growth kinematic profiles for individual expanding Arabidopsis stems we have been able to harvest and pool developmentally-matched tissue samples, and to use these for comparative analysis of global transcript profiles at four distinct phases of stem growth: the period of elongation rate increase, the point of maximum growth rate, the point of stem growth cessation and the fully matured stem. The resulting profiles identify numerous genes whose expression is affected as the stem tissues pass through these defined growth transitions, including both novel loci and genes identified in earlier studies. Of particular note is the preponderance of highly active genes associated with secondary cell wall deposition in the region of stem growth cessation, and of genes associated with defence and stress responses in the fully mature stem. The use of growth kinematic profiling to create tissue samples that are accurately positioned along the expansion growth continuum of Arabidopsis inflorescence stems establishes a new standard for transcript profiling analyses of such tissues. The resulting expression profiles identify a substantial number of genes whose expression is correlated for the first time with rapid cell wall extension and subsequent fortification, and thus provide an important new resource for plant biologists interested in gene discovery related to plant biomass accumulation.
Bajaj, Deepak; Upadhyaya, Hari D.; Khan, Yusuf; Das, Shouvik; Badoni, Saurabh; Shree, Tanima; Kumar, Vinod; Tripathi, Shailesh; Gowda, C. L. L.; Singh, Sube; Sharma, Shivali; Tyagi, Akhilesh K.; Chattopdhyay, Debasis; Parida, Swarup K.
2015-01-01
High experimental validation/genotyping success rate (94–96%) and intra-specific polymorphic potential (82–96%) of 1536 SNP and 472 SSR markers showing in silico polymorphism between desi ICC 4958 and kabuli ICC 12968 chickpea was obtained in a 190 mapping population (ICC 4958 × ICC 12968) and 92 diverse desi and kabuli genotypes. A high-density 2001 marker-based intra-specific genetic linkage map comprising of eight LGs constructed is comparatively much saturated (mean map-density: 0.94 cM) in contrast to existing intra-specific genetic maps in chickpea. Fifteen robust QTLs (PVE: 8.8–25.8% with LOD: 7.0–13.8) associated with pod and seed number/plant (PN and SN) and 100 seed weight (SW) were identified and mapped on 10 major genomic regions of eight LGs. One of 126.8 kb major genomic region harbouring a strong SW-associated robust QTL (Caq'SW1.1: 169.1–171.3 cM) has been delineated by integrating high-resolution QTL mapping with comprehensive marker-based comparative genome mapping and differential expression profiling. This identified one potential regulatory SNP (G/A) in the cis-acting element of candidate ERF (ethylene responsive factor) TF (transcription factor) gene governing seed weight in chickpea. The functionally relevant molecular tags identified have potential to be utilized for marker-assisted genetic improvement of chickpea. PMID:25786576
Salazar, Martin R; Carbajal, Horacio A; Espeche, Walter G; Aizpurúa, Marcelo; Leiva Sisnieguez, Carlos E; Leiva Sisnieguez, Betty C; March, Carlos E; Stavile, Rodolfo N; Balbín, Eduardo; Reaven, Gerald M
2014-10-01
This analysis evaluated the hypothesis that the plasma triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) concentration ratio can help identify patients with essential hypertension who are insulin-resistant, with the cardiovascular disease (CVD) risk profile associated with that defect. Data from a community-based study developed between 2003 and 2012 were used to compare CVD risk factors and outcome. Plasma TG/HDL-C cut-points of 2.5 (women) and 3.5 (men) subdivided normotensive (n = 574) and hypertensive (n = 373) subjects into "high" and "low" risk groups. Metabolic syndrome criteria (MetS) were also used to identify "high" and "low" risk groups. The baseline cardio-metabolic profile was significantly more adverse in 2003 in "high" risk subgroups, irrespective of BP classification or definition of risk (TG/HDL-C ratio vs. MetS criteria). Crude incidence of combined CVD events increased across risk groups, ranging from 1.9 in normotensive-low TG/HDL-C subjects to 19.9 in hypertensive-high TG/HDL-C ratio individuals (P for trends <.001). Adjusted hazard ratios for CVD events also increased with both hypertension and TG/HDL-C. Comparable findings were seen when CVD outcome was predicted by MetS criteria. The TG/HDL-C concentration ratio and the MetS criteria identify to a comparable degree hypertensive subjects who are at greatest cardio-metabolic risk and develop significantly more CVD.
Urinary volatile organic compounds as potential biomarkers for renal cell carcinoma
WANG, DONGCHUN; WANG, CHANGSONG; PI, XIN; GUO, LEI; WANG, YUE; LI, MINGJUAN; FENG, YUE; LIN, ZIWEI; HOU, WEI; LI, ENYOU
2016-01-01
Currently, there is no adequate, sensitive, reproducible, specific and noninvasive biomarker that can reliably be used to detect renal cell carcinoma (RCC). Previous studies have elucidated the urinary non-volatile metabolic profile of RCC. However, whether urinary volatile organic compound (VOC) profiles are able to identify RCC remains to be elucidated. In the present study, urine was collected from 22 patients with RCC and 25 healthy subjects. Principal component analysis and orthogonal partial least square discriminant analysis were used to compare the data of patients and healthy subjects, and preoperative and postoperative patients undergoing radical nephrectomy. In total, 11 VOC biomarkers were elevated in the RCC patients compared to the healthy subjects, which were phenol; decanal; 1,6-dioxacyclododecane-7,12-dione; 1-bromo-1-(3-methyl-1-pentenylidene)-2,2,3,3-tetramethyl-cyclopropane; nonanal; 3-ethyl-3-methylheptane; isolongifolene-5-ol; 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethylethyl); tetradecane; aniline; and 2,6,10,14-tetramethyl-pentadecane. Three biomarkers were decreased in RCC patients: styrene, 4-heptanone and dimethylsilanediol. In preoperative patients, 2-ethyl-1-hexanol and cyclohexanone were elevated, while 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne were decreased when compared to postoperative patients. Compared with the healthy subjects, RCC has a unique VOC profile, suggesting that VOC profiles may be a useful diagnostic assay for RCC. PMID:27347408
Comparing metabolite profiles of habitual diet in serum and urine123
Playdon, Mary C; Sampson, Joshua N; Cross, Amanda J; Sinha, Rashmi; Guertin, Kristin A; Moy, Kristin A; Rothman, Nathaniel; Irwin, Melinda L; Mayne, Susan T; Stolzenberg-Solomon, Rachael; Moore, Steven C
2016-01-01
Background: Diet plays an important role in chronic disease etiology, but some diet-disease associations remain inconclusive because of methodologic limitations in dietary assessment. Metabolomics is a novel method for identifying objective dietary biomarkers, although it is unclear what dietary information is captured from metabolites found in serum compared with urine. Objective: We compared metabolite profiles of habitual diet measured from serum with those measured from urine. Design: We first estimated correlations between consumption of 56 foods, beverages, and supplements assessed by a food-frequency questionnaire, with 676 serum and 848 urine metabolites identified by untargeted liquid chromatography mass spectrometry, ultra-high performance liquid chromatography tandem mass spectrometry, and gas chromatography mass spectrometry in a colon adenoma case–control study (n = 125 cases and 128 controls) while adjusting for age, sex, smoking, fasting, case-control status, body mass index, physical activity, education, and caloric intake. We controlled for multiple comparisons with the use of a false discovery rate of <0.1. Next, we created serum and urine multiple-metabolite models to predict food intake with the use of 10-fold crossvalidation least absolute shrinkage and selection operator regression for 80% of the data; predicted values were created in the remaining 20%. Finally, we compared predicted values with estimates obtained from self-reported intake for metabolites measured in serum and urine. Results: We identified metabolites associated with 46 of 56 dietary items; 417 urine and 105 serum metabolites were correlated with ≥1 food, beverage, or supplement. More metabolites in urine (n = 154) than in serum (n = 39) were associated uniquely with one food. We found previously unreported metabolite associations with leafy green vegetables, sugar-sweetened beverages, citrus, added sugar, red meat, shellfish, desserts, and wine. Prediction of dietary intake from multiple-metabolite profiles was similar between biofluids. Conclusions: Candidate metabolite biomarkers of habitual diet are identifiable in both serum and urine. Urine samples offer a valid alternative or complement to serum for metabolite biomarkers of diet in large-scale clinical or epidemiologic studies. PMID:27510537
Forbush, Kelsie T; Hagan, Kelsey E; Salk, Rachel H; Wildes, Jennifer E
2017-03-01
Bulimia nervosa can be reliably classified into subtypes based on dimensions of dietary restraint and negative affect. Community and clinical studies have shown that dietary-negative affect subtypes have greater test-retest reliability and concurrent and predictive validity compared to subtypes based on the Diagnostic and Statistical Manual of Mental Disorders (DSM). Although dietary-negative affect subtypes have shown utility for characterizing eating disorders that involve binge eating, this framework may have broader implications for understanding restrictive eating disorders. The purpose of this study was to test the concurrent and predictive validity of dietary-negative affect subtypes among patients with anorexia nervosa (AN; N = 194). Latent profile analysis was used to identify subtypes of AN based on dimensions of dietary restraint and negative affect. Chi-square and multivariate analysis of variance were used to characterize baseline differences between identified subtypes. Structural equation modeling was used to test whether dietary-negative affect subtypes would outperform DSM categories in predicting clinically relevant outcomes. Results supported a 2-profile model that replicated dietary-negative affect subtypes: Latent Profile 1 (n = 68) had clinically elevated scores on restraint only; Latent Profile 2 (n = 126) had elevated scores on both restraint and negative affect. Validation analyses showed that membership in the dietary-negative affect profile was associated with greater lifetime psychiatric comorbidity and psychosocial impairment compared to the dietary class. Dietary-negative affect subtypes only outperformed DSM categories in predicting quality-of-life impairment at 1-year follow-up. Findings highlight the clinical utility of subtyping AN based on dietary restraint and negative affect for informing future treatment-matching or personalized medicine strategies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Fanelli, Flaminia; Gambineri, Alessandra; Belluomo, Ilaria; Repaci, Andrea; Di Lallo, Valentina Diana; Di Dalmazi, Guido; Mezzullo, Marco; Prontera, Olga; Cuomo, Gaia; Zanotti, Laura; Paccapelo, Alexandro; Morselli-Labate, Antonio Maria; Pagotto, Uberto; Pasquali, Renato
2013-07-01
Physiological transient imbalance typical of adolescence needs to be distinguished from hyperandrogenism-related dysfunction. The accurate determination of circulating androgens is the best indicator of hyperandrogenism. However, reliable reference intervals for adolescent and young women are not available. The aim of the study was to define androgen reference intervals in young women and to analyze the impact of the menstrual phase and ovulation efficiency over the androgen profile as assessed by reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. Female high school students aged 16-19 years were included in the study. The study was performed on reference subjects properly selected among an unbiased population. Normal-weight, drug and disease free, eumenorrheic females with no signs of hyperandrogenism were included. The steroid hormone profile was determined by a validated in-house LC-MS/MS method. A statistical estimation of overall and menstrual phase-specific reference intervals was performed. A subgroup of anovulatory females was identified based on progesterone circulating levels. The impact of ovulation efficiency over hormonal profile was analyzed. A total of 159 females satisfied healthy criteria. Androgen levels did not vary according to menstrual phase, but a significantly higher upper reference limit was found for T in the luteal phase compared to the follicular phase. Higher T and androstenedione levels were observed in anovulatory compared to ovulatory females, paralleled by higher LH and FSH and lower 17-hydroxyprogesterone and 17β-estradiol levels. This is the first study providing LC-MS/MS-based, menstrual phase-specific reference intervals for the circulating androgen profile in young females. We identified a subgroup of anovulatory healthy females characterized by androgen imbalance.
Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach.
Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R; Plassman, Brenda L; Burke, James R; Browndyke, Jeffrey N; Welsh-Bohmer, Kathleen A
2014-11-01
Cognitive profiles for pre-clinical Alzheimer disease (AD) can be used to identify groups of individuals at risk for disease and better characterize pre-clinical disease. Profiles or patterns of performance as pre-clinical phenotypes may be more useful than individual test scores or measures of global decline. To evaluate patterns of cognitive performance in cognitively normal individuals to derive latent profiles associated with later onset of disease using a combination of factor analysis and latent profile analysis. The National Alzheimer Coordinating Centers collect data, including a battery of neuropsychological tests, from participants at 29 National Institute on Aging-funded Alzheimer Disease Centers across the United States. Prior factor analyses of this battery demonstrated a four-factor structure comprising memory, attention, language, and executive function. Factor scores from these analyses were used in a latent profile approach to characterize cognition among a group of cognitively normal participants (N = 3,911). Associations between latent profiles and disease outcomes an average of 3 years later were evaluated with multinomial regression models. Similar analyses were used to determine predictors of profile membership. Four groups were identified; each with distinct characteristics and significantly associated with later disease outcomes. Two groups were significantly associated with development of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B, and a contrast score (Delayed Recall - Trails B), significantly predicted group membership and later cognitive impairment. Latent profile analysis is a useful method to evaluate patterns of cognition in large samples for the identification of preclinical AD phenotypes; comparable results, however, can be achieved with very sensitive tests and contrast scores. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Label-free Quantitative Protein Profiling of vastus lateralis Muscle During Human Aging*
Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe
2014-01-01
Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers. PMID:24217021
Label-free quantitative protein profiling of vastus lateralis muscle during human aging.
Théron, Laëtitia; Gueugneau, Marine; Coudy, Cécile; Viala, Didier; Bijlsma, Astrid; Butler-Browne, Gillian; Maier, Andrea; Béchet, Daniel; Chambon, Christophe
2014-01-01
Sarcopenia corresponds to the loss of muscle mass occurring during aging, and is associated with a loss of muscle functionality. Proteomic links the muscle functional changes with protein expression pattern. To better understand the mechanisms involved in muscle aging, we performed a proteomic analysis of Vastus lateralis muscle in mature and older women. For this, a shotgun proteomic method was applied to identify soluble proteins in muscle, using a combination of high performance liquid chromatography and mass spectrometry. A label-free protein profiling was then conducted to quantify proteins and compare profiles from mature and older women. This analysis showed that 35 of the 366 identified proteins were linked to aging in muscle. Most of the proteins were under-represented in older compared with mature women. We built a functional interaction network linking the proteins differentially expressed between mature and older women. The results revealed that the main differences between mature and older women were defined by proteins involved in energy metabolism and proteins from the myofilament and cytoskeleton. This is the first time that label-free quantitative proteomics has been applied to study of aging mechanisms in human skeletal muscle. This approach highlights new elements for elucidating the alterations observed during aging and may lead to novel sarcopenia biomarkers.
A Linguistic Analysis of Suicide-Related Twitter Posts.
O'Dea, Bridianne; Larsen, Mark E; Batterham, Philip J; Calear, Alison L; Christensen, Helen
2017-09-01
Suicide is a leading cause of death worldwide. Identifying those at risk and delivering timely interventions is challenging. Social media site Twitter is used to express suicidality. Automated linguistic analysis of suicide-related posts may help to differentiate those who require support or intervention from those who do not. This study aims to characterize the linguistic profiles of suicide-related Twitter posts. Using a dataset of suicide-related Twitter posts previously coded for suicide risk by experts, Linguistic Inquiry and Word Count (LIWC) and regression analyses were conducted to determine differences in linguistic profiles. When compared with matched non-suicide-related Twitter posts, strongly concerning suicide-related posts were characterized by a higher word count, increased use of first-person pronouns, and more references to death. When compared with safe-to-ignore suicide-related posts, strongly concerning suicide-related posts were characterized by increased use of first-person pronouns, greater anger, and increased focus on the present. Other differences were found. The predictive validity of the identified features needs further testing before these results can be used for interventional purposes. This study demonstrates that strongly concerning suicide-related Twitter posts have unique linguistic profiles. The examination of Twitter data for the presence of such features may help to validate online risk assessments and determine those in need of further support or intervention.
Zhou, Zhong-Yin; Tao, DI-DI; Cao, Ji-Wang; Luo, He-Sheng
2013-06-01
The aim of the present study was to identify a specific biological marker for the diagnosis of colorectal adenomas through the analysis of variations in serum protein profiling in colorectal adenoma patients. The study was conducted at the Renmin Hospital of Wuhan University (Wuhan, China) between September 2011 and May 2012. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was performed to compare the serum protein profiles of 50 patients with colorectal adenoma and 50 healthy individuals. The obtained protein profiles were analyzed using Biomarker Wizard software. Twenty protein peaks were identified to exhibit differences in average intensity between colorectal adenomas compared with normal controls, including peaks 8,565.84, 8,694.51 and 5,910.50 Da, in which the intensity between the patients and control individuals was significantly different. Two peaks, 8,565.84 and 8,694.51 Da, were observed to be highly expressed in the colorectal adenomas, however, expression was low in the control samples. By contrast, 5,910.50 Da expression was low in the colorectal adenomas and high in the controls. The results of the current study indicate that the three protein peaks may represent specific biomarkers for colorectal adenomas.
Dufva, Olli; Kankainen, Matti; Kelkka, Tiina; Sekiguchi, Nodoka; Awad, Shady Adnan; Eldfors, Samuli; Yadav, Bhagwan; Kuusanmäki, Heikki; Malani, Disha; Andersson, Emma I; Pietarinen, Paavo; Saikko, Leena; Kovanen, Panu E; Ojala, Teija; Lee, Dean A; Loughran, Thomas P; Nakazawa, Hideyuki; Suzumiya, Junji; Suzuki, Ritsuro; Ko, Young Hyeh; Kim, Won Seog; Chuang, Shih-Sung; Aittokallio, Tero; Chan, Wing C; Ohshima, Koichi; Ishida, Fumihiro; Mustjoki, Satu
2018-04-19
Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data. Drug sensitivity profiling further demonstrates the role of the JAK-STAT pathway in the pathogenesis of NK-cell malignancies, identifying NK cells to be highly sensitive to JAK and BCL2 inhibition compared to other hematopoietic cell lineages. Our results provide insight into ANKL genetics and a framework for application of targeted therapies in NK-cell malignancies.
Buccoliero, Luca; Bellio, Elena; Mazzola, Maria; Solinas, Elisa
2016-02-09
The study aims at investigating the characteristics and the satisfaction determinants of the emerging patient profile. This profile appears to be more demanding and "empowered" compared to the ones traditionally conceived, asking for unconventional healthcare services and for a closer relationship with providers. Both qualitative (semi-structured interviews and focus groups) and quantitative (survey) analyses were performed on a random sample of 2808 Italian citizens-patients. Analyses entailed descriptive statistics, bivariate analysis and linear regressions. Four relevant dimensions of patient 2.0 experience were identified through a literature review on experiential marketing in healthcare. Beta coefficients exhibited the effect that different healthcare experiential elements have on patient 2.0 satisfaction. Results allow to state that a new marketing approach, based on patient 2.0 characteristics and value drivers, should be adopted in the healthcare sector. Critical satisfaction drivers and new technological healthcare guidelines are identified in order to match the new patient profile needs.
Tillfors, Maria; Furmark, Tomas; Carlbring, Per; Andersson, Gerhard
2015-06-01
In social anxiety disorder (SAD) co-morbid depressive symptoms as well as avoidance behaviors have been shown to predict insufficient treatment response. It is likely that subgroups of individuals with different profiles of risk factors for poor treatment response exist. This study aimed to identify subgroups of social avoidance and depressive symptoms in a clinical sample (N = 167) with SAD before and after guided internet-delivered CBT, and to compare these groups on diagnostic status and social anxiety. We further examined individual movement between subgroups over time. Using cluster analysis we identified four subgroups, including a high-problem cluster at both time-points. Individuals in this cluster showed less remission after treatment, exhibited higher levels of social anxiety at both assessments, and typically remained in the high-problem cluster after treatment. Thus, in individuals with SAD, high levels of social avoidance and depressive symptoms constitute a risk profile for poor treatment response. Copyright © 2015 Elsevier Ltd. All rights reserved.
Antibody profiling sensitivity through increased reporter antibody layering
Apel, William A.; Thompson, Vicki S.
2013-02-26
A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.
Antibody profiling sensitivity through increased reporter antibody layering
Apel, William A.; Thompson, Vicki S.
2017-03-28
A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.
Yin, Rui; Yang, Tongshu; Su, Hui; Ying, Li; Liu, Liyan; Sun, Changhao
2016-09-26
The aims were to investigate the serum free fatty acid (FFA) and esterified fatty acid (EFA) profiles and to identify biomarkers that can be used to identify patients with epithelial ovarian cancer (EOC) based on the metabolomics approach. We applied a targeted gas chromatography-mass spectrometry metabolomics approach to serum samples from 40 EOC patients and 35 healthy controls for achieving the FFA and EFA profiles. These metabolite profiles were processed using multivariate analysis to obtain potential biomarkers. And then, some independent samples were chosen to validate these potential biomarkers. There were higher saturated fatty acids and lower unsaturated fatty acids in EOC patients when compared with the healthy controls. EFA (C16:0), EFA (C18:0) and FFA (C16:0) were identified as potential biomarkers that distinguished EOC from the healthy controls. The areas under the curve from the EFA (C16:0), EFA (C18:0) and FFA (C16:0) in validated study were 0.745, 0.701, 0.682, respectively. Our study provides useful information to bridge the gaps in our understanding to the fatty acids metabolic alterations associated with EOC, and this study has demonstrated saturated fatty acid biomarkers might be helpful for the detection and characterization of EOC patients.
Men, Xin; Ma, Jun; Wu, Tong; Pu, Junyi; Wen, Shaojia; Shen, Jianfeng; Wang, Xun; Wang, Yamin; Chen, Chao; Dai, Penggao
2018-01-01
Tamoxifen (TAM) resistance is an important clinical problem in the treatment of breast cancer. In order to identify the mechanism of TAM resistance for estrogen receptor (ER)-positive breast cancer, we screened the transcriptome using RNA-seq and compared the gene expression profiles between the MCF-7 mamma carcinoma cell line and the TAM-resistant cell line TAMR/MCF-7, 52 significant differential expression genes (DEGs) were identified including SLIT2, ROBO, LHX, KLF, VEGFC, BAMBI, LAMA1, FLT4, PNMT, DHRS2, MAOA and ALDH. The DEGs were annotated in the GO, COG and KEGG databases. Annotation of the function of the DEGs in the KEGG database revealed the top three pathways enriched with the most DEGs, including pathways in cancer, the PI3K-AKT pathway, and focal adhesion. Then we compared the gene expression profiles between the Clinical progressive disease (PD) and the complete response (CR) from the cancer genome altas (TCGA). 10 common DEGs were identified through combining the clinical and cellular analysis results. Protein-protein interaction network was applied to analyze the association of ER signal pathway with the 10 DEGs. 3 significant genes (GFRA3, NPY1R and PTPRN2) were closely related to ER related pathway. These significant DEGs regulated many biological activities such as cell proliferation and survival, motility and migration, and tumor cell invasion. The interactions between these DEGs and drug resistance phenomenon need to be further elucidated at a functional level in further studies. Based on our findings, we believed that these DEGs could be therapeutic targets, which can be explored to develop new treatment options. PMID:29423105
The mapping competences of the nurse Case/Care Manager in the context of Intensive Care.
Alfieri, Emanuela; Ferrini, Anna Chiara; Gianfrancesco, Francesca; Lise, Gianluca; Messana, Giovanni; Tirelli, Lorenzo; Lorenzo, Ana; Sarli, Leopoldo
2017-03-15
Since the recent introduction of the Case/Care Manager's professional figure, it is quite difficult to identify properly his/her own particular features, which could be mainly be found revising mainly in American studies. Therefore, the present study intended to identify the Case/Care Manager's skills and professional profile in an Intensive Care Unit experience, taking into consideration the staff's activities, perception and expectations towards the Case/Care Manager. In particular, it has been compared the experience of an Intensive Care Units where the Case/Care Manager's profile is operational to a different Unit where a Case/Care Manager is not yet in force. a Levati's model was used to map the Case/Care Manager's skills, involving each unit whole working staff, executives and caregivers through semi-structured interviews. It has been taken into consideration the Anaesthesia Unit and Emergency Unit of Cesena's healthcare organisation (AUSL of Romagna) and a Cardiology Intensive Care Unit of Piacenza's healthcare organisation, where the Case/Care Manager's profile has not been experimented yet. Firstly, it a data collection in each healthcare organization has been organised. Subsequently, semi-structured interviews to doctors, unit nurses, caregivers, nurses' coordinators and medical staff have been used to compare each healthcare system. The interviewees' described their expectations in relation to the Case/Care Manager working in a critical area. Then, every data collected during interviews has been organised to map a Case/Care Manager's essential professional profile to work in a critical area together with medical staff. Piacenza's O.U. critical area experience reported a major demand for patients' and patient's families' assistance. On the other hand, the very same aspects seem to have been better achieved in Cesena's O.U., where a Case/Care Manager's recent introduction has actually helped to overcome the void in organising systems. a Case/Care Manager's profile has been drafted on the basis of the comparative analysis conducted. It has been noted how the Case/Care Manager's professional profile can really improve relationships and communications between medical staff and patients, promoting a major unity among the working team. According to the present research, the Case/Care Manager's profile has been proved helpful in positively influencing the team activity and to elicit major satisfaction both in patients and their family.
Gascoyne-Binzi, Deborah M.; Barlow, Rachael E. L.; Frothingham, Richard; Robinson, Grant; Collyns, Timothy A.; Gelletlie, Ruth; Hawkey, Peter M.
2001-01-01
Compared with solid media, broth-based mycobacterial culture systems have increased sensitivity but also have higher false-positive rates due to cross-contamination. Systematic strain typing is rarely undertaken because the techniques are technically demanding and the data are difficult to organize. Variable number tandem repeat (VNTR) analysis by PCR is rapid and reproducible. The digital profile is easily manipulated in a database. We undertook a retrospective study of Mycobacterium tuberculosis isolates collected over an 18-month period following the introduction of the BACTEC MGIT 960 system. VNTR allele profiles were determined with early positive broth cultures and entered into a database with the specimen processing date and other specimen data. We found 36 distinct VNTR profiles in cultures from 144 patients. Three common VNTR profiles accounted for 45% of true-positive cases. By combining VNTR results with specimen data, we identified nine cross-contamination incidents, six of which were previously unsuspected. These nine incidents resulted in 34 false-positive cultures for 29 patients. False-positive cultures were identified for three patients who had previously been culture positive for tuberculosis and were receiving treatment. Identification of cross-contamination incidents requires careful documentation of specimen data and good communication between clinical and laboratory staff. Automated broth culture systems should be supplemented with molecular analysis to identify cross-contamination events. VNTR analysis is reproducible and provides timely results when applied to early positive broth cultures. This method should ensure that patients are not placed on unnecessary tuberculosis therapy or that cases are not falsely identified as treatment failures. In addition, areas where existing procedures may be improved can be identified. PMID:11136751
Dellett, Margaret; O’Hagan, Kathleen Ann; Colyer, Hilary Ann Alexandra; Mills, Ken I.
2010-01-01
Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies. PMID:24179384
He, Dan; Xie, Xiao; Yang, Fan; Zhang, Heng; Su, Haomiao; Ge, Yun; Song, Haiping; Chen, Peng R
2017-11-13
A genetically encoded, multifunctional photocrosslinker was developed for quantitative and comparative proteomics. By bearing a bioorthogonal handle and a releasable linker in addition to its photoaffinity warhead, this probe enables the enrichment of transient and low-abundance prey proteins after intracellular photocrosslinking and prey-bait separation, which can be subject to stable isotope dimethyl labeling and mass spectrometry analysis. This quantitative strategy (termed isoCAPP) allowed a comparative proteomic approach to be adopted to identify the proteolytic substrates of an E. coli protease-chaperone dual machinery DegP. Two newly identified substrates were subsequently confirmed by proteolysis experiments. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Early detection of skin cancer via terahertz spectral profiling and 3D imaging.
Rahman, Anis; Rahman, Aunik K; Rao, Babar
2016-08-15
Terahertz scanning reflectometry, terahertz 3D imaging and terahertz time-domain spectroscopy have been used to identify features in human skin biopsy samples diagnosed for basal cell carcinoma (BCC) and compared with healthy skin samples. It was found from the 3D images that the healthy skin samples exhibit regular cellular pattern while the BCC skin samples indicate lack of regular cell pattern. The skin is a highly layered structure organ; this is evident from the thickness profile via a scan through the thickness of the healthy skin samples, where, the reflected intensity of the terahertz beam exhibits fluctuations originating from different skin layers. Compared to the healthy skin samples, the BCC samples' profiles exhibit significantly diminished layer definition; thus indicating a lack of cellular order. In addition, terahertz time-domain spectroscopy reveals significant and quantifiable differences between the healthy and BCC skin samples. Thus, a combination of three different terahertz techniques constitutes a conclusive route for detecting the BCC condition on a cellular level compared to the healthy skin. Copyright © 2016 Elsevier B.V. All rights reserved.
A Comparison of Personality Attributes of Science Teachers and Medical Technologists.
ERIC Educational Resources Information Center
Kazi, M. U.; Piper, Martha K.
1983-01-01
Identified personality traits (extroversion/introversion and neuroticism/stability) that distinguish medical technologists (N=83) and college-level biology, chemistry, and physics teachers (N=57) using the Eysnck Personality Inventory. Also compared personality profiles of these subjects using Holland's Vocational Preference Inventory. Results and…
Cognitive Subclinical Markers in Autism: Brief Report.
ERIC Educational Resources Information Center
Smalley, Susan L.; Asarnow, Robert F.
1990-01-01
The study compared 9 nonretarded autistic males and 25 of their first-degree relatives with 22 control relatives, to identify potential cognitive subclinical markers in autism and differences in emotion recognition and labeling. Subjects showed an atypical cognitive profile with above average visuospatial ability and difficulty in recognizing…
MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage.
Bache, Søren; Rasmussen, Rune; Rossing, Maria; Laigaard, Finn Pedersen; Nielsen, Finn Cilius; Møller, Kirsten
2017-09-01
Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI. In a prospective case-control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened and validated using 2 different high-throughput real-time quantification polymerase chain reaction techniques. The occurrence of DCI was documented in patient charts and subsequently reviewed independently by 2 physicians. MiRNA profiles from 27 SAH patients and 10 neurologically healthy patients passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients ( P <0.001); 2 (miR-21 and miR-221) showed a relative increase in SAH patients with DCI compared with those without ( P <0.05) in both the screening and validation. SAH is associated with marked changes in the cerebrospinal fluid miRNA profile. These changes could be associated to the development of DCI. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791257. © 2017 The Authors.
Secretome profiles of immortalized dental follicle cells using iTRAQ-based proteomic analysis.
Dou, Lei; Wu, Yan; Yan, Qifang; Wang, Jinhua; Zhang, Yan; Ji, Ping
2017-08-04
Secretomes produced by mesenchymal stromal cells (MSCs) were considered to be therapeutic potential. However, harvesting enough primary MSCs from tissue was time-consuming and costly, which impeded the application of MSCs secretomes. This study was to immortalize MSCs and compare the secretomes profile of immortalized and original MSCs. Human dental follicle cells (DFCs) were isolated and immortalized using pMPH86. The secretome profile of immortalized DFCs (iDFCs) was investigated and compared using iTRAQ labeling combined with mass spectrometry (MS) quantitative proteomics. The MS data was analyzed using ProteinPilotTM software, and then bioinformatic analysis of identified proteins was done. A total of 2092 secreted proteins were detected in conditioned media of iDFCs. Compared with primary DFCs, 253 differently expressed proteins were found in iDFCs secretome (142 up-regulated and 111 down-regulated). Intensive bioinformatic analysis revealed that the majority of secreted proteins were involved in cellular process, metabolic process, biological regulation, cellular component organization or biogenesis, immune system process, developmental process, response to stimulus and signaling. Proteomic profile of cell secretome wasn't largely affected after immortalization converted by this piggyBac immortalization system. The secretome of iDFCs may be a good candidate of primary DFCs for regenerative medicine.
Characterization of Salmonella Typhimurium isolates associated with septicemia in swine.
Bergeron, Nadia; Corriveau, Jonathan; Letellier, Ann; Daigle, France; Quessy, Sylvain
2010-01-01
Salmonella Typhimurium is frequently isolated from pigs and may also cause enteric disease in humans. In this study, 33 isolates of S. Typhimurium associated with septicemia in swine (CS) were compared to 33 isolates recovered from healthy animals at slaughter (WCS). The isolates were characterized using phenotyping and genotyping methods. For each isolate, the phage type, antimicrobial resistance, and pulsed-field gel electrophoresis (PFGE) DNA profiles were determined. In addition, the protein profiles of each isolate grown in different conditions were studied by Coomassie Blue-stained sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot. Various phage types were identified. The phage type PT 104 represented 36.4% of all isolates from septicemic pigs. Resistance to as many as 12 antimicrobial agents, including some natural resistances, was found in isolates from CS and WCS. Many genetic profiles were identified among the PT 104 phage types. Although it was not possible to associate one particular protein with septicemic isolates, several highly immunogenic proteins, present in all virulent isolates and in most isolates from clinically healthy animals, were identified. These results indicated that strains associated with septicemia belong to various genetic lineages that can also be recovered from asymptomatic animals at the time of slaughter.
Denadai-Souza, Alexandre; Bonnart, Chrystelle; Tapias, Núria Solà; Marcellin, Marlène; Gilmore, Brendan; Alric, Laurent; Bonnet, Delphine; Burlet-Schiltz, Odile; Hollenberg, Morley D; Vergnolle, Nathalie; Deraison, Céline
2018-05-18
While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients. Profiling of (Pro-Lys)-ABP bound proteases revealed that most of hyperactive proteases from IBD secretome are clustered at 28-kDa. We identified seven active proteases: the serine proteases cathepsin G, plasma kallikrein, plasmin, tryptase, chymotrypsin-like elastase 3 A, and thrombin and the aminopeptidase B. Only cathepsin G and thrombin were overactive in supernatants from IBD patient tissues compared to healthy controls. Gene expression analysis highlighted the transcription of genes encoding these proteases into intestinal mucosae. The functional ABP-targeted proteomic approach that we have used to identify active proteases in human colonic samples bears directly on the understanding of the role these enzymes may play in the pathophysiology of IBD.
Progression Rate Associated Peripheral Blood Biomarkers of Parkinson's Disease.
Fan, Yanxia; Xiao, Shuping
2018-06-23
Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.
Characterizing the fecal microbiota of infants with botulism.
Shirey, T Brian; Dykes, Janet K; Lúquez, Carolina; Maslanka, Susan E; Raphael, Brian H
2015-11-23
Infant botulism is the most prevalent form of botulism in the USA, representing 68.5 % of cases reported from 2001-2012. Infant botulism results when botulinum toxin-producing clostridia (BTPC) colonize the infant gut with concomitant in vivo production of the highly potent botulinum neurotoxin (BoNT). The gut microbiota of infants with botulism is largely uncharacterized; therefore, it remains unclear whether the microbiota profile of these patients are distinct in composition, abundance, or diversity. To address this uncertainty, we employed 16S rRNA gene profiling to characterize the fecal microbiota in 14 stool samples among laboratory-confirmed and non-confirmed infant botulism cases. Seven bacterial phyla were identified among all 14 infant stool samples examined. Compared to samples from non-confirmed cases, the fecal microbiota of infant botulism patients displayed significantly higher Proteobacteria abundance. Of the 20 bacterial families identified, Enterobacteriaceae was significantly more abundant in samples from infants with botulism. Firmicutes abundance and the abundance ratio of Firmicutes/Proteobacteria was significantly lower in samples from infants with botulism. Lactobacillus spp. abundance was notably reduced in 12 of the 14 samples. Clostridium botulinum and Clostridium baratii were identified in low relative abundances in confirmed and non-confirmed samples based on their 16S rRNA gene profiles, although their toxigenicity remained undetermined. No significant differences were observed in the number of operational taxonomic units (OTUs) observed or in fecal microbiota diversity between laboratory-confirmed and non-confirmed samples. Correlations between individual phylum abundances and infant age were variable, and no significant differences were shown in number of OTUs observed or in fecal microbiota diversity between samples delineated by overall mean age. Significant differences in Proteobacteria, Firmicutes, and Enterobacteriaceae abundances were identified in the fecal microbiota of infants with botulism when compared to samples from non-confirmed cases. Fecal microbiota diversity was not significantly altered in infants with botulism, and a limited presence of BTPC was shown. It could not be determined whether the fecal microbiota profiles shown here were comparable prior to patient illness, or whether they were the direct result of infant botulism. The results of this study do, however, provide a detailed and descriptive observation into the infant gut microbiota after intestinal colonization by BTPC.
Solitonic characteristics of Airy beam nonlinear propagation
NASA Astrophysics Data System (ADS)
Bouchet, Thomas; Marsal, Nicolas; Sciamanna, Marc; Wolfersberger, Delphine
2018-05-01
We analyze the nonlinear propagation of a one-dimensional Airy beam. Under nonlinear focusing conditions, the Airy beam splits into a weak accelerating structure and a beam that has been named an "off-shooting soliton." Experimental measurements and numerical results related to the off-shooting Airy beam are compared to soliton theoretical profiles and a good agreement is found in terms of transverse shape, width, and amplitude. We identify the different parameters to generate an Airy beam off-shooting soliton and demonstrate that its profile is also preserved through propagation over long distances.
Cuozzo, John W; Centrella, Paolo A; Gikunju, Diana; Habeshian, Sevan; Hupp, Christopher D; Keefe, Anthony D; Sigel, Eric A; Soutter, Holly H; Thomson, Heather A; Zhang, Ying; Clark, Matthew A
2017-05-04
We have identified and characterized novel potent inhibitors of Bruton's tyrosine kinase (BTK) from a single DNA-encoded library of over 110 million compounds by using multiple parallel selection conditions, including variation in target concentration and addition of known binders to provide competition information. Distinct binding profiles were observed by comparing enrichments of library building block combinations under these conditions; one enriched only at high concentrations of BTK and was competitive with ATP, and another enriched at both high and low concentrations of BTK and was not competitive with ATP. A compound representing the latter profile showed low nanomolar potency in biochemical and cellular BTK assays. Results from kinetic mechanism of action studies were consistent with the selection profiles. Analysis of the co-crystal structure of the most potent compound demonstrated a novel binding mode that revealed a new pocket in BTK. Our results demonstrate that profile-based selection strategies using DNA-encoded libraries form the basis of a new methodology to rapidly identify small molecule inhibitors with novel binding modes to clinically relevant targets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
NASA Technical Reports Server (NTRS)
Polacek, Denise C.; Passerini, Anthony G.; Shi, Congzhu; Francesco, Nadeene M.; Manduchi, Elisabetta; Grant, Gregory R.; Powell, Steven; Bischof, Helen; Winkler, Hans; Stoeckert, Christian J Jr;
2003-01-01
Although mRNA amplification is necessary for microarray analyses from limited amounts of cells and tissues, the accuracy of transcription profiles following amplification has not been well characterized. We tested the fidelity of differential gene expression following linear amplification by T7-mediated transcription in a well-established in vitro model of cytokine [tumor necrosis factor alpha (TNFalpha)]-stimulated human endothelial cells using filter arrays of 13,824 human cDNAs. Transcriptional profiles generated from amplified antisense RNA (aRNA) (from 100 ng total RNA, approximately 1 ng mRNA) were compared with profiles generated from unamplified RNA originating from the same homogeneous pool. Amplification accurately identified TNFalpha-induced differential expression in 94% of the genes detected using unamplified samples. Furthermore, an additional 1,150 genes were identified as putatively differentially expressed using amplified RNA which remained undetected using unamplified RNA. Of genes sampled from this set, 67% were validated by quantitative real-time PCR as truly differentially expressed. Thus, in addition to demonstrating fidelity in gene expression relative to unamplified samples, linear amplification results in improved sensitivity of detection and enhances the discovery potential of high-throughput screening by microarrays.
Tsai, Jack; Kasprow, Wesley J; Rosenheck, Robert A
2013-12-01
We identified risk and need profiles of homeless veterans and examined the relation between profiles and referrals and admissions to Department of Veterans Affairs (VA) homeless service programs. We examined data from the VA's new Homeless Operations Management and Evaluation System on 120,852 veterans from 142 sites nationally in 2011 and 2012 using latent class analyses based on 9 homeless risk factors. The final 4-class solution compared both referral and admission to VA homeless services. We identified 4 latent classes: relatively few problems, dual diagnosis, poverty-substance abuse-incarceration, and disabling medical problems. Homeless veterans in the first group were more likely to be admitted to the VA's permanent supportive housing program, whereas those in the second group were more likely to be admitted to more restrictive VA residential treatment. Homeless veterans in the third group were more likely to be admitted to the VA's prisoner re-entry program, and those in the fourth group were more likely to be directed to VA medical services. The heterogeneous risk and need profiles of homeless veterans supported the diversity of VA homeless services and encouraged the development of specialized services to meet their diverse needs.
Forbes, Shari L.; Perrault, Katelynn A.; Stefanuto, Pierre-Hugues; Nizio, Katie D.; Focant, Jean-François
2014-01-01
The investigation of volatile organic compounds (VOCs) associated with decomposition is an emerging field in forensic taphonomy due to their importance in locating human remains using biological detectors such as insects and canines. A consistent decomposition VOC profile has not yet been elucidated due to the intrinsic impact of the environment on the decomposition process in different climatic zones. The study of decomposition VOCs has typically occurred during the warmer months to enable chemical profiling of all decomposition stages. The present study investigated the decomposition VOC profile in air during both warmer and cooler months in a moist, mid-latitude (Cfb) climate as decomposition occurs year-round in this environment. Pig carcasses (Sus scrofa domesticus L.) were placed on a soil surface to decompose naturally and their VOC profile was monitored during the winter and summer months. Corresponding control sites were also monitored to determine the natural VOC profile of the surrounding soil and vegetation. VOC samples were collected onto sorbent tubes and analyzed using comprehensive two-dimensional gas chromatography – time-of-flight mass spectrometry (GC×GC-TOFMS). The summer months were characterized by higher temperatures and solar radiation, greater rainfall accumulation, and comparable humidity when compared to the winter months. The rate of decomposition was faster and the number and abundance of VOCs was proportionally higher in summer. However, a similar trend was observed in winter and summer demonstrating a rapid increase in VOC abundance during active decay with a second increase in abundance occurring later in the decomposition process. Sulfur-containing compounds, alcohols and ketones represented the most abundant classes of compounds in both seasons, although almost all 10 compound classes identified contributed to discriminating the stages of decomposition throughout both seasons. The advantages of GC×GC-TOFMS were demonstrated for detecting and identifying trace levels of VOCs, particularly ethers, which are rarely reported as decomposition VOCs. PMID:25412504
Forbes, Shari L; Perrault, Katelynn A; Stefanuto, Pierre-Hugues; Nizio, Katie D; Focant, Jean-François
2014-01-01
The investigation of volatile organic compounds (VOCs) associated with decomposition is an emerging field in forensic taphonomy due to their importance in locating human remains using biological detectors such as insects and canines. A consistent decomposition VOC profile has not yet been elucidated due to the intrinsic impact of the environment on the decomposition process in different climatic zones. The study of decomposition VOCs has typically occurred during the warmer months to enable chemical profiling of all decomposition stages. The present study investigated the decomposition VOC profile in air during both warmer and cooler months in a moist, mid-latitude (Cfb) climate as decomposition occurs year-round in this environment. Pig carcasses (Sus scrofa domesticus L.) were placed on a soil surface to decompose naturally and their VOC profile was monitored during the winter and summer months. Corresponding control sites were also monitored to determine the natural VOC profile of the surrounding soil and vegetation. VOC samples were collected onto sorbent tubes and analyzed using comprehensive two-dimensional gas chromatography--time-of-flight mass spectrometry (GC × GC-TOFMS). The summer months were characterized by higher temperatures and solar radiation, greater rainfall accumulation, and comparable humidity when compared to the winter months. The rate of decomposition was faster and the number and abundance of VOCs was proportionally higher in summer. However, a similar trend was observed in winter and summer demonstrating a rapid increase in VOC abundance during active decay with a second increase in abundance occurring later in the decomposition process. Sulfur-containing compounds, alcohols and ketones represented the most abundant classes of compounds in both seasons, although almost all 10 compound classes identified contributed to discriminating the stages of decomposition throughout both seasons. The advantages of GC × GC-TOFMS were demonstrated for detecting and identifying trace levels of VOCs, particularly ethers, which are rarely reported as decomposition VOCs.
Long non-coding RNA expression profile in cervical cancer tissues
Zhu, Hua; Chen, Xiangjian; Hu, Yan; Shi, Zhengzheng; Zhou, Qing; Zheng, Jingjie; Wang, Yifeng
2017-01-01
Cervical cancer (CC), one of the most common types of cancer of the female population, presents an enormous challenge in diagnosis and treatment. Long non-coding (lnc)RNAs, non-coding (nc)RNAs with length >200 nucleotides, have been identified to be associated with multiple types of cancer, including CC. This class of nc transcripts serves an important role in tumor suppression and oncogenic signaling pathways. In the present study, the microarray method was used to obtain the expression profile of lncRNAs and protein-coding mRNAs and to compare the expression of lncRNAs between CC tissues and corresponding adjacent non-cancerous tissues in order to screen potential lncRNAs for associations with CC. Overall, 3356 lncRNAs with significantly different expression pattern in CC tissues compared with adjacent non-cancerous tissues were identified, while 1,857 of them were upregulated. These differentially expressed lncRNAs were additionally classified into 5 subgroups. Reverse transcription quantitative polymerase chain reactions were performed to validate the expression pattern of 5 random selected lncRNAs, and 2lncRNAs were identified to have significantly different expression in CC samples compared with adjacent non-cancerous tissues. This finding suggests that those lncRNAs with different expression may serve important roles in the development of CC, and the expression data may provide information for additional study on the involvement of lncRNAs in CC. PMID:28789353
Flowers, Elena; Molina, César; Mathur, Ashish; Reaven, Gerald M
2015-01-01
Prevalence of insulin resistance and associated dyslipidaemia [high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations] are increased in South Asian individuals; likely contributing to their increased risk of type-2 diabetes and cardiovascular disease. The plasma concentration ratio of TG/HDL-C has been proposed as a simple way to identify apparently healthy individuals at high cardio-metabolic risk. This study was carried out to compare the cardio-metabolic risk profiles of high-risk South Asian individuals identified by an elevated TG/HDL-C ratio versus those with a diagnosis of the metabolic syndrome. Body mass index, waist circumference, blood pressure, and fasting plasma glucose, insulin, TG, and HDL-C concentrations were determined in apparently healthy men (n=498) and women (n=526). The cardio-metabolic risk profile of "high risk" individuals identified by TG/HDL-C ratios in men (≥ 3.5) and women (≥2.5) was compared to those identified by a diagnosis of the metabolic syndrome. More concentrations of all cardio-metabolic risk factors were significantly higher in "high risk" groups, identified by either the TG/HDL-C ratio or a diagnosis of the metabolic syndrome. TG, HDL-C, and insulin concentrations were not significantly different in "high risk" groups identified by either criterion, whereas plasma glucose and blood pressure were higher in those with the metabolic syndrome. Apparently healthy South Asian individuals at high cardio-metabolic risk can be identified using either the TG/HDL-C ratio or the metabolic syndrome criteria. The TG/HDL-C ratio may be used as a simple marker to identify such individuals.
NASA Astrophysics Data System (ADS)
Jung, Jongil; Hong, Ik-Seon; Cho, Eunjin; Yi, Yu
2016-03-01
Caves can serve as major outposts for future human exploration of the Moon and Mars. In addition, caves can protect people and electronic equipment from external hazards such as cosmic ray radiation and meteorites impacts and serve as a shelter. Numerous pit craters have been discovered on the Moon and Mars and are potential entrances to caves; the principal topographic features of pit craters are their visible internal floors and pits with vertical walls. We have devised two topographical models for investigating the relationship between the topographical characteristics and the inner void of pit craters. One of our models is a concave floor void model and the other is a convex floor tube model. For each model, optical photographs have been obtained under conditions similar to those in which optical photographs have been acquired for craters on the Moon and Mars. Brightness profiles were analyzed for determining the profile patterns of the void pit craters. The profile patterns were compared to the brightness profiles of Martian pit craters, because no good-quality images of lunar pit craters were available. In future studies, the model profile patterns will be compared to those of lunar pit craters, and the proposed method will likely become useful for finding lunar caves and consequently for planning lunar bases for manned lunar expeditions.
USDA-ARS?s Scientific Manuscript database
Pheasant and quail orthologues of avian ß-defensin 2 (AVBD2) were identified in methanol extracts of heterophil and bone marrow using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). We used comparative pattern profiling before and after reduction/alkyla...
Memory Profiles in Children with Mild Intellectual Disabilities: Strengths and Weaknesses
ERIC Educational Resources Information Center
Van der Molen, Mariet J.; Van Luit, Johannes E. H.; Jongmans, Marian J.; Van der Molen, Maurits W.
2009-01-01
Strengths and weaknesses in short-term memory (STM) and working memory (WM) were identified in children with mild intellectual disabilities (MID) by comparing their performance to typically developing children matched on chronological age (CA children) and to younger typically developing children with similar mental capacities (MA children).…
USDA-ARS?s Scientific Manuscript database
Transcription profiles of Glycine tomentella genotypes having different responses to soybean rust, caused by the fungal pathogen Phakopsora pachyrhizi, were compared using suppression subtractive hybridization (SSH). Four cDNA libraries were constructed from infected and non-infected leaves of resis...
Comparison of immune transcriptome response following infection with PRRSV, PCV2 and SIV
USDA-ARS?s Scientific Manuscript database
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine. Here we identified and compared gene expression changes in tracheobronchial lymph nodes (TBLN) following viral infection using Digital Gene Expression Tag Profiling (DGETP). Pigs were infected with 1 x 10**5 ce...
Language Profiles of Poor Comprehenders in English and French
ERIC Educational Resources Information Center
D'Angelo, Nadia; Chen, Xi
2017-01-01
This study explored components of language comprehension (vocabulary, grammar, and higher-level language) skills for poor comprehenders in French immersion. We identified three groups of bilingual comprehenders (poor, average, and good) based on English reading performance and compared their language comprehension skills in English L1 and French…
Photometric analysis of esthetically pleasant and unpleasant facial profile
Fortes, Helena Nunes da Rocha; Guimarães, Thamirys Correia; Belo, Ivana Mara Lira; da Matta, Edgard Norões Rodrigues
2014-01-01
Objective To identify which linear, angular and proportionality measures could influence a profile to be considered esthetically pleasant or unpleasant, and to assess sexual dimorphism. Methods 150 standardized facial profile photographs of dental students of both sexes were obtained and printed on photographic paper. Ten plastic surgeons, ten orthodontists and ten layperson answered a questionnaire characterizing each profile as pleasant, acceptable or unpleasant. With the use of a score system, the 15 most pleasant and unpleasant profiles of each sex were selected. The photographs were scanned into AutoCAD computer software. Linear, angular and proportion measurements were obtained using the software tools. The average values between groups were compared by the Student's t-test and the Mann-Whitney test at 5%. Results The linear measures LL-S, LL-H, LL-E, LL-B and Pn-H showed statistically significant differences (p < 0.05). Statistical differences were also found in the angular measures G'.Pn.Pg', G'.Sn.Pg' and Sn.Me'.C and in the proportions G'-Sn:Sn-Me' and Sn-Gn':Gn'-C (p < 0.05). Differences between sexes were found for the linear measure Ala-Pn, angles G'-Pg'.N-Pn, Sn.Me'.C, and proportions Gn'-Sn:Sn-Me' and Ala-Pn:N'-Sn. (p < 0.05). Conclusion The anteroposterior position of the lower lip, the amount of nose that influences the profile, facial convexity, total vertical proportion and lip-chin proportion appear to influence pleasantness of facial profile. Sexual dimorphism was identified in nasal length, nasofacial and lower third of the face angles, total vertical and nasal height/length proportions. PMID:24945516
Photometric analysis of esthetically pleasant and unpleasant facial profile.
Fortes, Helena Nunes da Rocha; Guimarães, Thamirys Correia; Belo, Ivana Mara Lira; da Matta, Edgard Norões Rodrigues
2014-01-01
To identify which linear, angular and proportionality measures could influence a profile to be considered esthetically pleasant or unpleasant, and to assess sexual dimorphism. 150 standardized facial profile photographs of dental students of both sexes were obtained and printed on photographic paper. Ten plastic surgeons, ten orthodontists and ten layperson answered a questionnaire characterizing each profile as pleasant, acceptable or unpleasant. With the use of a score system, the 15 most pleasant and unpleasant profiles of each sex were selected. The photographs were scanned into AutoCAD computer software. Linear, angular and proportion measurements were obtained using the software tools. The average values between groups were compared by the Student's t-test and the Mann-Whitney test at a significance level of 5%. The linear measures LL-S, LL-H, LL-E, LL-B and Pn-H showed statistically significant differences (p < 0.05). Statistical differences were also found in the angular measures G'.Pn.Pg', G'.Sn.Pg' and Sn.Me'.C and in the proportions G'-Sn:Sn-Me' and Sn-Gn':Gn'-C (p < 0.05). Differences between sexes were found for the linear measure Ala-Pn, angles G'-Pg'.N-Pn, Sn.Me'.C, and proportions Gn'-Sn:Sn-Me' and Ala-Pn:N'-Sn. (p < 0.05). The anteroposterior position of the lower lip, the amount of nose that influences the profile, facial convexity, total vertical proportion and lip-chin proportion appear to influence pleasantness of facial profile. Sexual dimorphism was identified in nasal length, nasofacial and lower third of the face angles, total vertical and nasal height/length proportions.
Behrendt, Silke; Bühringer, Gerhard; Höfler, Michael; Lieb, Roselind; Beesdo-Baum, Katja
2017-10-01
Comorbid internalizing mental disorders in alcohol use disorders (AUD) can be understood as putative independent risk factors for AUD or as expressions of underlying shared psychopathology vulnerabilities. However, it remains unclear whether: 1) specific latent internalizing psychopathology risk-profiles predict AUD-incidence and 2) specific latent internalizing comorbidity-profiles in AUD predict AUD-stability. To investigate baseline latent internalizing psychopathology risk profiles as predictors of subsequent AUD-incidence and -stability in adolescents and young adults. Data from the prospective-longitudinal EDSP study (baseline age 14-24 years) were used. The study-design included up to three follow-up assessments in up to ten years. DSM-IV mental disorders were assessed with the DIA-X/M-CIDI. To investigate risk-profiles and their associations with AUD-outcomes, latent class analysis with auxiliary outcome variables was applied. AUD-incidence: a 4-class model (N=1683) was identified (classes: normative-male [45.9%], normative-female [44.2%], internalizing [5.3%], nicotine dependence [4.5%]). Compared to the normative-female class, all other classes were associated with a higher risk of subsequent incident alcohol dependence (p<0.05). AUD-stability: a 3-class model (N=1940) was identified with only one class (11.6%) with high probabilities for baseline AUD. This class was further characterized by elevated substance use disorder (SUD) probabilities and predicted any subsequent AUD (OR 8.5, 95% CI 5.4-13.3). An internalizing vulnerability may constitute a pathway to AUD incidence in adolescence and young adulthood. In contrast, no indication for a role of internalizing comorbidity profiles in AUD-stability was found, which may indicate a limited importance of such profiles - in contrast to SUD-related profiles - in AUD stability. Copyright © 2017 Elsevier B.V. All rights reserved.
Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset.
Rogers, Angela J; Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B; Matthay, Michael A
2017-05-01
There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. Copyright © 2017 the American Physiological Society.
Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset
Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B.; Matthay, Michael A.
2017-01-01
There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This “high metabolite” endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. PMID:28258106
GTA: a game theoretic approach to identifying cancer subnetwork markers.
Farahmand, S; Goliaei, S; Ansari-Pour, N; Razaghi-Moghadam, Z
2016-03-01
The identification of genetic markers (e.g. genes, pathways and subnetworks) for cancer has been one of the most challenging research areas in recent years. A subset of these studies attempt to analyze genome-wide expression profiles to identify markers with high reliability and reusability across independent whole-transcriptome microarray datasets. Therefore, the functional relationships of genes are integrated with their expression data. However, for a more accurate representation of the functional relationships among genes, utilization of the protein-protein interaction network (PPIN) seems to be necessary. Herein, a novel game theoretic approach (GTA) is proposed for the identification of cancer subnetwork markers by integrating genome-wide expression profiles and PPIN. The GTA method was applied to three distinct whole-transcriptome breast cancer datasets to identify the subnetwork markers associated with metastasis. To evaluate the performance of our approach, the identified subnetwork markers were compared with gene-based, pathway-based and network-based markers. We show that GTA is not only capable of identifying robust metastatic markers, it also provides a higher classification performance. In addition, based on these GTA-based subnetworks, we identified a new bonafide candidate gene for breast cancer susceptibility.
Preliminary study on plasma proteins in pregnant and non-pregnant female dogs.
Szczubiał, Marek; Wawrzykowski, Jacek; Dąbrowski, Roman; Krawczyk, Magdalena; Kankofer, Marta
2017-07-15
In this study, we used a combined approach based on 2-dimensional electrophoresis (2-DE), difference in gel electrophoresis (DIGE), and mass spectrometry (MS) to identify the plasma protein composition in pregnant female dogs and compared it with non-pregnant female dogs. We used the plasma samples obtained from four female dogs during I, II, and III thirds of pregnancy, three days after parturition, as well as from four non-pregnant female dogs in diestrus phase. Analysis of 2-DE gel image exhibited of 249 protein spots. The intensity of staining of 35 spots differed significantly (P < 0.05) between the non-pregnant and pregnant female dogs. We used matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI TOF MS) to identify 47 spots corresponding to 52 different proteins. Five identified protein spots, including zinc finger BED domain-containing protein 5, hemoglobin subunit beta-2, integrator complex subunit 7, apolipoprotein A-I, and glutamyl aminopeptidase were differentially presented in the plasma of pregnant and non-pregnant female dogs. To the best of our knowledge, this is the first report on the plasma protein profile of pregnant and non-pregnant female dogs. In this study, we identified proteins that have not been previously identified in dogs. Our findings showed that numerous protein spots were differentially presented in the plasma of female dogs during normal pregnancy. Although we identified only a limited number of differentially presented proteins, our study demonstrated that the plasma protein profile changed during pregnancy in female dogs, which suggests its importance in maintaining pregnancy. Further studies are necessary to define complete plasma protein profile of pregnant female dogs and to identify all proteins that are differentially presented in the pregnant animals compared with the non-pregnant ones. In addition, studies are warranted to explain the role of those proteins in maintaining the pregnancy and their usefulness in detection of early pregnancy. Furthermore, our results indicated that DIGE technique is useful in the comparison of samples originated from different states and time points in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.
Biotransformation of the platinum drug JM216 following oral administration to cancer patients.
Raynaud, F I; Mistry, P; Donaghue, A; Poon, G K; Kelland, L R; Barnard, C F; Murrer, B A; Harrap, K R
1996-01-01
This study evaluates the metabolic profile of JM216 [bis(acetato)ammine-dichloro(cyclohexylamine) platinum(IV)], the first orally administrable platinum complex, in plasma ultrafiltrates of 12 patients (n = 2-4 time points per patient) following different doses of drug (120, 200, 340, 420, 560 mg/m2). The biotransformation profile was evaluated by high-performance liquid chromatography (HPLC) followed by atomic absorption spectrophotometry (AA). The AA profiles were compared with those previously identified by HPLC on line with mass spectrometry (HPLC-MS) in plasma incubated with JM216. A total of six platinum peaks (Rt = 5.5, 7.2, 10.6, 12.4, 15.6, and 21.6 min, respectively) were observed in patients' plasma ultrafiltrate samples, of which only four appeared during the first 6 h post-treatment. Four of these coeluted with those observed and identified previously in plasma incubation medium. No parent JM216 was detected. The major metabolite seen in patients was the Pt II complex JM118 [cis-amminedichloro-(cyclohexylamine)platinum(II)] and was observed in all the patients. Interestingly, the second metabolite was shown to coelute with the Pt IV species JM383 [bis-acetatoammine(cyclohexylamine)dihydroxoplatinum (IV)]. Both JM118 and JM383 were identified by HPLC-MS in a clinical sample. Peak C, which was a minor product (less than 5% of the free platinum), coeluted with JM559 [bis-acetatoammine-chloro(cyclohexylalamine)hydroxoplatin um(IV)]. The cytotoxicity profile of all three metabolites in a panel of cisplatin-sensitive and -resistant human ovarian carcinoma cell lines was very close to that of the parent drug. In addition, the concentrations of JM118 reached in patients' plasma ultrafiltrate were comparable with the cytotoxic levels of the compound determined in the ovarian carcinoma panel of cell lines. Two metabolites were seen in patients but not in the in vitro incubation medium, suggesting the involvement of a possible enzymatic reaction. Thus, the biotransformation profile following oral administration of JM216 shows a variety of Pt(IV) and Pt(Il) metabolites in plasma that differ significantly from other systemically applied platinum drugs.
NASA Astrophysics Data System (ADS)
Tang, Q.; Prather, M. J.
2012-03-01
We examine whether the individual ozone (O3) measurements from the four Aura instruments can quantify the stratosphere-troposphere exchange (STE) flux of O3, an important term of the tropospheric O3 budget. The level 2 (L2) Aura swath data and the nearly coincident ozone sondes for the years 2005-2006 are compared with the 4-D, high-resolution (1° × 1° × 40-layer × 0.5 h) model simulation of atmospheric ozone for the same period from the University of California, Irvine chemistry transport model (CTM). The CTM becomes a transfer standard for comparing individual profiles from these five, not-quite-coincident measurements of atmospheric ozone. Even with obvious model discrepancies identified here, the CTM can readily quantify instrument-instrument biases in the tropical upper troposphere and mid-latitude lower stratosphere. In terms of STE processes, all four Aura datasets have some skill in identifying stratosphere-troposphere folds, and we find several cases where both model and measurements see evidence of high-O3 stratospheric air entering the troposphere. In many cases identified in the model, however, the individual Aura profile retrievals in the upper troposphere and lower stratosphere show too much noise, as expected from their low sensitivity and coarse vertical resolution at and below the tropopause. These model-measurement comparisons of individual profiles do provide some level of confidence in the model-derived STE O3 flux, but it will be difficult to integrate this flux from the satellite data alone.
Chang, Yuwei; Zhao, Chunxia; Wu, Zeming; Zhou, Jia; Zhao, Sumin; Lu, Xin; Xu, Guowang
2012-08-01
In this work a chip-based nano HPLC coupled MS (HPLC-chip/MS) method with a simple sample preparation procedure was developed for the flavonoid profiling of soybean. The analytical properties of the method including the linearity (R(2) , 0.992-0.995), reproducibility (RSD, 1.50-7.66%), intraday precision (RSD, 1.41-5.14%) and interday precision (RSD, 2.76-16.90%) were satisfactory. Compared with the conventional HPLC/MS method, a fast extraction and analysis procedure was applied and more flavonoids were detected in a single run. Additionally, 13 flavonoids in soybean seed were identified for the first time. The method was then applied to the profiling of six varieties of soybean sowed at the same place. A clear discrimination was observed among different cultivars, three isoflavones, accounting for nearly 80% of total flavonoid contents, were found increased in the spring soybeans compared with the summer cultivars. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Swindell, William R.; Johnston, Andrew; Carbajal, Steve; Han, Gangwen; Wohn, Christian; Lu, Jun; Xing, Xianying; Nair, Rajan P.; Voorhees, John J.; Elder, James T.; Wang, Xiao-Jing; Sano, Shigetoshi; Prens, Errol P.; DiGiovanni, John; Pittelkow, Mark R.; Ward, Nicole L.; Gudjonsson, Johann E.
2011-01-01
Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. PMID:21483750
Ennett, Susan T.; Jackson, Christine; Cole, Veronica T.; Haws, Susan; Foshee, Vangie A.; Reyes, Heathe Luz McNaughton; Burns, Alison Reimuller; Cox, Melissa J.; Cai, Li
2015-01-01
We assessed a multidimensional model of parent alcohol socialization in which key socialization factors were considered simultaneously to identify combinations of factors that increase or decrease risk for development of adolescent alcohol misuse. Of interest was the interplay between putative risk and protective factors, such as whether the typically detrimental effects on youth drinking of parenting practices tolerant of some adolescent alcohol use are mitigated by an effective overall approach to parenting and parental modeling of modest alcohol use. The sample included 1,530 adolescents and their mothers; adolescents’ mean age was 13.0 (SD = .99) at the initial assessment. Latent profile analysis was conducted of mothers’ reports of their attitude toward teen drinking, alcohol-specific parenting practices, parental alcohol use and problem use, and overall approach to parenting. The profiles were used to predict trajectories of adolescent alcohol misuse from early to middle adolescence. Four profiles were identified: two profiles reflected conservative alcohol-specific parenting practices and two reflected alcohol-tolerant practices, all in the context of other attributes. Alcohol misuse accelerated more rapidly from grade 6 through 10 in the two alcohol-tolerant compared with conservative profiles. Results suggest that maternal tolerance of some youth alcohol use, even in the presence of dimensions of an effective parenting style and low parental alcohol use and problem use, is not an effective strategy for reducing risky adolescent alcohol use. PMID:26415053
De Meester, An; Maes, Jolien; Stodden, David; Cardon, Greet; Goodway, Jacqueline; Lenoir, Matthieu; Haerens, Leen
2016-11-01
The present study identified adolescents' motor competence (MC)-based profiles (e.g., high actual and low perceived MC), and accordingly investigated differences in motivation for physical education (PE), physical activity (PA) levels, and sports participation between profiles by using regression analyses. Actual MC was measured with the Körperkoordinationstest für Kinder. Adolescents (n = 215; 66.0% boys; mean age = 13.64 ± .58 years) completed validated questionnaires to assess perceived MC, motivation for PE, PA-levels, and sports participation. Actual and perceived MC were only moderately correlated and cluster analyses identified four groups. Two groups of overestimators (low - overestimation, average - overestimation) were identified (51%), who particularly displayed better motivation for PE when compared to their peers who accurately estimated themselves (low - accurate, average - accurate). Moreover, adolescents with low actual MC, but high perceived MC were significantly more active than adolescents with low actual MC who accurately estimated themselves. Results pointed in the same direction for organised sports participation. Underestimators were not found in the current sample, which is positive as underestimation might negatively influence adolescents' motivation to achieve and persist in PA and sports. In conclusion, results emphasise that developing perceived MC, especially among adolescents with low levels of actual MC, seems crucial to stimulate motivation for PE, and engagement in PA and sports.
Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods.
Wang, Liming; Zhu, L; Luan, R; Wang, L; Fu, J; Wang, X; Sui, L
2016-10-10
Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs) and microRNAs (miRNAs) of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT) were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family). Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1), potential TFs, as well as potential miRNAs, might be involved in DCM.
Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods
Wang, Liming; Zhu, L.; Luan, R.; Wang, L.; Fu, J.; Wang, X.; Sui, L.
2016-01-01
Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs) and microRNAs (miRNAs) of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT) were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family). Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1), potential TFs, as well as potential miRNAs, might be involved in DCM. PMID:27737314
Yang, Sunny Y; Ahmed, Shaimaa; Satheesh, Somisetty V; Matthews, Jason
2018-01-01
The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24 h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq). We identified 3915 AHR- and 2811 AHRR-bound regions, of which 974 (35%) were common to both datasets. When these 24-h datasets were also compared with AHR-bound regions identified after 45 min of TCDD treatment, 67% (1884) of AHRR-bound regions overlapped with those of AHR. This analysis identified 994 unique AHRR-bound regions. AHRR-bound regions mapped closer to promoter regions when compared with AHR-bound regions. The AHRE was identified and overrepresented in AHR:AHRR-co-bound regions, AHR-only regions, and AHRR-only regions. Candidate unique AHR- and AHRR-bound regions were validated by ChIP-qPCR and their ability to regulate gene expression was confirmed by luciferase reporter gene assays. Overall, this study reveals that AHR and AHRR exhibit similar but also distinct genome-wide binding profiles, supporting the notion that AHRR is a context- and gene-specific repressor of AHR activity.
Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen
2016-01-01
We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes. PMID:27150491
Transport of light, trace impurities in Alcator C-Mod
NASA Astrophysics Data System (ADS)
Rowan, W. L.; Bespamyatnov, I. O.; Liao, K. T.; Horton, W.; Fu, X. R.; Hughes, J. W.
2012-10-01
Light impurity profiles for boron were measured in ITB, H-mode, L-mode, and I-mode discharges in Alcator C-Mod. Within this wide range of modes, the profiles varied from peaked to hollow to flat. Specifically, hollow profiles are often observed in H-mode, while ITBs produce strong peaking, and L-mode produces moderate peaking. I-mode discharges are characterized by flat impurity profiles. For the study reported here, the profiles were measured with charge exchange recombination spectroscopy. The dependences of Rv/D were sought on dimensionless quantities including ion density scale length, effective charge, collisionality, and temperature scale length. We find that neoclassical transport consistently underestimates the measured transport. The excess measured transport is assumed to be turbulent. The strongest dependence of Rv/D is with temperature scale length. In addition, the measured transport was compared with the prediction of an analytical theory of drift wave turbulence that identifies transport implications for drift waves driven by ion and impurity density gradients.
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L
2008-08-15
The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.
Selvarajah, Gayathri T; Kirpensteijn, Jolle; van Wolferen, Monique E; Rao, Nagesha AS; Fieten, Hille; Mol, Jan A
2009-01-01
Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST). They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months) and long survivors (dogs with better prognosis: surviving 6 months or longer). Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the dog a suitable pre-clinical model for future 'novel' therapeutic approaches where the current research has provided new insights on prognostic genes, molecular pathways and mechanisms involved in OS pathogenesis and disease progression. PMID:19735553
Huang, Chiang-Ching; McDermott, Mary M; Liu, Kiang; Kuo, Ching-Hua; Wang, San-Yuan; Tao, Huimin; Tseng, Yufeng Jane
2013-10-01
Individuals with peripheral arterial disease (PAD) have a nearly two-fold increased risk of all-cause and cardiovascular disease mortality compared to those without PAD. This pilot study determined whether metabolomic profiling can accurately identify patients with PAD who are at increased risk of near-term mortality. We completed a case-control study using (1)H NMR metabolomic profiling of plasma from 20 decedents with PAD, without critical limb ischemia, who had blood drawn within 8 months prior to death (index blood draw) and within 10 to 28 months prior to death (preindex blood draw). Twenty-one PAD participants who survived more than 30 months after their index blood draw served as a control population. Results showed distinct metabolomic patterns between preindex decedent, index decedent, and survivor samples. The major chemical signals contributing to the differential pattern (between survivors and decedents) arose from the fatty acyl chain protons of lipoproteins and the choline head group protons of phospholipids. Using the top 40 chemical signals for which the intensity was most distinct between survivor and preindex decedent samples, classification models predicted near-term all-cause death with overall accuracy of 78% (32/41), a sensitivity of 85% (17/20), and a specificity of 71% (15/21). When comparing survivor with index decedent samples, the overall classification accuracy was optimal at 83% (34/41) with a sensitivity of 80% (16/20) and a specificity of 86% (18/21), using as few as the top 10 to 20 chemical signals. Our results suggest that metabolomic profiling of plasma may be useful for identifying PAD patients at increased risk for near-term death. Larger studies using more sensitive metabolomic techniques are needed to identify specific metabolic pathways associated with increased risk of near-term all-cause mortality among PAD patients. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Rocker, Jana M; Tan, Marcus C; Thompson, Lee W; Contreras, Carlo M; DiPalma, Jack A; Pannell, Lewis K
2016-01-01
OBJECTIVES: There are currently no reliable, non-invasive screening tests for pancreatic ductal adenocarcinoma. The fluid secreted from the pancreatic ductal system (“pancreatic juice”) has been well-studied as a potential source of cancer biomarkers. However, it is invasive to collect. We recently observed that the proteomic profile of intestinal effluent from the bowel in response to administration of an oral bowel preparation solution (also known as whole-gut lavage fluid, WGLF) contains large amounts of pancreas-derived proteins. We therefore hypothesized that the proteomic profile is similar to that of pancreatic juice. In this study, we compared the proteomic profiles of 77 patients undergoing routine colonoscopy with the profiles of 19 samples of pure pancreatic juice collected during surgery. METHODS: WGLF was collected from patients undergoing routine colonoscopy, and pancreatic juice was collected from patients undergoing pancreatic surgery. Protein was isolated from both samples using an optimized method and analyzed by LC-MS/MS. Identified proteins were compared between samples and groups to determine similarity of the two fluids. We then compared our results with literature reports of pancreatic juice-based studies to determine similarity. RESULTS: We found 104 proteins in our pancreatic juice samples, of which 90% were also found in our WGLF samples. The majority (67%) of the total proteins found in the WGLF were common to pancreatic juice, with intestine-specific proteins making up a smaller proportion. CONCLUSIONS: WGLF and pancreatic juice appear to have similar proteomic profiles. This supports the notion that WGLF is a non-invasive, surrogate bio-fluid for pancreatic juice. Further studies are required to further elucidate its role in the diagnosis of pancreatic cancer. PMID:27228405
Raouf, Joan; Idborg, Helena; Englund, Petter; Alexanderson, Helene; Dastmalchi, Maryam; Jakobsson, Per-Johan; Lundberg, Ingrid E; Korotkova, Marina
2018-05-02
Polymyositis (PM) and dermatomyositis (DM) are severe chronic autoimmune diseases, characterized by muscle fatigue and low muscle endurance. Conventional treatment includes high doses of glucocorticoids and immunosuppressive drugs; however, few patients recover full muscle function. One explanation of the persistent muscle weakness could be altered lipid metabolism in PM/DM muscle tissue as we previously reported. Using a targeted lipidomic approach we aimed to characterize serum lipid profiles in patients with PM/DM compared to healthy individuals (HI) in a cross-sectional study. Also, in the longitudinal study we compared serum lipid profiles in patients newly diagnosed with PM/DM before and after immunosuppressive treatment. Lipidomic profiles were analyzed in serum samples from 13 patients with PM/DM, 12 HI and 8 patients newly diagnosed with PM/DM before and after conventional immunosuppressive treatment using liquid chromatography tandem mass spectrometry (LC-MS/MS) and a gas-chromatography flame ionization detector (GC-FID). Functional Index (FI), as a test of muscle performance and serum levels of creatine kinase (s-CK) as a proxy for disease activity were analyzed. The fatty acid (FA) composition of total serum lipids was altered in patients with PM/DM compared to HI; the levels of palmitic (16:0) acid were significantly higher while the levels of arachidonic (20:4, n-6) acid were significantly lower in patients with PM/DM. The profiles of serum phosphatidylcholine and triacylglycerol species were changed in patients with PM/DM compared to HI, suggesting disproportionate levels of saturated and polyunsaturated FAs that might have negative effects on muscle performance. After immunosuppressive treatment the total serum lipid levels of eicosadienoic (20:2, n-6) and eicosapentaenoic (20:5, n-3) acids were increased and serum phospholipid profiles were altered in patients with PM/DM. The correlation between FI or s-CK and levels of several lipid species indicate the important role of lipid changes in muscle performance and inflammation. Serum lipids profiles are significantly altered in patients with PM/DM compared to HI. Moreover, immunosuppressive treatment in patients newly diagnosed with PM/DM significantly affected serum lipid profiles. These findings provide new evidence of the dysregulated lipid metabolism in patients with PM/DM that could possibly contribute to low muscle performance.
Sugimoto, Masahiro; Obiya, Shinichi; Kaneko, Miku; Enomoto, Ayame; Honma, Mayu; Wakayama, Masataka; Soga, Tomoyoshi; Tomita, Masaru
2017-01-18
Dry-cured hams are popular among consumers. To increase the attractiveness of the product, objective analytical methods and algorithms to evaluate the relationship between observable properties and consumer acceptability are required. In this study, metabolomics, which is used for quantitative profiling of hundreds of small molecules, was applied to 12 kinds of dry-cured hams from Japan and Europe. In total, 203 charged metabolites, including amino acids, organic acids, nucleotides, and peptides, were successfully identified and quantified. Metabolite profiles were compared for the samples with different countries of origin and processing methods (e.g., smoking or use of a starter culture). Principal component analysis of the metabolite profiles with sensory properties revealed significant correlations for redness, homogeneity, and fat whiteness. This approach could be used to design new ham products by objective evaluation of various features.
microRNA expression profiling in fetal single ventricle malformation identified by deep sequencing.
Yu, Zhang-Bin; Han, Shu-Ping; Bai, Yun-Fei; Zhu, Chun; Pan, Ya; Guo, Xi-Rong
2012-01-01
microRNAs (miRNAs) have emerged as key regulators in many biological processes, particularly cardiac growth and development, although the specific miRNA expression profile associated with this process remains to be elucidated. This study aimed to characterize the cellular microRNA profile involved in the development of congenital heart malformation, through the investigation of single ventricle (SV) defects. Comprehensive miRNA profiling in human fetal SV cardiac tissue was performed by deep sequencing. Differential expression of 48 miRNAs was revealed by sequencing by oligonucleotide ligation and detection (SOLiD) analysis. Of these, 38 were down-regulated and 10 were up-regulated in differentiated SV cardiac tissue, compared to control cardiac tissue. This was confirmed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Predicted target genes of the 48 differentially expressed miRNAs were analyzed by gene ontology and categorized according to cellular process, regulation of biological process and metabolic process. Pathway-Express analysis identified the WNT and mTOR signaling pathways as the most significant processes putatively affected by the differential expression of these miRNAs. The candidate genes involved in cardiac development were identified as potential targets for these differentially expressed microRNAs and the collaborative network of microRNAs and cardiac development related-mRNAs was constructed. These data provide the basis for future investigation of the mechanism of the occurrence and development of fetal SV malformations.
Ant and Mite Diversity Drives Toxin Variation in the Little Devil Poison Frog.
McGugan, Jenna R; Byrd, Gary D; Roland, Alexandre B; Caty, Stephanie N; Kabir, Nisha; Tapia, Elicio E; Trauger, Sunia A; Coloma, Luis A; O'Connell, Lauren A
2016-06-01
Poison frogs sequester chemical defenses from arthropod prey, although the details of how arthropod diversity contributes to variation in poison frog toxins remains unclear. We characterized skin alkaloid profiles in the Little Devil poison frog, Oophaga sylvatica (Dendrobatidae), across three populations in northwestern Ecuador. Using gas chromatography/mass spectrometry, we identified histrionicotoxins, 3,5- and 5,8-disubstituted indolizidines, decahydroquinolines, and lehmizidines as the primary alkaloid toxins in these O. sylvatica populations. Frog skin alkaloid composition varied along a geographical gradient following population distribution in a principal component analysis. We also characterized diversity in arthropods isolated from frog stomach contents and confirmed that O. sylvatica specialize on ants and mites. To test the hypothesis that poison frog toxin variability reflects species and chemical diversity in arthropod prey, we (1) used sequencing of cytochrome oxidase 1 to identify individual prey specimens, and (2) used liquid chromatography/mass spectrometry to chemically profile consumed ants and mites. We identified 45 ants and 9 mites in frog stomachs, including several undescribed species. We also showed that chemical profiles of consumed ants and mites cluster by frog population, suggesting different frog populations have access to chemically distinct prey. Finally, by comparing chemical profiles of frog skin and isolated prey items, we traced the arthropod source of four poison frog alkaloids, including 3,5- and 5,8-disubstituted indolizidines and a lehmizidine alkaloid. Together, the data show that toxin variability in O. sylvatica reflects chemical diversity in arthropod prey.
Delvecchio, Vito G; Connolly, Joseph P; Alefantis, Timothy G; Walz, Alexander; Quan, Marian A; Patra, Guy; Ashton, John M; Whittington, Jessica T; Chafin, Ryan D; Liang, Xudong; Grewal, Paul; Khan, Akbar S; Mujer, Cesar V
2006-09-01
Differentially expressed and immunogenic spore proteins of the Bacillus cereus group of bacteria, which includes Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis, were identified. Comparative proteomic profiling of their spore proteins distinguished the three species from each other as well as the virulent from the avirulent strains. A total of 458 proteins encoded by 232 open reading frames were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis for all the species. A number of highly expressed proteins, including elongation factor Tu (EF-Tu), elongation factor G, 60-kDa chaperonin, enolase, pyruvate dehydrogenase complex, and others exist as charge variants on two-dimensional gels. These charge variants have similar masses but different isoelectric points. The majority of identified proteins have cellular roles associated with energy production, carbohydrate transport and metabolism, amino acid transport and metabolism, posttranslational modifications, and translation. Novel vaccine candidate proteins were identified using B. anthracis polyclonal antisera from humans postinfected with cutaneous anthrax. Fifteen immunoreactive proteins were identified in B. anthracis spores, whereas 7, 14, and 7 immunoreactive proteins were identified for B. cereus and in the virulent and avirulent strains of B. thuringiensis spores, respectively. Some of the immunodominant antigens include charge variants of EF-Tu, glyceraldehyde-3-phosphate dehydrogenase, dihydrolipoamide acetyltransferase, Delta-1-pyrroline-5-carboxylate dehydrogenase, and a dihydrolipoamide dehydrogenase. Alanine racemase and neutral protease were uniquely immunogenic to B. anthracis. Comparative analysis of the spore immunome will be of significance for further nucleic acid- and immuno-based detection systems as well as next-generation vaccine development.
DelVecchio, Vito G.; Connolly, Joseph P.; Alefantis, Timothy G.; Walz, Alexander; Quan, Marian A.; Patra, Guy; Ashton, John M.; Whittington, Jessica T.; Chafin, Ryan D.; Liang, Xudong; Grewal, Paul; Khan, Akbar S.; Mujer, Cesar V.
2006-01-01
Differentially expressed and immunogenic spore proteins of the Bacillus cereus group of bacteria, which includes Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis, were identified. Comparative proteomic profiling of their spore proteins distinguished the three species from each other as well as the virulent from the avirulent strains. A total of 458 proteins encoded by 232 open reading frames were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis for all the species. A number of highly expressed proteins, including elongation factor Tu (EF-Tu), elongation factor G, 60-kDa chaperonin, enolase, pyruvate dehydrogenase complex, and others exist as charge variants on two-dimensional gels. These charge variants have similar masses but different isoelectric points. The majority of identified proteins have cellular roles associated with energy production, carbohydrate transport and metabolism, amino acid transport and metabolism, posttranslational modifications, and translation. Novel vaccine candidate proteins were identified using B. anthracis polyclonal antisera from humans postinfected with cutaneous anthrax. Fifteen immunoreactive proteins were identified in B. anthracis spores, whereas 7, 14, and 7 immunoreactive proteins were identified for B. cereus and in the virulent and avirulent strains of B. thuringiensis spores, respectively. Some of the immunodominant antigens include charge variants of EF-Tu, glyceraldehyde-3-phosphate dehydrogenase, dihydrolipoamide acetyltransferase, Δ-1-pyrroline-5-carboxylate dehydrogenase, and a dihydrolipoamide dehydrogenase. Alanine racemase and neutral protease were uniquely immunogenic to B. anthracis. Comparative analysis of the spore immunome will be of significance for further nucleic acid- and immuno-based detection systems as well as next-generation vaccine development. PMID:16957262
NASA Astrophysics Data System (ADS)
Sidi, Fatimah; Daud, Maslina; Ahmad, Sabariah; Zainuddin, Naqliyah; Anneisa Abdullah, Syafiqa; Jabar, Marzanah A.; Suriani Affendey, Lilly; Ishak, Iskandar; Sharef, Nurfadhlina Mohd; Zolkepli, Maslina; Nur Majdina Nordin, Fatin; Amat Sejani, Hashimah; Ramadzan Hairani, Saiful
2017-09-01
Information security has been identified by organizations as part of internal operations that need to be well implemented and protected. This is because each day the organizations face a high probability of increase of threats to their networks and services that will lead to information security issues. Thus, effective information security management is required in order to protect their information assets. Threat profiling is a method that can be used by an organization to address the security challenges. Threat profiling allows analysts to understand and organize intelligent information related to threat groups. This paper presents a comparative analysis that was conducted to study the existing threat profiling models. It was found that existing threat models were constructed based on specific objectives, thus each model is limited to only certain components or factors such as assets, threat sources, countermeasures, threat agents, threat outcomes and threat actors. It is suggested that threat profiling can be improved by the combination of components found in each existing threat profiling model/framework. The proposed model can be used by an organization in executing a proactive approach to incident management.
Development of a Pipeline for Exploratory Metabolic Profiling of Infant Urine
Jackson, Frances; Georgakopoulou, Nancy; Kaluarachchi, Manuja; Kyriakides, Michael; Andreas, Nicholas; Przysiezna, Natalia; Hyde, Matthew J.; Modi, Neena; Nicholson, Jeremy K.; Wijeyesekera, Anisha; Holmes, Elaine
2017-01-01
Numerous metabolic profiling pipelines have been developed to characterize the composition of human biofluids and tissues, the vast majority of these being for studies in adults. To accommodate limited sample volume and to take into account the compositional differences between adult and infant biofluids, we developed and optimized sample handling and analytical procedures for studying urine from newborns. A robust pipeline for metabolic profiling using NMR spectroscopy was established, encompassing sample collection, preparation, spectroscopic measurement, and computational analysis. Longitudinal samples were collected from five infants from birth until 14 months of age. Methods of extraction and effects of freezing and sample dilution were assessed, and urinary contaminants from breakdown of polymers in a range of diapers and cotton wool balls were identified and compared, including propylene glycol, acrylic acid, and tert-butanol. Finally, assessment of urinary profiles obtained over the first few weeks of life revealed a dramatic change in composition, with concentrations of phenols, amino acids, and betaine altering systematically over the first few months of life. Therefore, neonatal samples require more stringent standardization of experimental design, sample handling, and analysis compared to that of adult samples to accommodate the variability and limited sample volume. PMID:27476583
Selective estrogen receptor modulators in clinical practice: a safety overview.
Ellis, Amanda J; Hendrick, Vicky M; Williams, Robert; Komm, Barry S
2015-06-01
Selective estrogen receptor (ER) modulators (SERMs) are a class of nonsteroidal compounds that interact with ERs, each with a distinct tissue-specific profile. Depending upon the degree of ER agonism/antagonism at the target tissue, SERMs show efficacy for various indications including osteoporosis, dyspareunia, and breast cancer, and are associated with safety risks. This review describes the safety profile of SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, lasofoxifene, and ospemifene) and fulvestrant (a pure ER antagonist) from Phase III trials, long-term extension studies, and active comparator studies. Tamoxifen, a first-generation SERM, is indicated for breast cancer prevention and treatment but is associated with serious safety concerns including endometrial cancer, venous thromboembolic events (VTE), and stroke. Toremifene, raloxifene, bazedoxifene, lasofoxifene, and ospemifene present generally improved, though distinctly different, safety profiles compared with tamoxifen, especially with endometrial cancer and stroke. However, the risk of VTE remains a concern for most SERMs. Each SERM presents a unique risk/benefit profile based on varying indications and tissue-specific ER agonist and antagonist effects, making careful patient selection and ongoing patient monitoring crucial aspects of treatment. Future research may focus on identifying new SERMs for endocrine-resistant and endocrine-responsive cancers and post-menopausal symptoms.
High-resolution humidity profiles retrieved from wind profiler radar measurements
NASA Astrophysics Data System (ADS)
Saïd, Frédérique; Campistron, Bernard; Di Girolamo, Paolo
2018-03-01
The retrieval of humidity profiles from wind profiler radars has already been documented in the past 30 years and is known to be neither as straightforward and nor as robust as the retrieval of the wind velocity. The main constraint to retrieve the humidity profile is the necessity to combine measurements from the wind profiler and additional measurements (such as observations from radiosoundings at a coarser time resolution). Furthermore, the method relies on some assumptions and simplifications that restrict the scope of its application. The first objective of this paper is to identify the obstacles and limitations and solve them, or at least define the field of applicability. To improve the method, we propose using the radar capacity to detect transition levels, such as the top level of the boundary layer, marked by a maximum in the radar reflectivity. This forces the humidity profile from the free troposphere and from the boundary layer to coincide at this level, after an optimization of the calibration coefficients, and reduces the error. The resulting mean bias affecting the specific humidity profile never exceeds 0.25 g kg-1. The second objective is to explore the capability of the algorithm to retrieve the humidity vertical profiles for an operational purpose by comparing the results with observations from a Raman lidar.
1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling.
Sethi, Sumit; Pedrini, Mariana; Rizzo, Lucas B; Zeni-Graiff, Maiara; Mas, Caroline Dal; Cassinelli, Ana Cláudia; Noto, Mariane N; Asevedo, Elson; Cordeiro, Quirino; Pontes, João G M; Brasil, Antonio J M; Lacerda, Acioly; Hayashi, Mirian A F; Poppi, Ronei; Tasic, Ljubica; Brietzke, Elisa
2017-12-01
The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. Metabolomic profiling, employing 1 H-NMR, 1 H-NMR T 2 -edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.
Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas
Kuick, Rork; Thomas, Dafydd G.; Nadal, Ernest; Lin, Jules; Chang, Andrew C.; Reddy, Rishindra M.; Orringer, Mark B.; Taylor, Jeremy M. G.; Wang, Thomas D.; Beer, David G.
2016-01-01
The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies. PMID:27363029
Zhang, Ya-Zhou; Xu, Feng; Yi, Tao; Zhang, Jian-Ye; Xu, Jun; Tang, Yi-Na; He, Xi-Chen; Liu, Jing; Chen, Hu-Biao
2014-04-30
Danggui Buxue Tang (DBT) is a Traditional Chinese Medicine (TCM) formula primarily used to treat symptoms associated with menopause in women. Usually, DBT is composed of one portion of Radix Angelicae Sinensis (RAS) and five portions of Radix Astragali (RA). Clinically, Radix Hedysari (RH) is sometimes used by TCM physicians to replace RA in DBT. In order to verity whether the chemical constituents of the DBT1 (RA:RAS = 5:1, w/w) and DBT2 (RH:RAS = 5:1, w/w) share similarities the chemical profiles of the two DBTs crude extracts and urine samples were analyzed and compared with the aid of HPLC-DAD-ESI-IT-TOF-MSn, which determines the total ion chromatogram (TIC) and multi-stage mass spectra (MSn). Then, the DBT1 and DBT2 were identified and compared on the basis of the TIC and the MSn. In the first experiment (with crude extracts), 69 compounds (C1-C69) were identified from the DBT1; 46 compounds (c1-c46) were identified from the DBT2. In the second experiment(with urine samples), 44 compounds (M1-M44) were identified from the urine samples of rats that had been administered DBT1, and 34 compounds (m1-m34) were identified from the urine samples of rats that had been administered DBT2. Identification and comparison of the chemical compositions were carried out between the DBT1 and DBT2 of the crude extracts and urine samples respectively. Our results showed that the two crude extracts of the DBTs have quite different chemical profiles. The reasons for their differences were that the special astragalosides in DBT1 and the isoflavonoid glycosides formed the malonic acid esters undergo single esterification and acetyl esters undergo acetylation in DBT1. In contrast, the urine from DBT1-treated rats strongly resembled that of DBT2-treated rats. These metabolites originate mainly from formononetin, calycosin and their related glycosides, and they were formed mainly by the metabolic process of reduction, deglycosylation, demethylation, hydrogenation and sulfation. The HPLC-DAD-ESI-IT-TOF-MSn method was successfully applied for the rapid chemical profiles evaluation of two DBTs and their related urine samples.
Chen, Muyan; Storey, Kenneth B
2014-02-01
The sea cucumber Apostichopus japonicus withstands high water temperatures in the summer by suppressing its metabolic rate and entering a state of aestivation. We hypothesized that changes in the expression of miRNAs could provide important post-transcriptional regulation of gene expression during hypometabolism via control over mRNA translation. The present study analyzed profiles of miRNA expression in the sea cucumber respiratory tree using Solexa deep sequencing technology. We identified 279 sea cucumber miRNAs, including 15 novel miRNAs specific to sea cucumber. Animals sampled during deep aestivation (DA; after at least 15 days of continuous torpor) were compared with animals from a non-aestivation (NA) state (animals that had passed through aestivation and returned to an active state). We identified 30 differentially expressed miRNAs ([RPM (reads per million) >10, |FC| (|fold change|)≥1, FDR (false discovery rate)<0.01]) during aestivation, which were validated by two other miRNA profiling methods: miRNA microarray and real-time PCR. Among the most prominent miRNA species, miR-124, miR-124-3p, miR-79, miR-9 and miR-2010 were significantly over-expressed during deep aestivation compared with non-aestivation animals, suggesting that these miRNAs may play important roles in metabolic rate suppression during aestivation. High-throughput sequencing data and microarray data have been submitted to the GEO database with accession number: 16902695. Copyright © 2014 Elsevier B.V. All rights reserved.
Fairlie, Anne M.; Maggs, Jennifer L.; Lanza, Stephanie T.
2016-01-01
Objective: Types of college drinkers have been identified using traditional measures (e.g., 12-month drinking frequency). We used an alternative multidimensional approach based on daily reports of alcohol behaviors to identify college drinker statuses, each with a unique behavioral profile. The current study aimed to (a) identify drinker statuses at the week level across four semesters, (b) examine the predictive utility of drinker status by testing associations with senior-year hazardous drinking and dependence symptoms, and (c) identify concurrent predictors (gender, drinking motivations, hazardous drinking, any dependence symptoms) of senior-year drinker status. We also compared the week-level drinker statuses with drinker statuses identified using traditional measures. Method: A multi-ethnic sample of U.S. college students completed 14-day bursts of daily web surveys across college (91%–96% completed ≥6 daily reports of the sampled week). Analyses focus on nine alcohol-related behaviors (including estimated blood alcohol concentration, pregaming, and drinking games) assessed daily in spring/sophomore year to fall/senior year and drinking motivations, hazardous drinking, and dependence symptoms assessed fall/senior year (n = 569; 56% women). Results: Four week-level drinker statuses were replicated across semesters: Nondrinker, Light Weekend, Heavy Weekend, and Heavy Frequent. Across semesters, drinker status was associated with senior-year hazardous drinking and any dependence symptoms. Senior-year fun/social motivations were also associated with senior-year drinker status. Differences in behavioral profiles between week-level drinker statuses and those identified using traditional measures were found. Conclusions: Replicable week-level drinker statuses were identified, suggesting consistency in possible types of drinking weeks. Drinker statuses were predictive of senior-year hazardous drinking and dependence symptoms. PMID:26751353
Identifying Russian and Finnish Adolescents' Problem Behaviours
ERIC Educational Resources Information Center
Kemppainen, Ulla; Tossavainen, Kerttu; Vartiainen, Erkki; Puska, Pekka; Jokela, Veikko; Pantelejev, Vladimir; Uhanov, Mihail
2007-01-01
Purpose: The purpose of the paper is to show that a syndrome of problem behaviours, i.e. early substance abuse, school and family problems and sexual promiscuity impairs normal development in adolescence. This comparative study looked for differences in the problem behaviour profiles of 15-year-old adolescents in the Pitkaranta district in Russia…
Reading Skills in Children with Down Syndrome: A Meta-Analytic Review
ERIC Educational Resources Information Center
Naess, Kari-Anne B.; Melby-Lervag, Monica; Hulme, Charles; Lyster, Solveig-Alma Halaas
2012-01-01
The authors examine the reading profile in children with Down syndrome by comparing the nonword decoding skills in children with Down syndrome and typically developing children matched for word recognition level. Journal articles published before 04.05.2010 were identified by using the keyword Down* cross-referenced to "reading", "literacy",…
Issues in the Identification of Minority College Students with Learning Disabilities.
ERIC Educational Resources Information Center
Heggoy, Synnove; Grant, Dale
This study examined differences in the manifestation of learning disabilities (LD) between minority and non-minority students at a southeastern public college. Profiles of non-minority and minority college students not previously identified as learning disabled and with a history of academic difficulty were compared. Among trends noted in both…
USDA-ARS?s Scientific Manuscript database
Background: To identify the genes involved in the development of low temperature (LT) tolerance in hexaploid wheat, we examined the global changes in expression in response to cold of the 55,052 potentially unique genes represented in the Affymetrix Wheat Genome microarray. We compared the expressi...
Comparative Analysis of AhR-Mediated TCDD-Elicited Gene Expression in Human Liver Adult Stem Cells
Kim, Suntae; Dere, Edward; Burgoon, Lyle D.; Chang, Chia-Cheng; Zacharewski, Timothy R.
2009-01-01
Time course and dose-response studies were conducted in HL1-1 cells, a human liver cell line with stem cell–like characteristics, to assess the differential gene expression elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) compared with other established models. Cells were treated with 0.001, 0.01, 0.1, 1, 10, or 100nM TCDD or dimethyl sulfoxide vehicle control for 12 h for the dose-response study, or with 10nM TCDD or vehicle for 1, 2, 4, 8, 12, 24, or 48 h for the time course study. Elicited changes were monitored using a human cDNA microarray with 6995 represented genes. Empirical Bayes analysis identified 144 genes differentially expressed at one or more time points following treatment. Most genes exhibited dose-dependent responses including CYP1A1, CYP1B1, ALDH1A3, and SLC7A5 genes. Comparative analysis of HL1-1 differential gene expression to human HepG2 data identified 74 genes with comparable temporal expression profiles including 12 putative primary responses. HL1-1–specific changes were related to lipid metabolism and immune responses, consistent with effects elicited in vivo. Furthermore, comparative analysis of HL1-1 cells with mouse Hepa1c1c7 hepatoma cell lines and C57BL/6 hepatic tissue identified 18 and 32 commonly regulated orthologous genes, respectively, with functions associated with signal transduction, transcriptional regulation, metabolism and transport. Although some common pathways are affected, the results suggest that TCDD elicits species- and model-specific gene expression profiles. PMID:19684285
MicroRNA Changes in Cerebrospinal Fluid After Subarachnoid Hemorrhage
Rasmussen, Rune; Rossing, Maria; Laigaard, Finn Pedersen; Nielsen, Finn Cilius; Møller, Kirsten
2017-01-01
Background and Purpose— Delayed cerebral ischemia (DCI) accounts for a major part of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are pathophysiologically involved in acute cerebral ischemia. This study compared miRNA profiles in cerebrospinal fluid from neurologically healthy patients, as well as SAH patients with and without subsequent development of DCI. Methods— In a prospective case–control study of SAH patients treated with external ventricular drainage and neurologically healthy patients, miRNA profiles in cerebrospinal fluid were screened and validated using 2 different high-throughput real-time quantification polymerase chain reaction techniques. The occurrence of DCI was documented in patient charts and subsequently reviewed independently by 2 physicians. Results— MiRNA profiles from 27 SAH patients and 10 neurologically healthy patients passed quality control. In the validation, 66 miRNAs showed a relative increase in cerebrospinal fluid from SAH patients compared with neurologically healthy patients (P<0.001); 2 (miR-21 and miR-221) showed a relative increase in SAH patients with DCI compared with those without (P<0.05) in both the screening and validation. Conclusions— SAH is associated with marked changes in the cerebrospinal fluid miRNA profile. These changes could be associated to the development of DCI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01791257. PMID:28768799
Rechache, Nesrin S; Wang, Yonghong; Stevenson, Holly S; Killian, J Keith; Edelman, Daniel C; Merino, Maria; Zhang, Lisa; Nilubol, Naris; Stratakis, Constantine A; Meltzer, Paul S; Kebebew, Electron
2012-06-01
It is not known whether there are any DNA methylation alterations in adrenocortical tumors. The objective of the study was to determine the methylation profile of normal adrenal cortex and benign and malignant adrenocortical tumors. Genome-wide methylation status of CpG regions were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8), and metastatic malignant (n = 12) adrenocortical tissue samples. An integrated analysis of genome-wide methylation and mRNA expression in benign vs. malignant adrenocortical tissue samples was also performed. Methylation profiling revealed the following: 1) that methylation patterns were distinctly different and could distinguish normal, benign, primary malignant, and metastatic tissue samples; 2) that malignant samples have global hypomethylation; and 3) that the methylation of CpG regions are different in benign adrenocortical tumors by functional status. Normal compared with benign samples had the least amount of methylation differences, whereas normal compared with primary and metastatic adrenocortical carcinoma samples had the greatest variability in methylation (adjusted P ≤ 0.01). Of 215 down-regulated genes (≥2-fold, adjusted P ≤ 0.05) in malignant primary adrenocortical tumor samples, 52 of these genes were also hypermethylated. Malignant adrenocortical tumors are globally hypomethylated as compared with normal and benign tumors. Methylation profile differences may accurately distinguish between primary benign and malignant adrenocortical tumors. Several differentially methylated sites are associated with genes known to be dysregulated in malignant adrenocortical tumors.
Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus.
Li, Xu-Zhao; Yang, Xu-Yan; Wang, Yu; Zhang, Shuai-Nan; Zou, Wei; Wang, Yan; Li, Xiao-Nan; Wang, Ling-Shu; Zhang, Zhi-Gang; Xie, Liang-Zhen
2017-01-01
Oral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. Metabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease. In total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP. The dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.
Clarke, Luka A; Botelho, Hugo M; Sousa, Lisete; Falcao, Andre O; Amaral, Margarida D
2015-11-01
A meta-analysis of 13 independent microarray data sets was performed and gene expression profiles from cystic fibrosis (CF), similar disorders (COPD: chronic obstructive pulmonary disease, IPF: idiopathic pulmonary fibrosis, asthma), environmental conditions (smoking, epithelial injury), related cellular processes (epithelial differentiation/regeneration), and non-respiratory "control" conditions (schizophrenia, dieting), were compared. Similarity among differentially expressed (DE) gene lists was assessed using a permutation test, and a clustergram was constructed, identifying common gene markers. Global gene expression values were standardized using a novel approach, revealing that similarities between independent data sets run deeper than shared DE genes. Correlation of gene expression values identified putative gene regulators of the CF transmembrane conductance regulator (CFTR) gene, of potential therapeutic significance. Our study provides a novel perspective on CF epithelial gene expression in the context of other lung disorders and conditions, and highlights the contribution of differentiation/EMT and injury to gene signatures of respiratory disease. Copyright © 2015 Elsevier Inc. All rights reserved.
Profiling primary care physicians for a new managed care network.
Ozminkowski, R J; Noether, M; Nathanson, P; Smith, K M; Raney, B E; Mickey, D; Hawley, P M
1997-08-01
We developed methods for comparing physicians who would be selected to participate in a major employer's self-insurance program. These methods used insurance claims data to identify and profile physicians according to deviations from prevailing practice and outcome patterns, after considering differences in case-mix and severity of illness among the patients treated by those providers. The discussion notes the usefulness and limitations of claims data for this and other purposes. We also comment on policy implications and the relationships between our methods and health care reform strategies designed to influence overall health care costs.
NASA Technical Reports Server (NTRS)
Anikouchine, W. A. (Principal Investigator)
1973-01-01
The author has identified the following significant results. Radiance profiles drawn along cruise tracks have been examined for use in correlating digital radiance levels with ground truth data. Preliminary examination results are encouraging. Adding weighted levels from the 4 MSS bands appears to enhance specular surface reflections while rendering sensor noise white. Comparing each band signature to the added specular signature ought to enhance non-specular effects caused by ocean turbidity. Preliminary examination of radiance profiles and ground truth turbidity measurements revealed substantial correlation.
Prevailing clone (ST69) of Vibrio cholerae O139 in India over 10 years.
Anandan, Shalini; Devanga Ragupathi, Naveen Kumar; Muthuirulandi Sethuvel, Dhiviya Prabaa; Thangamani, Suji; Veeraraghavan, Balaji
2017-01-01
Vibrio cholerae is responsible for the cause of severe life-threatening infection known as cholera. The study aimed to analyze the genetic make-up of V. cholerae O139 isolates from India and compare its phylogeny with the global strains. The genome data revealed that all isolates were of same sequence type (ST69) which belongs to seventh pandemic clone, with same virulence gene profile and, antimicrobial resistance gene profile except for two isolates. No known CRISPR repeats were identified in any of these isolates. Three different phages were identified among the isolates. All the isolates were found to harbour int SXT and seventh pandemic-specific gene (VC2346). Results from this study enhance our understanding on the persistence of ST69 V. cholerae O139 over 20 years.
The CBCL Bipolar Profile and Attention, Mood, and Behavior Dysregulation
ERIC Educational Resources Information Center
Doerfler, Leonard A.; Connor, Daniel F.; Toscano, Peter F.
2011-01-01
Biederman and colleagues reported that a CBCL profile identified youngsters who were diagnosed with bipolar disorder. Some studies found that this CBCL profile does not reliably identify children who present with bipolar disorder, but nonetheless this CBCL does identify youngsters with severe dysfunction. However, the nature of the impairment of…
Gill, Jessica M; Lee, Hyunhwa; Baxter, Tristin; Reddy, Swarnalatha Y; Barr, Taura; Kim, Hyung-Suk; Wang, Dan; Mysliwiec, Vincent
2015-07-01
Sleep disturbance is a common and disturbing symptom in military personnel, with many individuals progressing to the development of insomnia, which is characterized by increased arousals, wakefulness after sleep onset, and distorted sleep architecture. The molecular mechanisms underlying insomnia remain elusive, limiting future therapeutic development to address this critical issue. We examined whole gene expression profiles associated with insomnia. We compared subjects with insomnia (n = 25) to controls (n = 13) without insomnia using microarray gene expression profiles obtained from peripheral samples of whole blood obtained from military personnel. Compared to controls, participants with insomnia had differential expression of 44 transcripts from 43 identified genes. Among the identified genes, urotensin 2 was downregulated by more than 6 times in insomnia participants, and the fold-change remained significant after controlling for depression, posttraumatic stress disorder, and medication use. Urotensin 2 is involved in regulation of orexin A and B activity and rapid eye movement during sleep. These findings suggest that differential expression of these sleep-regulating genes contributes to symptoms of insomnia and, specifically, that switching between rapid eye movement and nonrapid eye movement sleep stages underlies insomnia symptoms. Future work to identify therapeutic agents that are able to regulate these pathways may provide novel treatments for insomnia. © The Author(s) 2015.
Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay
2015-01-01
The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060
Brief report: Academic amotivation in light of the dark side of identity formation.
Cannard, Christine; Lannegrand-Willems, Lyda; Safont-Mottay, Claire; Zimmermann, Grégoire
2016-02-01
The study intended to determine motivational profiles of first-year undergraduates and aimed their characterization in terms of identity processes. First, a cluster analysis revealed five motivational profiles: combined (i.e., high quantity of motivation, low amotivation); intrinsic (i.e., high intrinsic, low introjected and external regulation, low amotivation); "demotivated" (i.e., very low quantity of motivation and amotivation); extrinsic (i.e., high extrinsic and identified regulation and low intrinsic and amotivation); and "amotivated" (i.e., low intrinsic and identified, very high amotivation). Second, using Lebart's (2000) methodology, the most characteristic identity processes were listed for each motivational cluster. Demotivated and amotivated profiles were refined in terms of adaptive and maladaptive forms of exploration. Notably, exploration in breadth and in depth were underrepresented in demotivated students compared to the total sample; commitment and ruminative exploration were under and overrepresented respectively in amotivated students. Educational and clinical implications are proposed and future research is suggested. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.
Mudge, Elizabeth; Lopes-Lutz, Daise; Brown, Paula; Schieber, Andreas
2011-08-10
Alkylamides are a class of compounds present in plants of the genus Echinacea (Asteraceae), which have been shown to have high bioavailability and immunomodulatory effects. Fast analysis to identify these components in a variety of products is essential to profile products used in clinical trials and for quality control of these products. A method based on ultrafast liquid chromatography (UFLC) coupled with diode array detection and electrospray ionization mass spectrometry was developed for the analysis of alkylamides from the roots of Echinacea angustifolia (DC.) Hell., Echinacea purpurea (L.) Moench, and commercial dietary supplements. A total of 24 alkylamides were identified by LC-MS. The analysis time for these components is 15 min. Compared to the alkylamide profiles determined in the Echinacea root materials, the commercial products showed a more complex profile due to the blending of root and aerial parts of E. purpurea. This versatile method allows for the identification of alkylamides in a variety of Echinacea products and presents the most extensive characterization of alkylamides in E. angustifolia roots so far.
Eyles, Helen; Gorton, Delvina; Ni Mhurchu, Cliona
2010-09-10
To determine whether a modified version of the Heart Foundation Tick (MHFT) nutrient profiling model appropriately classifies supermarket foods to endorse its use for identifying 'healthier' products eligible for promotion in a supermarket intervention trial. Top-selling products (n=550) were selected from an existing supermarket nutrient composition database. Percentage of products classified as 'healthier' by the MHFT and a modified comparator model (Food Standards Australia New Zealand; MFSANZ) were calculated. Percentage agreement, consistency (kappa statistic), and average nutrient values were assessed overall, and across seven food groups. The MHFT model categorised 16% fewer products as 'healthier' than the MFSANZ model. Agreement and consistency between models were 72% and kappa=0.46 (P=0.00), respectively. For both models, 'healthier' products were on average lower in energy, protein, saturated fat, sugar, and sodium than their 'less healthy' counterparts. The MHFT nutrient profiling model categorised regularly purchased supermarket foods similarly to the MFSANZ model, and both appear to distinguish appropriately between 'healthier' and 'less healthy' options. Therefore, both models have the potential to appropriately identify 'healthier' foods for promotion and positively influence food choices.
Martinez-Urtaza, Jaime; Lozano-Leon, Antonio; Viña-Feas, Alejandro; de Novoa, Jacobo; Garcia-Martin, Oscar
2006-02-01
Genetic differences in clinical and environmental strains of Vibrio parahaemolyticus have been widely used as criteria in identifying pathogenic isolates. However, few studies have been carried out to assess the differences in biochemical characteristics of V. parahaemolyticus isolates from human and environmental sources. We compared the biochemical profiles obtained by the characterization of V. parahaemolyticus isolates from human infections and the marine environment using the API 20E system. Environmental and clinical isolates showed significant differences in the gelatin and arabinose tests. Additionally, clinical isolates were correctly identified according to the API 20E profile using 0.85% NaCl diluent, but they presented nonspecific profiles with 2% NaCl diluent. In contrast, use of 2% NaCl diluent facilitated correct identification of the environmental isolates. Clinical isolates showed significant differences in up to five biochemical tests with respect to the API 20E database. The API 20E system is widely used in routine identification of bacteria in clinical laboratories, and this discrepancy in an important number of biochemical tests may lead to misidentification of V. parahaemolyticus infection.
Personality heterogeneity in PTSD: distinct temperament and interpersonal typologies.
Thomas, Katherine M; Hopwood, Christopher J; Donnellan, M Brent; Wright, Aidan G C; Sanislow, Charles A; McDevitt-Murphy, Meghan E; Ansell, Emily B; Grilo, Carlos M; McGlashan, Thomas H; Shea, M Tracie; Markowitz, John C; Skodol, Andrew E; Zanarini, Mary C; Morey, Leslie C
2014-03-01
Researchers examining personality typologies of posttraumatic stress disorder (PTSD) have consistently identified 3 groups: low pathology, internalizing, and externalizing. These groups have been found to predict functional severity and psychiatric comorbidity. In this study, we employed Latent Profile Analysis to compare this previously established typology, grounded in temperament traits (negative emotionality; positive emotionality; constraint), to a novel typology rooted in interpersonal traits (dominance; warmth) in a sample of individuals with PTSD (n = 155). Using Schedule for Nonadaptive and Adaptive Personality (SNAP) traits to create latent profiles, the 3-group temperament model was replicated. Using Interpersonal Circumplex (IPC) traits to create latent profiles, we identified a 4-group solution with groups varying in interpersonal style. These models were nonredundant, indicating that the depiction of personality variability in PTSD depends on how personality is assessed. Whereas the temperament model was more effective for distinguishing individuals based on distress and comorbid disorders, the interpersonal model was more effective for predicting the chronicity of PTSD over the 10 year course of the study. We discuss the potential for integrating these complementary temperament and interpersonal typologies in the clinical assessment of PTSD. 2014 APA
Ye, Xiaolan; Cao, Di; Zhao, Xin; Song, Fenyun; Huang, Qinghua; Fan, Guorong; Wu, Fuhai
2014-11-01
A method incorporating HPLC-PDA-IT-MS(n) with HPLC-Quadrupole-Orbitrap-MS was developed for the investigation of chemical fingerprint of Citrus reticulate 'Chachi' decoction (CRCD) and metabolic profile of SD rat plasma sample after oral administration of CRCD (1.5 g herb/kg). A total of 27 chemical constituents of CRCD were identified from their MW, UV spectra, MS(n) data and retention behavior by comparing the results with those of the reference standards or literature. And 43 compounds were detected in dosed SD rat plasma samples, including 9 prototypes which were identified as hesperetin, isosinensetin, sinensetin, tetramethyl-O-isoscutellarein, nobiletin, tetramethyl-O-scutellarein, HMF (3,5,6,7,8,3',4'-heptamethoxyflavone), tangeretin and 5-demethylnobiletin and 34 metabolites underwent metabolic process of demethylation, glucuronide conjugation, sulfate conjugation or mixed modes. This is the first research for the metabolic profile of CRCD in SD rats, which could lay a foundation for the further studies of CRC or its formulation. Copyright © 2014 Elsevier B.V. All rights reserved.
Antibody profiling sensitivity through increased reporter antibody layering
DOE Office of Scientific and Technical Information (OSTI.GOV)
Apel, William A.; Thompson, Vicki S
A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immunemore » complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.« less
Characterization of Salmonella Typhimurium isolates associated with septicemia in swine
Bergeron, Nadia; Corriveau, Jonathan; Letellier, Ann; Daigle, France; Quessy, Sylvain
2010-01-01
Salmonella Typhimurium is frequently isolated from pigs and may also cause enteric disease in humans. In this study, 33 isolates of S. Typhimurium associated with septicemia in swine (CS) were compared to 33 isolates recovered from healthy animals at slaughter (WCS). The isolates were characterized using phenotyping and genotyping methods. For each isolate, the phage type, antimicrobial resistance, and pulsed-field gel electrophoresis (PFGE) DNA profiles were determined. In addition, the protein profiles of each isolate grown in different conditions were studied by Coomassie Blue-stained sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot. Various phage types were identified. The phage type PT 104 represented 36.4% of all isolates from septicemic pigs. Resistance to as many as 12 antimicrobial agents, including some natural resistances, was found in isolates from CS and WCS. Many genetic profiles were identified among the PT 104 phage types. Although it was not possible to associate one particular protein with septicemic isolates, several highly immunogenic proteins, present in all virulent isolates and in most isolates from clinically healthy animals, were identified. These results indicated that strains associated with septicemia belong to various genetic lineages that can also be recovered from asymptomatic animals at the time of slaughter. PMID:20357952
Molecular events of apical bud formation in white spruce, Picea glauca.
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
2011-03-01
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 molecular 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.
Bökenkamp, Regina; van Brempt, Ronald; van Munsteren, Jacoba Cornelia; van den Wijngaert, Ilse; de Hoogt, Ronald; Finos, Livio; Goeman, Jelle; Groot, Adriana Cornelia Gittenberger-de; Poelmann, Robert Eugen; Blom, Nicolaas Andreas; DeRuiter, Marcus Cornelis
2014-01-01
Closure of the ductus arteriosus (DA) is a crucial step in the transition from fetal to postnatal life. Patent DA is one of the most common cardiovascular anomalies in children with significant clinical consequences especially in premature infants. We aimed to identify genes that specify the DA in the fetus and differentiate it from the aorta. Comparative microarray analysis of laser-captured microdissected endothelial (ECs) and vascular smooth muscle cells (SMCs) from the DA and aorta of fetal rats (embryonic day 18 and 21) identified vessel-specific transcriptional profiles. We found a strong age-dependency of gene expression. Among the genes that were upregulated in the DA the regulator of the G-protein coupled receptor 5 (Rgs5) and the transcription factor distal-less homeobox 1 (Dlx1) exhibited the highest and most significant level of differential expression. The aorta showed a significant preferential expression of the Purkinje cell protein 4 (Pcp4) gene. The results of the microarray analysis were validated by real-time quantitative PCR and immunohistochemistry. Our study confirms vessel-specific transcriptional profiles in ECs and SMCs of rat DA and aorta. Rgs5 and Dlx1 represent novel molecular targets for the regulation of DA maturation and closure. PMID:24489801
Longuespée, Rémi; Tastet, Christophe; Desmons, Annie; Kerdraon, Olivier; Day, Robert
2014-01-01
Abstract Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and profiling technology have become the easiest methods for quickly accessing the protein composition of a tissue area. Unfortunately, the demand for the identification of these proteins remains unmet. To overcome this bottleneck, we combined several strategies to identify the proteins detected via MALDI profiling including on-tissue protein extraction using hexafluoroIsopropanol (1,1,1,3,3,3-hexafluoro-2-propanol, HFIP) coupled with two-dimensional cetyl trimethylammonium bromide/sodium dodecyl sulfate–polyacrylamide gel electrophoresis (2D CTAB/SDS-PAGE) for separation followed by trypsin digestion and MALDI-MS analyses for identification. This strategy was compared with an on-tissue bottom-up strategy that we previously developed. The data reflect the complementarity of the approaches. An increase in the number of specific proteins identified has been established. This approach demonstrates the potential of adapted extraction procedures and the combination of parallel identification approaches for personalized medicine applications. The anatomical context provides important insight into identifying biomarkers and may be considered a first step for tissue-based biomarker research, as well as the extemporaneous examination of biopsies during surgery. PMID:24841221
Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants: A Case-control Study.
Hasegawa, Kohei; Linnemann, Rachel W; Mansbach, Jonathan M; Ajami, Nadim J; Espinola, Janice A; Petrosino, Joseph F; Piedra, Pedro A; Stevenson, Michelle D; Sullivan, Ashley F; Thompson, Amy D; Camargo, Carlos A
2017-11-01
Little is known about the relationship of airway microbiota with bronchiolitis in infants. We aimed to identify nasal airway microbiota profiles and to determine their association with the likelihood of bronchiolitis in infants. A case-control study was conducted. As a part of a multicenter prospective study, we collected nasal airway samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 110 age-matched healthy controls. By applying 16S ribosomal RNA gene sequencing and an unbiased clustering approach to these 150 nasal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. Overall, the median age was 3 months and 56% were male. Unbiased clustering of airway microbiota identified 4 distinct profiles: Moraxella-dominant profile (37%), Corynebacterium/Dolosigranulum-dominant profile (27%), Staphylococcus-dominant profile (15%) and mixed profile (20%). Proportion of bronchiolitis was lowest in infants with Moraxella-dominant profile (14%) and highest in those with Staphylococcus-dominant profile (57%), corresponding to an odds ratio of 7.80 (95% confidence interval, 2.64-24.9; P < 0.001). In the multivariable model, the association between Staphylococcus-dominant profile and greater likelihood of bronchiolitis persisted (odds ratio for comparison with Moraxella-dominant profile, 5.16; 95% confidence interval, 1.26-22.9; P = 0.03). By contrast, Corynebacterium/Dolosigranulum-dominant profile group had low proportion of infants with bronchiolitis (17%); the likelihood of bronchiolitis in this group did not significantly differ from those with Moraxella-dominant profile in both unadjusted and adjusted analyses. In this case-control study, we identified 4 distinct nasal airway microbiota profiles in infants. Moraxella-dominant and Corynebacterium/Dolosigranulum-dominant profiles were associated with low likelihood of bronchiolitis, while Staphylococcus-dominant profile was associated with high likelihood of bronchiolitis.
ChIP-chip versus ChIP-seq: Lessons for experimental design and data analysis
2011-01-01
Background Chromatin immunoprecipitation (ChIP) followed by microarray hybridization (ChIP-chip) or high-throughput sequencing (ChIP-seq) allows genome-wide discovery of protein-DNA interactions such as transcription factor bindings and histone modifications. Previous reports only compared a small number of profiles, and little has been done to compare histone modification profiles generated by the two technologies or to assess the impact of input DNA libraries in ChIP-seq analysis. Here, we performed a systematic analysis of a modENCODE dataset consisting of 31 pairs of ChIP-chip/ChIP-seq profiles of the coactivator CBP, RNA polymerase II (RNA PolII), and six histone modifications across four developmental stages of Drosophila melanogaster. Results Both technologies produce highly reproducible profiles within each platform, ChIP-seq generally produces profiles with a better signal-to-noise ratio, and allows detection of more peaks and narrower peaks. The set of peaks identified by the two technologies can be significantly different, but the extent to which they differ varies depending on the factor and the analysis algorithm. Importantly, we found that there is a significant variation among multiple sequencing profiles of input DNA libraries and that this variation most likely arises from both differences in experimental condition and sequencing depth. We further show that using an inappropriate input DNA profile can impact the average signal profiles around genomic features and peak calling results, highlighting the importance of having high quality input DNA data for normalization in ChIP-seq analysis. Conclusions Our findings highlight the biases present in each of the platforms, show the variability that can arise from both technology and analysis methods, and emphasize the importance of obtaining high quality and deeply sequenced input DNA libraries for ChIP-seq analysis. PMID:21356108
Tardieu, Sophie; Bottero, Alain; Blin, Patrick; Bohbot, Michael; Goni, Sylvia; Gerard, Alain; Gasquet, Isabelle
2006-01-01
Background Little is known about depressed patients' profiles and how they are managed. The aim of the study is to compare GPs and psychiatrists for 1°) sociodemographic and clinical profile of their patients considered as depressed 2°) patterns of care provision. Methods The study design is an observational cross-sectional study on a random sample of GPs and psychiatrists working in France. Consecutive inclusion of patients seen in consultation considered as depressed by the physician. GPs enrolled 6,104 and psychiatrists 1,433 patients. Data collected: sociodemographics, psychiatric profile, environmental risk factors of depression and treatment. All clinical data were collected by participating physicians; there was no direct independent clinical assessment of patients to check the diagnosis of depressive disorder. Results Compared to patients identified as depressed by GPs, those identified by psychiatrists were younger, more often urban (10.5% v 5.4% – OR = 2.4), educated (42.4% v 25.4% – OR = 3.9), met DSM-IV criteria for depression (94.6% v 85.6% – OR = 2.9), had been hospitalized for depression (26.1% v 15.6% – OR = 2.0) and were younger at onset of depressive problems (all adjusted p < .001). No difference was found for psychiatric and somatic comorbidity, suicide attempt and severity of current depression. Compared to GPs, psychiatrists more often prescribed tricyclics and very novel antidepressants (7.8% v 2.3% OR = 5.0 and 6.8% v 3.0% OR = 3.8) with longer duration of antidepressant treatment. GPs' patients received more "non-conventional" treatment (8.8% v 2.4% OR = 0.3) and less psychotherapy (72.2% v 89.1% OR = 3.1) (all adjusted p < .001). Conclusion Differences between patients mainly concerned educational level and area of residence with few differences regarding clinical profile. Differences between practices of GPs and psychiatrists appear to reflect more the organization of the French care system than the competence of providers. PMID:16445855
Guo, Chun Yu; Yin, Hui Jun; Jiang, Yue Rong; Xue, Mei; Zhang, Lu; Shi, Da Zhuo
2008-06-18
To construct the differential genes expressed profile in the ischemic myocardium tissue reduced from acute myocardial infarction(AMI), and determine the biological functions of target genes. AMI model was generated by ligation of the left anterior descending coronary artery in Wistar rats. Total RNA was extracted from the normal and the ischemic heart tissues under the ligation point 7 days after the operation. Differential gene expression profiles of the two samples were constructed using Long Serial Analysis of Gene Expression(LongSAGE). Real time fluorescence quantitative PCR was used to verify gene expression profile and to identify the expression of 2 functional genes. The activities of enzymes from functional genes were determined by histochemistry. A total of 15,966 tags were screened from the normal and the ischemic LongSAGE maps. The similarities of the sequences were compared using the BLAST algebra in NCBI and 7,665 novel tags were found. In the ischemic tissue 142 genes were significantly changed compared with those in the normal tissue (P<0.05). These differentially expressed genes represented the proteins which might play important roles in the pathways of oxidation and phosphorylation, ATP synthesis and glycolysis. The partial genes identified by LongSAGE were confirmed using real time fluorescence quantitative PCR. Two genes related to energy metabolism, COX5a and ATP5e, were screened and quantified. Expression of two functional genes down-regulated at their mRNA levels and the activities of correlative functional enzymes decreased compared with those in the normal tissue. AMI causes a series of changes in gene expression, in which the abnormal expression of genes related to energy metabolism could be one of the molecular mechanisms of AMI. The intervention of the expressions of COX5a and ATP5e may be a new target for AMI therapy.
Oliosa, Polyana Romano; Zaniqueli, Divanei; Alvim, Rafael de Oliveira; Barbosa, Miriam Carmo Rodrigues; Mill, José Geraldo
2018-01-05
To assess whether the indicators of weight status body mass index and waist-to-height ratio are similar to body fat percentage to identify obese children and adolescents with unfavorable lipid profile. This was a cross-sectional study involving 840 children and adolescents (6-18 years). The same individuals were classified as non-obese (
Coping profiles, perceived stress and health-related behaviors: a cluster analysis approach.
Doron, Julie; Trouillet, Raphael; Maneveau, Anaïs; Ninot, Grégory; Neveu, Dorine
2015-03-01
Using cluster analytical procedure, this study aimed (i) to determine whether people could be differentiated on the basis of coping profiles (or unique combinations of coping strategies); and (ii) to examine the relationships between these profiles and perceived stress and health-related behaviors. A sample of 578 French students (345 females, 233 males; M(age)= 21.78, SD(age)= 2.21) completed the Perceived Stress Scale-14 ( Bruchon-Schweitzer, 2002), the Brief COPE ( Muller and Spitz, 2003) and a series of items measuring health-related behaviors. A two-phased cluster analytic procedure (i.e. hierarchical and non-hierarchical-k-means) was employed to derive clusters of coping strategy profiles. The results yielded four distinctive coping profiles: High Copers, Adaptive Copers, Avoidant Copers and Low Copers. The results showed that clusters differed significantly in perceived stress and health-related behaviors. High Copers and Avoidant Copers displayed higher levels of perceived stress and engaged more in unhealthy behavior, compared with Adaptive Copers and Low Copers who reported lower levels of stress and engaged more in healthy behaviors. These findings suggested that individuals' relative reliance on some strategies and de-emphasis on others may be a more advantageous way of understanding the manner in which individuals cope with stress. Therefore, cluster analysis approach may provide an advantage over more traditional statistical techniques by identifying distinct coping profiles that might best benefit from interventions. Future research should consider coping profiles to provide a deeper understanding of the relationships between coping strategies and health outcomes and to identify risk groups. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Genomic profiling of CHEK2*1100delC-mutated breast carcinomas.
Massink, Maarten P G; Kooi, Irsan E; Martens, John W M; Waisfisz, Quinten; Meijers-Heijboer, Hanne
2015-11-09
CHEK2*1100delC is a moderate-risk breast cancer susceptibility allele with a high prevalence in the Netherlands. We performed copy number and gene expression profiling to investigate whether CHEK2*1100delC breast cancers harbor characteristic genomic aberrations, as seen for BRCA1 mutated breast cancers. We performed high-resolution SNP array and gene expression profiling of 120 familial breast carcinomas selected from a larger cohort of 155 familial breast tumors, including BRCA1, BRCA2, and CHEK2 mutant tumors. Gene expression analyses based on a mRNA immune signature was used to identify samples with relative low amounts of tumor infiltrating lymphocytes (TILs), which were previously found to disturb tumor copy number and LOH (loss of heterozygosity) profiling. We specifically compared the genomic and gene expression profiles of CHEK2*1100delC breast cancers (n = 14) with BRCAX (familial non-BRCA1/BRCA2/CHEK2*1100delC mutated) breast cancers (n = 34) of the luminal intrinsic subtypes for which both SNP-array and gene expression data is available. High amounts of TILs were found in a relatively small number of luminal breast cancers as compared to breast cancers of the basal-like subtype. As expected, these samples mostly have very few copy number aberrations and no detectable regions of LOH. By unsupervised hierarchical clustering of copy number data we observed a great degree of heterogeneity amongst the CHEK2*1100delC breast cancers, comparable to the BRCAX breast cancers. Furthermore, copy number aberrations were mostly seen at low frequencies in both the CHEK2*1100delC and BRCAX group of breast cancers. However, supervised class comparison identified copy number loss of chromosomal arm 1p to be associated with CHEK2*1100delC status. In conclusion, in contrast to basal-like BRCA1 mutated breast cancers, no apparent specific somatic copy number aberration (CNA) profile for CHEK2*1100delC breast cancers was found. With the possible exception of copy number loss of chromosomal arm 1p in a subset of tumors, which might be involved in CHEK2 tumorigenesis. This difference in CNAs profiles might be explained by the need for BRCA1-deficient tumor cells to acquire survival factors, by for example specific copy number aberrations, to expand. Such factors may not be needed for breast tumors with a defect in a non-essential gene such as CHEK2.
Kasprow, Wesley J.; Rosenheck, Robert A.
2013-01-01
Objectives. We identified risk and need profiles of homeless veterans and examined the relation between profiles and referrals and admissions to Department of Veterans Affairs (VA) homeless service programs. Methods. We examined data from the VA’s new Homeless Operations Management and Evaluation System on 120 852 veterans from 142 sites nationally in 2011 and 2012 using latent class analyses based on 9 homeless risk factors. The final 4-class solution compared both referral and admission to VA homeless services. Results. We identified 4 latent classes: relatively few problems, dual diagnosis, poverty–substance abuse–incarceration, and disabling medical problems. Homeless veterans in the first group were more likely to be admitted to the VA’s permanent supportive housing program, whereas those in the second group were more likely to be admitted to more restrictive VA residential treatment. Homeless veterans in the third group were more likely to be admitted to the VA’s prisoner re-entry program, and those in the fourth group were more likely to be directed to VA medical services. Conclusions. The heterogeneous risk and need profiles of homeless veterans supported the diversity of VA homeless services and encouraged the development of specialized services to meet their diverse needs. PMID:24148048
Smith, S. Jerrod; Becker, Carol J.
2011-01-01
In 2007, the USGS well profiler was used to investigate saline water intrusion in a deep public-supply well completed in the Ozark (Roubidoux) aquifer. In northeast Oklahoma, where the Ozark aquifer is known to be susceptible to contamination from mining activities, the well profiler also could be used to investigate sources (depths) of metals contamination and to identify routes of entry of metals to production wells.Water suppliers can consider well rehabilitation as a potential remediation strategy because of the ability to identify changes in contaminant concentrations with depth in individual wells with the USGS well profiler. Well rehabilitation methods, which are relatively inexpensive compared to drilling and completing new wells, involve modifying the construction or operation of a well to enhance the production of water from zones with lesser concentrations of a contaminant or to limit the production of water from zones with greater concentrations of a contaminant. One of the most effective well rehabilitation methods is zonal isolation, in which water from contaminated zones is excluded from production through installation of cement plugs or packers. By using relatively simple and inexpensive well rehabilitation methods, water suppliers may be able to decrease exposure of customers to contaminants and avoid costly installation of additional wells, conveyance infrastructure, and treatment technologies.
Ebner, Jennifer; Aşçı Arslan, Ayşe; Fedorova, Maria; Hoffmann, Ralf; Küçükçetin, Ahmet; Pischetsrieder, Monika
2015-03-18
Kefir has a long tradition in human nutrition due to its presupposed health promoting effects. To investigate the potential contribution of bioactive peptides to the physiological effects of kefir, comprehensive analysis of the peptide profile was performed by nano-ESI-LTQ-Orbitrap MS coupled to nano-ultrahigh-performance liquid chromatography. Thus, 257 peptides were identified, mainly released from β-casein, followed by αS1-, κ-, and αS2-casein. Most (236) peptides were uniquely detected in kefir, but not in raw milk indicating that the fermentation step does not only increase the proteolytic activity 1.7- to 2.4-fold compared to unfermented milk, but also alters the composition of the peptide fraction. The influence of the microflora was determined by analyzing kefir produced from traditional kefir grains or commercial starter culture. Kefir from starter culture featured 230 peptide sequences and showed a significantly, 1.4-fold higher proteolytic activity than kefir from kefir grains with 127 peptides. A match of 97 peptides in both varieties indicates the presence of a typical kefir peptide profile that is not influenced by the individual composition of the microflora. Sixteen of the newly identified peptides were previously described as bioactive, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, immunomodulating, opioid, mineral binding, antioxidant, and antithrombotic effects. The present study describes a comprehensive peptide profile of kefir comprising 257 sequences. The peptide list was used to identify 16 bioactive peptides with ACE-inhibitory, antioxidant, antithrombotic, mineral binding, antimicrobial, immunomodulating and opioid activity in kefir. Furthermore, it was shown that a majority of the kefir peptides were not endogenously present in the raw material milk, but were released from milk caseins by proteases of the microbiota and are therefore specific for the product. Consequently, the proteolytic activity and the composition of the peptide profile can be controlled by the applied microflora (grains or starter culture). On the other hand, a considerable portion of the peptide profile was identified to be typical for kefir in general and independent from production parameters. In summary, the generated kefir peptide profile helped to reveal its origin and to identify bioactive peptides in kefir, which may advance the understanding of health benefits of this food product. The results further indicate that subsets of the kefir peptide list can be used as markers to control food authenticity, for example, to distinguish different types of kefir. Copyright © 2015 Elsevier B.V. All rights reserved.
Lamberts, Laetitia E; de Groot, Derk Jan A; Bense, Rico D; de Vries, Elisabeth G E; Fehrmann, Rudolf S N
2015-09-29
The membrane bound glycoprotein mesothelin (MSLN) is a highly specific tumor marker, which is currently exploited as target for drugs. There are only limited data available on MSLN expression by human tumors. Therefore we determined overexpression of MSLN across different tumor types with Functional Genomic mRNA (FGM) profiling of a large cancer database. Results were compared with data in articles reporting immunohistochemical (IHC) MSLN tumor expression. FGM profiling is a technique that allows prediction of biologically relevant overexpression of proteins from a robust data set of mRNA microarrays. This technique was used in a database comprising 19,746 tumors to identify for 41 tumor types the percentage of samples with an overexpression of MSLN compared to a normal background. A literature search was performed to compare the FGM profiling data with studies reporting IHC MSLN tumor expression. FGM profiling showed MSLN overexpression in gastrointestinal (12-36%) and gynecological tumors (20-66%), non-small cell lung cancer (21%) and synovial sarcomas (30%). The overexpression found in thyroid cancers (5%) and renal cell cancers (10%) was not yet reported with IHC analyses. We observed that MSLN amplification rate within esophageal cancer depends on the histotype (31% for adenocarcinomas versus 3% for squamous-cell carcinomas). Subset analysis in breast cancer showed MSLN amplification rates of 28% in triple-negative breast cancer (TNBC) and 33% in basal-like breast cancer. Further subtype analysis of TNBCs showed the highest amplification rate (42%) in the basal-like 1 subtype and the lowest amplification rate (9%) in the luminal androgen receptor subtype.
Microarray expression profiling in adhesion and normal peritoneal tissues.
Ambler, Dana R; Golden, Alicia M; Gell, Jennifer S; Saed, Ghassan M; Carey, David J; Diamond, Michael P
2012-05-01
To identify molecular markers associated with adhesion and normal peritoneal tissue using microarray expression profiling. Comparative study. University hospital. Five premenopausal women. Adhesion and normal peritoneal tissue samples were obtained from premenopausal women. Ribonucleic acid was extracted using standard protocols and processed for hybridization to Affymetrix Whole Transcript Human Gene Expression Chips. Microarray data were obtained from five different patients, each with adhesion tissue and normal peritoneal samples. Real-time polymerase chain reaction was performed for confirmation using standard protocols. Gene expression in postoperative adhesion and normal peritoneal tissues. A total of 1,263 genes were differentially expressed between adhesion and normal tissues. One hundred seventy-three genes were found to be up-regulated and 56 genes were down-regulated in the adhesion tissues compared with normal peritoneal tissues. The genes were sorted into functional categories according to Gene Ontology annotations. Twenty-six up-regulated genes and 11 down-regulated genes were identified with functions potentially relevant to the pathophysiology of postoperative adhesions. We evaluated and confirmed expression of 12 of these specific genes via polymerase chain reaction. The pathogenesis, natural history, and optimal treatment of postoperative adhesive disease remains unanswered. Microarray analysis of adhesions identified specific genes with increased and decreased expression when compared with normal peritoneum. Knowledge of these genes and ontologic pathways with altered expression provide targets for new therapies to treat patients who have or are at risk for postoperative adhesions. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Çağlar, Emine; Aşçı, F. Hülya
2010-01-01
The primary purpose of the present study was to identify motivational profiles of adolescent athletes using cluster analysis in non-Western culture. A second purpose was to examine relationships between physical self-perception differences of adolescent athletes and motivational profiles. One hundred and thirty six male (Mage = 17.46, SD = 1.25 years) and 80 female adolescent athletes (Mage = 17.61, SD = 1.19 years) from a variety of team sports including basketball, soccer, volleyball, and handball volunteered to participate in this study. The Sport Motivation Scale (SMS) and Physical Self-Perception Profile (PSPP) were administered to all participants. Hierarchical cluster analysis revealed a four-cluster solution for this sample: amotivated, low motivated, moderate motivated, and highly motivated. A 4 x 5 (Cluster x PSPP Subscales) MANOVA revealed no significant main effect of motivational clusters on physical self-perception levels (p > 0.05). As a result, findings of the present study showed that motivational types of the adolescent athletes constituted four different motivational clusters. Highly and moderate motivated athletes consistently scored higher than amotivated athletes on the perceived sport competence, physical condition, and physical self-worth subscales of PSPP. This study identified motivational profiles of competitive youth-sport participants. Key points Highly motivated athletes have a tendency to perceive themselves competent in psychomotor domains as compared to the amotivated athletes As the athletes feel more competent in psychomotor domain, they are more intrinsically motivated. The information about motivational profiles of adolescent athletes could be used for developing strategies and interventions designed to improve the strength and quality of sport participants’ motivation. PMID:24149690
Meyer, Stephanie E; Carlson, Gabrielle A; Youngstrom, Eric; Ronsaville, Donna S; Martinez, Pedro E; Gold, Philip W; Hakak, Rashelle; Radke-Yarrow, Marian
2009-03-01
Recent studies have identified a Child Behavior Checklist (CBCL) profile that characterizes children with severe aggression, inattention, and mood instability. This profile has been coined the CBCL-Pediatric Bipolar Disorder (PBD) phenotype, because it is commonly seen among children with bipolar disorder. However, mounting evidence suggests that the CBCL-PBD may be a better tool for identifying children with severe functional impairment and broad-ranging psychiatric comorbidities rather than bipolar disorder itself. No studies have followed individuals with the CBCL-PBD profile through adulthood, so its long-term implications remain unclear. The present authors examined diagnostic and functional trajectories of individuals with the CBCL-PBD profile from early childhood through young adulthood using data from a longitudinal high-risk study. Participants (n=101) are part of a 23-year study of youth at risk for major mood disorder who have completed diagnostic and functional assessments at regular intervals. Across development, participants with the CBCL-PBD phenotype exhibited marked psychosocial impairment, increased rates of suicidal thoughts and behaviors and heightened risk for comorbid anxiety, bipolar disorder, cluster B personality disorders and ADHD in young adulthood, compared to participants without this presentation. However, diagnostic accuracy for any one particular disorder was found to be low. Children with the CBCL-PBD profile are at risk for ongoing, severe, psychiatric symptomatology including behavior and emotional comorbidities in general, and bipolar disorder, anxiety, ADHD, cluster B personality disorders in particular. However, the value of this profile may be in predicting ongoing comorbidity and impairment, rather than any one specific DSM-IV diagnosis.
Abbott, Sunshine S; Harrison, T Mark; Schmitt, Axel K; Mojzsis, Stephen J
2012-08-21
Few terrestrial localities preserve more than a trace lithic record prior to ca. 3.8 Ga greatly limiting our understanding of the first 700 Ma of Earth history, a period inferred to have included a spike in the bolide flux to the inner solar system at ca. 3.85-3.95 Ga (the Late Heavy Bombardment, LHB). An accessible record of this era may be found in Hadean detrital zircons from the Jack Hills, Western Australia, in the form of μm-scale epitaxial overgrowths. By comparing crystallization temperatures of pre-3.8 Ga zircon overgrowths to the archive of zircon temperature spectra, it should, in principle, be possible to identify a distinctive impact signature. We have developed Ti-U-Th-Pb ion microprobe depth profiling to obtain age and temperature information within these zircon overgrowths and undertaken a feasibility study of its possible use in identifying impact events. Of eight grains profiled in this fashion, four have overgrowths of LHB-era age. Age vs. temperature profiles reveal a period between ca. 3.85-3.95 Ga (i.e., LHB era) characterized by significantly higher temperatures (approximately 840-875 °C) than do older or younger zircons or zircon domains (approximately 630-750 °C). However, temperatures approaching 900 °C can result in Pb isotopic exchange rendering interpretation of these profiles nonunique. Coupled age-temperature depth profiling shows promise in this role, and the preliminary data we report could represent the first terrestrial evidence for impact-related heating during the LHB.
He, Xianmin; Wei, Qing; Sun, Meiqian; Fu, Xuping; Fan, Sichang; Li, Yao
2006-05-01
Biological techniques such as Array-Comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH) and affymetrix single nucleotide pleomorphism (SNP) array have been used to detect cytogenetic aberrations. However, on genomic scale, these techniques are labor intensive and time consuming. Comparative genomic microarray analysis (CGMA) has been used to identify cytogenetic changes in hepatocellular carcinoma (HCC) using gene expression microarray data. However, CGMA algorithm can not give precise localization of aberrations, fails to identify small cytogenetic changes, and exhibits false negatives and positives. Locally un-weighted smoothing cytogenetic aberrations prediction (LS-CAP) based on local smoothing and binomial distribution can be expected to address these problems. LS-CAP algorithm was built and used on HCC microarray profiles. Eighteen cytogenetic abnormalities were identified, among them 5 were reported previously, and 12 were proven by CGH studies. LS-CAP effectively reduced the false negatives and positives, and precisely located small fragments with cytogenetic aberrations.
Xie, Jiangan; Codd, Christopher; Mo, Kevin; He, Yongqun
2016-01-01
M. bovis strain Bacillus Calmette–Guérin (BCG) has been the only licensed live attenuated vaccine against tuberculosis (TB) for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs) have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE)-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis), skin (e.g., skin ulceration and cyanosis), and respiratory system (e.g., cough and pneumonia); in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria). With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased) shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG-associated death outcome. PMID:27749923
NASA Astrophysics Data System (ADS)
Roberts, T. J.; Dütsch, M.; Hole, L. R.; Voss, P. B.
2015-10-01
Observations from CMET (Controlled Meteorological) balloons are analyzed in combination with mesoscale model simulations to provide insights into tropospheric meteorological conditions (temperature, humidity, wind-speed) around Svalbard, European High Arctic. Five Controlled Meteorological (CMET) balloons were launched from Ny-Ålesund in Svalbard over 5-12 May 2011, and measured vertical atmospheric profiles above Spitsbergen Island and over coastal areas to both the east and west. One notable CMET flight achieved a suite of 18 continuous soundings that probed the Arctic marine boundary layer over a period of more than 10 h. The CMET profiles are compared to simulations using the Weather Research and Forecasting (WRF) model using nested grids and three different boundary layer schemes. Variability between the three model schemes was typically smaller than the discrepancies between the model runs and the observations. Over Spitsbergen, the CMET flights identified temperature inversions and low-level jets (LLJ) that were not captured by the model. Nevertheless, the model largely reproduced time-series obtained from the Ny-Ålesund meteorological station, with exception of surface winds during the LLJ. Over sea-ice east of Svalbard the model underestimated potential temperature and overestimated wind-speed compared to the CMET observations. This is most likely due to the full sea-ice coverage assumed by the model, and consequent underestimation of ocean-atmosphere exchange in the presence of leads or fractional coverage. The suite of continuous CMET soundings over a sea-ice free region to the northwest of Svalbard are analysed spatially and temporally, and compared to the model. The observed along-flight daytime increase in relative humidity is interpreted in terms of the diurnal cycle, and in the context of marine and terrestrial air-mass influences. Analysis of the balloon trajectory during the CMET soundings identifies strong wind-shear, with a low-level channeled flow. The study highlights the challenges of modelling the Arctic atmosphere, especially in coastal zones with varying topography, sea-ice and surface conditions. In this context, CMET balloons provide a valuable technology for profiling the free atmosphere and boundary layer in remote regions where few other observations are available for model validation.
Roessner, Ute; Willmitzer, Lothar; Fernie, Alisdair R.
2001-01-01
We conducted a comprehensive metabolic phenotyping of potato (Solanum tuberosum L. cv Desiree) tuber tissue that had been modified either by transgenesis or exposure to different environmental conditions using a recently developed gas chromatography-mass spectrometry profiling protocol. Applying this technique, we were able to identify and quantify the major constituent metabolites of the potato tuber within a single chromatographic run. The plant systems that we selected to profile were tuber discs incubated in varying concentrations of fructose, sucrose, and mannitol and transgenic plants impaired in their starch biosynthesis. The resultant profiles were then compared, first at the level of individual metabolites and then using the statistical tools hierarchical cluster analysis and principal component analysis. These tools allowed us to assign clusters to the individual plant systems and to determine relative distances between these clusters; furthermore, analyzing the loadings of these analyses enabled identification of the most important metabolites in the definition of these clusters. The metabolic profiles of the sugar-fed discs were dramatically different from the wild-type steady-state values. When these profiles were compared with one another and also with those we assessed in previous studies, however, we were able to evaluate potential phenocopies. These comparisons highlight the importance of such an approach in the functional and qualitative assessment of diverse systems to gain insights into important mediators of metabolism. PMID:11706160
The virialization density of peaks with general density profiles under spherical collapse
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rubin, Douglas; Loeb, Abraham, E-mail: dsrubin@physics.harvard.edu, E-mail: aloeb@cfa.harvard.edu
2013-12-01
We calculate the non-linear virialization density, Δ{sub c}, of halos under spherical collapse from peaks with an arbitrary initial and final density profile. This is in contrast to the standard calculation of Δ{sub c} which assumes top-hat profiles. Given our formalism, the non-linear halo density can be calculated once the shape of the initial peak's density profile and the shape of the virialized halo's profile are provided. We solve for Δ{sub c} for halos in an Einstein de-Sitter and a ΛCDM universe. As examples, we consider power-law initial profiles as well as spherically averaged peak profiles calculated from the statisticsmore » of a Gaussian random field. We find that, depending on the profiles used, Δ{sub c} is smaller by a factor of a few to as much as a factor of 10 as compared to the density given by the standard calculation ( ≈ 200). Using our results, we show that, for halo finding algorithms that identify halos through an over-density threshold, the halo mass function measured from cosmological simulations can be enhanced at all halo masses by a factor of a few. This difference could be important when using numerical simulations to assess the validity of analytic models of the halo mass function.« less
Proteome profiling in the aorta and kidney of type 1 diabetic rats
Zhu, Rui; Jaffa, Miran A.; Zhao, Jingfu; Mirzaei, Parvin; Ahmed, Adnan; Kobeissy, Firas; Ziyadeh, Fuad N.; Mechref, Yehia
2017-01-01
Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats. In addition, systems biology analyses were employed to identify key protein markers that can provide insights into molecular pathways and processes that are differentially regulated in the aorta and kidney of type 1 diabetic rats. Our results indicated that 188 (111 downregulated and 77 upregulated) proteins were significantly identified in the aorta of diabetic rats compared to normal controls. A total of 223 (109 downregulated and 114 upregulated) proteins were significantly identified in the kidney of diabetic rats compared to normal controls. When the protein profiles from the kidney and aorta of diabetic and control rats were analyzed by principal component analysis, a distinct separation of the groups was observed. In addition, diabetes resulted in a significant increase in PTM (oxidation, phosphorylation, and acetylation) of proteins in the kidney and aorta and this effect was partially reversed by insulin treatment. Ingenuity pathway analysis performed on the list of differentially expressed proteins depicted mitochondrial dysfunction, oxidative phosphorylation and acute phase response signaling to be among the altered canonical pathways by diabetes in both tissues. The findings of the present study provide a global proteomics view of markers that highlight the mechanisms and putative processes that modulate renal and vascular injury in diabetes. PMID:29121074
Proteome profiling in the aorta and kidney of type 1 diabetic rats.
Al Hariri, Moustafa; Elmedawar, Mohamad; Zhu, Rui; Jaffa, Miran A; Zhao, Jingfu; Mirzaei, Parvin; Ahmed, Adnan; Kobeissy, Firas; Ziyadeh, Fuad N; Mechref, Yehia; Jaffa, Ayad A
2017-01-01
Diabetes is associated with a number of metabolic and cardiovascular risk factors that contribute to a high rate of microvascular and macrovascular complications. The risk factors and mechanisms that contribute to the development of micro- and macrovascular disease in diabetes are not fully explained. In this study, we employed mass spectrometric analysis using tandem LC-MS/MS to generate a proteomic profile of protein abundance and post-translational modifications (PTM) in the aorta and kidney of diabetic rats. In addition, systems biology analyses were employed to identify key protein markers that can provide insights into molecular pathways and processes that are differentially regulated in the aorta and kidney of type 1 diabetic rats. Our results indicated that 188 (111 downregulated and 77 upregulated) proteins were significantly identified in the aorta of diabetic rats compared to normal controls. A total of 223 (109 downregulated and 114 upregulated) proteins were significantly identified in the kidney of diabetic rats compared to normal controls. When the protein profiles from the kidney and aorta of diabetic and control rats were analyzed by principal component analysis, a distinct separation of the groups was observed. In addition, diabetes resulted in a significant increase in PTM (oxidation, phosphorylation, and acetylation) of proteins in the kidney and aorta and this effect was partially reversed by insulin treatment. Ingenuity pathway analysis performed on the list of differentially expressed proteins depicted mitochondrial dysfunction, oxidative phosphorylation and acute phase response signaling to be among the altered canonical pathways by diabetes in both tissues. The findings of the present study provide a global proteomics view of markers that highlight the mechanisms and putative processes that modulate renal and vascular injury in diabetes.
Ivonne Wence-Chavez, Laura; Palomares-Chacon, Ulises; Pablo Flores-Gutierrez, Juan; Felipe Jave-Suarez, Luis; Del Carmen Aguilar-Lemarroy, Adriana; Barros-Nunez, Patricio; Esperanza Flores-Martinez, Silvia; Sanchez-Corona, Jose; Alejandra Rosales-Reynoso, Monica
2017-01-01
Several studies have shown a strong association between diabetes mellitus (DM) and increased risk of colorectal cancer (CRC). The fundamental mechanisms that support this association are not entirely understood; however, it is believed that hyperinsulinemia and hyperglycemia may be involved. Some proposed mechanisms include upregulation of mitogenic signaling pathways like MAPK, PI3K, mTOR, and WNT, which are involved in cell proliferation, growth, and cancer cell survival. The purpose of this study was to evaluate the gene expression profile and identify differently expressed genes involved in mitogenic pathways in CRC patients with and without DM. In this study, microarray analysis of gene expression followed by quantitative PCR (qPCR) was performed in cancer tissue from CRC patients with and without DM to identify the gene expression profiles and validate the differently expressed genes. Among the study groups, some differently expressed genes were identified. However, when bioinformatics clustering tools were used, a significant modulation of genes involved in the WNT pathway was evident. Therefore, we focused on genes participating in this pathway, such as WNT3A, LRP6, TCF7L2, and FRA-1. Validation of the expression levels of those genes by qPCR showed that CRC patients without type 2 diabetes mellitus (T2DM) expressed significantly more WNT3Ay LRP6, but less TCF7L2 and FRA-1 compared to controls, while in CRC patients with DM the expression levels of WNT3A, LRP6, TCF7L2, and FRA-1 were significantly higher compared to controls. Our results suggest that WNT/β-catenin pathway is upregulated in patients with CRC and DM, demonstrating its importance and involvement in both pathologies.
Mina, Suzan A; Melek, Farouk R; Adeeb, Rania M; Hagag, Eman G
2016-11-01
In this study, a comparative liquid chromatography/mass spectroscopy (LC/ESI-MS/MS) profiling of different fractions of Ulmus parvifolia leaves and stems was performed. Identification of compounds was based on comparing the mass spectrometric information obtained including m/z values and individual compound fragmentation pattern to tandem mass spectral library search and literature data. Eleven compounds were tentatively identified in the different analyzed fractions. One of the major constituents of this plant was isolated and identified as Icariside E4 [dihydro-dehydro-diconiferyl alcohol-4-O-α-L-rhamnopyranoside] (5). The evaluation of anti-inflammatory activity of the total methanolic extract using nitric oxide inhibition on LPS-stimulated RAW 264.7 cells model strong anti-inflammatory activity with 17.5% inhibition of nitric oxide production versus 10% inhibition for dexamethasone. The cytotoxic activity of the methanolic extract and Icariside E4 was evaluated against four types of human cell lines using MTT assay. Icariside E4 showed cytotoxic effect against Hep-G2, MCF-7, and CACO-2 cell lines compared to a negligible activity for the total extract. The same extract showed a moderate antioxidant activity with SC50=362.5 μg/mL.
Molsberry, Samantha A; Cheng, Yu; Kingsley, Lawrence; Jacobson, Lisa; Levine, Andrew J; Martin, Eileen; Miller, Eric N; Munro, Cynthia A; Ragin, Ann; Sacktor, Ned; Becker, James T
2018-05-11
Mild forms of HIV-associated neurocognitive disorder (HAND) remain prevalent in the combination anti-retroviral therapy (cART) era. This study's objective was to identify neuropsychological subgroups within the Multicenter AIDS Cohort Study (MACS) based on the participant-based latent structure of cognitive function and to identify factors associated with subgroups. The MACS is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men. Using neuropsychological domain scores we used a cluster variable selection algorithm to identify the optimal subset of domains with cluster information. Latent profile analysis was applied using scores from identified domains. Exploratory and post-hoc analyses were conducted to identify factors associated with cluster membership and the drivers of the observed associations. Cluster variable selection identified all domains as containing cluster information except for Working Memory. A three-profile solution produced the best fit for the data. Profile 1 performed below average on all domains, Profile 2 performed average on executive functioning, motor, and speed and below average on learning and memory, Profile 3 performed at or above average across all domains. Several demographic, cognitive, and social factors were associated with profile membership; these associations were driven by differences between Profile 1 and the other profiles. There is an identifiable pattern of neuropsychological performance among MACS members determined by all domains except Working Memory. Neither HIV nor HIV-related biomarkers were related with cluster membership, consistent with other findings that cognitive performance patterns do not map directly onto HIV serostatus.
Cho, Chung Y; Oles, Carolyn; Nowatzke, William; Oliver, Kerry; Garber, Eric A E
2017-10-01
The homology between proteins in legumes and tree nuts makes it common for individuals with food allergies to be allergic to multiple legumes and tree nuts. This propensity for allergenic and antigenic cross-reactivity means that commonly employed commercial immunodiagnostic assays (e.g., dipsticks) for the detection of food allergens may not always accurately detect, identify, and quantitate legumes and tree nuts unless additional orthogonal analytical methods or secondary measures of analysis are employed. The xMAP ® Multiplex Food Allergen Detection Assay (FADA) was used to determine the cross-reactivity patterns and the utility of multi-antibody antigenic profiling to distinguish between legumes and tree nuts. Pure legumes and tree nuts extracted using buffered detergent displayed a high level of cross-reactivity that decreased upon dilution or by using a buffer (UD buffer) designed to increase the stringency of binding conditions and reduce the occurrence of false positives due to plant-derived lectins. Testing for unexpected food allergens or the screening for multiple food allergens often involves not knowing the identity of the allergen present, its concentration, or the degree of modification during processing. As such, the analytical response measured may represent multiple antigens of varying antigenicity (cross-reactivity). This problem of multiple potential analytes is usually unresolved and the focus becomes the primary analyte, the antigen the antibody was raised against, or quantitative interpretation of the content of the analytical sample problematic. The alternative solution offered here to this problem is the use of an antigenic profile as generated by the xMAP FADA using multiple antibodies (bead sets). By comparing the antigenic profile to standards, the allergen may be identified along with an estimate of the concentration present. Cluster analysis of the xMAP FADA data was also performed and agreed with the known phylogeny of the legumes and tree nuts being analyzed. Graphical abstract The use of cluster analysis to compare the multi-antigen profiles of food allergens.
Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.
2015-01-01
Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID:25552301
Weinberg, Benjamin A.; Gowen, Kyle; Lee, Thomas K.; Ou, Sai‐Hong Ignatius; Bristow, Robert; Krill, Lauren; Almira‐Suarez, M. Isabel; Ali, Siraj M.; Miller, Vincent A.; Liu, Stephen V.
2017-01-01
Abstract Background. Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer‐specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios. Materials and Methods. We identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next‐generation sequencing‐based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities. Results. A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination. Conclusions. Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. Implications for Practice. Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management. PMID:28193735
Chen, Der-Yuan; Chen, Yi-Ming; Chien, Han-Ju; Lin, Chi-Chen; Hsieh, Chia-Wei; Chen, Hsin-Hua; Hung, Wei-Ting; Lai, Chien-Chen
2016-01-01
Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still's disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome. Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites. Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05). Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.
Differences in practice and personal profiles between male and female ophthalmologists.
Danesh-Meyer, Helen V; Deva, Narme C; Ku, Judy Y F; Carroll, Stuart C; Tan, Yu Wee; Gamble, Greg
2007-01-01
To assess practice profiles and attitudes towards career and family among ophthalmologists in Australia and New Zealand, with an emphasis on identifying gender differences. A 43-part confidential survey addressing professional and personal issues was sent to all female ophthalmologists and to randomly selected age-matched male ophthalmologists, registered with the Royal Australian and New Zealand College of Ophthalmologists in 2005. A total of 254 (75%) of the surveys were returned, with no significant difference in response rate between genders. Differences in practice profiles were identified: females preferentially practise in the city (89.6% vs. 76.1%, P<0.001), work fewer hours (70% of males working 40 hours per week, compared with 41% of females, P<0.0001) and work part time (57.5% vs. 13.6%, P<0.0001). Female ophthalmologists earn less (average income being NZ/Aus$37,913 [95% confidence interval 25,600-50,226] less, P<0.0001); the difference remained significant (P<0.0001) even when adjusted for hours worked. Up to 93.3% of male ophthalmologists are married or in a stable relationship, compared with 75.6% of females (P=0.0003), and males are more likely to have children (P=0.0007). There was no significant difference in overall career satisfaction between male and female ophthalmologists; however, females expressed greater frustration with managing professional and family commitments, and unequal career advancement opportunities. Significant differences exist in practice profiles and personal circumstances between male and female ophthalmologists. Females appear to balance work and personal responsibilities by working fewer hours, and for lower income. Despite this, they are less likely to be in a stable relationship, or to have children. However, there is no difference between the two groups in overall career satisfaction.
Grayson, M Lindsay; Macesic, Nenad; Huang, G Khai; Bond, Katherine; Fletcher, Jason; Gilbert, Gwendolyn L; Gordon, David L; Hellsten, Jane F; Iredell, Jonathan; Keighley, Caitlin; Stuart, Rhonda L; Xuereb, Charles S; Cruickshank, Marilyn
2015-01-01
Important culture-change initiatives (e.g. improving hand hygiene compliance) are frequently associated with variable uptake among different healthcare worker (HCW) categories. Inherent personality differences between these groups may explain change uptake and help improve future intervention design. We used an innovative personality-profiling tool (ColourGrid®) to assess personality differences among standard HCW categories at five large Australian hospitals using two data sources (HCW participant surveys [PS] and generic institution-wide human resource [HR] data) to: a) compare the relative accuracy of these two sources; b) identify differences between HCW groups and c) use the observed profiles to guide design strategies to improve uptake of three clinically-important initiatives (improved hand hygiene, antimicrobial stewardship and isolation procedure adherence). Results from 34,243 HCWs (HR data) and 1045 survey participants (PS data) suggest that HCWs were different from the general population, displaying more individualism, lower power distance, less uncertainty avoidance and greater cynicism about advertising messages. HR and PS data were highly concordant in identifying differences between the three key HCW categories (doctors, nursing/allied-health, support services) and predicting appropriate implementation strategies. Among doctors, the data suggest that key messaging should differ between full-time vs part-time (visiting) senior medical officers (SMO, VMO) and junior hospital medical officers (HMO), with SMO messaging focused on evidence-based compliance, VMO initiatives emphasising structured mandatory controls and prestige loss for non-adherence, and for HMOs focusing on leadership opportunity and future career risk for non-adherence. Compared to current standardised approaches, targeted interventions based on personality differences between HCW categories should result in improved infection control-related culture-change uptake. Personality profiling based on HR data may represent a useful means of developing a national culture-change "blueprint" for HCW education.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Su, Dian; Shukla, Anil K.; Chen, Baowei
2013-04-01
S-nitrosylation (SNO) is an important reversible thiol oxidation event that has been increasingly recognized for its role in cell signaling. While many proteins susceptible to S-nitrosylation have been reported, site-specific identification of physiologically relevant SNO modifications remains an analytical challenge due to the low-abundance and labile nature of the modification. Herein we present further improvement and optimization of the recently reported, resin-assisted cysteinyl peptide enrichment protocol for SNO identification and the extension of this application to mouse skeletal muscle to identify specific sites sensitive to S-nitrosylation by quantitative reactivity profiling. The results of our data indicate that the protein- andmore » peptide-level enrichment protocols provide comparable specificity and coverage of SNO-peptide identifications. S-nitrosylation reactivity profiling was performed by quantitatively comparing the site-specific SNO modification levels in samples treated with S-nitrosoglutathione (GSNO), an NO donor, at two different physiologically relevant concentrations (i.e., 10 μM and 100 μM). The reactivity profiling experiments overall identified 489 SNO-modified cysteine sites from 197 proteins with the specificity of 95.2% at the unique-peptide-level based on the percentage of Cys-peptides. Among these sites, 260 sites from 135 proteins were observed with relatively high reactivity to S-nitrosylation; such SNO-sensitive sites are more likely to be physiologically relevant. Many of the SNO-sensitive proteins are preferentially localized in mitochondria, contractile fiber and actin cytoskeleton, suggesting the susceptibility of these subcellular compartments to redox regulation. Moreover, the SNO-sensitive proteins seem to be primarily involved in metabolic pathways, including TCA cycle, glycolysis/gluconeogenesis, glutathione metabolism, and fatty acid metabolism, suggesting the importance of redox regulation in muscle metabolism and insulin action.« less
Identification of key microRNAs and genes in preeclampsia by bioinformatics analysis
Luo, Shouling; Cao, Nannan; Tang, Yao; Gu, Weirong
2017-01-01
Preeclampsia is a leading cause of perinatal maternal–foetal mortality and morbidity. The aim of this study is to identify the key microRNAs and genes in preeclampsia and uncover their potential functions. We downloaded the miRNA expression profile of GSE84260 and the gene expression profile of GSE73374 from the Gene Expression Omnibus database. Differentially expressed miRNAs and genes were identified and compared to miRNA-target information from MiRWalk 2.0, and a total of 65 differentially expressed miRNAs (DEMIs), including 32 up-regulated miRNAs and 33 down-regulated miRNAs, and 91 differentially expressed genes (DEGs), including 83 up-regulated genes and 8 down-regulated genes, were identified. The pathway enrichment analyses of the DEMIs showed that the up-regulated DEMIs were enriched in the Hippo signalling pathway and MAPK signalling pathway, and the down-regulated DEMIs were enriched in HTLV-I infection and miRNAs in cancers. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses of the DEGs were performed using Multifaceted Analysis Tool for Human Transcriptome. The up-regulated DEGs were enriched in biological processes (BPs), including the response to cAMP, response to hydrogen peroxide and cell-cell adhesion mediated by integrin; no enrichment of down-regulated DEGs was identified. KEGG analysis showed that the up-regulated DEGs were enriched in the Hippo signalling pathway and pathways in cancer. A PPI network of the DEGs was constructed by using Cytoscape software, and FOS, STAT1, MMP14, ITGB1, VCAN, DUSP1, LDHA, MCL1, MET, and ZFP36 were identified as the hub genes. The current study illustrates a characteristic microRNA profile and gene profile in preeclampsia, which may contribute to the interpretation of the progression of preeclampsia and provide novel biomarkers and therapeutic targets for preeclampsia. PMID:28594854
Crawford, Megan R.; Chirinos, Diana A.; Iurcotta, Toni; Edinger, Jack D.; Wyatt, James K.; Manber, Rachel; Ong, Jason C.
2017-01-01
Study Objectives: This study examined empirically derived symptom cluster profiles among patients who present with insomnia using clinical data and polysomnography. Methods: Latent profile analysis was used to identify symptom cluster profiles of 175 individuals (63% female) with insomnia disorder based on total scores on validated self-report instruments of daytime and nighttime symptoms (Insomnia Severity Index, Glasgow Sleep Effort Scale, Fatigue Severity Scale, Beliefs and Attitudes about Sleep, Epworth Sleepiness Scale, Pre-Sleep Arousal Scale), mean values from a 7-day sleep diary (sleep onset latency, wake after sleep onset, and sleep efficiency), and total sleep time derived from an in-laboratory PSG. Results: The best-fitting model had three symptom cluster profiles: “High Subjective Wakefulness” (HSW), “Mild Insomnia” (MI) and “Insomnia-Related Distress” (IRD). The HSW symptom cluster profile (26.3% of the sample) reported high wake after sleep onset, high sleep onset latency, and low sleep efficiency. Despite relatively comparable PSG-derived total sleep time, they reported greater levels of daytime sleepiness. The MI symptom cluster profile (45.1%) reported the least disturbance in the sleep diary and questionnaires and had the highest sleep efficiency. The IRD symptom cluster profile (28.6%) reported the highest mean scores on the insomnia-related distress measures (eg, sleep effort and arousal) and waking correlates (fatigue). Covariates associated with symptom cluster membership were older age for the HSW profile, greater obstructive sleep apnea severity for the MI profile, and, when adjusting for obstructive sleep apnea severity, being overweight/obese for the IRD profile. Conclusions: The heterogeneous nature of insomnia disorder is captured by this data-driven approach to identify symptom cluster profiles. The adaptation of a symptom cluster-based approach could guide tailored patient-centered management of patients presenting with insomnia, and enhance patient care. Citation: Crawford MR, Chirinos DA, Iurcotta T, Edinger JD, Wyatt JK, Manber R, Ong JC. Characterization of patients who present with insomnia: is there room for a symptom cluster-based approach? J Clin Sleep Med. 2017;13(7):911–921. PMID:28633722
ERIC Educational Resources Information Center
Penke, Martina; Rothweiler, Monika
2018-01-01
The study aims at identifying characteristic phenotypes for children with SLI and children with sensorineural hearing impairment (HI) in language and in domains associated with language. We focus on verbal agreement inflection and phonological short-term memory, phenomena that have been repeatedly found to be impaired in both groups of children. A…
USDA-ARS?s Scientific Manuscript database
A set of 23 local varieties from Slovenia and 218 fig accessions from Californian fig germplasm collection were compared to determine the identity of genotypes and their possible genetic relationships. Figs were genotyped using twelve microsatellite loci. One hundred alleles were identified over all...
Fine bakery wares with label claims in Europe and their categorisation by nutrient profiling models.
Trichterborn, J; Harzer, G; Kunz, C
2011-03-01
This study assesses a range of commercially available fine bakery wares with nutrition or health related on-pack communication against the criteria of selected nutrient profiling models. Different purposes of the application of nutrient profiles were considered, including front-of-pack signposting and the regulation of claims or advertising. More than 200 commercially available fine bakery wares carrying claims were identified in Germany, France, Spain, Sweden and United Kingdom and evaluated against five nutrient profiling models. All models were assessed regarding their underlying principles, generated results and inter-model agreement levels. Total energy, saturated fatty acids, sugars, sodium and fibre were critical parameters for the categorisation of products. The Choices Programme was the most restrictive model in this category, while the Food and Drug Administration model allowed the highest number of products to qualify. According to all models, more savoury than sweet products met the criteria. On average, qualifying products contained less than half the amounts of nutrients to limit and more than double the amount of fibre compared with all the products in the study. None of the models had a significant impact on the average energy contents. Nutrient profiles can be applied to identify fine bakery wares with a significantly better nutritional composition than the average range of products positioned as healthier. Important parameters to take into account include energy, saturated fatty acids, sugars, sodium and fibre. Different criteria sets for subcategories of fine bakery wares do not seem necessary.
Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers.
Carlson, Alyssa K; Rawle, Rachel A; Adams, Erik; Greenwood, Mark C; Bothner, Brian; June, Ronald K
2018-05-05
Osteoarthritis affects over 250 million individuals worldwide. Currently, there are no options for early diagnosis of osteoarthritis, demonstrating the need for biomarker discovery. To find biomarkers of osteoarthritis in human synovial fluid, we used high performance liquid-chromatography mass spectrometry for global metabolomic profiling. Metabolites were extracted from human osteoarthritic (n = 5), rheumatoid arthritic (n = 3), and healthy (n = 5) synovial fluid, and a total of 1233 metabolites were detected. Principal components analysis clearly distinguished the metabolomic profiles of diseased from healthy synovial fluid. Synovial fluid from rheumatoid arthritis patients contained expected metabolites consistent with the inflammatory nature of the disease. Similarly, unsupervised clustering analysis found that each disease state was associated with distinct metabolomic profiles and clusters of co-regulated metabolites. For osteoarthritis, co-regulated metabolites that were upregulated compared to healthy synovial fluid mapped to known disease processes including chondroitin sulfate degradation, arginine and proline metabolism, and nitric oxide metabolism. We utilized receiver operating characteristic analysis to determine the diagnostic value of each metabolite and identified 35 metabolites as potential biomarkers of osteoarthritis, with an area under the receiver operating characteristic curve >0.9. These metabolites included phosphatidylcholine, lysophosphatidylcholine, ceramides, myristate derivatives, and carnitine derivatives. This pilot study provides strong justification for a larger cohort-based study of human osteoarthritic synovial fluid using global metabolomics. The significance of these data is the demonstration that metabolomic profiling of synovial fluid can identify relevant biomarkers of joint disease. Copyright © 2018 Elsevier Inc. All rights reserved.
Koo, Hyunmin; Hakim, Joseph A; Morrow, Casey D; Eipers, Peter G; Davila, Alfonso; Andersen, Dale T; Bej, Asim K
2017-09-01
In this study, using NextGen sequencing of the collective 16S rRNA genes obtained from two sets of samples collected from Lake Obersee, Antarctica, we compared and contrasted two bioinformatics tools, PICRUSt and Tax4Fun. We then developed an R script to assess the taxonomic and predictive functional profiles of the microbial communities within the samples. Taxa such as Pseudoxanthomonas, Planctomycetaceae, Cyanobacteria Subsection III, Nitrosomonadaceae, Leptothrix, and Rhodobacter were exclusively identified by Tax4Fun that uses SILVA database; whereas PICRUSt that uses Greengenes database uniquely identified Pirellulaceae, Gemmatimonadetes A1-B1, Pseudanabaena, Salinibacterium and Sinobacteraceae. Predictive functional profiling of the microbial communities using Tax4Fun and PICRUSt separately revealed common metabolic capabilities, while also showing specific functional IDs not shared between the two approaches. Combining these functional predictions using a customized R script revealed a more inclusive metabolic profile, such as hydrolases, oxidoreductases, transferases; enzymes involved in carbohydrate and amino acid metabolisms; and membrane transport proteins known for nutrient uptake from the surrounding environment. Our results present the first molecular-phylogenetic characterization and predictive functional profiles of the microbial mat communities in Lake Obersee, while demonstrating the efficacy of combining both the taxonomic assignment information and functional IDs using the R script created in this study for a more streamlined evaluation of predictive functional profiles of microbial communities. Copyright © 2017 Elsevier B.V. All rights reserved.
Hintzsche, Jennifer D; Gorden, Nicholas T; Amato, Carol M; Kim, Jihye; Wuensch, Kelsey E; Robinson, Steven E; Applegate, Allison J; Couts, Kasey L; Medina, Theresa M; Wells, Keith R; Wisell, Joshua A; McCarter, Martin D; Box, Neil F; Shellman, Yiqun G; Gonzalez, Rene C; Lewis, Karl D; Tentler, John J; Tan, Aik Choon; Robinson, William A
2017-06-01
Mucosal melanomas are a rare subtype of melanoma, arising in mucosal tissues, which have a very poor prognosis due to the lack of effective targeted therapies. This study aimed to better understand the molecular landscape of these cancers and find potential new therapeutic targets. Whole-exome sequencing was performed on mucosal melanomas from 19 patients and 135 sun-exposed cutaneous melanomas, with matched peripheral blood samples when available. Mutational profiles were compared between mucosal subgroups and sun-exposed cutaneous melanomas. Comparisons of molecular profiles identified 161 genes enriched in mucosal melanoma (P<0.05). KIT and NF1 were frequently comutated (32%) in the mucosal subgroup, with a significantly higher incidence than that in cutaneous melanoma (4%). Recurrent SF3B1 R625H/S/C mutations were identified and validated in 7 of 19 (37%) mucosal melanoma patients. Mutations in the spliceosome pathway were found to be enriched in mucosal melanomas when compared with cutaneous melanomas. Alternative splicing in four genes were observed in SF3B1-mutant samples compared with the wild-type samples. This study identified potential new therapeutic targets for mucosal melanoma, including comutation of NF1 and KIT, and recurrent R625 mutations in SF3B1. This is the first report of SF3B1 R625 mutations in vulvovaginal mucosal melanoma, with the largest whole-exome sequencing project of mucosal melanomas to date. The results here also indicated that the mutations in SF3B1 lead to alternative splicing in multiple genes. These findings expand our knowledge of this rare disease.
Hintzsche, Jennifer D.; Gorden, Nicholas T.; Amato, Carol M.; Kim, Jihye; Wuensch, Kelsey E.; Robinson, Steven E.; Applegate, Allison J.; Couts, Kasey L.; Medina, Theresa M.; Wells, Keith R.; Wisell, Joshua A.; McCarter, Martin D.; Box, Neil F.; Shellman, Yiqun G.; Gonzalez, Rene C.; Lewis, Karl D.; Tentler, John J.
2017-01-01
Mucosal melanomas are a rare subtype of melanoma, arising in mucosal tissues, which have a very poor prognosis due to the lack of effective targeted therapies. This study aimed to better understand the molecular landscape of these cancers and find potential new therapeutic targets. Whole-exome sequencing was performed on mucosal melanomas from 19 patients and 135 sun-exposed cutaneous melanomas, with matched peripheral blood samples when available. Mutational profiles were compared between mucosal subgroups and sun-exposed cutaneous melanomas. Comparisons of molecular profiles identified 161 genes enriched in mucosal melanoma (P<0.05). KIT and NF1 were frequently comutated (32%) in the mucosal subgroup, with a significantly higher incidence than that in cutaneous melanoma (4%). Recurrent SF3B1 R625H/S/C mutations were identified and validated in 7 of 19 (37%) mucosal melanoma patients. Mutations in the spliceosome pathway were found to be enriched in mucosal melanomas when compared with cutaneous melanomas. Alternative splicing in four genes were observed in SF3B1-mutant samples compared with the wild-type samples. This study identified potential new therapeutic targets for mucosal melanoma, including comutation of NF1 and KIT, and recurrent R625 mutations in SF3B1. This is the first report of SF3B1 R625 mutations in vulvovaginal mucosal melanoma, with the largest whole-exome sequencing project of mucosal melanomas to date. The results here also indicated that the mutations in SF3B1 lead to alternative splicing in multiple genes. These findings expand our knowledge of this rare disease. PMID:28296713
Beckstrom, Andrew C; Humston, Elizabeth M; Snyder, Laura R; Synovec, Robert E; Juul, Sandra E
2011-04-08
Perinatal asphyxia is a leading cause of brain injury in infants, occurring in 2-4 per 1000 live births. The clinical response to asphyxia is variable and difficult to predict with current diagnostic tests. Reliable biomarkers are needed to help predict the timing and severity of asphyxia, as well as response to treatment. Two-dimensional gas chromatography-time-of-flight-mass spectrometry (GC×GC-TOFMS) was used herein, in conjunction with chemometric data analysis approaches for metabolomic analysis in order to identify significant metabolites affected by birth asphyxia. Blood was drawn before and after 15 or 18 min of cord occlusion in a Macaca nemestrina model of perinatal asphyxia. Postnatal samples were drawn at 5 min of age (n=20 subjects). Metabolomic profiles of asphyxiated animals were compared to four controls delivered at comparable gestational age. Fifty metabolites with the greatest change pre- to post-asphyxia were identified and quantified. The metabolic profile of post-asphyxia samples showed marked variability compared to the pre-asphyxia samples. Fifteen of the 50 metabolites showed significant elevation in response to asphyxia, ten of which remained significant upon comparison to the control animals. This metabolomic analysis confirmed lactate and creatinine as markers of asphyxia and discovered new metabolites including succinic acid and malate (intermediates in the Krebs cycle) and arachidonic acid (a brain fatty acid and inflammatory marker) as potential biomarkers. GC×GC-TOFMS coupled with chemometric data analysis are useful tools to identify acute biomarkers of brain injury. Further study is needed to correlate these metabolites with severity of disease, and response to treatment. Copyright © 2011 Elsevier B.V. All rights reserved.
Beckstrom, Andrew C.; Humston, Elizabeth M.; Snyder, Laura R.; Synovec, Robert E.; Juul, Sandra E.
2011-01-01
Perinatal asphyxia is a leading cause of brain injury in infants, occurring in 2–4 per 1000 live births. The clinical response to asphyxia is variable and difficult to predict with current diagnostic tests. Reliable biomarkers are needed to help predict the timing and severity of asphyxia, as well as response to treatment. Two-dimensional gas chromatography-time-of-flight-mass spectrometry (GC x GC-TOFMS) was used herein, in conjunction with chemometric data analysis approaches for metabolomic analysis in order to identify significant metabolites affected by birth asphyxia. Blood was drawn before and after 15 or 18 minutes of cord occlusion in a Macaca nemestrina model of perinatal asphyxia. Postnatal samples were drawn at 5 minutes of age (n=20 subjects). Metabolomic profiles of asphyxiated animals were compared to four controls delivered at comparable gestational age. Fifty metabolites with the greatest change pre- to post-asphyxia were identified and quantified. The metabolic profile of post-asphyxia samples showed marked variability compared to the pre-asphyxia samples. Fifteen of the 50 metabolites showed significant elevation in response to asphyxia, ten of which remained significant upon comparison to the control animals. This metabolomic analysis confirmed lactate and creatinine as markers of asphyxia and discovered new metabolites including succinic acid and malate (intermediates in the Krebs cycle) and arachidonic acid (a brain fatty acid and inflammatory marker) as potential biomarkers. GC × GC-TOFMS coupled with chemometric data analysis are useful tools to identify acute biomarkers of brain injury. Further study is needed to correlate these metabolites with severity of disease, and response to treatment. PMID:21353677
Analysis of microRNA profile of Anopheles sinensis by deep sequencing and bioinformatic approaches.
Feng, Xinyu; Zhou, Xiaojian; Zhou, Shuisen; Wang, Jingwen; Hu, Wei
2018-03-12
microRNAs (miRNAs) are small non-coding RNAs widely identified in many mosquitoes. They are reported to play important roles in development, differentiation and innate immunity. However, miRNAs in Anopheles sinensis, one of the Chinese malaria mosquitoes, remain largely unknown. We investigated the global miRNA expression profile of An. sinensis using Illumina Hiseq 2000 sequencing. Meanwhile, we applied a bioinformatic approach to identify potential miRNAs in An. sinensis. The identified miRNA profiles were compared and analyzed by two approaches. The selected miRNAs from the sequencing result and the bioinformatic approach were confirmed with qRT-PCR. Moreover, target prediction, GO annotation and pathway analysis were carried out to understand the role of miRNAs in An. sinensis. We identified 49 conserved miRNAs and 12 novel miRNAs by next-generation high-throughput sequencing technology. In contrast, 43 miRNAs were predicted by the bioinformatic approach, of which two were assigned as novel. Comparative analysis of miRNA profiles by two approaches showed that 21 miRNAs were shared between them. Twelve novel miRNAs did not match any known miRNAs of any organism, indicating that they are possibly species-specific. Forty miRNAs were found in many mosquito species, indicating that these miRNAs are evolutionally conserved and may have critical roles in the process of life. Both the selected known and novel miRNAs (asi-miR-281, asi-miR-184, asi-miR-14, asi-miR-nov5, asi-miR-nov4, asi-miR-9383, and asi-miR-2a) could be detected by quantitative real-time PCR (qRT-PCR) in the sequenced sample, and the expression patterns of these miRNAs measured by qRT-PCR were in concordance with the original miRNA sequencing data. The predicted targets for the known and the novel miRNAs covered many important biological roles and pathways indicating the diversity of miRNA functions. We also found 21 conserved miRNAs and eight counterparts of target immune pathway genes in An. sinensis based on the analysis of An. gambiae. Our results provide the first lead to the elucidation of the miRNA profile in An. sinensis. Unveiling the roles of mosquito miRNAs will undoubtedly lead to a better understanding of mosquito biology and mosquito-pathogen interactions. This work lays the foundation for the further functional study of An. sinensis miRNAs and will facilitate their application in vector control.
Delineating advanced practice nursing in New Zealand: a national survey.
Carryer, J; Wilkinson, J; Towers, A; Gardner, G
2018-03-01
A variety of advanced practice nursing roles and titles have proliferated in response to the changing demands of a population characterized by increasing age and chronic illness. Whilst similarly identified as advanced practice roles, they do not share a common practice profile, educational requirements or legislative direction. The lack of clarity limits comparative research that can inform policy and health service planning. To identify advanced practice roles within nursing titles employed in New Zealand and practice differences between advanced practice and other roles. Replicating recent Australian research, 3255 registered nurses/nurse practitioners in New Zealand completed the amended Advanced Practice Delineation survey tool. The mean domain scores of the predominant advanced practice position were compared with those of other positions. Differences between groups were explored using one-way ANOVA and post hoc between group comparisons. Four nursing position bands were identified: nurse practitioner, clinical nurse specialist, domain-specific and registered nurse. Significant differences between the bands were found on many domain scores. The nurse practitioner and clinical nurse specialist bands had the most similar practice profiles, nurse practitioners being more involved in direct care and professional leadership. Similar to the position of clinical nurse consultant in Australia, those practicing as clinical nurse specialists were deemed to reflect the threshold for advanced practice nursing. The results identified different practice patterns for the identified bands and distinguish the advanced practice nursing roles. By replicating the Australian study of Gardener et al. (2016), this NZ paper extends the international data available to support more evidence-based nursing workforce planning and policy development. © 2017 International Council of Nurses.
Millen, Barbara E; Quatromoni, Paula A; Pencina, Michael; Kimokoti, Ruth; Nam, Byung-H O; Cobain, Sonia; Kozak, Waldemar; Appugliese, Danielle P; Ordovas, Jose; D'Agostino, Ralph B
2005-11-01
To identify the dietary patterns of adult men and examine their relationships with nutrient intake and chronic disease risk over long-term follow-up. Baseline 145-item food frequency questionnaires from 1,666 Framingham Offspring-Spouse cohort men were used to identify comprehensive dietary patterns. Independent 3-day dietary records at baseline and 8 years later provided estimates of subjects' nutrient intake by dietary pattern. Chronic disease risk factor status was compared at baseline and 16-year follow-up across all male dietary patterns. Cluster analysis was applied to food frequency data to identify non-overlapping male dietary patterns. Analysis of covariance and logistic regression were used to compare nutrient intake, summary nutritional risk scores, and chronic disease risk status at baseline and follow-up by male dietary pattern. Five distinct and comprehensive dietary patterns of Framingham Offspring-Spouse men were identified and ordered according to overall nutritional risk: Transition to Heart Healthy, Higher Starch, Average Male, Lower Variety, and Empty Calories. Nutritional risk was high and varied by dietary pattern; key nutrient contrasts were stable over 8-year follow-up. Chronic disease risk also varied by dietary pattern and specific subgroup differences persisted over 16 years, notably rates of overweight/obesity and smoking. Quantitative cluster analysis applied to food frequency questionnaire data identified five distinct, comprehensive, and stable dietary patterns of adult Framingham Offspring-Spouse cohort men. The close associations between the dietary patterns, nutritional risk, and chronic disease profiles of men emphasize the importance of targeted preventive nutrition interventions to promote health in the male population.
Jinawath, Natini; Furukawa, Yoichi; Hasegawa, Suguru; Li, Meihua; Tsunoda, Tatsuhiko; Satoh, Seiji; Yamaguchi, Toshiharu; Imamura, Hiroshi; Inoue, Masatomo; Shiozaki, Hitoshi; Nakamura, Yusuke
2004-09-02
Gastric cancer is the fourth leading cause of cancer-related death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 laser-microbeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23,040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cell-matrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.
Approaches to integrating germline and tumor genomic data in cancer research
Feigelson, Heather Spencer; Goddard, Katrina A.B.; Hollombe, Celine; Tingle, Sharna R.; Gillanders, Elizabeth M.; Mechanic, Leah E.; Nelson, Stefanie A.
2014-01-01
Cancer is characterized by a diversity of genetic and epigenetic alterations occurring in both the germline and somatic (tumor) genomes. Hundreds of germline variants associated with cancer risk have been identified, and large amounts of data identifying mutations in the tumor genome that participate in tumorigenesis have been generated. Increasingly, these two genomes are being explored jointly to better understand how cancer risk alleles contribute to carcinogenesis and whether they influence development of specific tumor types or mutation profiles. To understand how data from germline risk studies and tumor genome profiling is being integrated, we reviewed 160 articles describing research that incorporated data from both genomes, published between January 2009 and December 2012, and summarized the current state of the field. We identified three principle types of research questions being addressed using these data: (i) use of tumor data to determine the putative function of germline risk variants; (ii) identification and analysis of relationships between host genetic background and particular tumor mutations or types; and (iii) use of tumor molecular profiling data to reduce genetic heterogeneity or refine phenotypes for germline association studies. We also found descriptive studies that compared germline and tumor genomic variation in a gene or gene family, and papers describing research methods, data sources, or analytical tools. We identified a large set of tools and data resources that can be used to analyze and integrate data from both genomes. Finally, we discuss opportunities and challenges for cancer research that integrates germline and tumor genomics data. PMID:25115441
Identifying Patterns of Situational Antecedents to Heavy Drinking among College Students
Lau-Barraco, Cathy; Linden-Carmichael, Ashley N.; Braitman, Abby L.; Stamates, Amy L.
2016-01-01
Background Emerging adults have the highest prevalence of heavy drinking as compared to all other age groups. Given the negative consequences associated with such drinking, additional research efforts focused on at-risk consumption are warranted. The current study sought to identify patterns of situational antecedents to drinking and to examine their associations with drinking motivations, alcohol involvement, and mental health functioning in a sample of heavy drinking college students. Method Participants were 549 (65.8% women) college student drinkers. Results Latent profile analysis identified three classes based on likelihood of heavy drinking across eight situational precipitants. The “High Situational Endorsement” group reported the greatest likelihood of heavy drinking in most situations assessed. This class experienced the greatest level of alcohol-related harms as compared to the “Low Situational Endorsement” and “Moderate Situational Endorsement” groups. The Low Situational Endorsement class was characterized by the lowest likelihood of heavy drinking across all situational antecedents and they experienced the fewest alcohol-related harms, relative to the other classes. Class membership was related to drinking motivations with the “High Situational Endorsement” class endorsing the highest coping- and conformity-motivated drinking. The “High Situational Endorsement” class also reported experiencing more mental health symptoms than other groups. Conclusions The current study contributed to the larger drinking literature by identifying profiles that may signify a particularly risky drinking style. Findings may help guide intervention work with college heavy drinkers. PMID:28163666
Identifying areas of basin-floor recharge in the Trans-Pecos region and the link to vegetation
Walvoord, Michelle Ann; Phillips, Fred M.
2004-01-01
Comparative water potential and chloride profiles (∼10 m deep) collected from four vegetation communities in the Trans-Pecos region of the Chihuahuan Desert were assessed to evaluate the potential for using vegetation patterns as a means of efficiently improving large-scale estimates of basin-floor recharge in semiarid and arid regions. Analytical solutions and multiphase flow and transport modeling constrained flux histories and current fluxes across the water table at each site. Chloride bulge profiles containing ∼12–15 kyr of atmospheric deposition and long-term drying water potential profiles typified most desertscrub and grassland sites. In contrast, evidence of episodic sub-root zone percolation and chloride profiles containing <250 yr of atmospheric deposition characterized the woodland site. The results suggested that the desertscrub and grassland areas support small upward fluxes across the water table (nonrecharge), whereas the woodland site supports significant downward fluxes across the water table (recharge). A nonrecharge–recharge transition was identified to be collocated with a grassland–woodland ecotone. The establishment of vegetation–recharge relationships such as this will improve estimates of basin-scale recharge by identifying regions where no recharge is expected and regions where recharge is expected and point measurements should be concentrated. An approach integrating remotely sensed spatial distributions of vegetation and indicator relationships to recharge is both timely and warranted, although several caveats, as revealed in this study, should be noted. For example, the relative importance and distribution of vertical conduits that permit percolation to the water table merits future investigation.
A clustering approach to identify severe bronchiolitis profiles in children
Dumas, Orianne; Mansbach, Jonathan M; Jartti, Tuomas; Hasegawa, Kohei; Sullivan, Ashley F; Piedra, Pedro A; Camargo, Carlos A
2016-01-01
Objective Although bronchiolitis is generally considered a single disease, recent studies suggest heterogeneity. We aimed to identify severe bronchiolitis profiles using a clustering approach. Methods We analyzed data from two prospective, multi-center cohorts of children younger than 2 years hospitalized with bronchiolitis, one in the U.S. (2007–2010 winter seasons, n=2,207) and one in Finland (2008–2010 winter seasons, n=408). Severe bronchiolitis profiles were determined by latent class analysis, classifying children based on clinical factors and viral etiology. Results In the U.S. study, four profiles were identified. Profile A (12%) was characterized by history of wheezing and eczema, wheezing at the ED presentation and rhinovirus infection. Profile B (36%) included children with wheezing at the ED presentation, but, in contrast to profile A, most did not have history of wheezing or eczema; this profile had the largest probability of RSV-infection. Profile C (34%) was the most severely ill group, with longer hospital stay and moderate-to-severe retractions. Profile D (17%) had the least severe illness, including non-wheezing children with shorter length-of-stay. Two of these profiles (A and D) were replicated in the Finnish cohort; a third group (“BC”) included Finnish children with characteristics of profiles B and/or C in the U.S. population. Conclusion Several distinct clinical profiles (phenotypes) were identified by a clustering approach in two multicenter studies of children hospitalized for bronchiolitis. The observed heterogeneity has important implications for future research on the etiology, management and long-term outcomes of bronchiolitis, such as future risk of childhood asthma. PMID:27339060
Apel, William A.; Thompson, Vicki S; Lacey, Jeffrey A.; Gentillon, Cynthia A.
2016-08-09
A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.
Thompson, Vicki S; Lacey, Jeffrey A; Gentillon, Cynthia A; Apel, William A
2015-03-03
A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.
Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa.
Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen
2017-05-09
Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics.
Etzbach, Lara; Pfeiffer, Anne; Weber, Fabian; Schieber, Andreas
2018-04-15
Carotenoid profiles of goldenberry (Physalis peruviana L.) fruits differing in ripening states and in different fruit fractions (peel, pulp, and calyx of ripe fruits) were investigated by HPLC-DAD-APCI-MS n . Out of the 53 carotenoids detected, 42 were tentatively identified. The carotenoid profile of unripe fruits is dominated by (all-E)-lutein (51%), whereas in ripe fruits, (all-E)-β-carotene (55%) and several carotenoid fatty acid esters, especially lutein esters esterified with myristic and palmitic acid as monoesters or diesters, were found. In overripe fruits, carotenoid conversion products and a higher proportion of carotenoid monoesters to diesters compared to ripe fruits were observed. Overripe fruits showed a significant decrease in total carotenoids of about 31% due to degradation. The observed conversion and degradation processes included epoxidation, isomerization, and deesterification. The peel of ripe goldenberries showed a 2.8 times higher total carotenoid content of 332.00 µg/g dw compared to the pulp. Copyright © 2017 Elsevier Ltd. All rights reserved.
Winstock, Adam R; Kaar, Stephen; Borschmann, Rohan
2014-01-01
This paper presents original research on prevalence, user characteristics and effect profile of N,N-dimethyltryptamine (DMT), a potent hallucinogenic which acts primarily through the serotonergic system. Data were obtained from the Global Drug Survey (an anonymous online survey of people, many of whom have used drugs) conducted between November and December 2012 with 22,289 responses. Lifetime prevalence of DMT use was 8.9% (n=1980) and past year prevalence use was 5.0% (n=1123). We explored the effect profile of DMT in 472 participants who identified DMT as the last new drug they had tried for the first time and compared it with ratings provided by other respondents on psilocybin (magic mushrooms), LSD and ketamine. DMT was most often smoked and offered a strong, intense, short-lived psychedelic high with relatively few negative effects or "come down". It had a larger proportion of new users compared with the other substances (24%), suggesting its popularity may increase. Overall, DMT seems to have a very desirable effect profile indicating a high abuse liability that maybe offset by a low urge to use more.
Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.
2012-01-01
In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386
Heat Transfer Effects on Laminar Velocity Profiles in Pipe Flow
NASA Astrophysics Data System (ADS)
Powell, Robert; Jenkins, Thomas
1998-11-01
Heat Transfer Effects on Laminar Velocity Profiles in Pipe Flow. Robert L. Powell, Thomas P. Jenkins Department of Chemical Engineering & Materials Science University of California, Davis, CA 95616 Using laser Doppler velocimetry, we have measured the axial velocity profiles for steady, pressure driven, laminar flow of water in a circular tube. The flow was established in a one inch diameter seamless glass tube. The entry length prior to the measuring section was over one hundred diameters. Reynolds numbers in the range 500-2000 were used. Under conditions where the temperature difference between the fluid and the surroundings differed by as little as 0.2C, we found significant asymmetries in the velocity profiles. This asymmetry was most pronounced in the vertical plane. Varying the temperature difference moved the velocity maximum either above or below the centerline depending upon whether the fluid was warmer or cooler than the room. These results compare well to existing calculations. Using the available theory and our experiments it is possible to identify parameter ranges where non-ideal conditions(not parabolic velocity profiles) will be found. Supported by the EMSP Program of DOE.
NASA Astrophysics Data System (ADS)
Estapa, M. L.
2016-02-01
Autonomous, bio-optical profiling floats are poised to broaden the number and spatiotemporal resolution of observations of the ocean's biological pump. Here, we used multiple optical sensors aboard two bio-optical profiling floats (Navis BGCi, Sea-Bird) deployed in the Sargasso Sea to derive in situ proxies for particulate carbon (PC) flux, sub-mixed layer net community production (NCP) and to drive a model of net primary production (NPP). Profiles were collected at approximately 2-day resolution, and drift-phase PC flux observations were collected at subdaily resolution at a rotating cycle of observation depths between 150 and 1000 m. The magnitudes of NPP, PC flux, and their annually-averaged ratio were generally consistent with observations at the nearby Bermuda Atlantic Timeseries Study (BATS) site. PC flux and the export ratio were enhanced in the autumn as well as in the spring, and varied over short timescales possibly due to the influence of mesoscale eddies. The relatively shallow park depths and short profile cycle lengths allow us to identify ephemeral, subsurface bio-optical features and compare them to measured fluxes and satellite-observed surface properties.
Monaco, Luca; Biagi, Chiara; Conti, Valentino; Melis, Mauro; Donati, Monia; Venegoni, Mauro; Vaccheri, Alberto; Motola, Domenico
2017-07-01
Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase. Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P ≤ 0.05 were statistically significant. We retrieved 32 972 reports. We identified 204 ADRs with a ROR >1 (P ≤ 0.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47-1.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28-0.34)]. We identified other potential signals that have not been associated with DOACs previously. As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred. © 2017 The British Pharmacological Society.
Newbold, Retha R.; Jefferson, Wendy N.; Grissom, Sherry F.; Padilla-Banks, Elizabeth; Snyder, Ryan J.; Lobenhofer, Edward K.
2008-01-01
Previously, we described a mouse model where the well-known reproductive carcinogen with estrogenic activity, diethylstilbestrol (DES), caused uterine adenocarcinoma following neonatal treatment. Tumor incidence was dose-dependent reaching >90% by 18 mo following neonatal treatment with 1000 μg/kg/d of DES. These tumors followed the initiation/promotion model of hormonal carcinogenesis with developmental exposure as initiator, and exposure to ovarian hormones at puberty as the promoter. To identify molecular pathways involved in DES-initiation events, uterine gene expression profiles were examined in prepubertal mice exposed to DES (1, 10, or 1000 μg/kg/d) on days 1–5 and compared to controls. Of more than 20 000 transcripts, approximately 3% were differentially expressed in at least one DES treatment group compared to controls; some transcripts demonstrated dose–responsiveness. Assessment of gene ontology annotation revealed alterations in genes associated with cell growth, differentiation, and adhesion. When expression profiles were compared to published studies of uteri from 5-d-old DES-treated mice, or adult mice treated with 17β estradiol, similarities were seen suggesting persistent differential expression of estrogen responsive genes following developmental DES exposure. Moreover, several altered genes were identified in human uterine adenocarcinomas. Four altered genes [lactotransferrin (Ltf), transforming growth factor beta inducible (Tgfb1), cyclin D1 (Ccnd1), and secreted frizzled-related protein 4 (Sfrp4)], selected for real-time RT-PCR analysis, correlated well with the directionality of the microarray data. These data suggested altered gene expression profiles observed 2 wk after treatment ceased, were established at the time of developmental exposure and maybe related to the initiation events resulting in carcinogenesis. PMID:17394237
Newbold, Retha R; Jefferson, Wendy N; Grissom, Sherry F; Padilla-Banks, Elizabeth; Snyder, Ryan J; Lobenhofer, Edward K
2007-09-01
Previously, we described a mouse model where the well-known reproductive carcinogen with estrogenic activity, diethylstilbestrol (DES), caused uterine adenocarcinoma following neonatal treatment. Tumor incidence was dose-dependent reaching >90% by 18 mo following neonatal treatment with 1000 microg/kg/d of DES. These tumors followed the initiation/promotion model of hormonal carcinogenesis with developmental exposure as initiator, and exposure to ovarian hormones at puberty as the promoter. To identify molecular pathways involved in DES-initiation events, uterine gene expression profiles were examined in prepubertal mice exposed to DES (1, 10, or 1000 microg/kg/d) on days 1-5 and compared to controls. Of more than 20 000 transcripts, approximately 3% were differentially expressed in at least one DES treatment group compared to controls; some transcripts demonstrated dose-responsiveness. Assessment of gene ontology annotation revealed alterations in genes associated with cell growth, differentiation, and adhesion. When expression profiles were compared to published studies of uteri from 5-d-old DES-treated mice, or adult mice treated with 17beta estradiol, similarities were seen suggesting persistent differential expression of estrogen responsive genes following developmental DES exposure. Moreover, several altered genes were identified in human uterine adenocarcinomas. Four altered genes [lactotransferrin (Ltf), transforming growth factor beta inducible (Tgfb1), cyclin D1 (Ccnd1), and secreted frizzled-related protein 4 (Sfrp4)], selected for real-time RT-PCR analysis, correlated well with the directionality of the microarray data. These data suggested altered gene expression profiles observed 2 wk after treatment ceased, were established at the time of developmental exposure and maybe related to the initiation events resulting in carcinogenesis. (c) 2007 Wiley-Liss, Inc.
Analysis of Pfizer compounds in EPA's ToxCast chemicals-assay space.
Shah, Falgun; Greene, Nigel
2014-01-21
The U.S. Environmental Protection Agency (EPA) launched the ToxCast program in 2007 with the goal of evaluating high-throughput in vitro assays to prioritize chemicals that need toxicity testing. Their goal was to develop predictive bioactivity signatures for toxic compounds using a set of in vitro assays and/or in silico properties. In 2009, Pfizer joined the ToxCast initiative by contributing 52 compounds with preclinical and clinical data for profiling across the multiple assay platforms available. Here, we describe the initial analysis of the Pfizer subset of compounds within the ToxCast chemical (n = 1814) and in vitro assay (n = 486) space. An analysis of the hit rate of Pfizer compounds in the ToxCast assay panel allowed us to focus our mining of assays potentially most relevant to the attrition of our compounds. We compared the bioactivity profile of Pfizer compounds to other compounds in the ToxCast chemical space to gain insights into common toxicity pathways. Additionally, we explored the similarity in the chemical and biological spaces between drug-like compounds and environmental chemicals in ToxCast and compared the in vivo profiles of a subset of failed pharmaceuticals having high similarity in both spaces. We found differences in the chemical and biological spaces of pharmaceuticals compared to environmental chemicals, which may question the applicability of bioactivity signatures developed exclusively based on the latter to drug-like compounds if used without prior validation with the ToxCast Phase-II chemicals. Finally, our analysis has allowed us to identify novel interactions for our compounds in particular with multiple nuclear receptors that were previously not known. This insight may help us to identify potential liabilities with future novel compounds.
Mull, Hillary J; Chen, Qi; O'Brien, William J; Shwartz, Michael; Borzecki, Ann M; Hanchate, Amresh; Rosen, Amy K
2013-07-01
The Centers for Medicare and Medicaid Services' (CMS) all-cause readmission measure and the 3M Health Information System Division Potentially Preventable Readmissions (PPR) measure are both used for public reporting. These 2 methods have not been directly compared in terms of how they identify high-performing and low-performing hospitals. To examine how consistently the CMS and PPR methods identify performance outliers, and explore how the PPR preventability component impacts hospital readmission rates, public reporting on CMS' Hospital Compare website, and pay-for-performance under CMS' Hospital Readmission Reduction Program for 3 conditions (acute myocardial infarction, heart failure, and pneumonia). We applied the CMS all-cause model and the PPR software to VA administrative data to calculate 30-day observed FY08-10 VA hospital readmission rates and hospital profiles. We then tested the effect of preventability on hospital readmission rates and outlier identification for reporting and pay-for-performance by replacing the dependent variable in the CMS all-cause model (Yes/No readmission) with the dichotomous PPR outcome (Yes/No preventable readmission). The CMS and PPR methods had moderate correlations in readmission rates for each condition. After controlling for all methodological differences but preventability, correlations increased to >90%. The assessment of preventability yielded different outlier results for public reporting in 7% of hospitals; for 30% of hospitals there would be an impact on Hospital Readmission Reduction Program reimbursement rates. Despite uncertainty over which readmission measure is superior in evaluating hospital performance, we confirmed that there are differences in CMS-generated and PPR-generated hospital profiles for reporting and pay-for-performance, because of methodological differences and the PPR's preventability component.
KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma.
Nadal, Ernest; Chen, Guoan; Prensner, John R; Shiratsuchi, Hiroe; Sam, Christine; Zhao, Lili; Kalemkerian, Gregory P; Brenner, Dean; Lin, Jules; Reddy, Rishindra M; Chang, Andrew C; Capellà, Gabriel; Cardenal, Felipe; Beer, David G; Ramnath, Nithya
2014-10-01
The aim of this study was to examine the effects of KRAS mutant subtypes on the outcome of patients with resected lung adenocarcinoma (AC). Using clinical and sequencing data, we identified 179 patients with resected lung AC for whom KRAS mutational status was determined. A multivariate Cox model was used to identify factors associated with disease-free survival (DFS) and overall survival (OS). Publicly available mutation and gene-expression data from lung cancer cell lines and lung AC were used to assess whether distinct KRAS mutant variants have a different profile. Patients with KRAS mutation had a significantly shorter DFS compared with those with KRAS wild-type (p = 0.009). Patients with KRAS-G12C mutant tumors had significantly shorter DFS compared with other KRAS mutants and KRAS wild-type tumors (p < 0.001). In the multivariate Cox model, KRAS-G12C remained as an independent prognostic marker for DFS (Hazard ratio = 2.46, 95% confidence interval 1.51-4.00, p < 0.001) and for OS (Hazard ratio = 2.35, 95% confidence interval 1.35-4.10, p = 0.003). No genes were statistically significant when comparing the mutational or transcriptional profile of lung cancer cell lines and lung AC harboring KRAS-G12C with other KRAS mutant subtypes. Gene set enrichment analysis revealed that KRAS-G12C mutants overexpressed epithelial to mesenchymal transition genes and expressed lower levels of genes predicting KRAS dependency. KRAS-G12C mutation is associated with worse DFS and OS in resected lung AC. Gene-expression profiles in lung cancer cell lines and surgically resected lung AC revealed that KRAS-G12C mutants had an epithelial to mesenchymal transition and a KRAS-independent phenotype.
Physiologic profile of professional cricketers.
Johnstone, James A; Ford, Paul A
2010-11-01
This study aims to provide a physiologic profile of professional cricketers and note positional differences at the start of the 2007/08 competitive season. Fifteen participants (9 bowlers, 6 batsmen) aged 25.0 ± 5.0 years (mean ± SD) took part in this study. Participants (bowlers and batsmen) completed a series of field-based fitness assessments: body composition (sum of 7 skinfolds, 72.5 ± 16.5 and 65.5 ± 19.3 mm, respectively), flexibility (sit and reach 8.1 ± 10.3 and 6.0 ± 6.2 cm, respectively), predicted maximal oxygen uptake (multistage shuttle run, 54.1 ± 2.8 and 56.1 ± 4.5 ml-1·kg-1·min-1, respectively), upper- (medicine ball throw, 7.7 ± 0.6 and 7.0 ± 0.1 m, respectively) and lower-body strength (countermovement jump, 45.7 ± 5.8 and 43.9 ± 4.1 cm, respectively), speed (sprint 17.7 m, 2.76 ± 0.6 and 2.77 ± 0.1 s, respectively), and explosive power (repeated jump, 31.0 ± 2.0 and 34.1 ± 4.8 cm, respectively). The data provided the physical fitness profile for each player, which, compared with normative data, identified that this cohort of professional cricketers had some superior fitness parameters compared with the general population, and where applicable, were comparable with other professional athletes. In addition, after effect size calculations, the results showed that some physical fitness differences existed between playing positions. Cricket professionals possess a superior level of physical fitness and strength, and conditioning coaches should seek to progress these physical parameters and further identify position-specific physical requirements to progress the modern game.
Xu, Hong-Xia; Li, Xiao-Ying; Chen, Jun-Wei
2017-09-01
Loquat (Eriobotrya japonica Lindl.) is an important subtropical, commercial fruit in China. It blossoms during autumn and winter in most areas of China and its fruitlets usually suffer from freezing stress. However, studies about the mechanisms underlying freezing stress in loquat are very limited. The gene expression profiles of loquat fruitlets subjected to freezing (G2 library) versus non-treated ones (G1 library) were investigated using Illumina sequencing technology to elucidate the molecular mechanisms and identify the genes that play vital roles in the freezing stress response. The results showed that approximately 157.63 million reads in total were obtained from freeze-treated and non-treated loquat fruitlets. These reads were assembled into 87,379 unigenes with an average length of 710 bp and an N50 of 1,200 bp. After comparing the profiles obtained from the G1 and G2 libraries, 2,892 differentially expressed genes were identified, of which 1,883 were up-regulated and 1,009 were down-regulated in the treated samples compared to non-treated ones. These unigenes showed significant differences in expression for carbohydrate transport and metabolism, amino acid metabolism, energy metabolism, and lipid metabolism, which are involved in defense against freezing stress. Glycolysis/gluconeogenesis was one of the most significantly regulated pathways. Freezing also significantly damaged the membrane system of loquat fruitlets, and several defense mechanisms were induced. Some selected genes related to low temperature resistance were validated by quantitative real-time PCR (qRT-PCR). The results revealed many genes and pathways that are part of freezing resistance processes and expand our understanding of the complex molecular events involved in freezing stress.
Granero-Gallegos, Antonio; Baena-Extremera, Antonio; Pérez-Quero, Francisco J; Ortiz-Camacho, Maria M; Bracho-Amador, Clara
2012-01-01
The purpose of this study was to analyze the motivational profiles of satisfaction with and importance of physical education in high school students and its relation with gender and the practice of sport. The sample comprised 2002 students aged from 12 to 19 who completed the Sport Motivation Scale (Núñez et al., 2006), the Sport Satisfaction Instrument (Baena-Extremera et al., 2012) and the Importance of Physical Education Scale (Moreno et al., 2009). Descriptive analyzes, correlations between the scales, a cluster analysis for profiles, and a MANOVA were conducted to examine differences by gender. Three clusters (profiles) were identified. The first profile identified was "moderate" motivation (n = 463) and was associated with boys who practice physical activity for less than 3 hours per week. The second profile identified was "low" motivation (n = 545) and was associated mainly with girls who practice physical activity for less than 3 hours per week. And lastly the third profile identified was "high" motivation (n = 910), which was found to be greater in boys who practiced physical exercise for more than 3 hours a week.
NASA Technical Reports Server (NTRS)
Misra, Amit; Tripathi, S. N.; Kaul, D. S.; Welton, Ellsworth J.
2012-01-01
The level 2 aerosol backscatter and extinction profiles from the NASA Micropulse Lidar Network (MPLNET) at Kanpur, India, have been studied from May 2009 to September 2010. Monthly averaged extinction profiles from MPLNET shows high extinction values near the surface during October March. Higher extinction values at altitudes of 24 km are observed from April to June, a period marked by frequent dust episodes. Version 3 level 2 Cloud Aerosol Lidar with Orthogonal Polarization (CALIOP) aerosol profile products have been compared with corresponding data from MPLNET over Kanpur for the above-mentioned period. Out of the available backscatter profiles, the16 profiles used in this study have time differences less than 3 h and distances less than 130 km. Among these profiles, four cases show good comparison above 400 m with R2 greater than 0.7. Comparison with AERONET data shows that the aerosol type is properly identified by the CALIOP algorithm. Cloud contamination is a possible source of error in the remaining cases of poor comparison. Another source of error is the improper backscatter-to-extinction ratio, which further affects the accuracy of extinction coefficient retrieval.
Miller, Daniel J; Zhang, Zhibo; Ackerman, Andrew S; Platnick, Steven; Baum, Bryan A
2016-04-27
Passive optical retrievals of cloud liquid water path (LWP), like those implemented for Moderate Resolution Imaging Spectroradiometer (MODIS), rely on cloud vertical profile assumptions to relate optical thickness ( τ ) and effective radius ( r e ) retrievals to LWP. These techniques typically assume that shallow clouds are vertically homogeneous; however, an adiabatic cloud model is plausibly more realistic for shallow marine boundary layer cloud regimes. In this study a satellite retrieval simulator is used to perform MODIS-like satellite retrievals, which in turn are compared directly to the large-eddy simulation (LES) output. This satellite simulator creates a framework for rigorous quantification of the impact that vertical profile features have on LWP retrievals, and it accomplishes this while also avoiding sources of bias present in previous observational studies. The cloud vertical profiles from the LES are often more complex than either of the two standard assumptions, and the favored assumption was found to be sensitive to cloud regime (cumuliform/stratiform). Confirming previous studies, drizzle and cloud top entrainment of dry air are identified as physical features that bias LWP retrievals away from adiabatic and toward homogeneous assumptions. The mean bias induced by drizzle-influenced profiles was shown to be on the order of 5-10 g/m 2 . In contrast, the influence of cloud top entrainment was found to be smaller by about a factor of 2. A theoretical framework is developed to explain variability in LWP retrievals by introducing modifications to the adiabatic r e profile. In addition to analyzing bispectral retrievals, we also compare results with the vertical profile sensitivity of passive polarimetric retrieval techniques.
Miller, Daniel J.; Zhang, Zhibo; Ackerman, Andrew S.; Platnick, Steven; Baum, Bryan A.
2018-01-01
Passive optical retrievals of cloud liquid water path (LWP), like those implemented for Moderate Resolution Imaging Spectroradiometer (MODIS), rely on cloud vertical profile assumptions to relate optical thickness (τ) and effective radius (re) retrievals to LWP. These techniques typically assume that shallow clouds are vertically homogeneous; however, an adiabatic cloud model is plausibly more realistic for shallow marine boundary layer cloud regimes. In this study a satellite retrieval simulator is used to perform MODIS-like satellite retrievals, which in turn are compared directly to the large-eddy simulation (LES) output. This satellite simulator creates a framework for rigorous quantification of the impact that vertical profile features have on LWP retrievals, and it accomplishes this while also avoiding sources of bias present in previous observational studies. The cloud vertical profiles from the LES are often more complex than either of the two standard assumptions, and the favored assumption was found to be sensitive to cloud regime (cumuliform/stratiform). Confirming previous studies, drizzle and cloud top entrainment of dry air are identified as physical features that bias LWP retrievals away from adiabatic and toward homogeneous assumptions. The mean bias induced by drizzle-influenced profiles was shown to be on the order of 5–10 g/m2. In contrast, the influence of cloud top entrainment was found to be smaller by about a factor of 2. A theoretical framework is developed to explain variability in LWP retrievals by introducing modifications to the adiabatic re profile. In addition to analyzing bispectral retrievals, we also compare results with the vertical profile sensitivity of passive polarimetric retrieval techniques. PMID:29637042
Screening for prenatal substance use: development of the Substance Use Risk Profile-Pregnancy scale.
Yonkers, Kimberly A; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B; Rounsaville, Bruce J
2010-10-01
To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.
Braaten, Alyssa J; Parsons, Thomas D; McCue, Robert; Sellers, Alfred; Burns, William J
2006-11-01
Similarities in presentation of Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder, pose differential diagnosis challenges. The current study identifies specific neuropsychological patterns of scores for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. Neuropsychological domains directly assessed in the study included: immediate memory, delayed memory, confrontational naming, verbal fluency, attention, concentration, and executive functioning. The results reveal specific neuropsychological comparative profiles for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. The identification of these profiles will assist in the differential diagnosis of these disorders and aid in patient treatment.
Comparative transcriptional profiling of human Merkel cells and Merkel cell carcinoma.
Mouchet, Nicolas; Coquart, Nolwenn; Lebonvallet, Nicolas; Le Gall-Ianotto, Christelle; Mogha, Ariane; Fautrel, Alain; Boulais, Nicholas; Dréno, Brigitte; Martin, Ludovic; Hu, Weiguo; Galibert, Marie-Dominique; Misery, Laurent
2014-12-01
Merkel cell carcinoma is believed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly understood events. Transcriptional profiling using cDNA microarrays was performed on cells from MCPy-negative and MCPy-positive Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and some downregulated genes. The extensive list of genes that were identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Williams, Vonetta M.; Kokoza, Anatolii; Bashkirova, Svetlana; Duerksen-Hughes, Penelope
2014-01-01
Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy. PMID:25478571
Luck, Margaux; Schmitt, Caroline; Talbi, Neila; Gouya, Laurent; Caradeuc, Cédric; Puy, Hervé; Bertho, Gildas; Pallet, Nicolas
2018-01-01
Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease. In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses. Urine 1 H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained. Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients. These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism.
Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia.
Tangerås, Line H; Austdal, Marie; Skråstad, Ragnhild B; Salvesen, Kjell Å; Austgulen, Rigmor; Bathen, Tone F; Iversen, Ann-Charlotte
2015-11-01
Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders. The study cohort consisted of 548 pregnant Norwegian women who were either multiparous with previous gestational hypertension or preeclampsia or were nulliparous. Maternal sera at gestational weeks 11(0)-13(6) were assayed for 27 cytokines, C-reactive protein, total cholesterol, high-density lipoprotein, triglyceride, creatinine, calcium, uric acid, and placental growth factor. Compared with normotensive women, women with both hypertensive conditions presented an atherogenic lipid profile at early gestation, but only those later developing gestational hypertension had significantly higher serum levels of interleukin (IL)-5 and IL-12. Comparing the 2 hypertensive pregnancy disorders, women subsequently developing gestational hypertension had higher serum levels of IL-1β, IL-5, IL-7, IL-8, IL-13, basic fibroblast growth factor, and vascular endothelial growth factor than the women subsequently developing preeclampsia. This study identifies early pregnancy differences in serum cytokine profiles for gestational hypertension and preeclampsia. © 2015 American Heart Association, Inc.
Cognitive profiles in euthymic patients with bipolar disorders: results from the FACE-BD cohort.
Roux, Paul; Raust, Aurélie; Cannavo, Anne Sophie; Aubin, Valérie; Aouizerate, Bruno; Azorin, Jean-Michel; Bellivier, Frank; Belzeaux, Raoul; Bougerol, Thierry; Cussac, Iréna; Courtet, Philippe; Etain, Bruno; Gard, Sébastien; Job, Sophie; Kahn, Jean-Pierre; Leboyer, Marion; Olié, Emilie; Henry, Chantal; Passerieux, Christine
2017-03-01
Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD. We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster. Subsequently, subjects from each cluster were compared on demographic, clinical functioning, and pharmacological variables. A four-cluster solution was identified. The global cognitive performance was above normal in one cluster and below normal in another. The other two clusters had a near-normal cognitive performance, with above and below average verbal memory, respectively. Among the four clusters, significant differences were observed in estimated intelligence quotient and social functioning, which were lower for the low cognitive performers compared to the high cognitive performers. These results confirm the existence of several distinct cognitive profiles in BD. Identification of these profiles may help to develop profile-specific cognitive remediation programs, which might improve functioning in BD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kusano, Miyako; Kobayashi, Makoto; Iizuka, Yumiko; Fukushima, Atsushi; Saito, Kazuki
2016-02-29
Plants produce and emit important volatile organic compounds (VOCs), which have an essential role in biotic and abiotic stress responses and in plant-plant and plant-insect interactions. In order to study the bouquets from plants qualitatively and quantitatively, a comprehensive, analytical method yielding reproducible results is required. We applied in-tube extraction (ITEX) and solid-phase microextraction (SPME) for studying the emissions of Allium plants. The collected HS samples were analyzed by gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS), and the results were subjected to multivariate analysis. In case of ITEX-method Allium cultivars released more than 300 VOCs, out of which we provisionally identified 50 volatiles. We also used the VOC profiles of Allium samples to discriminate among groups of A. fistulosum, A. chinense (rakkyo), and A. tuberosum (Oriental garlic). As we found 12 metabolite peaks including dipropyl disulphide with significant changes in A. chinense and A. tuberosum when compared to the control cultivar, these metabolite peaks can be used for chemotaxonomic classification of A. chinense, tuberosum, and A. fistulosum. Compared to SPME-method our ITEX-based VOC profiling technique contributes to automatic and reproducible analyses. Hence, it can be applied to high-throughput analyses such as metabolite profiling.
Liposomal bupivacaine for regional anesthesia.
Uskova, Anna; O'Connor, Jessica E
2015-10-01
Using a regional block in a multimodal approach to postoperative analgesia management involves addressing, which local anesthetic and how much should be used to ensure adequate pain relief to reduce related morbidity and mortality. This article will review literature surrounding the recently approved formulation of slow release liposomal bupivacaine, define its proven benefits, and identify ongoing studies to further examine the utility of this novel formulation by various routes. Recent Phase II and III clinical trials have demonstrated the ability of liposomal bupivacaine to provide prolonged analgesia, maintain a high safety profile in therapeutic doses, and decrease opioid requirements when compared with placebo in local infiltration applications for up to 24 h. Between 24 and 72 h after study drug administration, there was minimal to no difference between EXPAREL and placebo treatments on mean pain intensity. Conventional bupivacaine or ropivacaine groups (current standard practice in many hospitals in the USA) were not compared. In addition, the analgesic efficacy, cost-effectiveness, and safety profile of liposomal bupivacaine has not thoroughly been studied in various standard clinical settings such as perineural, intrathecal, and epidural administration. Current published data do not provide superior clinical results for EXPAREL over conventional bupivacaine based upon the lack of adequately powered multicentered clinical trials with comparison groups. Further investigation is necessary to identify the analgesic efficacy and safety profile of liposomal bupivacaine versus standard local anesthetics and to define the optimal clinical indication for liposomal bupivacaine administration in regional anesthesia.
Stability-indicating HPLC-DAD/UV-ESI/MS impurity profiling of the anti-malarial drug lumefantrine.
Verbeken, Mathieu; Suleman, Sultan; Baert, Bram; Vangheluwe, Elien; Van Dorpe, Sylvia; Burvenich, Christian; Duchateau, Luc; Jansen, Frans H; De Spiegeleer, Bart
2011-02-28
Lumefantrine (benflumetol) is a fluorene derivative belonging to the aryl amino alcohol class of anti-malarial drugs and is commercially available in fixed combination products with β-artemether. Impurity characterization of such drugs, which are widely consumed in tropical countries for malaria control programmes, is of paramount importance. However, until now, no exhaustive impurity profile of lumefantrine has been established, encompassing process-related and degradation impurities in active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs). Using HPLC-DAD/UV-ESI/ion trap/MS, a comprehensive impurity profile was established based upon analysis of market samples as well as stress, accelerated and long-term stability results. In-silico toxicological predictions for these lumefantrine related impurities were made using Toxtree® and Derek®. Several new impurities are identified, of which the desbenzylketo derivative (DBK) is proposed as a new specified degradant. DBK and the remaining unspecified lumefantrine related impurities are predicted, using Toxtree® and Derek®, to have a toxicity risk comparable to the toxicity risk of the API lumefantrine itself. From unstressed, stressed and accelerated stability samples of lumefantrine API and FPPs, nine compounds were detected and characterized to be lumefantrine related impurities. One new lumefantrine related compound, DBK, was identified and characterized as a specified degradation impurity of lumefantrine in real market samples (FPPs). The in-silico toxicological investigation (Toxtree® and Derek®) indicated overall a toxicity risk for lumefantrine related impurities comparable to that of the API lumefantrine itself.
Gartstein, Maria A; Prokasky, Amanda; Bell, Martha Ann; Calkins, Susan; Bridgett, David J; Braungart-Rieker, Julia; Leerkes, Esther; Cheatham, Carol L; Eiden, Rina D; Mize, Krystal D; Jones, Nancy Aaron; Mireault, Gina; Seamon, Erich
2017-10-01
There is renewed interest in person-centered approaches to understanding the structure of temperament. However, questions concerning temperament types are not frequently framed in a developmental context, especially during infancy. In addition, the most common person-centered techniques, cluster analysis (CA) and latent profile analysis (LPA), have not been compared with respect to derived temperament types. To address these gaps, we set out to identify temperament types for younger and older infants, comparing LPA and CA techniques. Multiple data sets (N = 1,356; 672 girls, 677 boys) with maternal ratings of infant temperament obtained using the Infant Behavior Questionnaire-Revised (Gartstein & Rothbart, 2003) were combined. All infants were between 3 and 12 months of age (M = 7.85; SD = 3.00). Due to rapid development in the first year of life, LPA and CA were performed separately for younger (n = 731; 3 to 8 months of age) and older (n = 625; 9 to 12 months of age) infants. Results supported 3-profile/cluster solutions as optimal for younger infants, and 5-profile/cluster solutions for the older subsample, indicating considerable differences between early/mid and late infancy. LPA and CA solutions produced relatively comparable types for younger and older infants. Results are discussed in the context of developmental changes unique to the end of the first year of life, which likely account for the present findings. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Emotional Intelligence Profiles and Learning Strategies in Secondary School Students
ERIC Educational Resources Information Center
Inglés, Cándido J.; Martínez-Monteagudo, María C.; Pérez Fuentes, Maria C.; García-Fernández, José M.; Molero, María del Mar; Suriá-Martinez, Raquel; Gázquez, José J.
2017-01-01
The aim of this study was to analyse the relationship among emotional intelligence (EI) and learning strategies, identifying different emotional intelligence profiles and determining possible statistically significant differences in learning strategies through the identified profiles. Thousand and seventy-one Spaniards secondary school students…
Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines.
Pane, Josep; Coloma, Preciosa M; Verhamme, Katia M C; Sturkenboom, Miriam C J M; Rebollo, Irene
2017-01-01
Recent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our objectives were to compare the current processes and methodologies for the assessment of NAIMD safety profiles with those for medicines, identify potential gaps, and make recommendations for the adoption of new methodologies for the ongoing benefit-risk monitoring of these devices throughout their entire life cycle. A literature review served to examine the current tools for the safety evaluation of NAIMDs and those for medicines. We searched MEDLINE using these two categories. We supplemented this search with Google searches using the same key terms used in the MEDLINE search. Using a comparative approach, we summarized the new product design, development cycle (preclinical and clinical phases), and post-market phases for NAIMDs and drugs. We also evaluated and compared the respective processes to integrate and assess safety data during the life cycle of the products, including signal detection, signal management, and subsequent potential regulatory actions. The search identified a gap in NAIMD safety signal generation: no global program exists that collects and analyzes adverse events and product quality issues. Data sources in real-world settings, such as electronic health records, need to be effectively identified and explored as additional sources of safety information, particularly in some areas such as the EU and USA where there are plans to implement the unique device identifier (UDI). The UDI and other initiatives will enable more robust follow-up and assessment of long-term patient outcomes. The safety evaluation system for NAIMDs differs in many ways from those for drugs, but both systems face analogous challenges with respect to monitoring real-world usage. Certain features of the drug safety evaluation process could, if adopted and adapted for NAIMDs, lead to better and more systematic evaluations of the latter.
Ehrhardt, Christopher J; Chu, Vivian; Brown, TeeCie; Simmons, Terrie L; Swan, Brandon K; Bannan, Jason; Robertson, James M
2010-03-01
The goal of this study was to determine if cellular fatty acid methyl ester (FAME) profiling could be used to distinguish among spore samples from a single species (Bacillus cereus T strain) that were prepared on 10 different medium formulations. To analyze profile differences and identify FAME biomarkers diagnostic for the chemical constituents in each sporulation medium, a variety of statistical techniques were used, including nonmetric multidimensional scaling (nMDS), analysis of similarities (ANOSIM), and discriminant function analysis (DFA). The results showed that one FAME biomarker, oleic acid (18:1 omega9c), was exclusively associated with spores grown on Columbia agar supplemented with sheep blood and was indicative of blood supplements that were present in the sporulation medium. For spores grown in other formulations, multivariate comparisons across several FAME biomarkers were required to discern profile differences. Clustering patterns in nMDS plots and R values from ANOSIM revealed that dissimilarities among FAME profiles were most pronounced when spores grown with disparate sources of complex additives or protein supplements were compared (R > 0.8), although other factors also contributed to FAME differences. DFA indicated that differentiation could be maximized with a targeted subset of FAME variables, and the relative contributions of branched FAME biomarkers to group dissimilarities changed when different media were compared. When taken together, these analyses indicate that B. cereus spore samples grown in different media can be resolved with FAME profiling and that this may be a useful technique for providing intelligence about the production methods of Bacillus organisms in a forensic investigation.
Religiousness and Levels of Hazardous Alcohol Use: A Latent Profile Analysis.
Jankowski, Peter J; Hardy, Sam A; Zamboanga, Byron L; Ham, Lindsay S; Schwartz, Seth J; Kim, Su Yeong; Forthun, Larry F; Bersamin, Melina M; Donovan, Roxanne A; Whitbourne, Susan Krauss; Hurley, Eric A; Cano, Miguel Ángel
2015-10-01
Prior person-centered research has consistently identified a subgroup of highly religious participants that uses significantly less alcohol when compared to the other subgroups. The construct of religious motivation is absent from existing examinations of the nuanced combinations of religiousness dimensions within persons, and alcohol expectancy valuations have yet to be included as outcome variables. Variable-centered approaches have found religious motivation and alcohol expectancy valuations to play a protective role against individuals' hazardous alcohol use. The current study examined latent religiousness profiles and hazardous alcohol use in a large, multisite sample of ethnically diverse college students. The sample consisted of 7412 college students aged 18-25 (M age = 19.77, SD age = 1.61; 75% female; 61% European American). Three latent profiles were derived from measures of religious involvement, salience, and religious motivations: Quest-Intrinsic Religiousness (highest levels of salience, involvement, and quest and intrinsic motivations; lowest level of extrinsic motivation), Moderate Religiousness (intermediate levels of salience, involvement, and motivations) and Extrinsic Religiousness (lowest levels of salience, involvement, and quest and intrinsic motivations; highest level of extrinsic motivation). The Quest-Intrinsic Religiousness profile scored significantly lower on hazardous alcohol use, positive expectancy outcomes, positive expectancy valuations, and negative expectancy valuations, and significantly higher on negative expectancy outcomes, compared to the other two profiles. The Extrinsic and Moderate Religiousness profiles did not differ significantly on positive expectancy outcomes, negative expectancy outcomes, negative expectancy valuations, or hazardous alcohol use. The results advance existing research by demonstrating that the protective influence of religiousness on college students' hazardous alcohol use may involve high levels on both quest and intrinsic religious motivation.
Ehrhardt, Christopher J.; Chu, Vivian; Brown, TeeCie; Simmons, Terrie L.; Swan, Brandon K.; Bannan, Jason; Robertson, James M.
2010-01-01
The goal of this study was to determine if cellular fatty acid methyl ester (FAME) profiling could be used to distinguish among spore samples from a single species (Bacillus cereus T strain) that were prepared on 10 different medium formulations. To analyze profile differences and identify FAME biomarkers diagnostic for the chemical constituents in each sporulation medium, a variety of statistical techniques were used, including nonmetric multidimensional scaling (nMDS), analysis of similarities (ANOSIM), and discriminant function analysis (DFA). The results showed that one FAME biomarker, oleic acid (18:1 ω9c), was exclusively associated with spores grown on Columbia agar supplemented with sheep blood and was indicative of blood supplements that were present in the sporulation medium. For spores grown in other formulations, multivariate comparisons across several FAME biomarkers were required to discern profile differences. Clustering patterns in nMDS plots and R values from ANOSIM revealed that dissimilarities among FAME profiles were most pronounced when spores grown with disparate sources of complex additives or protein supplements were compared (R > 0.8), although other factors also contributed to FAME differences. DFA indicated that differentiation could be maximized with a targeted subset of FAME variables, and the relative contributions of branched FAME biomarkers to group dissimilarities changed when different media were compared. When taken together, these analyses indicate that B. cereus spore samples grown in different media can be resolved with FAME profiling and that this may be a useful technique for providing intelligence about the production methods of Bacillus organisms in a forensic investigation. PMID:20097814
Identifying cancer biomarkers by mass spectrometry-based glycomics
Mechref, Yehia; Hu, Yunli; Garcia, Aldo; Hussein, Ahmed
2013-01-01
Correlations between aberrant glycosylation and cancer have been established for decades. The major advances in mass spectrometry (MS) and separation science have rapidly advanced detailed characterization of the changes associated with cancer development and progression. Over the past 10 years, many reports have described MS-based glycomic methods directed toward comparing the glycomic profiles of different human specimens collected from disease-free individuals and patients with cancers. Glycomic profiling of glycoproteins isolated from human specimens originating from disease-free individuals and patients with cancers have also been performed. Profiling of native, labeled, and permethylated glycans has been acquired using MALDI-MS and LC-MS. This review focuses on describing, discussing, and evaluating the different glycomic methods employed to characterize and quantify glycomic changes associated with cancers of different organs, including breast, colon, esophagus, liver, ovarian, pancreas, and prostate. PMID:22740464
Jang, Yuri; Park, Nan Sook; Yoon, Hyunwoo; Huang, Ya-Ching; Rhee, Min-Kyoung; Chiriboga, David A; Kim, Miyong T
2018-01-01
Using data from the 2015 Asian American Quality of Life Survey (N = 2,609), latent profile analysis was conducted on general (health insurance, usual place for care and income) and immigrant-specific (nativity, length of stay in the U.S., English proficiency and acculturation) risk factors of healthcare access. Latent profile analysis identified a three-cluster model (low-risk, moderate-risk and high-risk groups). Compared with the low-risk group, the odds of having an unmet healthcare need was 1.52 times greater in the moderate-risk group and 2.24 times greater in the high-risk group. Challenging the myth of model minority, the present sample of Asian Americans demonstrates its vulnerability in access to healthcare. Findings also show the heterogeneity in healthcare access risk profiles. © 2017 John Wiley & Sons Ltd.
Self-regulated learning and self-directed study in a pre-college sample
Abar, Beau; Loken, Eric
2009-01-01
Self-regulated learning (SRL) is a multi-dimensional construct that has been difficult to operationalize using traditional, variable-centered methodologies. The current paper takes a person-centered approach to the study of SRL in a sample of 205 high-school students. Using latent profile analysis on self-reports of seven aspects of SRL, three groups were identified: high SRL, low SRL, and average SRL. Student self-reports of goal orientation were used as validation for the profile solution, with the high academic self- regulation group reporting the highest levels of mastery orientation while the low self-regulation group reported highest levels of avoidant orientation. Profiles were also compared on independently collected, behavioral measures of study behaviors, with the highly self-regulated group tending to study more material and for a longer time than less self-regulated individuals. PMID:20161484
NASA Technical Reports Server (NTRS)
Yue, G. K.; Veiga, R. E.; Poole, L. R.; Zawodny, J. M.; Proffitt, M. H.
1994-01-01
An empirical time-series model for estimating ozone mixing ratios based on Stratospheric Aerosols and Gas Experiment II (SAGE II) monthly mean ozone data for the period October 1984 through June 1991 has been developed. The modeling results for ozone mixing ratios in the 10- to 30- km region in early months of 1993 are presented. In situ ozone profiles obtained by a dual-beam UV-absorption ozone photometer during the Stratospheric Photochemistry, Aerosols and Dynamics Expedition (SPADE) campaign, May 1-14, 1993, are compared with the model results. With the exception of two profiles at altitudes below 16 km, ozone mixing ratios derived by the model and measured by the ozone photometer are in relatively good agreement within their individual uncertainties. The identified discrepancies in the two profiles are discussed.
Measurements and modeling of radio frequency field structures in a helicon plasma
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, C. A.; Chen, Guangye; Arefiev, A. V.
2011-01-01
Measurements of the radio frequency (rf) field structure, plasma density, and electron temperature are presented for a 1 kW argon helicon plasma source. The measured profiles change considerably when the equilibrium magnetic field is reversed. The measured rf fields are identified as fields of radially localized helicon waves, which propagate in the axial direction. The rf field structure is compared to the results of two-dimensional cold plasma full-wave simulations for the measured density profiles. Electron collision frequency is adjusted in the simulations to match the simulated and measured field profiles. The resulting frequency is anomalously high, which is attributed tomore » the excitation of an ion-acoustic instability. The calculated power deposition is insensitive to the collision frequency and accounts for most of the power supplied by the rf-generator.« less
Joshi, Gagan; Wozniak, Janet; Fitzgerald, Maura; Faraone, Stephen; Fried, Ronna; Galdo, Maribel; Furtak, Stephannie L; Conroy, Kristina; Kilcullen, J Ryan; Belser, Abigail; Biederman, Joseph
2018-04-19
To assess prevalence and severity of emotional dysregulation (ED) in psychiatrically referred youth with autism spectrum disorder (ASD). ASD youth (N = 123) were compared to youth with attention-deficit/hyperactivity disorder (ADHD) and controls. The majority of psychiatrically referred youth with ASD had positive Child Behavior Checklist-ED (CBCL-ED) profile that was significantly higher than in youth with ADHD (82 vs. 53%; p < 0.001). The severe emotional dysregulation (SED) profile was significantly greater in ASD youth than ADHD (44 vs. 15%; p < 0.001). In the presence of SED profile ASD youth suffered from greater severity of autism, associated psychopathology, and psychosocial dysfunction. Greater than expected prevalence of SED in psychiatrically referred youth with ASD that identifies distinct clinical correlates associated with severe morbidity and dysfunction.
Electronic cigarette solutions and resultant aerosol profiles.
Herrington, Jason S; Myers, Colton
2015-10-30
Electronic cigarettes (e-cigarettes) are growing in popularity exponentially. Despite their ever-growing acceptance, their aerosol has not been fully characterized. The current study focused on evaluating e-cigarette solutions and their resultant aerosol for potential differences. A simple sampling device was developed to draw e-cigarette aerosol into a multi-sorbent thermal desorption (TD) tube, which was then thermally extracted and analyzed via a gas chromatography (GC) mass spectrometry (GC-MS) method. This novel application provided detectable levels of over one hundred fifteen volatile organic compounds (VOCs) and semivolatile organic compounds (SVOCs) from a single 40mL puff. The aerosol profiles from four commercially available e-cigarettes were compared to their respective solution profiles with the same GC-MS method. Solution profiles produced upwards of sixty four unidentified and identified (some only tentatively) constituents and aerosol profiles produced upwards of eighty two compounds. Results demonstrated distinct analyte profiles between liquid and aerosol samples. Most notably, formaldehyde, acetaldehyde, acrolein, and siloxanes were found in the aerosol profiles; however, these compounds were never present in the solutions. These results implicate the aerosolization process in the formation of compounds not found in solutions; have potential implications for human health; and stress the need for an emphasis on electronic cigarette aerosol testing. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Urasaki, Yasuyo; Fiscus, Ronald R; Le, Thuc T
2016-04-01
We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Diagnostic performance of the "MESACUP anti-Skin profile TEST".
Horváth, Orsolya N; Varga, Rita; Kaneda, Makoto; Schmidt, Enno; Ruzicka, Thomas; Sárdy, Miklós
2016-01-01
The "MESACUP anti-Skin profile TEST" is a new, commercially available ELISA kit to detect circulating IgG autoantibodies against desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen, both simultaneously and more rapidly than previous assays. The aim of this study was to evaluate the diagnostic accuracy of this kit for the diagnosis of pemphigus foliaceus, pemphigus vulgaris, bullous pemphigoid and epidermolysis bullosa acquisita. Dual-centre retrospective study in which 138 patients with autoimmune blistering diseases were compared to 40 controls Using the MESACUP anti-Skin profile TEST, both sensitivities and specificities for desmoglein 1, desmoglein 3, BP180, BP230, and type VII collagen autoantibodies were similar to those obtained using previous, specific ELISA systems and 88% of the results were concordant without any significant difference. The MESACUP anti-Skin profile TEST had a similar performance to previously produced ELISA systems. The novel kit can be used for rapid diagnosis of most common autoimmune blistering diseases and is especially suitable for identifying overlapping disorders.
Harris, R. Alan; Wang, Ting; Coarfa, Cristian; Nagarajan, Raman P.; Hong, Chibo; Downey, Sara L.; Johnson, Brett E.; Fouse, Shaun D.; Delaney, Allen; Zhao, Yongjun; Olshen, Adam; Ballinger, Tracy; Zhou, Xin; Forsberg, Kevin J.; Gu, Junchen; Echipare, Lorigail; O’Geen, Henriette; Lister, Ryan; Pelizzola, Mattia; Xi, Yuanxin; Epstein, Charles B.; Bernstein, Bradley E.; Hawkins, R. David; Ren, Bing; Chung, Wen-Yu; Gu, Hongcang; Bock, Christoph; Gnirke, Andreas; Zhang, Michael Q.; Haussler, David; Ecker, Joseph; Li, Wei; Farnham, Peggy J.; Waterland, Robert A.; Meissner, Alexander; Marra, Marco A.; Hirst, Martin; Milosavljevic, Aleksandar; Costello, Joseph F.
2010-01-01
Sequencing-based DNA methylation profiling methods are comprehensive and, as accuracy and affordability improve, will increasingly supplant microarrays for genome-scale analyses. Here, four sequencing-based methodologies were applied to biological replicates of human embryonic stem cells to compare their CpG coverage genome-wide and in transposons, resolution, cost, concordance and its relationship with CpG density and genomic context. The two bisulfite methods reached concordance of 82% for CpG methylation levels and 99% for non-CpG cytosine methylation levels. Using binary methylation calls, two enrichment methods were 99% concordant, while regions assessed by all four methods were 97% concordant. To achieve comprehensive methylome coverage while reducing cost, an approach integrating two complementary methods was examined. The integrative methylome profile along with histone methylation, RNA, and SNP profiles derived from the sequence reads allowed genome-wide assessment of allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression. PMID:20852635
Exploring neighborhoods in the metagenome universe.
Aßhauer, Kathrin P; Klingenberg, Heiner; Lingner, Thomas; Meinicke, Peter
2014-07-14
The variety of metagenomes in current databases provides a rapidly growing source of information for comparative studies. However, the quantity and quality of supplementary metadata is still lagging behind. It is therefore important to be able to identify related metagenomes by means of the available sequence data alone. We have studied efficient sequence-based methods for large-scale identification of similar metagenomes within a database retrieval context. In a broad comparison of different profiling methods we found that vector-based distance measures are well-suitable for the detection of metagenomic neighbors. Our evaluation on more than 1700 publicly available metagenomes indicates that for a query metagenome from a particular habitat on average nine out of ten nearest neighbors represent the same habitat category independent of the utilized profiling method or distance measure. While for well-defined labels a neighborhood accuracy of 100% can be achieved, in general the neighbor detection is severely affected by a natural overlap of manually annotated categories. In addition, we present results of a novel visualization method that is able to reflect the similarity of metagenomes in a 2D scatter plot. The visualization method shows a similarly high accuracy in the reduced space as compared with the high-dimensional profile space. Our study suggests that for inspection of metagenome neighborhoods the profiling methods and distance measures can be chosen to provide a convenient interpretation of results in terms of the underlying features. Furthermore, supplementary metadata of metagenome samples in the future needs to comply with readily available ontologies for fine-grained and standardized annotation. To make profile-based k-nearest-neighbor search and the 2D-visualization of the metagenome universe available to the research community, we included the proposed methods in our CoMet-Universe server for comparative metagenome analysis.
Exploring Neighborhoods in the Metagenome Universe
Aßhauer, Kathrin P.; Klingenberg, Heiner; Lingner, Thomas; Meinicke, Peter
2014-01-01
The variety of metagenomes in current databases provides a rapidly growing source of information for comparative studies. However, the quantity and quality of supplementary metadata is still lagging behind. It is therefore important to be able to identify related metagenomes by means of the available sequence data alone. We have studied efficient sequence-based methods for large-scale identification of similar metagenomes within a database retrieval context. In a broad comparison of different profiling methods we found that vector-based distance measures are well-suitable for the detection of metagenomic neighbors. Our evaluation on more than 1700 publicly available metagenomes indicates that for a query metagenome from a particular habitat on average nine out of ten nearest neighbors represent the same habitat category independent of the utilized profiling method or distance measure. While for well-defined labels a neighborhood accuracy of 100% can be achieved, in general the neighbor detection is severely affected by a natural overlap of manually annotated categories. In addition, we present results of a novel visualization method that is able to reflect the similarity of metagenomes in a 2D scatter plot. The visualization method shows a similarly high accuracy in the reduced space as compared with the high-dimensional profile space. Our study suggests that for inspection of metagenome neighborhoods the profiling methods and distance measures can be chosen to provide a convenient interpretation of results in terms of the underlying features. Furthermore, supplementary metadata of metagenome samples in the future needs to comply with readily available ontologies for fine-grained and standardized annotation. To make profile-based k-nearest-neighbor search and the 2D-visualization of the metagenome universe available to the research community, we included the proposed methods in our CoMet-Universe server for comparative metagenome analysis. PMID:25026170
Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers
Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer
2017-01-01
The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686
DOE Office of Scientific and Technical Information (OSTI.GOV)
Amy, P.S.; Haldeman, D.L.; Hall, D.H.
1992-10-01
One water and three rock samples were taken from a mined tunnel system, U12n, in Rainier Mesa at the Nevada Test Site. Endolithic microorganisms were cultured from ashfall tuff, which was crushed and made into slurries with a formulation of artificial pore water, on R2A agar plates. Microbial counts ranged from 10{sup 2} viable cells per ml. Many of the isolates were very small (<1{mu}m) when viewed in the rock matrix and remained small even when cultured. Most were gram-negative rods. Individual isolates were profiled by API-NFT strip number, antibiotic and metal resistance patterns, and colony and cellular morphologies. Threemore » identification systems, API-NFT strips, BIOLOG, and MIDI, were compared. Each system identified only a small percentage of the total isolates, and in only seven cases were the isolates identified the same way by more than one system. The same genus was identified in three of these cases, but different species were indicated. The genus Pseudomonas was the most commonly identified. The isolate profiles and the three identification systems demonstrated that water isolates were considerably different from endolithic isolates.« less
Abbott, Sunshine S.; Harrison, T. Mark; Schmitt, Axel K.; Mojzsis, Stephen J.
2012-01-01
Few terrestrial localities preserve more than a trace lithic record prior to ca. 3.8 Ga greatly limiting our understanding of the first 700 Ma of Earth history, a period inferred to have included a spike in the bolide flux to the inner solar system at ca. 3.85–3.95 Ga (the Late Heavy Bombardment, LHB). An accessible record of this era may be found in Hadean detrital zircons from the Jack Hills, Western Australia, in the form of μm-scale epitaxial overgrowths. By comparing crystallization temperatures of pre-3.8 Ga zircon overgrowths to the archive of zircon temperature spectra, it should, in principle, be possible to identify a distinctive impact signature. We have developed Ti-U-Th-Pb ion microprobe depth profiling to obtain age and temperature information within these zircon overgrowths and undertaken a feasibility study of its possible use in identifying impact events. Of eight grains profiled in this fashion, four have overgrowths of LHB-era age. Age vs. temperature profiles reveal a period between ca. 3.85–3.95 Ga (i.e., LHB era) characterized by significantly higher temperatures (approximately 840–875 °C) than do older or younger zircons or zircon domains (approximately 630–750 °C). However, temperatures approaching 900 °C can result in Pb isotopic exchange rendering interpretation of these profiles nonunique. Coupled age-temperature depth profiling shows promise in this role, and the preliminary data we report could represent the first terrestrial evidence for impact-related heating during the LHB. PMID:22869711
Hao, Piliang; Ren, Yan; Dutta, Bamaprasad; Sze, Siu Kwan
2013-04-26
ERLIC and high-pH RP (Hp-RP) have been reported to be promising alternatives to strong cation exchange (SCX) in proteome fractionation. Here we compared the performance of ERLIC, concatenated ERLIC and concatenated Hp-RP in proteome profiling. The protein identification is comparable in these three strategies, but significantly more unique peptides are identified by the two concatenation methods, resulting in a significant increase of the average protein sequence coverage. The pooling of fractions from spaced intervals results in more uniform distribution of peptides in each fraction compared with the chromatogram-based pooling of adjacent fractions. ERLIC fractionates peptides according to their pI and GRAVY values. These properties remains but becomes less remarkable in concatenated ERLIC. In contrast, the average pI and GRAVY values of the peptides are comparable in each fraction in concatenated Hp-RP. ERLIC performs the best in identifying peptides with pI>9 among the three strategies, while concatenated Hp-RP is good at identifying peptides with pI<4. These advantages are useful when either basic or acidic peptides/proteins are analytical targets. The power of ERLIC in identification of basic peptides seems to be due to their efficient separation from acidic peptides. This study facilitates the choice of proper fractionation strategies based on specific objectives. For in-depth proteomic analysis of a cell, tissue and plasma, multidimensional liquid chromatography (MDLC) is still necessary to reduce sample complexity for improving analytical dynamic range and proteome coverage. This work conducts a direct comparison of three promising first-dimensional proteome fractionation methods. They are comparable in identifying proteins, but concatenated ERLIC and concatenated Hp-RP identify significantly more unique peptides than ERLIC. ERLIC is good at analyzing basic peptides, while concatenated Hp-RP performs the best in analyzing acidic peptides with pI<4. This will facilitate the choice of the proper peptide fractionation strategy based on a specific need. A combination of different fractionation strategies can be used to increase the sequence coverage and number of protein identification due to the complementary effect between different methods. Copyright © 2013 Elsevier B.V. All rights reserved.
Killoren, Sarah E; Zeiders, Katharine H; Updegraff, Kimberly A; Umaña-Taylor, Adriana J
2016-05-01
Given the negative developmental risks associated with adolescent motherhood, it is important to examine the sociocultural context of adolescent mothers' lives to identify those most at risk for poor outcomes. Our goals were to identify profiles of Mexican-origin pregnant adolescents' cultural orientations and their attitudes toward teen pregnancy, and to investigate how these profiles were linked to adolescents' pregnancy intentions, family resources, and short-term family, educational, and parenting outcomes. With a sample of 205 Mexican-origin adolescent mothers, we identified three profiles based on cultural orientations and attitudes toward teen pregnancy: Bicultural-Moderate Attitudes, Acculturated-Moderate Attitudes, and Enculturated-Low Attitudes. The results indicated that enculturated pregnant adolescents had the least favorable attitudes toward teen pregnancy, and the lowest levels of family income, pregnancy intentions, pregnancy support, and educational expectations compared to acculturated and bicultural pregnant adolescents; acculturated adolescents (with the highest family income and high levels of pregnancy support) had the highest levels of parenting efficacy 10 months postpartum. Our findings suggest that enculturated adolescent mothers (with less positive attitudes toward teen pregnancy) may benefit from educational support programs and enculturated and bicultural adolescent mothers (with moderately positive attitudes toward teen pregnancy) may benefit from programs to increase parenting efficacy. Such targeted interventions may, in turn, reduce the likelihood of adolescent mothers experiencing negative educational and parenting outcomes.
Killoren, Sarah E.; Zeiders, Katharine H.; Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.
2016-01-01
Given the negative developmental risks associated with adolescent motherhood, it is important to examine the sociocultural context of adolescent mothers’ lives to identify those most at risk for poor outcomes. Our goals were to identify profiles of Mexican-origin pregnant adolescents’ cultural orientations and their attitudes toward teen pregnancy, and to investigate how these profiles were linked to adolescents’ pregnancy intentions, family resources, and short-term family, educational, and parenting outcomes. With a sample of 205 Mexican-origin adolescent mothers, we identified three profiles based on cultural orientations and attitudes toward teen pregnancy: Bicultural-Moderate Attitudes, Acculturated-Moderate Attitudes, and Enculturated-Low Attitudes. The results indicated that enculturated pregnant adolescents had the least favorable attitudes toward teen pregnancy, and the lowest levels of family income, pregnancy intentions, pregnancy support, and educational expectations compared to acculturated and bicultural pregnant adolescents; acculturated adolescents (with the highest family income and high levels of pregnancy support) had the highest levels of parenting efficacy 10 months postpartum. Our findings suggest that enculturated adolescent mothers (with less positive attitudes toward teen pregnancy) may benefit from educational support programs and enculturated and bicultural adolescent mothers (with moderately positive attitudes toward teen pregnancy) may benefit from programs to increase parenting efficacy. Such targeted interventions may, in turn, reduce the likelihood of adolescent mothers experiencing negative educational and parenting outcomes. PMID:26573862
Tariq, Rezwan; Wang, Chunlian; Qin, Tengfei; Xu, Feifei; Tang, Yongchao; Gao, Ying; Ji, Zhiyuan; Zhao, Kaijun
2018-03-02
Bacterial blight, caused by Xanthomonas oryzae pv. oryzae ( Xoo ), is an overwhelming disease in rice-growing regions worldwide. Our previous studies revealed that the executor R gene Xa23 confers broad-spectrum disease resistance to all naturally occurring biotypes of Xoo . In this study, comparative transcriptomic profiling of two near-isogenic lines (NILs), CBB23 (harboring Xa23 ) and JG30 (without Xa23 ), before and after infection of the Xoo strain, PXO99 A , was done by RNA sequencing, to identify genes associated with the resistance. After high throughput sequencing, 1645 differentially expressed genes (DEGs) were identified between CBB23 and JG30 at different time points. Gene Ontlogy (GO) analysis categorized the DEGs into biological process, molecular function, and cellular component. KEGG analysis categorized the DEGs into different pathways, and phenylpropanoid biosynthesis was the most prominent pathway, followed by biosynthesis of plant hormones, flavonoid biosynthesis, and glycolysis/gluconeogenesis. Further analysis led to the identification of differentially expressed transcription factors (TFs) and different kinase responsive genes in CBB23, than that in JG30. Besides TFs and kinase responsive genes, DEGs related to ethylene, jasmonic acid, and secondary metabolites were also identified in both genotypes after PXO99 A infection. The data of DEGs are a precious resource for further clarifying the network of Xa23 -mediated resistance.
Tariq, Rezwan; Wang, Chunlian; Qin, Tengfei; Xu, Feifei; Tang, Yongchao; Gao, Ying; Ji, Zhiyuan; Zhao, Kaijun
2018-01-01
Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is an overwhelming disease in rice-growing regions worldwide. Our previous studies revealed that the executor R gene Xa23 confers broad-spectrum disease resistance to all naturally occurring biotypes of Xoo. In this study, comparative transcriptomic profiling of two near-isogenic lines (NILs), CBB23 (harboring Xa23) and JG30 (without Xa23), before and after infection of the Xoo strain, PXO99A, was done by RNA sequencing, to identify genes associated with the resistance. After high throughput sequencing, 1645 differentially expressed genes (DEGs) were identified between CBB23 and JG30 at different time points. Gene Ontlogy (GO) analysis categorized the DEGs into biological process, molecular function, and cellular component. KEGG analysis categorized the DEGs into different pathways, and phenylpropanoid biosynthesis was the most prominent pathway, followed by biosynthesis of plant hormones, flavonoid biosynthesis, and glycolysis/gluconeogenesis. Further analysis led to the identification of differentially expressed transcription factors (TFs) and different kinase responsive genes in CBB23, than that in JG30. Besides TFs and kinase responsive genes, DEGs related to ethylene, jasmonic acid, and secondary metabolites were also identified in both genotypes after PXO99A infection. The data of DEGs are a precious resource for further clarifying the network of Xa23-mediated resistance. PMID:29498672
Elder Abuse in the Iberian Peninsula and Bolivia: A Multicountry Comparative Study.
Carmona-Torres, Juan Manuel; Carvalhal, Rosa; Gálvez-Rioja, Ruth Mary; Ruiz-Gandara, África; Goergen, Thomas; Rodríguez-Borrego, Mª Aurora
2017-06-01
The objective of this study is to determine the prevalence of abuse of vulnerable older persons in the family and community environment in the following regions-Spain (Andalusia-Córdoba), Portugal (Azores), and Bolivia (Santa Cruz de la Sierra)-and to identify risk factors and delineate a profile of abused older persons. For this, a descriptive cross-sectional study was conducted. The sample consisted of people in the age group 65 years plus living in the catchment areas of health centers. The following were used as instruments to collect data: the medical record of the patients of relevant health centers, Mini-Mental State Examination (MMSE), daily activities autonomy test, adaptability, partnership, growth, affection, and resolve (APGAR) familiar test, The Elder Abuse Suspicion Index (EASI) and the Social Work Evaluation Form. Multivariable logistic regression was performed to identify factors associated with abuse. Suspected abuse was identified in 6.9% of the elderly who participated in the study in Spain, 39% in Bolivia, and 24.5% in Azores. In all areas, studied psychological abuse was the most common type of abuse. In conclusion, although the prevalence of abuse to older people in the family and community environment differs in the areas studied, it is present in all countries and the data are comparable with other developing and European countries. The profile of the abused older persons appears to be similar in all countries.
ERIC Educational Resources Information Center
Paulet, J. L.
This report summarizes in tabular form the results of national studies that were conducted in Belgium, France, Germany, Italy, and the United Kingdom to identify the job skills and knowledge required of persons employed in the fields of rehabilitation and conservation of historic buildings. Presented in chapter 1 is a comparative analysis of the…
ERIC Educational Resources Information Center
Janzen, Troy M.; Saklofske, Donald H.; Das, J. P.
2013-01-01
Two Canadian First Nations samples of Grades 3 and 4 children were assessed for cognitive processing, word reading, and phonological awareness skills. Both groups were from Plains Cree rural reservations in different provinces. The two groups showed significant differences on several key cognitive variables although there were more similarities…
Accused murderers: five MMPI personality types.
Anderson, W P; Holcomb, W R
1983-09-01
A cluster analysis of the MMPIs of 110 men accused of capital and first-degree murder identified five profile types. When these types were compared on 24 sociological and behavioral variables, they differed on 16. Significant variables include family history, drug and alcohol use, events preceding the crime, and relationship between the accused and victim. Comparisons were made with several other systems of classifying murderers.
USDA-ARS?s Scientific Manuscript database
The present study was undertaken to investigate the flavonoids profile in four species of ber (Ziziphus mauritiana Lamk) fruit and to compare various techniques for the analysis of total phenolic acids. The 12 flavonoids identified were quercetin 3-O-robinobioside, quercetin 3-O-rutinoside, querceti...
Identification of metabolic profiling of cell culture of licorice compared with its native one.
Man, Shuli; Guo, Songbo; Gao, Wenyuan; Wang, Juan; Zhang, Liming; Li, Xinglin
2013-04-01
Glycyrrhiza uralensis has long been used as a flavoring and sweetening agent in food products. In the last ten years, suspensions of Glycyrhiza cells have been successfully established. However, there is no report of full metabolic profiling research on these cells. To identify their composition we used HPLC-DAD coupled with ESI(+/-)-MS (n) to compare the constituents of cultured Glycyrhiza (CG) cells with those the native cells (NG). We identified 60 compounds including flavonoids, phenols, and triterpenoids. Among these compounds, 42 occurred both in NG and CG, nine were present in NG only and nine were present in CG alone. The number of the triterpenoid aglycones without glycones in CG was smaller than that in NG. The number of flavanone, isoflavone, isoflavan, and benzenoid compounds was also smaller in CG than that in NG, whereas the number of pterocarpans was much higher. Although differences existed between CG and NG, the extract of CG was similar to that of NG. With the development of cell suspension culture-based biotransformation, cell culture of Glycyrrhiza has the potential to be more profitable than field cultivation in some areas.
Haraldsson, Stefan; Klarskov, Louise; Nilbert, Mef; Bernstein, Inge; Bonde, Jesper; Holck, Susanne
2017-01-01
Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins. We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX. Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch syndrome ( p < 0.001), whereas MUC2, MUC5AC and MUC6 were overexpressed in Lynch syndrome tumors compared with FCCTX tumors ( p = 0.001, < 0.01, and < 0.001, respectively). We observed no differences in the expression patterns of CK7 and CDX2. In summary, we identified significant differences in the immunoprofiles of colorectal cancers linked to FCCTX and Lynch syndrome with a more sporadic-like profile in the former group and a more distinct profile with frequent MUC6 positivity in the latter group.
Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis
2009-01-01
The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates. PMID:19171801
Alastruey-Izquierdo, Ana; Castelli, Maria Victoria; Cuesta, Isabel; Monzon, Araceli; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis
2009-04-01
The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates.
What Are Adolescents Showing the World About Their Health Risk Behaviors on MySpace?
Moreno, Megan A.; Parks, Malcolm; Richardson, Laura P.
2007-01-01
Context MySpace is a popular social networking Web site where users create individual Web profiles. Little data are available about what types of health risk behaviors adolescents display on MySpace profiles. There are potential risks and intervention opportunities associated with posting such information on a public Web site. Objective To examine publicly available 16- and 17-year-old MySpace Web profiles and determine the prevalence of personal risk behavior descriptions and identifiable information. Design Cross-sectional observational study using content analysis of Web profiles. Setting www.MySpace.com Patients In order to target frequently visited adolescent Web profiles, we sequentially selected 142 publicly available Web profiles of 16 and 17 year olds from the class of 2008 MySpace group. Interventions None. Main outcome measures Prevalence of displayed health risk behaviors pertaining to substance use or sexual behavior, prevalence of personally identifying information, date of last log-in to Web profile. Results Of Web profiles, 47% contained risk behavior information: Twenty-one percent described sexual activity; 25% described alcohol use; 9% described cigarette use; and 6% described drug use. 97.2% Contained personally identifying information: Seventy-four percent included an identifiable picture; 75% included subjects' first names or surnames; and 78% included subjects' hometowns. Eighty-six percent of users had visited their own profiles within 24 hours. Conclusions Most 16- and 17-year-old MySpace profiles include identifiable information, are frequently accessed by owners, and half include personal risk behavior information. Further study is needed to assess the risks associated with displaying personal information and to evaluate the use of social networking sites for health behavior interventions targeting at-risk teens. PMID:18311359
The deposition and characterization of starch in Brachypodium distachyon
Tanackovic, Vanja; Svensson, Jan T.; Jensen, Susanne L.; Buléon, Alain; Blennow, Andreas
2014-01-01
Brachypodium distachyon is a non-domesticated cereal. Nonetheless, Brachypodium was recently introduced as a model plant for temperate cereals. This study compares grain starch metabolism in Brachypodium and barley (Hordeum vulgare). In Brachypodium, we identified and annotated 28 genes involved in starch metabolism and identified important motifs including transit peptides and putative carbohydrate-binding modules (CBMs) of the families CBM20, CBM45, CBM48, and CBM53. Starch content was markedly lower in Brachypodium grains (12%) compared to barley grains (47%). Brachypodium starch granules were doughnut shaped and bimodally distributed into distinct small B-type (2.5–10 µm) and very small C-type (0.5–2.5 µm) granules. Large A-type granules, typical of cereals, were absent. Starch-bound phosphate, important for starch degradation, was 2-fold lower in Brachypodium compared with barley indicating different requirements for starch mobilization. The amylopectin branch profiles were similar and the amylose content was only slightly higher compared with barley cv. Golden Promise. The crystallinity of Brachypodium starch granules was low (10%) compared to barley (20%) as determined by wide-angle X-ray scattering (WAXS) and molecular disorder was confirmed by differential scanning calorimetry (DSC). The expression profiles in grain for most genes were distinctly different for Brachypodium compared to barley, typically showing earlier decline during the course of development, which can explain the low starch content and differences in starch molecular structure and granule characteristics. High transitory starch levels were observed in leaves of Brachypodium (2.8% after 14h of light) compared to barley (1.9% after 14h of light). The data suggest important pre-domesticated features of cereals. PMID:25056772
Predicting new drug indications from network analysis
NASA Astrophysics Data System (ADS)
Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan
This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.
Wong, Mabel T.; Wang, Weijun; Couturier, Marie; Razeq, Fakhria M.; Lombard, Vincent; Lapebie, Pascal; Edwards, Elizabeth A.; Terrapon, Nicolas; Henrissat, Bernard; Master, Emma R.
2017-01-01
To identify carbohydrate-active enzymes (CAZymes) that might be particularly relevant for wood fiber processing, we performed a comparative metagenomic analysis of digestive systems from Canadian beaver (Castor canadensis) and North American moose (Alces americanus) following 3 years of enrichment on either microcrystalline cellulose or poplar hydrolysate. In total, 9,386 genes encoding CAZymes and carbohydrate-binding modules (CBMs) were identified, with up to half predicted to originate from Firmicutes, Bacteroidetes, Chloroflexi, and Proteobacteria phyla, and up to 17% from unknown phyla. Both PCA and hierarchical cluster analysis distinguished the annotated glycoside hydrolase (GH) distributions identified herein, from those previously reported for grass-feeding mammals and herbivorous foragers. The CAZyme profile of moose rumen enrichments also differed from a recently reported moose rumen metagenome, most notably by the absence of GH13-appended dockerins. Consistent with substrate-driven convergence, CAZyme profiles from both poplar hydrolysate-fed cultures differed from cellulose-fed cultures, most notably by increased numbers of unique sequences belonging to families GH3, GH5, GH43, GH53, and CE1. Moreover, pairwise comparisons of moose rumen enrichments further revealed higher counts of GH127 and CE15 families in cultures fed with poplar hydrolysate. To expand our scope to lesser known carbohydrate-active proteins, we identified and compared multi-domain proteins comprising both a CBM and domain of unknown function (DUF) as well as proteins with unknown function within the 416 predicted polysaccharide utilization loci (PULs). Interestingly, DUF362, identified in iron–sulfur proteins, was consistently appended to CBM9; on the other hand, proteins with unknown function from PULs shared little identity unless from identical PULs. Overall, this study sheds new light on the lignocellulose degrading capabilities of microbes originating from digestive systems of mammals known for fiber-rich diets, and highlights the value of enrichment to select new CAZymes from metagenome sequences for future biochemical characterization. PMID:29326667
2012-01-01
Background MicroRNAs (miRNAs) are a class of endogenous, small, non-coding RNAs that regulate gene expression by mediating gene silencing at transcriptional and post-transcriptional levels in high plants. However, the diversity of miRNAs and their roles in floral development in Japanese apricot (Prunus mume Sieb. et Zucc) remains largely unexplored. Imperfect flowers with pistil abortion seriously decrease production yields. To understand the role of miRNAs in pistil development, pistil development-related miRNAs were identified by Solexa sequencing in Japanese apricot. Results Solexa sequencing was used to identify and quantitatively profile small RNAs from perfect and imperfect flower buds of Japanese apricot. A total of 22,561,972 and 24,952,690 reads were sequenced from two small RNA libraries constructed from perfect and imperfect flower buds, respectively. Sixty-one known miRNAs, belonging to 24 families, were identified. Comparative profiling revealed that seven known miRNAs exhibited significant differential expression between perfect and imperfect flower buds. A total of 61 potentially novel miRNAs/new members of known miRNA families were also identified by the presence of mature miRNAs and corresponding miRNA*s in the sRNA libraries. Comparative analysis showed that six potentially novel miRNAs were differentially expressed between perfect and imperfect flower buds. Target predictions of the 13 differentially expressed miRNAs resulted in 212 target genes. Gene ontology (GO) annotation revealed that high-ranking miRNA target genes are those implicated in the developmental process, the regulation of transcription and response to stress. Conclusions This study represents the first comparative identification of miRNAomes between perfect and imperfect Japanese apricot flowers. Seven known miRNAs and six potentially novel miRNAs associated with pistil development were identified, using high-throughput sequencing of small RNAs. The findings, both computationally and experimentally, provide valuable information for further functional characterisation of miRNAs associated with pistil development in plants. PMID:22863067
Belstrøm, Daniel; Jersie-Christensen, Rosa R; Lyon, David; Damgaard, Christian; Jensen, Lars J; Holmstrup, Palle; Olsen, Jesper V
2016-01-01
The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode. We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity.
Montenegro, Gloria; Díaz-Forestier, Javiera; Fredes, Carolina; Rodríguez, Sharon
2013-01-01
Quillaja saponaria Mol. (Quillajaceae) is one of the most important melliferous species in Chile, mainly as a source of monofloral honey. Honey made by A. mellifera presents biological activity against pathogens and antioxidant capacity associated with the presence of phenolic compounds deriving from the nectar, as a result of bee honey foraging. The aim of this study was to identify and quantify the phenolic compounds from the floral nectar of Q. saponaria and the honey made in apiaries in the central zone, and compare the composition of the chromatographic profiles of nectar and honey to known phenolic compounds. The results obtained by HPLC-DAD (high-performance liquid chromatography with diode-array detection) showed a similar profile of phenolic compounds, in which gallic acid, myricetin, rutin, quercetin and naringenin were identified. The phenolic compounds detected could be used as a reference for future studies for determining potential chemical markers of this honey, complementing the present identification of honeys by determining their botanical origin. The identification of bioindicators of the floral origins for honey of this species could provide added value to honey commercialization by certifying the botanical origin of their chemical features and biological attributes.
Metabolic profiling of sourdough fermented wheat and rye bread.
Koistinen, Ville M; Mattila, Outi; Katina, Kati; Poutanen, Kaisa; Aura, Anna-Marja; Hanhineva, Kati
2018-04-09
Sourdough fermentation by lactic acid bacteria is commonly used in bread baking, affecting several attributes of the final product. We analyzed whole-grain wheat and rye breads and doughs prepared with baker's yeast or a sourdough starter including Candida milleri, Lactobacillus brevis and Lactobacillus plantarum using non-targeted metabolic profiling utilizing LC-QTOF-MS. The aim was to determine the fermentation-induced changes in metabolites potentially contributing to the health-promoting properties of whole-grain wheat and rye. Overall, we identified 118 compounds with significantly increased levels in sourdough, including branched-chain amino acids (BCAAs) and their metabolites, small peptides with high proportion of BCAAs, microbial metabolites of phenolic acids and several other potentially bioactive compounds. We also identified 69 compounds with significantly decreased levels, including phenolic acid precursors, nucleosides, and nucleobases. Intensive sourdough fermentation had a higher impact on the metabolite profile of whole-grain rye compared to milder whole-grain wheat sourdough fermentation. We hypothesize that the increased amount of BCAAs and potentially bioactive small peptides may contribute to the insulin response of rye bread, and in more general, the overall protective effect against T2DM and CVD.
Ye, Bang-Ce; Zhang, Yan; Yu, Hui; Yu, Wen-Bang; Liu, Bao-Hong; Yin, Bin-Cheng; Yin, Chun-Yun; Li, Yuan-Yuan; Chu, Ju; Zhang, Si-Liang
2009-01-01
Microorganisms can restructure their transcriptional output to adapt to environmental conditions by sensing endogenous metabolite pools. In this paper, an Agilent customized microarray representing 4,106 genes was used to study temporal transcript profiles of Bacillus subtilis in response to valine, glutamate and glutamine pulses over 24 h. A total of 673, 835, and 1135 amino-acid-regulated genes were identified having significantly changed expression at one or more time points in response to valine, glutamate, and glutamine, respectively, including genes involved in cell wall, cellular import, metabolism of amino-acids and nucleotides, transcriptional regulation, flagellar motility, chemotaxis, phage proteins, sporulation, and many genes of unknown function. Different amino acid treatments were compared in terms of both the global temporal profiles and the 5-minute quick regulations, and between-experiment differential genes were identified. The highlighted genes were analyzed based on diverse sources of gene functions using a variety of computational tools, including T-profiler analysis, and hierarchical clustering. The results revealed the common and distinct modes of action of these three amino acids, and should help to elucidate the specific signaling mechanism of each amino acid as an effector. PMID:19763274
García-Sánchez, Sara; Matalí, Josep Lluís; Martín-Fernández, María; Pardo, Marta; Lleras, Maria; Castellano-Tejedor, Carmina; Haro, Josep Maria
2016-10-06
Cannabis is the illicit substance most widely used by adolescents. Certain personality traits such as impulsivity and sensation seeking, and the subjective effects experienced after substance use (e.g. euphoria or relaxation) have been identified as some of the main etiological factors of consumption. This study aims to categorize a sample of adolescent cannabis users based on their most dominant personality traits (internalizing and externalizing profile). Then, to make a comparison of both profiles considering a set of variables related to consumption, clinical severity and subjective effects experienced. From a cross-sectional design, 173 adolescents (104 men and 69 women) aged 13 to 18 asking for treatment for cannabis use disorder in an Addictive Behavior Unit (UCAD) from the hospital were recruited. For the assessment, an ad hoc protocol was employed to register consumption, the Millon Adolescent Clinical Inventory (MACI) and the Addiction Research Center Inventory (ARCI) 49-item short form were also administered. Factor analysis suggested a two-profile solution: Introverted, Inhibited, Doleful, Dramatizing (-), Egotistic (-), Self-demeaning and Borderline tendency scales composed the internalizing profile, and Submissive (-), Unruly, Forceful, Conforming (-) and Oppositional scales composed the externalizing profile. The comparative analysis showed that the internalizing profile has higher levels of clinical severity and more subjective effects reported than the externalizing profile. These results suggest the need to design specific intervention strategies for each profile.
Kim, Su Yeong; Wang, Yijie; Orozco-Lapray, Diana; Shen, Yishan; Murtuza, Mohammed
2013-01-01
“Tiger parenting,” as described by Chua (2011), has put parenting in Asian American families in the spotlight. The current study identified parenting profiles in Chinese American families and explored their effects on adolescent adjustment. In a three-wave longitudinal design spanning eight years, from early adolescence to emerging adulthood, adolescents (54% female), fathers and mothers from 444 Chinese American families reported on eight parenting dimensions (e.g., warmth and shaming) and six developmental outcomes (e.g., GPA and academic pressure). Latent profile analyses on the eight parenting dimensions demonstrated four parenting profiles: supportive, tiger, easygoing, and harsh parenting. Over time, the percentage of parents classified as tiger parents decreased among mothers but increased among fathers. Path analyses showed that the supportive parenting profile, which was the most common, was associated with the best developmental outcomes, followed by easygoing parenting, tiger parenting, and harsh parenting. Compared with the supportive parenting profile, a tiger parenting profile was associated with lower GPA and educational attainment, as well as less of a sense of family obligation; it was also associated with more academic pressure, more depressive symptoms and a greater sense of alienation. The current study suggests that, contrary to the common perception, tiger parenting is not the most typical parenting profile in Chinese American families, nor does it lead to optimal adjustment among Chinese American adolescents. PMID:23646228
Niu, Hai Tao; Zhang, Yi Bing; Jiang, Hai Ping; Cheng, Bo; Sun, Guang; Wang, Yi; E, Ya Jun; Pang, De Quan; Chang, Ji Wu
2009-01-01
This study was undertaken to identify differences in protein expression profiles between superficial bladder transitional cell carcinoma (BTCC) and normal urothelial cells. We used laser capture microdissection (LCM) to harvest purified cells, and used two-dimensional liquid chromatography (2D-LC) followed by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to separate and identify the peptide mixture. A total of 440/438 proteins commonly appeared in 4 paired specimens. Multi-step bioinformatic procedures were used for the analysis of identified proteins; 175/179 of the 293/287 proteins that were specific expressed in tumor/normal cells own gene ontology (GO) biological process annotation. Compared with the entire list of the international protein index (IPI), there are 52/46 GO terms exhibited as enriched and 6/10 exhibited as depleted, respectively. Significantly altered pathways between tumor and normal cells mainly include oxidative phosphorylation, focal adhesion, etc. Finally, descriptive statistics show that the shotgun proteomics strategy has practice directive significance for biomarker discovery by two-dimensional electrophoresis (2-DE) technology.
Image-based drug screen identifies HDAC inhibitors as novel Golgi disruptors synergizing with JQ1
Gendarme, Mathieu; Baumann, Jan; Ignashkova, Tatiana I.; Lindemann, Ralph K.; Reiling, Jan H.
2017-01-01
The Golgi apparatus is increasingly recognized as a major hub for cellular signaling and is involved in numerous pathologies, including neurodegenerative diseases and cancer. The study of Golgi stress-induced signaling pathways relies on the selectivity of the available tool compounds of which currently only a few are known. To discover novel Golgi-fragmenting agents, transcriptomic profiles of cells treated with brefeldin A, golgicide A, or monensin were generated and compared with a database of gene expression profiles from cells treated with other bioactive small molecules. In parallel, a phenotypic screen was performed for compounds that alter normal Golgi structure. Histone deacetylase (HDAC) inhibitors and DNA-damaging agents were identified as novel Golgi disruptors. Further analysis identified HDAC1/HDAC9 as well as BRD8 and DNA-PK as important regulators of Golgi breakdown mediated by HDAC inhibition. We provide evidence that combinatorial HDACi/(+)-JQ1 treatment spurs synergistic Golgi dispersal in several cancer cell lines, pinpointing a possible link between drug-induced toxicity and Golgi morphology alterations. PMID:29074567
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hong, Tianzhen; Buhl, Fred; Haves, Philip
2008-09-20
EnergyPlus is a new generation building performance simulation program offering many new modeling capabilities and more accurate performance calculations integrating building components in sub-hourly time steps. However, EnergyPlus runs much slower than the current generation simulation programs. This has become a major barrier to its widespread adoption by the industry. This paper analyzed EnergyPlus run time from comprehensive perspectives to identify key issues and challenges of speeding up EnergyPlus: studying the historical trends of EnergyPlus run time based on the advancement of computers and code improvements to EnergyPlus, comparing EnergyPlus with DOE-2 to understand and quantify the run time differences,more » identifying key simulation settings and model features that have significant impacts on run time, and performing code profiling to identify which EnergyPlus subroutines consume the most amount of run time. This paper provides recommendations to improve EnergyPlus run time from the modeler?s perspective and adequate computing platforms. Suggestions of software code and architecture changes to improve EnergyPlus run time based on the code profiling results are also discussed.« less
Junza, A; Saurina, J; Barrón, D; Minguillón, C
2016-08-19
High resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was used in the search and identification of metabolites in raw milk from cows medicated with enrofloxacin. Data consisting of m/z features were taken throughout the entire chromatogram of milk samples from medicated animals and were compared with blank samples. Twenty six different compounds were identified. Some of them were attributed to structures related to enrofloxacin while others were dipeptides or tripeptides. Additionally, enrofloxacin was administered in a controlled treatment for three days. Milk was collected daily from the first day of treatment and until four days after in the search for the identified compounds. The obtained data were chemometrically treated by Principal Component Analysis. Samples were classified by this method into three different groups corresponding to days 1-2, day 3 and days 4-7 considering the different concentration profile evolution of metabolites during the days studied. Tentative metabolic pathways were designed to rationalize the presence of the newly identified compounds. Copyright © 2016 Elsevier B.V. All rights reserved.
Comparative Transcriptome Analysis of Cultivated and Wild Watermelon during Fruit Development
Guo, Shaogui; Sun, Honghe; Zhang, Haiying; Liu, Jingan; Ren, Yi; Gong, Guoyi; Jiao, Chen; Zheng, Yi; Yang, Wencai; Fei, Zhangjun; Xu, Yong
2015-01-01
Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an important vegetable crop world-wide. Watermelon fruit quality is a complex trait determined by various factors such as sugar content, flesh color and flesh texture. Fruit quality and developmental process of cultivated and wild watermelon are highly different. To systematically understand the molecular basis of these differences, we compared transcriptome profiles of fruit tissues of cultivated watermelon 97103 and wild watermelon PI296341-FR. We identified 2,452, 826 and 322 differentially expressed genes in cultivated flesh, cultivated mesocarp and wild flesh, respectively, during fruit development. Gene ontology enrichment analysis of these genes indicated that biological processes and metabolic pathways related to fruit quality such as sweetness and flavor were significantly changed only in the flesh of 97103 during fruit development, while those related to abiotic stress response were changed mainly in the flesh of PI296341-FR. Our comparative transcriptome profiling analysis identified critical genes potentially involved in controlling fruit quality traits including α-galactosidase, invertase, UDP-galactose/glucose pyrophosphorylase and sugar transporter genes involved in the determination of fruit sugar content, phytoene synthase, β-carotene hydroxylase, 9-cis-epoxycarotenoid dioxygenase and carotenoid cleavage dioxygenase genes involved in carotenoid metabolism, and 4-coumarate:coenzyme A ligase, cellulose synthase, pectinesterase, pectinesterase inhibitor, polygalacturonase inhibitor and α-mannosidase genes involved in the regulation of flesh texture. In addition, we found that genes in the ethylene biosynthesis and signaling pathway including ACC oxidase, ethylene receptor and ethylene responsive factor showed highly ripening-associated expression patterns, indicating a possible role of ethylene in fruit development and ripening of watermelon, a non-climacteric fruit. Our analysis provides novel insights into watermelon fruit quality and ripening biology. Furthermore, the comparative expression profile data we developed provides a valuable resource to accelerate functional studies in watermelon and facilitate watermelon crop improvement. PMID:26079257
Relationships between Self-Concept and Resilience Profiles in Young People with Disabilities
ERIC Educational Resources Information Center
Suriá Martínez, Raquel
2016-01-01
Introduction: The present study aims to identify different profiles in self-concept and resilience. In addition, statistically significant differences in self-concept domains among the profiles previously identified are analyzed. Method: The AF5 Self-Concept Questionnaire ("Cuestionario de Autoconcepto AF5") and the Resilience Scale were…
ERIC Educational Resources Information Center
Borg, Elin
2015-01-01
Latent profile analysis was used to identify different categories of students having different "profiles" using self-reported classroom behaviour. Four categories of students with unique classroom behaviour profiles were identified among secondary school students in Oslo, Norway (n = 1570). Analyses examined how classroom behaviour…
Profiles of Reactivity in Cocaine-Exposed Children
ERIC Educational Resources Information Center
Schuetze, Pamela; Molnar, Danielle S.; Eiden, Rina D.
2012-01-01
This study explored the possibility that specific, theoretically consistent profiles of reactivity could be identified in a sample of cocaine-exposed infants and whether these profiles were associated with a range of infant and/or maternal characteristics. Cluster analysis was used to identify distinct groups of infants based on physiological,…
Egieyeh, Samuel Ayodele; Syce, James; Malan, Sarel F; Christoffels, Alan
2016-01-29
A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). Natural products with in vitro antiplasmodial activities (NAA) were compiled from various sources. These natural products were sub-divided into four groups based on inhibitory concentration (IC50). Key molecular descriptors and physicochemical properties were computed for these compounds and analysis of variance used to assess statistical significance amongst the sets of compounds. Molecular similarity analysis, estimation of drug-likeness, in silico pharmacokinetic profiling, and exploration of structure-activity landscape were also carried out on these sets of compounds. A total of 1040 natural products were selected and a total of 13 molecular descriptors were analysed. Significant differences were observed among the sub-groups of NAA and CRAD for at least 11 of the molecular descriptors, including number of hydrogen bond donors and acceptors, molecular weight, polar and hydrophobic surface areas, chiral centres, oxygen and nitrogen atoms, and shape index. The remaining molecular descriptors, including clogP, number of rotatable bonds and number of aromatic rings, did not show any significant difference when comparing the two compound sets. Molecular similarity and chemical space analysis identified natural products that were structurally diverse from CRAD. Prediction of the pharmacokinetic properties and drug-likeness of these natural products identified over 50% with desirable drug-like properties. Nearly 70% of all natural products were identified as potentially promiscuous compounds. Structure-activity landscape analysis highlighted compound pairs that form 'activity cliffs'. In all, prioritization strategies for the NAA were proposed. Chemo-informatic profiling of NAA and CRAD have produced a wealth of information that may guide decisions and facilitate anti-malarial drug development from natural products. Articulation of the information provided within an interactive data-mining environment led to a prioritized list of NAA.
Fang, H; Tong, W; Perkins, R; Shi, L; Hong, H; Cao, X; Xie, Q; Yim, SH; Ward, JM; Pitot, HC; Dragan, YP
2005-01-01
Background The completion of the sequencing of human, mouse and rat genomes and knowledge of cross-species gene homologies enables studies of differential gene expression in animal models. These types of studies have the potential to greatly enhance our understanding of diseases such as liver cancer in humans. Genes co-expressed across multiple species are most likely to have conserved functions. We have used various bioinformatics approaches to examine microarray expression profiles from liver neoplasms that arise in albumin-SV40 transgenic rats to elucidate genes, chromosome aberrations and pathways that might be associated with human liver cancer. Results In this study, we first identified 2223 differentially expressed genes by comparing gene expression profiles for two control, two adenoma and two carcinoma samples using an F-test. These genes were subsequently mapped to the rat chromosomes using a novel visualization tool, the Chromosome Plot. Using the same plot, we further mapped the significant genes to orthologous chromosomal locations in human and mouse. Many genes expressed in rat 1q that are amplified in rat liver cancer map to the human chromosomes 10, 11 and 19 and to the mouse chromosomes 7, 17 and 19, which have been implicated in studies of human and mouse liver cancer. Using Comparative Genomics Microarray Analysis (CGMA), we identified regions of potential aberrations in human. Lastly, a pathway analysis was conducted to predict altered human pathways based on statistical analysis and extrapolation from the rat data. All of the identified pathways have been known to be important in the etiology of human liver cancer, including cell cycle control, cell growth and differentiation, apoptosis, transcriptional regulation, and protein metabolism. Conclusion The study demonstrates that the hepatic gene expression profiles from the albumin-SV40 transgenic rat model revealed genes, pathways and chromosome alterations consistent with experimental and clinical research in human liver cancer. The bioinformatics tools presented in this paper are essential for cross species extrapolation and mapping of microarray data, its analysis and interpretation. PMID:16026603
Global Properties of M31's Stellar Halo from the SPLASH Survey. I. Surface Brightness Profile
NASA Astrophysics Data System (ADS)
Gilbert, Karoline M.; Guhathakurta, Puragra; Beaton, Rachael L.; Bullock, James; Geha, Marla C.; Kalirai, Jason S.; Kirby, Evan N.; Majewski, Steven R.; Ostheimer, James C.; Patterson, Richard J.; Tollerud, Erik J.; Tanaka, Mikito; Chiba, Masashi
2012-11-01
We present the surface brightness profile of M31's stellar halo out to a projected radius of 175 kpc. The surface brightness estimates are based on confirmed samples of M31 red giant branch stars derived from Keck/DEIMOS spectroscopic observations. A set of empirical spectroscopic and photometric M31 membership diagnostics is used to identify and reject foreground and background contaminants. This enables us to trace the stellar halo of M31 to larger projected distances and fainter surface brightnesses than previous photometric studies. The surface brightness profile of M31's halo follows a power law with index -2.2 ± 0.2 and extends to a projected distance of at least ~175 kpc (~2/3 of M31's virial radius), with no evidence of a downward break at large radii. The best-fit elliptical isophotes have b/a = 0.94 with the major axis of the halo aligned along the minor axis of M31's disk, consistent with a prolate halo, although the data are also consistent with M31's halo having spherical symmetry. The fact that tidal debris features are kinematically cold is used to identify substructure in the spectroscopic fields out to projected radii of 90 kpc and investigate the effect of this substructure on the surface brightness profile. The scatter in the surface brightness profile is reduced when kinematically identified tidal debris features in M31 are statistically subtracted; the remaining profile indicates that a comparatively diffuse stellar component to M31's stellar halo exists to large distances. Beyond 90 kpc, kinematically cold tidal debris features cannot be identified due to small number statistics; nevertheless, the significant field-to-field variation in surface brightness beyond 90 kpc suggests that the outermost region of M31's halo is also comprised to a significant degree of stars stripped from accreted objects. The data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.
Wang, Dan; Sun, Yong; Chang, Lili; Tong, Zheng; Xie, Quanliang; Jin, Xiang; Zhu, Liping; He, Peng; Li, Hongbin; Wang, Xuchu
2018-06-30
Rubber particle (RP) is a specific organelle for natural rubber biosynthesis (NRB) and storage in rubber tree Hevea brasiliensis. NRB is processed by RP membrane-localized proteins, which were traditionally purified by repeated washing. However, we noticed many proteins in the discarded washing solutions (WS) from RP. Here, we compared the proteome profiles of WS, C-serum (CS) and RP by 2-DE, and identified 233 abundant proteins from WS by mass spectrometry. Many spots on 2-DE gels were identified as different protein species. We further performed shotgun analysis of CS, WS and RP and identified 1837, 1799 and 1020 unique proteins, respectively. Together with 2-DE, we finally identified 1825 proteins from WS, 246 were WS-specific. These WS-specific proteins were annotated in Gene Ontology, indicating most abundant pathways are organic substance metabolic process, protein degradation, primary metabolic process, and energy metabolism. Protein-protein interaction analysis revealed these WS-specific proteins are mainly involved in ribosomal metabolism, proteasome system, vacuolar protein sorting and endocytosis. Label free and Western blotting revealed many WS-specific proteins and protein complexes are crucial for NRB initiation. These findings not only deepen our understanding of WS proteome, but also provide new evidences on the roles of RP membrane proteins in NRB. Natural rubber is stored in rubber particle from the rubber tree. Rubber particles were traditionally purified by repeated washing, but many proteins were identified from the washing solutions (WS). We obtained the first visualization proteome profiles with 1825 proteins from WS, including 246 WS-specific ones. These WS proteins contain almost all enzymes for polyisoprene initiation and may play important roles in rubber biosynthesis. Copyright © 2018 Elsevier B.V. All rights reserved.
Faria, M M P; Conly, J M; Surette, M G
2015-10-16
The application of molecular based diagnostics in sepsis has had limited success to date. Molecular community profiling methods have indicated that polymicrobial infections are more common than suggested by standard clinical culture. A molecular profiling approach was developed to investigate the propensity for polymicrobial infections in patients predicted to have bacterial sepsis. Disruption of blood cells with saponin and hypotonic shock enabled the recovery of microbial cells with no significant changes in microbial growth when compared to CFU/ml values immediately prior to the addition of saponin. DNA extraction included a cell-wall digestion step with both lysozyme and mutanolysin, which increased the recovery of terminal restriction fragments by 2.4 fold from diverse organisms. Efficiencies of recovery and limits of detection using Illumina sequencing of the 16S rRNA V3 region were determined for both viable cells and DNA using mock bacterial communities inoculated into whole blood. Bacteria from pre-defined communities could be recovered following lysis and removal of host cells with >97% recovery of total DNA present. Applying the molecular profiling methodology to three septic patients in the intensive care unit revealed microbial DNA from blood had consistent alignment with cultured organisms from the primary infection site providing evidence for a bloodstream infection in the absence of a clinical lab positive blood culture result in two of the three cases. In addition, the molecular profiling indicated greater diversity was present in the primary infection sample when compared to clinical diagnostic culture. A method for analyzing bacterial DNA from whole blood was developed in order to characterize the bacterial DNA profile of sepsis infections. Preliminary results indicated that sepsis infections were polymicrobial in nature with the bacterial DNA recovered suggesting a more complex etiology when compared to blood culture data.
Latent Profiles of Perceived Time Adequacy for Paid Work, Parenting, and Partner Roles
Lee, Soomi; Almeida, David M.; Davis, Kelly D.; King, Rosalind B.; Hammer, Leslie B.; Kelly, Erin L.
2015-01-01
This study examined feelings of having enough time (i.e., perceived time adequacy) in a sample of employed parents (N=880) in information technology and extended-care industries. Adapting a person-centered latent profile approach, we identified three profiles of perceived time adequacy for paid work, parenting, and partner roles: Family Time Protected, Family Time Sacrificed, and Time Balanced. Drawing upon the Conservation of Resources theory (Hobfòll, 1989), we examined the associations of stressors and resources with the time adequacy profiles. Parents in the Family Time Sacrificed profile were more likely to be younger, women, have younger children, work in the extended-care industry, and have nonstandard work schedules compared to those in the Family Time Protected profile. Results from multinomial logistic regression analyses revealed that, with the Time Balanced profile as the reference group, having fewer stressors and more resources in the family context (less parent-child conflict and more partner support), work context (longer company tenure, higher schedule control and job satisfaction), and work-family interface (lower work-to-family conflict) was linked to a higher probability of membership in the Family Time Protected profile. By contrast, having more stressors and fewer resources, in the forms of less partner support and higher work-to-family conflict, predicted a higher likelihood of being in the Family Time Sacrificed profile. Our findings suggest that low work-to-family conflict is the most critical predictor of membership in the Family Time Protected profile, whereas lack of partner support is the most important factor to be included in the Family Time Sacrificed profile. PMID:26075739
Zhang, Ning; Chen, Haitao; Sun, Baoguo; Mao, Xueying; Zhang, Yuyu; Zhou, Ying
2016-01-01
To compare the volatile compounds of Chinese black truffle and white truffle from Yunnan province, this study presents the application of a direct solvent extraction/solvent-assisted flavor evaporation (DSE-SAFE) coupled with a comprehensive two-dimensional gas chromatography (GC × GC) high resolution time-of-flight mass spectrometry (HR-TOF/MS) and an electronic nose. Both of the analytical methods could distinguish the aroma profile of the two samples. In terms of the overall profile of truffle samples in this research, more kinds of acids were detected via the method of DSE-SAFE. Besides, compounds identified in black truffle (BT), but not in white truffle (WT), or vice versa, and those detected in both samples at different levels were considered to play an important role in differentiating the two samples. According to the analysis of electronic nose, the two samples could be separated, as well. PMID:27058524
NASA Astrophysics Data System (ADS)
Megan Gillies, D.; Knudsen, D.; Donovan, E.; Jackel, B.; Gillies, R.; Spanswick, E.
2017-08-01
We present a comprehensive survey of 630 nm (red-line) emission discrete auroral arcs using the newly deployed Redline Emission Geospace Observatory. In this study we discuss the need for observations of 630 nm aurora and issues with the large-altitude range of the red-line aurora. We compare field-aligned currents (FACs) measured by the Swarm constellation of satellites with the location of 10 red-line (630 nm) auroral arcs observed by all-sky imagers (ASIs) and find that a characteristic emission height of 200 km applied to the ASI maps gives optimal agreement between the two observations. We also compare the new FAC method against the traditional triangulation method using pairs of all-sky imagers (ASIs), and against electron density profiles obtained from the Resolute Bay Incoherent Scatter Radar-Canadian radar, both of which are consistent with a characteristic emission height of 200 km.
Gene expression profiling in the hippocampus of learned helpless and nonhelpless rats.
Kohen, R; Kirov, S; Navaja, G P; Happe, H Kevin; Hamblin, M W; Snoddy, J R; Neumaier, J F; Petty, F
2005-01-01
In the learned helplessness (LH) animal model of depression, failure to attempt escape from avoidable environmental stress, LH, indicates behavioral despair, whereas nonhelpless (NH) behavior reflects behavioral resilience to the effects of environmental stress. Comparing hippocampal gene expression with large-scale oligonucleotide microarrays, we found that stress-resilient (NH) rats, although behaviorally indistinguishable from controls, showed a distinct gene expression profile compared to LH, sham stressed, and naïve control animals. Genes that were confirmed as differentially expressed in the NH group by quantitative PCR strongly correlated in their levels of expression across all four animal groups. Differential expression could not be confirmed at the protein level. We identified several shared degenerate sequence motifs in the 3' untranslated region (3'UTR) of differentially expressed genes that could be a factor in this tight correlation of expression levels among differentially expressed genes.
Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis.
Laffaire, Julien; Everhard, Sibille; Idbaih, Ahmed; Crinière, Emmanuelle; Marie, Yannick; de Reyniès, Aurelien; Schiappa, Renaud; Mokhtari, Karima; Hoang-Xuan, Khê; Sanson, Marc; Delattre, Jean-Yves; Thillet, Joëlle; Ducray, François
2011-01-01
Extensive genomic and gene expression studies have been performed in gliomas, but the epigenetic alterations that characterize different subtypes of gliomas remain largely unknown. Here, we analyzed the methylation patterns of 807 genes (1536 CpGs) in a series of 33 low-grade gliomas (LGGs), 36 glioblastomas (GBMs), 8 paired initial and recurrent gliomas, and 9 controls. This analysis was performed with Illumina's Golden Gate Bead methylation arrays and was correlated with clinical, histological, genomic, gene expression, and genotyping data, including IDH1 mutations. Unsupervised hierarchical clustering resulted in 2 groups of gliomas: a group corresponding to de novo GBMs and a group consisting of LGGs, recurrent anaplastic gliomas, and secondary GBMs. When compared with de novo GBMs and controls, this latter group was characterized by a very high frequency of IDH1 mutations and by a hypermethylated profile similar to the recently described glioma CpG island methylator phenotype. MGMT methylation was more frequent in this group. Among the LGG cluster, 1p19q codeleted LGG displayed a distinct methylation profile. A study of paired initial and recurrent gliomas demonstrated that methylation profiles were remarkably stable across glioma evolution, even during anaplastic transformation, suggesting that epigenetic alterations occur early during gliomagenesis. Using the Cancer Genome Atlas data set, we demonstrated that GBM samples that had an LGG-like hypermethylated profile had a high rate of IDH1 mutations and a better outcome. Finally, we identified several hypermethylated and downregulated genes that may be associated with LGG and GBM oncogenesis, LGG oncogenesis, 1p19q codeleted LGG oncogenesis, and GBM oncogenesis.
Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis
Laffaire, Julien; Everhard, Sibille; Idbaih, Ahmed; Crinière, Emmanuelle; Marie, Yannick; de Reyniès, Aurelien; Schiappa, Renaud; Mokhtari, Karima; Hoang-Xuan, Khê; Sanson, Marc; Delattre, Jean-Yves; Thillet, Joëlle; Ducray, François
2011-01-01
Extensive genomic and gene expression studies have been performed in gliomas, but the epigenetic alterations that characterize different subtypes of gliomas remain largely unknown. Here, we analyzed the methylation patterns of 807 genes (1536 CpGs) in a series of 33 low-grade gliomas (LGGs), 36 glioblastomas (GBMs), 8 paired initial and recurrent gliomas, and 9 controls. This analysis was performed with Illumina's Golden Gate Bead methylation arrays and was correlated with clinical, histological, genomic, gene expression, and genotyping data, including IDH1 mutations. Unsupervised hierarchical clustering resulted in 2 groups of gliomas: a group corresponding to de novo GBMs and a group consisting of LGGs, recurrent anaplastic gliomas, and secondary GBMs. When compared with de novo GBMs and controls, this latter group was characterized by a very high frequency of IDH1 mutations and by a hypermethylated profile similar to the recently described glioma CpG island methylator phenotype. MGMT methylation was more frequent in this group. Among the LGG cluster, 1p19q codeleted LGG displayed a distinct methylation profile. A study of paired initial and recurrent gliomas demonstrated that methylation profiles were remarkably stable across glioma evolution, even during anaplastic transformation, suggesting that epigenetic alterations occur early during gliomagenesis. Using the Cancer Genome Atlas data set, we demonstrated that GBM samples that had an LGG-like hypermethylated profile had a high rate of IDH1 mutations and a better outcome. Finally, we identified several hypermethylated and downregulated genes that may be associated with LGG and GBM oncogenesis, LGG oncogenesis, 1p19q codeleted LGG oncogenesis, and GBM oncogenesis. PMID:20926426
Quantitative microbiome profiling links gut community variation to microbial load.
Vandeputte, Doris; Kathagen, Gunter; D'hoe, Kevin; Vieira-Silva, Sara; Valles-Colomer, Mireia; Sabino, João; Wang, Jun; Tito, Raul Y; De Commer, Lindsey; Darzi, Youssef; Vermeire, Séverine; Falony, Gwen; Raes, Jeroen
2017-11-23
Current sequencing-based analyses of faecal microbiota quantify microbial taxa and metabolic pathways as fractions of the sample sequence library generated by each analysis. Although these relative approaches permit detection of disease-associated microbiome variation, they are limited in their ability to reveal the interplay between microbiota and host health. Comparative analyses of relative microbiome data cannot provide information about the extent or directionality of changes in taxa abundance or metabolic potential. If microbial load varies substantially between samples, relative profiling will hamper attempts to link microbiome features to quantitative data such as physiological parameters or metabolite concentrations. Saliently, relative approaches ignore the possibility that altered overall microbiota abundance itself could be a key identifier of a disease-associated ecosystem configuration. To enable genuine characterization of host-microbiota interactions, microbiome research must exchange ratios for counts. Here we build a workflow for the quantitative microbiome profiling of faecal material, through parallelization of amplicon sequencing and flow cytometric enumeration of microbial cells. We observe up to tenfold differences in the microbial loads of healthy individuals and relate this variation to enterotype differentiation. We show how microbial abundances underpin both microbiota variation between individuals and covariation with host phenotype. Quantitative profiling bypasses compositionality effects in the reconstruction of gut microbiota interaction networks and reveals that the taxonomic trade-off between Bacteroides and Prevotella is an artefact of relative microbiome analyses. Finally, we identify microbial load as a key driver of observed microbiota alterations in a cohort of patients with Crohn's disease, here associated with a low-cell-count Bacteroides enterotype (as defined through relative profiling).
2010-01-01
Background Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. PMID:21062462
A pilot study of circulating microRNAs as potential biomarkers of Fabry disease.
Cammarata, Giuseppe; Scalia, Simone; Colomba, Paolo; Zizzo, Carmela; Pisani, Antonio; Riccio, Eleonora; Montalbano, Michaela; Alessandro, Riccardo; Giordano, Antonello; Duro, Giovanni
2018-06-08
Patients suffering from Fabry disease (FD), a lysosomal storage disorder, show a broad range of symptoms and the diagnosis followed by the therapeutic decision remains a great challenge. The biomarkers available today have not proven to be useful for predicting the evolution of the disease and for assessing response to therapy in many patients. Here, we used high-throughput microRNA profiling methodology to identify a specific circulating microRNA profile in FD patients. We discovered a pattern of 10 microRNAs able to identify FD patients when compared to healthy controls. Notably, two of these: the miR199a-5p and the miR-126-3p are able to discriminate FDs from the control subjects with left ventricular hypertrophy, a frequent but non-specific FD symptom. These same microRNAs are also sensitive to enzyme replacement therapy showing variation in the subjects under treatment. Furthermore, two other microRNAs of the profile, the miR-423-5p and the miR-451a, seem useful to highlight cardiac involvement in FD patients. A literature and database search revealed that miR-199a-5p, miR-126-3p, miR-423-5p and miR-451a are known to be linked to pathological states that occur during the FD development. In particular, miR-199a-5p, and miR-126-3p are involved in endothelial dysfunction and miR-423-5p and miR-451a in myocardial remodeling. In conclusion, in this study we identified a common plasma microRNA profile in FD patients, useful not only for the correct classification of Fabry patients regardless of sex and age, but also to evaluate the response to therapy. Furthermore, our observations suggest that some microRNAs of this profile demonstrate prognostic qualities.
Brody, Thomas; Yavatkar, Amarendra S; Park, Dong Sun; Kuzin, Alexander; Ross, Jermaine; Odenwald, Ward F
2017-06-01
Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest. We have adapted EvoPrinter alignment algorithms for the rapid comparative analysis of Flavivirus or Filovirus sequences including Zika and Ebola strains. The user can input a full genome or partial viral sequence and then view either individual comparisons or generate color-coded readouts that superimpose hundreds of one-on-one alignments to identify unique or shared identity SNPs that reveal ancestral relationships between strains. The user can also opt to select a database genome in order to access a library of pre-aligned genomes of either 1,094 Flaviviruses or 460 Filoviruses for rapid comparative analysis with all database entries or a select subset. Using EvoPrinter search and alignment programs, we show the following: 1) superimposing alignment data from many related strains identifies lineage identity SNPs, which enable the assessment of sublineage complexity within viral outbreaks; 2) whole-genome SNP profile screens uncover novel Dengue2 and Zika recombinant strains and their parental lineages; 3) differential SNP profiling identifies host cell A-to-I hyper-editing within Ebola and Marburg viruses, and 4) hundreds of superimposed one-on-one Ebola genome alignments highlight ultra-conserved regulatory sequences, invariant amino acid codons and evolutionarily variable protein-encoding domains within a single genome. EvoPrinter allows for the assessment of lineage complexity within Flavivirus or Filovirus outbreaks, identification of recombinant strains, highlights sequences that have undergone host cell A-to-I editing, and identifies unique input and database SNPs within highly conserved sequences. EvoPrinter's ability to superimpose alignment data from hundreds of strains onto a single genome has allowed us to identify unique Zika virus sublineages that are currently spreading in South, Central and North America, the Caribbean, and in China. This new set of integrated alignment programs should serve as a useful addition to existing tools for the comparative analysis of these viruses.
Lin, Albert Y.; Chua, Mei-Sze; Choi, Yoon-La; Yeh, William; Kim, Young H.; Azzi, Raymond; Adams, Gregg A.; Sainani, Kristin; van de Rijn, Matt; So, Samuel K.; Pollack, Jonathan R.
2011-01-01
Purpose We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). Patients and Methods We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC. Results Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1. Conclusion Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. PMID:21383983
Gill, Upinder S; Uppalapati, Srinivasa R; Nakashima, Jin; Mysore, Kirankumar S
2015-05-08
Switchgrass rust, caused by Puccinia emaculata, is an important disease of switchgrass, a potential biofuel crop in the United States. In severe cases, switchgrass rust has the potential to significantly affect biomass yield. In an effort to identify novel sources of resistance against switchgrass rust, we explored nonhost resistance against P. emaculata by characterizing its interactions with six monocot nonhost plant species. We also studied the genetic variations for resistance among Brachypodium inbred accessions and the involvement of various defense pathways in nonhost resistance of Brachypodium. We characterized P. emaculata interactions with six monocot nonhost species and identified Brachypodium distachyon (Bd21) as a suitable nonhost model to study switchgrass rust. Interestingly, screening of Brachypodium accessions identified natural variations in resistance to switchgrass rust. Brachypodium inbred accessions Bd3-1 and Bd30-1 were identified as most and least resistant to switchgrass rust, respectively, when compared to tested accessions. Transcript profiling of defense-related genes indicated that the genes which were induced in Bd21after P. emaculata inoculation also had higher basal transcript abundance in Bd3-1 when compared to Bd30-1 and Bd21 indicating their potential involvement in nonhost resistance against switchgrass rust. In the present study, we identified Brachypodium as a suitable nonhost model to study switchgrass rust which exhibit type I nonhost resistance. Variations in resistance response were also observed among tested Brachypodium accessions. Brachypodium nonhost resistance against P. emaculata may involve various defense pathways as indicated by transcript profiling of defense related genes. Overall, this study provides a new avenue to utilize novel sources of nonhost resistance in Brachypodium against switchgrass rust.
Staff nurse commitment, work relationships, and turnover intentions: a latent profile analysis.
Gellatly, Ian R; Cowden, Tracy L; Cummings, Greta G
2014-01-01
The three-component model of organization commitment has typically been studied using a variable-centered rather than a person-centered approach, preventing a more complete understanding of how these forms of commitment are felt and expressed as a whole. Latent profile analysis was used to identify qualitatively distinct categories or profiles of staff nurses' commitment. Then, associations of the profiles with perceived work unit relations and turnover intentions were examined. Three hundred thirty-six registered nurses provided data on affective, normative, and continuance commitment, perceived work unit relations, and turnover intentions. Latent profile analysis of the nurses' commitment scores revealed six distinct profile groups. Work unit relations and turnover intentions were compared in the six profile-defined groups. Staff nurses with profiles characterized by high affective commitment and/or high normative commitment in relation to other components experienced stronger work unit relations and reported lower turnover intentions. Profiles characterized by high continuance commitment relative to other components or by low overall commitment experienced poorer work unit relations, and the turnover risk was higher. High continuance commitment in combination with high affective and normative commitment was experienced differently than high continuance commitment in combination with low affective and normative commitment. Healthcare organizations often foster commitment by using continuance commitment-enhancing strategies (e.g., offer high salaries and attractive benefits) that may inadvertently introduce behavioral risk. This work suggests the importance of changing the context in which continuance commitment occurs by strengthening the other two components.
Prince, Mark A.; Connors, Gerard J.; Maisto, Stephen A.; Dearing, Ronda L.
2016-01-01
While past research has demonstrated a positive relationship between the therapeutic alliance (TA) and improved drinking outcomes, specific aspects of the alliance have received less attention. In this study, we examined the association between alliance characteristics during treatment and 4-month follow-up drinking reports. 65 treatment-seeking alcohol dependent clients who participated in 12 weeks of individual outpatient treatment provided weekly TA ratings during treatment and reported on pre-treatment, during treatment, and post-treatment alcohol use. Latent profile analysis was conducted to discern distinct profiles of client and therapist ratings of therapeutic alliance with similar alliance characteristics. TA profiles were based on clients’ and therapists’ mean alliance rating, minimum alliance rating, maximum alliance rating, the range of alliance ratings, and the difference in session number between maximum and minimum alliance ratings. 1- through 4- class models were fit to the data. Model fit was judged by comparative fit indices, substantive interpretability, and parsimony. Wald tests of mean equality determined whether classes differed on follow-up percentage of days abstinent (PDA) at 4 months posttreatment. 3-profile solutions provided the best fit for both client and therapist ratings of the therapeutic alliance. Client alliance rating profiles predicted drinking in the follow-up period, but therapist rating profiles did not. These results suggest that distinct profiles of the therapeutic alliance can be identified and that client alliance rating profiles are associated with frequency of alcohol use following outpatient treatment. PMID:26999350
Analysis of blood-based gene expression in idiopathic Parkinson disease.
Shamir, Ron; Klein, Christine; Amar, David; Vollstedt, Eva-Juliane; Bonin, Michael; Usenovic, Marija; Wong, Yvette C; Maver, Ales; Poths, Sven; Safer, Hershel; Corvol, Jean-Christophe; Lesage, Suzanne; Lavi, Ofer; Deuschl, Günther; Kuhlenbaeumer, Gregor; Pawlack, Heike; Ulitsky, Igor; Kasten, Meike; Riess, Olaf; Brice, Alexis; Peterlin, Borut; Krainc, Dimitri
2017-10-17
To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks. A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1 , ATP5A1 , and VDAC3 . We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers. © 2017 American Academy of Neurology.
Pillai, Bhinu V. S.; Swarup, Sanjay
2002-01-01
Flavonoids are 15-carbon plant secondary metabolites exuded in the rhizosphere that hosts several flavonoid-degrading bacteria. We studied flavonoid catabolism in a plant growth-promoting rhizobacterial strain of Pseudomonas by using a combination of biochemical and genetic approaches. Transposants carrying mini-Tn5gfp insertions were screened for flavonoid auxotrophy, and these mutant strains were found to be unable to grow in the flavonols naringenin and quercetin, while their growth in glycerol was comparable to that of the parental strain. In order to understand flavonoid catabolism, culture supernatants, whole-cell fractions, cell lysate, and cell debris of the wild-type and mutant strains were analyzed. Intermediates that accumulated intracellularly and those secreted in the medium were identified by a combination of reversed-phase high-pressure liquid chromatography and electrospray ionization-mass spectrometry. Structures of four key intermediates were confirmed by one-dimensional nuclear magnetic resonance spectroscopy. Comparative metabolic profiling of the compounds in the wild-type and mutant strains allowed us to understand the degradation events and to identify six metabolic intermediates. The first step in the pathway involves 3,3′-didehydroxylation, followed by hydrolysis and cleavage of the C-ring, leading via subsequent oxidations to the formation of protocatechuate. This is the first report on quercetin dehydroxylation in aerobic conditions leading to naringenin accumulation. PMID:11772620
Newborn Screening for Glutaric Aciduria-II: The New England Experience.
Sahai, I; Garganta, C L; Bailey, J; James, P; Levy, H L; Martin, M; Neilan, E; Phornphutkul, C; Sweetser, D A; Zytkovicz, T H; Eaton, R B
2014-01-01
Newborn screening (NBS) using tandem mass spectrometry (MS/MS) permits detection of neonates with Glutaric Aciduria-Type II (GA-II). We report follow-up of positive GA-II screens by the New England Newborn Screening Program. 1.5 million infants were screened for GA-II (Feb 1999-Dec 2012). Specialist consult was suggested for infants with two or more acylcarnitine elevations suggestive of GA-II. 82 neonates screened positive for GA-II, 21 weighing > 1.5 kg and 61 weighing ≤ 1.5 kg. Seven (one weighing < 1.5 kg), were confirmed with GA-II. Four of these had the severe form (died < 1 week). The other three have a milder form and were identified because of newborn screening. Two (ages > 5 years) have a G-Tube in place, had multiple hospitalizations and are slightly hypotonic. The third infant remains asymptomatic (9 months old). Two GA-II carriers were also identified. The remaining positive screens were classified as false positives (FP). Six infants (> 1.5 kg) classified as FP had limited diagnostic work-up. Characteristics and outcomes of all specimens and neonates with a positive screen were reviewed, and marker profiles of the cases and FP were compared to identify characteristic profiles. In addition to the severe form of GA-II, milder forms of GA-II and some GA-II carriers are identified by newborn screening. Some positive screens classified as FP may be affected with a milder form of the disorder. Characteristic GA-II profiles, quantified as GA-II indexes, may be utilized to predict probability of disorder and direct urgency of intervention for positive screens.
Moffitt, C.M.; Mobin, S.M.A.
2006-01-01
We describe the resident heterotrophic aerobic microflora of the salmonid posterior intestine before, during, and after the administration of rations with erythromycin in a hatchery raceway environment. We compare the profiles of medicated Chinook salmon Oncorhynchus tshawytscha with those of control fish that were not fed erythromycin. The combined counts of bacteria and yeasts per gram of fish intestine originating from four upstream raceways ranged from 3.0 ?? 102 to 9.6 ?? 105 colony-forming units (CFU) over the study period. Yeasts were commonly identified in the gut, and abundances ranged from 0% to more than 80% of the CFU. Erythromycin therapy decreased the total microbial population and altered the bacterial diversity in the gut during treatment. The intestinal microbial populations in fish medicated with erythromycin increased rapidly after treatment ceased, and by 25 d after treatment the CFU were similar in samples from both medicated and control fish populations. Of 325 isolates from fish selected for biochemical profiles, we identified a total of eight gram-positive and eight gram-negative genera. Bacillus spp. were common throughout sampling and were identified in samples of fish feed. Erythromycin-resistant, gram-positive bacteria were observed throughout the sampling in medicated and control fish. We identified seven gram-positive and two gram-negative genera in 74 selected isolates from control and erythromycin feeds. Our studies suggest that the aerobic microflora of the posterior intestine varies over time, and it is likely that few resistant genera of concern to human health are present.
Ford, Julian D; Elhai, Jon D; Connor, Daniel F; Frueh, B Christopher
2010-06-01
Adolescents exposed to multiple forms of psychological trauma ("poly-victimization," Finkelhor et al. Child Abuse Negl 2007;31:7-26) may be at high risk for psychiatric and behavioral problems. This study empirically identifies trauma profiles in a national sample of adolescents to ascertain correlates of poly-victimization. Latent Class analyses and logistic regression analyses were used with data from the National Survey of Adolescents to identify trauma profiles and each profile's risk of posttraumatic stress disorder, major depressive disorder, substance use disorders, and delinquency involvement and deviant peer group relationships. Poly-victimization classes were also compared to classes with trauma exposure of lesser complexity. Six mutually exclusive trauma profiles (latent classes) were identified. Four classes were characterized by high likelihood of poly-victimization, including abuse victims (8%), physical assault victims (9%), and community violence victims (15.5%). Poly-victimization class members, especially abuse and assault victims, were more likely than do youth traumatized by witnessing violence or exposure to disaster/accident trauma to have psychiatric diagnosis and (independent of psychiatric diagnoses or demographics) to be involved in delinquency with delinquent peers. Poly-victimization is prevalent among adolescents and places youth at high risk for psychiatric impairment and for delinquency. Moreover, poly-victimized youths' risk of delinquency cannot be fully accounted for by posttraumatic stress disorder, depression, or substance use problems, suggesting that adolescent healthcare providers should consider poly-victimization as a risk for behavioral and legal problems even when PTSD, depression, or addiction symptoms are not clinically significant. Copyright 2010 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Profiling the humoral immune response of acute and chronic Q fever by protein microarray.
Vigil, Adam; Chen, Chen; Jain, Aarti; Nakajima-Sasaki, Rie; Jasinskas, Algimantas; Pablo, Jozelyn; Hendrix, Laura R; Samuel, James E; Felgner, Philip L
2011-10-01
Antigen profiling using comprehensive protein microarrays is a powerful tool for characterizing the humoral immune response to infectious pathogens. Coxiella burnetii is a CDC category B bioterrorist infectious agent with worldwide distribution. In order to assess the antibody repertoire of acute and chronic Q fever patients we have constructed a protein microarray containing 93% of the proteome of Coxiella burnetii, the causative agent of Q fever. Here we report the profile of the IgG and IgM seroreactivity in 25 acute Q fever patients in longitudinal samples. We found that both early and late time points of infection have a very consistent repertoire of IgM and IgG response, with a limited number of proteins undergoing increasing or decreasing seroreactivity. We also probed a large collection of acute and chronic Q fever patient samples and identified serological markers that can differentiate between the two disease states. In this comparative analysis we confirmed the identity of numerous IgG biomarkers of acute infection, identified novel IgG biomarkers for acute and chronic infections, and profiled for the first time the IgM antibody repertoire for both acute and chronic Q fever. Using these results we were able to devise a test that can distinguish acute from chronic Q fever. These results also provide a unique perspective on isotype switch and demonstrate the utility of protein microarrays for simultaneously examining the dynamic humoral immune response against thousands of proteins from a large number of patients. The results presented here identify novel seroreactive antigens for the development of recombinant protein-based diagnostics and subunit vaccines, and provide insight into the development of the antibody response.
2013-01-01
Background Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colon cancer have mainly been demonstrated in primary tumors. Poorly overlapping sets of oncomiRs, tumor suppressor miRNAs and metastamiRs have been linked with distinct stages in the progression of colorectal cancer. To identify changes in both miRNA and gene expression levels among normal colon mucosa, primary tumor and liver metastasis samples, and to classify miRNAs into functional networks, in this work miRNA and gene expression profiles in 158 samples from 46 patients were analysed. Results Most changes in miRNA and gene expression levels had already manifested in the primary tumors while these levels were almost stably maintained in the subsequent primary tumor-to-metastasis transition. In addition, comparing normal tissue, tumor and metastasis, we did not observe general impairment or any rise in miRNA biogenesis. While only few mRNAs were found to be differentially expressed between primary colorectal carcinoma and liver metastases, miRNA expression profiles can classify primary tumors and metastases well, including differential expression of miR-10b, miR-210 and miR-708. Of 82 miRNAs that were modulated during tumor progression, 22 were involved in EMT. qRT-PCR confirmed the down-regulation of miR-150 and miR-10b in both primary tumor and metastasis compared to normal mucosa and of miR-146a in metastases compared to primary tumor. The upregulation of miR-201 in metastasis compared both with normal and primary tumour was also confirmed. A preliminary survival analysis considering differentially expressed miRNAs suggested a possible link between miR-10b expression in metastasis and patient survival. By integrating miRNA and target gene expression data, we identified a combination of interconnected miRNAs, which are organized into sub-networks, including several regulatory relationships with differentially expressed genes. Key regulatory interactions were validated experimentally. Specific mixed circuits involving miRNAs and transcription factors were identified and deserve further investigation. The suppressor activity of miR-182 on ENTPD5 gene was identified for the first time and confirmed in an independent set of samples. Conclusions Using a large dataset of CRC miRNA and gene expression profiles, we describe the interplay of miRNA groups in regulating gene expression, which in turn affects modulated pathways that are important for tumor development. PMID:23987127
Student Engagement and School Burnout in Finnish Lower-Secondary Schools: Latent Profile Analysis
ERIC Educational Resources Information Center
Virtanen, T. E.; Lerkkanen, M.-K.; Poikkeus, A.-M.; Kuorelahti, M.
2018-01-01
Self-ratings of behavioural engagement, cognitive engagement and school burnout were used in person-centred analyses to identify latent profiles among 2,485 Finnish lower-secondary school students. Three profiles were identified: high-engagement/low-burnout (40.6% of the sample), average-engagement/average-burnout (53.9%), and…
Facial profile esthetic preferences: perception in two Brazilian states.
Oliveira, Marina Detoni Vieira de; Silveira, Bruno Lopes da; Mattos, Cláudia Trindade; Marquezan, Mariana
2015-01-01
The aim of this study was to assess the regional influence on the perception of facial profile esthetics in Rio de Janeiro state (RJ) and Rio Grande do Sul state (RS), Brazil. Two Caucasian models, a man and a woman, with balanced facial profiles, had their photographs digitally manipulated so as to produce seven different profiles. First year dental students (laypeople) assessed the images and classified them according to their esthetic preference. The result of the t test for independent samples showed differences among states for certain facial profiles. The female photograph identified with the letter 'G' (mandibular retrusion) received higher scores in RS state (p = 0.006). No differences were found for male photographs (p > 0.007). The evaluators' sex seemed not to influence their esthetic perception (p > 0.007). Considering all evaluators together, ANOVA/Tukey's test showed differences among the profiles (p ≤ 0.05) for both male and female photographs. The female photograph that received the highest score was the one identified with the letter 'F' (dentoalveolar bimaxillary retrusion/ straight profile). For the male profiles, photograph identified with the letter 'E' (dentoalveolar bimaxillary protrusion/ straight profile) received the best score. Regional differences were observed regarding preferences of facial profile esthetics. In Rio de Janeiro state, more prominent lips were preferred while in Rio Grande do Sul state, profiles with straight lips were favored. Class III profiles were considered less attractive.
Polyphenolic profile as a useful tool to identify the wood used in wine aging.
Sanz, Miriam; Fernández de Simón, Brígida; Cadahía, Estrella; Esteruelas, Enrique; Muñoz, Angel Ma; Hernández, Ma Teresa; Estrella, Isabel
2012-06-30
Although oak wood is the main material used in cooperage, other species are being considered as possible sources of wood for the production of wines and their derived products. In this work we have compared the phenolic composition of acacia (Robinia pseudoacacia), chestnut (Castanea sativa), cherry (Prunus avium) and ash (Fraxinus excelsior and F. americana) heartwoods, by using HPLC-DAD/ESI-MS/MS (some of these data have been showed in previous paper), as well as the changes that toasting intensity at cooperage produce in each polyphenolic profile. Before toasting, each wood shows a different and specific polyphenolic profile, with both qualitative and quantitative differences among them. Toasting notably changed these profiles, in general, proportionally to toasting intensity and led to a minor differentiation among species in toasted woods, although we also found phenolic markers in toasted woods. Thus, methyl syringate, benzoic acid, methyl vanillate, p-hydroxybenzoic acid, 3,4,5-trimethylphenol and p-coumaric acid, condensed tannins of the procyanidin type, and the flavonoids naringenin, aromadendrin, isosakuranetin and taxifolin will be a good tool to identify cherry wood. In acacia wood the chemical markers will be the aldehydes gallic and β-resorcylic and two not fully identified hydroxycinnamic compounds, condensed tannins of the prorobinetin type, and when using untoasted wood, dihydrorobinetin, and in toasted acacia wood, robinetin. In untoasted ash wood, the presence of secoiridoids, phenylethanoid glycosides, or di and oligolignols will be a good tool, especially oleuropein, ligstroside and olivil, together verbascoside and isoverbascoside in F. excelsior, and oleoside in F. americana. In toasted ash wood, tyrosol, syringaresinol, cyclolovil, verbascoside and olivil, could be used to identify the botanical origin. In addition, in ash wood, seasoned and toasted, neither hydrolysable nor condensed tannins were detected. Lastly, in chestnut wood, gallic and ellagic acids and hydrolysable tannins of both the gallotannin and ellagitannin type, can be used as chemical markers. Copyright © 2011 Elsevier B.V. All rights reserved.
Comparative analyses identify molecular signature of MRI-classified SVZ-associated glioblastoma
Lin, Chin-Hsing Annie; Rhodes, Christopher T.; Lin, ChenWei; Phillips, Joanna J.; Berger, Mitchel S.
2017-01-01
ABSTRACT Glioblastoma (GBM) is a highly aggressive brain cancer with limited therapeutic options. While efforts to identify genes responsible for GBM have revealed mutations and aberrant gene expression associated with distinct types of GBM, patients with GBM are often diagnosed and classified based on MRI features. Therefore, we seek to identify molecular representatives in parallel with MRI classification for group I and group II primary GBM associated with the subventricular zone (SVZ). As group I and II GBM contain stem-like signature, we compared gene expression profiles between these 2 groups of primary GBM and endogenous neural stem progenitor cells to reveal dysregulation of cell cycle, chromatin status, cellular morphogenesis, and signaling pathways in these 2 types of MRI-classified GBM. In the absence of IDH mutation, several genes associated with metabolism are differentially expressed in these subtypes of primary GBM, implicating metabolic reprogramming occurs in tumor microenvironment. Furthermore, histone lysine methyltransferase EZH2 was upregulated while histone lysine demethylases KDM2 and KDM4 were downregulated in both group I and II primary GBM. Lastly, we identified 9 common genes across large data sets of gene expression profiles among MRI-classified group I/II GBM, a large cohort of GBM subtypes from TCGA, and glioma stem cells by unsupervised clustering comparison. These commonly upregulated genes have known functions in cell cycle, centromere assembly, chromosome segregation, and mitotic progression. Our findings highlight altered expression of genes important in chromosome integrity across all GBM, suggesting a common mechanism of disrupted fidelity of chromosome structure in GBM. PMID:28278055
Chaillou, Thomas; Jackson, Janna R; England, Jonathan H; Kirby, Tyler J; Richards-White, Jena; Esser, Karyn A; Dupont-Versteegden, Esther E; McCarthy, John J
2015-01-01
The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading. Copyright © 2015 the American Physiological Society.
Chaillou, Thomas; Jackson, Janna R.; England, Jonathan H.; Kirby, Tyler J.; Richards-White, Jena; Esser, Karyn A.; Dupont-Versteegden, Esther E.
2014-01-01
The purpose of this study was to compare the gene expression profile of mouse skeletal muscle undergoing two forms of growth (hypertrophy and regrowth) with the goal of identifying a conserved set of differentially expressed genes. Expression profiling by microarray was performed on the plantaris muscle subjected to 1, 3, 5, 7, 10, and 14 days of hypertrophy or regrowth following 2 wk of hind-limb suspension. We identified 97 differentially expressed genes (≥2-fold increase or ≥50% decrease compared with control muscle) that were conserved during the two forms of muscle growth. The vast majority (∼90%) of the differentially expressed genes was upregulated and occurred at a single time point (64 out of 86 genes), which most often was on the first day of the time course. Microarray analysis from the conserved upregulated genes showed a set of genes related to contractile apparatus and stress response at day 1, including three genes involved in mechanotransduction and four genes encoding heat shock proteins. Our analysis further identified three cell cycle-related genes at day and several genes associated with extracellular matrix (ECM) at both days 3 and 10. In conclusion, we have identified a core set of genes commonly upregulated in two forms of muscle growth that could play a role in the maintenance of sarcomere stability, ECM remodeling, cell proliferation, fast-to-slow fiber type transition, and the regulation of skeletal muscle growth. These findings suggest conserved regulatory mechanisms involved in the adaptation of skeletal muscle to increased mechanical loading. PMID:25554798
Liu, Yufei; Wang, Chang; Wang, Ran; Wu, Yike; Zhang, Liang; Liu, Bi-Feng; Cheng, Liming; Liu, Xin
2018-06-15
Glycosylation is one of the most important post-translational modifications of protein. Recently, global profiling of human serum glycomics has become a noninvasive method for cancer-related biomarker discovery and many studies have focused on compositional glycan profiling. In contrast, structure-specific glycan profiling may provide more potential biomarkers with higher specificity than compositional profiling. In this work, N-glycans released from human serum were neutralized with methylamine and reduced by ammonia-borane complex prior to profiling using nanoLC-ESI-MS with porous graphitized carbon (PGC) and relative abundances of over 280 isomers were compared between pancreatic cancer (PC) cases (n = 32) and healthy controls (n = 32). Statistical analysis identified 25 specific-isomeric biomarkers with significant differences (p-value < 0.05). ROC and PCA analysis were performed to assess the potential biomarkers which were identified as being significantly altered in cancer. The AUCs of the significantly changed specific-isomers were ranging from 0.712 to 0.949. In addition, with the combination of all potential biomarkers, a higher AUC of 0.976 with sensitivity (93.5%) and specificity (90.6%) was obtained. Overall, the proposed strategy coupled to relative quantitative analysis of isomeric glycans make it possible to discover new biomarkers for the diagnosis of PC. Pancreatic cancer (PC) has a poor prognosis with a five-year survival rate <5%. Therefore, a strategy for accurate diagnosis of PC is indeed required. In this paper, a dual-derivatized strategy for structure-specific glycan profiling has been used and according to our best knowledge, this is the first application of this strategy for PC biomarker discovery, in which the separation, identification and relative quantification of isomeric glycans can be simultaneously obtained. In addition, by in-depth analysis of isomeric glycans, the full description of the stereo- and region- diversity of glycans can also be achieved, which might provide more potential information for PC biomarker discovery. Copyright © 2018 Elsevier B.V. All rights reserved.
Profiling of Atmospheric Water Vapor from the SSM/T-2 Radiometric Measurements
NASA Technical Reports Server (NTRS)
Wang, J. R.
2000-01-01
An advantage of using the millimeter-wave measurements for water vapor profiling is the ability to probe beyond a moderate cloud cover. Such a capability has been demonstrated from an airborne MIR (Millimeter-wave Imaging Radiometer) flight over the Pacific Ocean during an intense observation period of TOGA/COARE (Tropical Ocean Global Atmosphere/ Couple Ocean Atmospheric Response Experiment) in early 1993. A Cloud Lidar System (CLS) and MODIS Airborne Simulator (MAS) were on board the same aircraft to identify the presence of clouds and cloud type. The retrieval algorithm not only provides output of a water vapor profile, but also the cloud liquid water and approximate cloud altitude required to satisfy convergence of the retrieval. The validity of these cloud parameters has not been verified previously. In this document, these cloud parameters are compared with those derived from concurrent measurements from the CLS and AMPR (Advanced Microwave Precipitation Radiometer).
The Cancer Genome Atlas Pan-Cancer Analysis Project
Weinstein, John N.; Collisson, Eric A.; Mills, Gordon B.; Shaw, Kenna M.; Ozenberger, Brad A.; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M.
2014-01-01
Cancer can take hundreds of different forms depending on the location, cell of origin and spectrum of genomic alterations that promote oncogenesis and affect therapeutic response. Although many genomic events with direct phenotypic impact have been identified, much of the complex molecular landscape remains incompletely charted for most cancer lineages. For that reason, The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumours to discover molecular aberrations at the DNA, RNA, protein, and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences, and emergent themes across tumour lineages. The Pan-Cancer initiative compares the first twelve tumour types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumour types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849
Larance, Mark; Kirkwood, Kathryn J.; Tinti, Michele; Brenes Murillo, Alejandro; Ferguson, Michael A. J.; Lamond, Angus I.
2016-01-01
We present a methodology using in vivo crosslinking combined with HPLC-MS for the global analysis of endogenous protein complexes by protein correlation profiling. Formaldehyde crosslinked protein complexes were extracted with high yield using denaturing buffers that maintained complex solubility during chromatographic separation. We show this efficiently detects both integral membrane and membrane-associated protein complexes,in addition to soluble complexes, allowing identification and analysis of complexes not accessible in native extracts. We compare the protein complexes detected by HPLC-MS protein correlation profiling in both native and formaldehyde crosslinked U2OS cell extracts. These proteome-wide data sets of both in vivo crosslinked and native protein complexes from U2OS cells are freely available via a searchable online database (www.peptracker.com/epd). Raw data are also available via ProteomeXchange (identifier PXD003754). PMID:27114452
1H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver
Xu, Chuang; Sun, Ling-wei; Xia, Cheng; Zhang, Hong-you; Zheng, Jia-san; Wang, Jun-song
2016-01-01
Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using 1H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows. PMID:26732447
The eigenvalue spectrum of the Orr-Sommerfeld problem
NASA Technical Reports Server (NTRS)
Antar, B. N.
1976-01-01
A numerical investigation of the temporal eigenvalue spectrum of the ORR-Sommerfeld equation is presented. Two flow profiles are studied, the plane Poiseuille flow profile and the Blasius boundary layer (parallel): flow profile. In both cases a portion of the complex c-plane bounded by 0 less than or equal to CR sub r 1 and -1 less than or equal to ci sub i 0 is searched and the eigenvalues within it are identified. The spectra for the plane Poiseuille flow at alpha = 1.0 and R = 100, 1000, 6000, and 10000 are determined and compared with existing results where possible. The spectrum for the Blasius boundary layer flow at alpha = 0.308 and R = 998 was found to be infinite and discrete. Other spectra for the Blasius boundary layer at various Reynolds numbers seem to confirm this result. The eigenmodes belonging to these spectra were located and discussed.
Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients.
Jansen, Erik; Laven, Joop S E; Dommerholt, Henri B R; Polman, Jan; van Rijt, Cindy; van den Hurk, Caroline; Westland, Jolanda; Mosselman, Sietse; Fauser, Bart C J M
2004-12-01
Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 5-10% of women of reproductive age. The etiology of PCOS is still unknown. The current study is the first to describe consistent differences in gene expression profiles in human ovaries comparing PCOS patients vs. healthy normoovulatory individuals. The microarray analysis of PCOS vs. normal ovaries identifies dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, and immunological factors. Resulting data may provide novel clues for ovarian dysfunction in PCOS. Intriguingly, the gene expression profiles of ovaries from (long-term) androgen-treated female-to-male transsexuals (TSX) show considerable overlap with PCOS. This observation provides supportive evidence that androgens play a key role in the pathogenesis of PCOS. Presented data may contribute to a better understanding of dysregulated pathways in PCOS, which might ultimately reveal novel leads for therapeutic intervention.
Use of Magsat anomaly data for crustal structure and mineral resources in the US midcontinent
NASA Technical Reports Server (NTRS)
Carmichael, R. S. (Principal Investigator)
1981-01-01
Magnetic profiles on individual satellites tracks were examined to identify bad (nonterrestrially-based) data points r profiles. Anomaly profiles for the same satellite track, but at different passes were compared for parallel tracks and for tracks that cross. The selected and processed data were plotted and contoured to develop a preliminary magnetic anomaly map. The map is similar in general morphology to NASA's Magsat global scalar anomaly map, but has more detail which is related to crustal properties. Efforts have begun to interpret the satellite magnetic anomalies in terms of crustal character. The correlation of magnetics with crustal petrology may have a much larger tectonic implication. Th possibility of there being an ultramafic lower crust along one zone as a consequence of a continental collision/subduction which helped form the midcontinent craton in Precambrian times is being investigated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pena-Castillo, Lourdes; Mercer, Ryan; Gurinovich, Anastasia
2014-08-28
The genus Rhodobacter contains purple nonsulfur bacteria found mostly in freshwater environments. Representative strains of two Rhodobacter species, R. capsulatus and R. sphaeroides, have had their genomes fully sequenced and both have been the subject of transcriptional profiling studies. Gene co-expression networks can be used to identify modules of genes with similar expression profiles. Functional analysis of gene modules can then associate co-expressed genes with biological pathways, and network statistics can determine the degree of module preservation in related networks. In this paper, we constructed an R. capsulatus gene co-expression network, performed functional analysis of identified gene modules, and investigatedmore » preservation of these modules in R. capsulatus proteomics data and in R. sphaeroides transcriptomics data. Results: The analysis identified 40 gene co-expression modules in R. capsulatus. Investigation of the module gene contents and expression profiles revealed patterns that were validated based on previous studies supporting the biological relevance of these modules. We identified two R. capsulatus gene modules preserved in the protein abundance data. We also identified several gene modules preserved between both Rhodobacter species, which indicate that these cellular processes are conserved between the species and are candidates for functional information transfer between species. Many gene modules were non-preserved, providing insight into processes that differentiate the two species. In addition, using Local Network Similarity (LNS), a recently proposed metric for expression divergence, we assessed the expression conservation of between-species pairs of orthologs, and within-species gene-protein expression profiles. Conclusions: Our analyses provide new sources of information for functional annotation in R. capsulatus because uncharacterized genes in modules are now connected with groups of genes that constitute a joint functional annotation. We identified R. capsulatus modules enriched with genes for ribosomal proteins, porphyrin and bacteriochlorophyll anabolism, and biosynthesis of secondary metabolites to be preserved in R. sphaeroides whereas modules related to RcGTA production and signalling showed lack of preservation in R. sphaeroides. In addition, we demonstrated that network statistics may also be applied within-species to identify congruence between mRNA expression and protein abundance data for which simple correlation measurements have previously had mixed results.« less
2015-09-30
hired to conduct WRF model experiments. • We conducted Weather Research and Forecast ( WRF ) model simulations for the summer of 2014 and compared with... WRF simulations under different synoptic conditions will help to more 10 clearly identify the deficiencies in the representation of these processes
ERIC Educational Resources Information Center
Farrow, Robert; de los Arcos, Beatriz; Pitt, Rebecca; Weller, Martin
2015-01-01
Open educational resources (OER) have been identified as having the potential to extend opportunities for learning to non-formal learners. However, little research has been conducted into the impact of OER on non-formal learners. This paper presents the results of a systematic survey of more than 3,000 users of open educational resources (OER).…
ERIC Educational Resources Information Center
Greenberg, Daphne; Wise, Justin C.; Frijters, Jan C.; Morris, Robin; Fredrick, Laura D.; Rodrigo, Victoria; Hall, Ryan
2013-01-01
Adult literacy programs are characterized by high attrition rates. Rigorous exploration of student persistence in adult reading classes is lacking. This study was an attempt to understand the profiles of adults who completed reading classes compared to a group of adults who made it to the midpoint and a group of adults who did not make it to the…
Altering the Speed Profiles of Wheelchair Rugby Players With Game-Simulation Drill Design.
Rhodes, James M; Mason, Barry S; Paulson, Thomas A W; Goosey-Tolfrey, Victoria L
2018-01-01
To examine the speed profiles of elite wheelchair rugby (WCR) players during game-simulation training drills of differing player number and shot-clock regulations. A secondary aim was to determine whether the profiles were further influenced by player classification. Eight elite WCR players (low-point n = 3, high-point n = 5) were monitored using a radio-frequency-based indoor tracking system during training sessions over a 5-mo period. Speed profiles were collected for 3 modified game-simulation drills-3-versus-3 drills (n = 8 observations), 30-s shot clock (n = 24 observations), and 15-s shot clock (n = 16 observations)-and were compared with regular game-simulation drills (4 vs 4, 40-s shot clock; n = 16 observations). Measures included mean and peak speed; exercise-intensity ratios, defined as the ratio of time spent performing at high and low speeds; and the number of high-speed activities performed. Compared with regular game-simulation drills, 3-versus-3 drills elicited a moderate increase in mean speed (6.3%; effect size [ES] = 0.7) and the number of high-speed activities performed (44.1%; ES = 1.1). Minimal changes in speed profiles were observed during the 30-s shot clock, although moderate to large increases in all measures were observed during the 15-s shot-clock drills. Classification-specific differences were further identified, with increased activity observed for high-point players during the 3-versus-3 drill and for low-point players during the 15-s shot clock. By reducing the number of players on court and the shot clock to 15 s, coaches can significantly increase elite WCR players' speed profiles during game-simulation drills.
NASA Astrophysics Data System (ADS)
Roberts, Tjarda J.; Dütsch, Marina; Hole, Lars R.; Voss, Paul B.
2016-09-01
Observations from CMET (Controlled Meteorological) balloons are analysed to provide insights into tropospheric meteorological conditions (temperature, humidity, wind) around Svalbard, European High Arctic. Five Controlled Meteorological (CMET) balloons were launched from Ny-Ålesund in Svalbard (Spitsbergen) over 5-12 May 2011 and measured vertical atmospheric profiles over coastal areas to both the east and west. One notable CMET flight achieved a suite of 18 continuous soundings that probed the Arctic marine boundary layer (ABL) over a period of more than 10 h. Profiles from two CMET flights are compared to model output from ECMWF Era-Interim reanalysis (ERA-I) and to a high-resolution (15 km) Arctic System Reanalysis (ASR) product. To the east of Svalbard over sea ice, the CMET observed a stable ABL profile with a temperature inversion that was reproduced by ASR but not captured by ERA-I. In a coastal ice-free region to the west of Svalbard, the CMET observed a stable ABL with strong wind shear. The CMET profiles document increases in ABL temperature and humidity that are broadly reproduced by both ASR and ERA-I. The ASR finds a more stably stratified ABL than observed but captured the wind shear in contrast to ERA-I. Detailed analysis of the coastal CMET-automated soundings identifies small-scale temperature and humidity variations with a low-level flow and provides an estimate of local wind fields. We demonstrate that CMET balloons are a valuable approach for profiling the free atmosphere and boundary layer in remote regions such as the Arctic, where few other in situ observations are available for model validation.
Screening for Prenatal Substance Use
Yonkers, Kimberly A.; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B.; Rounsaville, Bruce J.
2011-01-01
OBJECTIVE To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. METHODS Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into “training” (n=1,610) and “validation” (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. RESULTS The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike’s Information Criterion=579.75, Nagelkerke R2=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). CONCLUSION The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. PMID:20859145
Elam, Kit K; Sandler, Irwin; Wolchik, Sharlene; Tein, Jenn-Yun
2016-03-01
Variable-centered research has found complex relationships between child well-being and two critical aspects of the post-divorce family environment: the level of non-residential father involvement (i.e., contact and supportive relationship) with their children and the level of conflict between the father and mother. However, these analyses fail to capture individual differences based on distinct patterns of interparental conflict, father support and father contact. Using a person-centered latent profile analysis, the present study examined (1) profiles of non-residential father contact, support, and interparental conflict in the 2 years following divorce (N = 240), when children (49 % female) were between 9 and 12 years of age and (2) differences across profiles in concurrent child adjustment outcomes as well as outcomes 6 years later. Four profiles of father involvement were identified: High Contact-Moderate Conflict-Moderate Support, Low Contact-Moderate Conflict-Low Support, High Conflict-Moderate Contact-Moderate Support, and Low Conflict-Moderate Contact-Moderate Support. Concurrently, children with fathers in the group with high conflict were found to have significantly greater internalizing and externalizing problems compared to all other groups. Six years later, children with fathers in the group with low contact and low support were found to have greater internalizing and externalizing problems compared to children with fathers in the high conflict group, and also greater internalizing problems compared to children with fathers in the low conflict group. These results provide insight into the complex relationship among non-residential fathers' conflict, contact, and support in child adjustment within divorcing families.
Liver Gene Expression Profiles of Rats Treated with Clofibric Acid
Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric
2003-01-01
Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor α, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci. PMID:14633594
Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric
2003-12-01
Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor alpha, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci.
Pawaskar, Priyanka N; Shirali, Arun; Prabhu, M Venkatraya; Pai, Sheila R; Kumar, Nayanatara Arun; Pawaskar, Niwas G
2015-08-01
Anthropometry is a simple reliable method for quantifying body proportions by measuring body length, weight and circumferences. Our intention in this study was to compare sensitivities and positive predictive values of waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR) and body mass index (BMI) in identifying healthy subjects, males and females separately for identifying obesity associated dyslipidemia. We analysed randomly selected 100 healthy subjects (males:58%, females:42%) between 25 and 60 years of age attending tertiary health care center in South India, after obtaining informed consent and Institutional Ethical Clearance. WC, WHR, WHtR and BMI of all the enrolled subjects were measured and estimated. Their fasting serum lipid profile was assessed. Subjects were divided based on their gender and each group was then categorized as obese and non-obese using anthropometric parameters and their individual serum lipid profile values depending on the cut off standards as per WHO and ATP III guidelines and compared. Data obtained was statistically analysed. Mean values of WC, WHR, WHtR and BMI were highly significant (p<0.000) in obese in both males (97.43 ± 6.21cm, 0.96 ± 0.04, 0.61 ± 0.05, 27.72 ± 2.45kg/m(2)) and females (91.82 ± 5.18cm, 0.92 ± 0.06, 0.60 ± 0.04, 27.70 ± 3.44kg/m(2)) when considered separately compared to non-obese males (82.27 ± 5.33cm, 0.83 ± 0.033, 0.51 ± 0.03, 22.80 ± 2.11kg/m(2)) and females (71.68 ± 7.33cm, 0.78 ± 0.03, 0.48 ± 0.03, 21.82 ± 1.98kg/m(2) respectively). WC was more sensitive for predicting the altered lipid profile (85%) in females and WHR (65%) in males. WHR showed higher ability to correctly predict the occurrence of dyslipidemia in the obese males (90% positive predictive value) and WHtR in females (92%). The present study inferred that WC, WHR are more sensitive while WHR and WHtR have a higher positive predictive value than BMI in identifying dyslipidemia in healthy males and females.
Dong, Pan; Xiong, Fangjie; Que, Yumei; Wang, Kai; Yu, Lihua; Li, Zhengguo; Ren, Maozhi
2015-01-01
Target of rapamycin (TOR) acts as a master regulator to control cell growth by integrating nutrient, energy, and growth factors in all eukaryotic species. TOR plays an evolutionarily conserved role in regulating the transcription of genes associated with anabolic and catabolic processes in Arabidopsis, but little is known about the functions of TOR in photosynthesis and phytohormone signaling, which are unique features of plants. In this study, AZD8055 (AZD) was screened as the strongest active-site TOR inhibitor (asTORi) in Arabidopsis compared with TORIN1 and KU63794 (KU). Gene expression profiles were evaluated using RNA-seq after treating Arabidopsis seedlings with AZD. More than three-fold differentially expressed genes (DEGs) were identified in AZD-treated plants relative to rapamycin-treated plants in previous studies. Most of the DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in cell wall elongation, ribosome biogenesis, and cell autophagy were common to both AZD- and rapamycin-treated samples, but AZD displayed much broader and more efficient inhibition of TOR compared with rapamycin. Importantly, the suppression of TOR by AZD resulted in remodeling of the expression profile of the genes associated with photosynthesis and various phytohormones, indicating that TOR plays a crucial role in modulating photosynthesis and phytohormone signaling in Arabidopsis. These newly identified DEGs expand the understanding of TOR signaling in plants. This study elucidates the novel functions of TOR in photosynthesis and phytohormone signaling and provides a platform to study the downstream targets of TOR in Arabidopsis. PMID:26442001
Informatic selection of a neural crest-melanocyte cDNA set for microarray analysis
Loftus, S. K.; Chen, Y.; Gooden, G.; Ryan, J. F.; Birznieks, G.; Hilliard, M.; Baxevanis, A. D.; Bittner, M.; Meltzer, P.; Trent, J.; Pavan, W.
1999-01-01
With cDNA microarrays, it is now possible to compare the expression of many genes simultaneously. To maximize the likelihood of finding genes whose expression is altered under the experimental conditions, it would be advantageous to be able to select clones for tissue-appropriate cDNA sets. We have taken advantage of the extensive sequence information in the dbEST expressed sequence tag (EST) database to identify a neural crest-derived melanocyte cDNA set for microarray analysis. Analysis of characterized genes with dbEST identified one library that contained ESTs representing 21 neural crest-expressed genes (library 198). The distribution of the ESTs corresponding to these genes was biased toward being derived from library 198. This is in contrast to the EST distribution profile for a set of control genes, characterized to be more ubiquitously expressed in multiple tissues (P < 1 × 10−9). From library 198, a subset of 852 clustered ESTs were selected that have a library distribution profile similar to that of the 21 neural crest-expressed genes. Microarray analysis demonstrated the majority of the neural crest-selected 852 ESTs (Mel1 array) were differentially expressed in melanoma cell lines compared with a non-neural crest kidney epithelial cell line (P < 1 × 10−8). This was not observed with an array of 1,238 ESTs that was selected without library origin bias (P = 0.204). This study presents an approach for selecting tissue-appropriate cDNAs that can be used to examine the expression profiles of developmental processes and diseases. PMID:10430933
Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data.
Ţieranu, Cristian George; Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Popa, Caterina; Mănuc, Mircea; Ţieranu, Ioana; Preda, Carmen Monica; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel
2017-01-01
Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state. ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.
Bafandeh, Saeed; Haghi, Fakhri; Zeighami, Habib
2015-05-01
Enteroaggregative Escherichia coli (EAEC) is an important agent of diarrhoeal diseases worldwide. The role of EAEC virulence factors in the clinical outcome of infection is not completely defined. This case-control study investigated the prevalence of EAEC, its virulence genes and the antimicrobial resistance profile of adult patients with and without diarrhoea attending three different hospitals in Zanjan, Iran. A total of 550 individual stool specimens (350 from diarrhoeal patients and 200 from patients without diarrhoea) were collected. One hundred and forty-one EAEC isolates were identified by a HEp-2 cell assay and PCR. EAEC isolates were detected with slightly higher frequency in patients with (27.7%) than in patients without (22%) diarrhoea (P ≥ 0.05). The EAEC genes aggR, aap and pet were identified more frequently in case patients compared with controls (P ≤ 0.05). Many of the EAEC isolates from the diarrhoeal patients had two or more virulence genes compared with those without diarrhoea (P ≤ 0.05). EAEC isolates exhibited high-level resistance to amoxicillin (82.3%), co-amoxiclav (78%), aztreonam (73.8%), tetracycline (66.6%) and ceftazidime (63.8%). In addition, 53.2% of isolates were resistant to at least three different classes of antimicrobial agents and were considered to be multidrug resistant. These results indicate a high prevalence and heterogeneity of gene profiles of EAEC in diarrhoeal and control patients, and suggest that the presence of aggR, aap and pet, the number of genes present and the antimicrobial resistance profile may be markers for more-virulent EAEC isolates. © 2015 The Authors.
2016-01-01
temporal changes in urinary metabolite profiles mirrored cognitive performance during continuous wakefulness. Additionally , subjects identified by...profiles mirrored cognitive performance during continuous wakefulness. Additionally , subjects identified by cognitive assessments as having a high...field studies and would have little useful application in occupational or military operational environments. Addition - ally, their usefulness is
Castada, Hardy Z; Wick, Cheryl; Taylor, Kaitlyn; Harper, W James
2014-04-01
Splits/cracks are recurring product defects that negatively affect the Swiss cheese industry. Investigations to understand the biophysicochemical aspects of these defects, and thus determine preventive measures against their occurrence, are underway. In this study, selected-ion, flow tube mass spectrometry was employed to determine the volatile organic compound (VOC) profiles present in the headspace of split compared with nonsplit cheeses. Two sampling methodologies were employed: split compared with nonsplit cheese vat pair blocks; and comparison of blind, eye, and split segments within cheese blocks. The variability in VOC profiles was examined to evaluate the potential biochemical pathway chemistry differences within and between cheese samples. VOC profile inhomogeneity was most evident in cheeses between factories. Evaluation of biochemical pathways leading to the formation of key VOCs differentiating the split from the blind and eye segments within factories indicated release of additional carbon dioxide by-product. These results suggest a factory-dependent cause of split formation that could develop from varied fermentation pathways in the blind, eye, and split areas within a cheese block. The variability of VOC profiles within and between factories exhibit varied biochemical fermentation pathways that could conceivably be traced back in the making process to identify parameters responsible for split defect. © 2014 Institute of Food Technologists®
A comparative analysis of microbial profile of Guinea fowl and chicken using metagenomic approach
Bhogoju, Sarayu; Wang, Xiaofei; Darris, Carl; Kilonzo-Nthenge, Agnes
2018-01-01
Probiotics are live microbial feed supplements that promote growth and health to the host by minimizing non-essential and pathogenic microorganisms in the host’s gastrointestinal tract (GIT). The campaign to minimize excessive use of antibiotics in poultry production has necessitated development of probiotics with broad application in multiple poultry species. Design of such probiotics requires understanding of the diversity or similarity in microbial profiles among avian species of economic importance. Therefore, the objective of this research was to establish and compare the microbial profiles of the GIT of Guinea fowl and chicken and to establish the microbial diversity or similarity between the two avian species. A metagenomic approach consisting of the amplification and sequence analysis of the hypervariable regions V1-V9 of the 16S rRNA gene was used to identify the GIT microbes. Collectively, we detected more than 150 microbial families. The total number of microbial species detected in the chicken GIT was higher than that found in the Guinea Fowl GIT. Our studies also revealed phylogenetic diversity among the microbial species found in chicken and guinea fowl. The phylum Firmicutes was most abundant in both avian species whereas Phylum Actinobacteria was most abundant in chickens than Guinea fowls. The diversity of the microbial profiles found in broiler chickens and Guinea fowls suggest that the design of effective avian probiotics would require species specificity. PMID:29494648
Priya, Syama Hari; Prakasan, Nisha; Purushothaman, Jayamurthy
2017-01-01
The medicinally important phytochemicals present in Syzygium cumini seeds probably accounts for its wide use in traditional systems of medicines in India, like Ayurveda, Unani, and Siddha. The aim of the study was to determine the antioxidant potential of three different geographical variants of S. cumini seeds and to compare the phenolic profiling to know the effect of geographical variation in phenolic composition. Total phenolic and flavonoid content of S. cumini seeds were analyzed. Antioxidant activities in terms of 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), nitric oxide and superoxide radical scavenging assays were performed. The most active fractions were subjected to high-performance liquid chromatography (HPLC) profiling to identify the phenolic composition. Among all the fractions, 70% methanol fraction of S. cumini seed showed significant antioxidant potential. There existed a linear correlation between phenolic content and antioxidant activity. HPLC profiling of 70% methanol (ME) fractions of all the variants revealed the presence of phenolic compounds with high concentrations of ellagic acid and gallic acid. The differences in phenolic concentration due to geographical changes might be the reason for higher antioxidant potential showed by 70% ME of Trivandrum variant. 70% methanolic fraction of S. cumini can act as a novel source of natural antioxidant.
2004-10-01
informative in this regard. Key signature genes will serve as the basis for rapid diagnostic approaches that could be accessed when an outbreak is suspected...AD Award Number: DAMD17-01-1-0787 TITLE: Use of DNA Microarrays to Identify Diagnostic Signature Transcription Profiles for Host Responses to...Sep 2004) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Use of DNA Microarrays to Identify Diagnostic Signature DAMD17-01-1-0787 Transcription Profiles for
mRNA expression profiling of laser microbeam microdissected cells from slender embryonic structures.
Scheidl, Stefan J; Nilsson, Sven; Kalén, Mattias; Hellström, Mats; Takemoto, Minoru; Håkansson, Joakim; Lindahl, Per
2002-03-01
Microarray hybridization has rapidly evolved as an important tool for genomic studies and studies of gene regulation at the transcriptome level. Expression profiles from homogenous samples such as yeast and mammalian cell cultures are currently extending our understanding of biology, whereas analyses of multicellular organisms are more difficult because of tissue complexity. The combination of laser microdissection, RNA amplification, and microarray hybridization has the potential to provide expression profiles from selected populations of cells in vivo. In this article, we present and evaluate an experimental procedure for global gene expression analysis of slender embryonic structures using laser microbeam microdissection and laser pressure catapulting. As a proof of principle, expression profiles from 1000 cells in the mouse embryonic (E9.5) dorsal aorta were generated and compared with profiles for captured mesenchymal cells located one cell diameter further away from the aortic lumen. A number of genes were overexpressed in the aorta, including 11 previously known markers for blood vessels. Among the blood vessel markers were endoglin, tie-2, PDGFB, and integrin-beta1, that are important regulators of blood vessel formation. This demonstrates that microarray analysis of laser microbeam micro-dissected cells is sufficiently sensitive for identifying genes with regulative functions.
Profile Analysis of Psychological Symptoms Associated With Misophonia: A Community Sample.
McKay, Dean; Kim, Se-Kang; Mancusi, Lauren; Storch, Eric A; Spankovich, Christopher
2018-03-01
Misophonia is characterized by extreme aversive reactions to certain classes of sounds. It has recently been recognized as a condition associated with significant disability. Research has begun to evaluate psychopathological correlates of misophonia. This study sought to identify profiles of psychopathology that characterize misophonia in a large community sample. A total of N = 628 adult participants completed a battery of measures assessing anxiety and anxiety sensitivity, depression, stress responses, anger, dissociative experiences, obsessive-compulsive symptoms and beliefs, distress tolerance, bodily perceptions, as well as misophonia severity. Profile Analysis via Multidimensional Scaling (PAMS) was employed to evaluate profiles associated with elevated misophonia and those without symptoms. Three profiles were extracted. The first two accounted for 70% total variance and did not show distinctions between groups. The third profile accounted for 11% total variance, and showed that misophonia is associated with lower obsessive-compulsive symptoms for neutralizing, obsessions generally, and washing compared to those not endorsing misophonia, and higher levels of obsessive-compulsive symptoms associated with ordering and harm avoidance. This third profile extracted also showed significant differences between those with and without misophonia on the scale assessing physical concerns (that is, sensitivity to interoceptive sensations) as assessed with the ASI-3. Further research is called for involving diagnostic interviewing and experimental methods to clarify these putative mechanisms associated with misophonia. Copyright © 2017. Published by Elsevier Ltd.
Cho, Kye Man; Lim, Ho-Jeong; Kim, Mi-So; Kim, Da Som; Hwang, Chung Eun; Nam, Sang Hae; Joo, Ok Soo; Lee, Byong Won; Kim, Jae Kyeom; Shin, Eui-Cheol
2017-07-01
In this study, we investigated the effects of the potential probiotic Bacillus subtilis CSY191 on the fatty acid profiles of Cheonggukjang, a fermented soybean paste, prepared using new Korean brown soybean cultivars, protein-rich cultivar (Saedanbaek), and oil-rich cultivar (Neulchan). Twelve fatty acids were identified in the sample set-myristic, palmitic, palmitoleic, stearic, oleic, vaccenic, linoleic, α-linolenic, arachidic, gondoic, behenic, and lignoceric acids-yet, no specific changes driven by fermentation were noted in the fatty acid profiles. To further explore the effects of fermentation of B. subtilis CSY191, complete profiles of volatiles were monitored. In total, 121, 136, and 127 volatile compounds were detected in the Saedanbaek, Daewon (control cultivar), and Neulchan samples, respectively. Interestingly, the content of pyrazines-compounds responsible for pungent and unpleasant Cheonggukjang flavors-was significantly higher in Neulchan compared to that in Saedanbaek. Although the fermentation period was not a strong factor affecting the observed changes in fatty acid profiles, we noted that profiles of volatiles in Cheonggukjang changed significantly over time, and different cultivars represented specific volatile profiles. Thus, further sensory evaluation might be needed to determine if such differences influence consumers' preferences. Furthermore, additional studies to elucidate the associations between B. subtilis CSY191 fermentation and other nutritional components (e.g., amino acids) and their health-promoting potential are warranted. Copyright © 2016. Published by Elsevier B.V.
NASA Astrophysics Data System (ADS)
Lin, Z.; Li, D.
2017-12-01
The lower troposphere, including the planetary boundary layer, is strongly influenced by the land surface at diurnal scales. However, investigations of diurnal land-atmosphere coupling are significantly hindered by the lack of profile measurements that resolve the diurnal cycle. This study aims to bridge this gap by developing a decade-long (from 2007 to 2016) data record of diurnal temperature profiles in the lower troposphere (from the surface to about 4 km above the surface), which is based on the Aircrafts Communications Addressing and Reporting System (ACARS) meteorological observations. We first identify the number of profiles within an hour for each airport over the CONUS. At each airport, only data that passed at least level-1 quality check are retained. 40 airports out of 275 are then selected, which have data for more than 12 hours per day. These selected airports are mainly located along the east and west coasts, as expected. Because the data are recorded at irregular heights, we resample each profile in the lowest 4 km or so to pre-defined vertical coordinates. These temperature profiles are further bias-corrected by comparing to collocated radiosonde observations. This consistent data record of diurnal temperature profiles in the lower troposphere can be also used for regional climatology research, short-term weather forecasts, and numerical model evaluation.
Schnarrs, Phillip W.; Rosario, Margaret; Garofalo, Robert; Mustanski, Brian
2014-01-01
Objectives. We examined disparities in risk determinants and risk behaviors for sexually transmitted infections (STIs) between gay-identified, bisexual-identified, and heterosexual-identified young men who have sex with men (YMSM) and heterosexual-identified young men who have sex with women (YMSW) using a school-based sample of US sexually active adolescent males. Methods. We analyzed a pooled data set of Youth Risk Behavior Surveys from 2005 and 2007 that included information on sexual orientation identity, sexual behaviors, and multiple STI risk factors. Results. Bisexual-identified adolescents were more likely to report multiple STI risk behaviors (number of sex partners, concurrent sex partners, and age of sexual debut) compared with heterosexual YMSW as well as heterosexual YMSM and gay-identified respondents. Gay, bisexual, and heterosexual YMSM were significantly more likely to report forced sex compared with heterosexual YMSW. Conclusions. Our results provide evidence that sexual health disparities emerge early in the life course and vary by both sexual orientation identity and sexual behaviors. In particular, they show that bisexual-identified adolescent males exhibit a unique risk profile that warrants targeted sexual health interventions. PMID:24825214
Esibizione, Diana; Cui, Chang-Yi; Schlessinger, David
2009-01-01
EDA, the gene mutated in anhidrotic ectodermal dysplasia, encodes ectodysplasin, a TNF superfamily member that activates NF-kB mediated transcription. To identify EDA target genes, we have earlier used expression profiling to infer genes differentially expressed at various developmental time points in Tabby (Eda-deficient) compared to wild-type mouse skin. To increase the resolution to find genes whose expression may be restricted to epidermal cells, we have now extended studies to primary keratinocyte cultures established from E19 wild-type and Tabby skin. Using microarrays bearing 44,000 gene probes, we found 385 preliminary candidate genes whose expression was significantly affected by Eda loss. By comparing expression profiles to those from Eda-A1 transgenic skin, we restricted the list to 38 “candidate EDA targets”, 14 of which were already known to be expressed in hair follicles or epidermis. We confirmed expression changes for 3 selected genes, Tbx1, Bmp7, and Jag1, both in keratinocytes and in whole skin, by Q-PCR and Western blotting analyses. Thus, by the analysis of keratinocytes, novel candidate pathways downstream of EDA were detected. PMID:18848976
Profiles of family needs of children and youth with cerebral palsy.
Almasri, N; Palisano, R J; Dunst, C; Chiarello, L A; O'Neil, M E; Polansky, M
2012-11-01
To identify profiles of family needs of families of children and youth with cerebral palsy (CP), and determine whether profile membership is related to child, family and service characteristics. Participants were mostly mothers (80%) of 579 children and youth with CP. A family member completed modified version of the Family Needs Survey and questionnaires about their child, family and services. Research assistants determined the Gross Motor Function Classification System levels. K-means cluster analysis identified profiles of needs. Cluster membership was analysed to examine differences in clusters based on selected characteristics. Four profiles of needs were identified: Low needs, Needs related to community and financial resources, Needs related to child health condition and High needs. Profile membership was differentiated based on child/youth gross motor function, adaptive behaviour, family relationships, family income, access and effort to co-ordinate services. Despite heterogeneity among individuals with CP and their families, four profiles of family needs were identified. In total, 51% of families had low needs suggesting that they are effectively managing their children's health conditions while 11% of families had high needs that may require high levels of services and supports. Service providers are encouraged to partner with families, provide anticipatory guidance and co-ordinate services. © 2011 Blackwell Publishing Ltd.
Profiles of drug addicts in relation to personality variables and disorders.
Carou, María; Romero, Estrella; Luengo, Mª Ángeles
2016-10-07
In recent decades, research has identified a set of impulsive/disinhibited personality variables closely associated with drug addiction. As well as this, disorders linked with these variables, such as ADHD and personality disorders, are being closely studied in the field of drug addiction. Although much knowledge has been accumulated about the relation of these variables and disorders taken separately, less is known about how these constructs allow identify-specific profiles within the drug dependent population to be identified. This work, on the basis of data collected on a sample of drug addicts in treatment, analyzes how impulsiveness, sensation seeking, self-control, ADHD and personality disorders contribute to identifying specific profiles of addicts. Cluster analysis allowed two profiles to be outlined according to these personality and psychopathology characteristics. Self-control, impulsiveness, impulsive and antisocial personality disorders, as well as scores in ADHD, emerge as the variables that contribute more to profile differentiation. One of these profiles (56.1% of participants) with a high disinhibition pattern, is associated with severe indicators of consumption and criminal career patterns. These results allow us to emphasize the role of personality and impulsiveness-related disorders in the identification of distinctive profiles within the addict population, and suggest the need to generate treatment strategies adapted to personal/psychopathology configurations of drug addicts.
Choi, Hye Jeong; Miller-Day, Michelle; Shin, YoungJu; Hecht, Michael L.; Pettigrew, Jonathan; Krieger, Janice L.; Lee, JeongKyu; Graham, John W.
2017-01-01
This current study identifies distinct parent prevention communication profiles and examines whether youth with different parental communication profiles have varying substance use trajectories over time. Eleven schools in two rural school districts in the Midwestern United States were selected, and 784 students were surveyed at three time points from the beginning of 7th grade to the end of 8th grade. A series of latent profile analyses were performed to identify discrete profiles/subgroups of substance-specific prevention communication (SSPC). The results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active-Silent, and Passive-Silent. A growth curve model revealed different rates of lifetime substance use depending on the youth’s SSPC profile. These findings have implications for parenting interventions and tailoring messages for parents to fit specific SSPC profiles. PMID:29056872
Power Profiles of Commercial Multifocal Soft Contact Lenses.
Kim, Eon; Bakaraju, Ravi C; Ehrmann, Klaus
2017-02-01
To evaluate the optical power profiles of commercially available soft multifocal contact lenses and compare their optical designs. The power profiles of 38 types of multifocal contact lenses-three lenses each-were measured in powers +6D, +3D, +1D, -1D, -3D, and -6D using NIMO TR1504 (Lambda-X, Belgium). All lenses were measured in phosphate buffered saline across 8 mm optic zone diameter. Refractive index of each lens material was measured using CLR 12-70 (Index Instruments, UK), which was used for converting measured power in the medium to in-air radial power profiles. Three basic types of power profiles were identified: center-near, center-distance, and concentric-zone ring-type designs. For most of the lens types, the relative plus with respect to prescription power was lower than the corresponding spectacle add. For some lens types, the measured power profiles were shifted by up to 1D across the power range relative to their labeled power. Most of the lenses were designed with noticeable amounts of spherical aberration. The sign and magnitude of spherical aberration can either be power dependent or consistent across the power range. Power profiles can vary widely between the different lens types; however, certain similarities were also observed between some of the center-near designs. For the more recently released lens types, there seems to be a trend emerging to reduce the relative plus with respect to prescription power, include negative spherical aberration, and keep the power profiles consistent across the power range.
Ma, Chun-ming; Liu, Xiao-li; Yin, Fu-Zai; Gao, Guo-qin; Wang, Rui; Lu, Qiang
2015-09-01
Hypertriglyceridemic waist (HW) phenotype was associated with an atherogenic lipid profile in adolescents. But unlike adults, the cutoffs of waist circumference are age- and gender-specific standards and are less feasible for non-professional use. The present study tested the hypothesis that simple variables, such as waist-to-height ratio (WHtR) and serum triacylglycerol (TG) concentrations, could be used as screening tools for the identification of adolescents characterized by atherogenic lipid profile. In 2006, anthropometric and biochemical measurements were assessed in a cross-sectional population-based study of 3136 Han adolescents, aged 13-17 years. The hypertriglyceridemic waist-to-height ratio (HWHtR) phenotype was defined as serum TG concentrations ≥1.47 mmol/L and WHtR ≥0.48 for boys and ≥0.46 for girls. Hypercholesterolemia (total cholesterol ≥5.18 mmol/L), high low-density lipoprotein cholesterol (LDL-C ≥3.37 mmol/L), low high-density lipoprotein cholesterol (HDL-C <1.03 mmol/L), and high non-HDL-C (≥3.76 mmol/L) were considered as atherogenic lipid profiles. After control for age and sex, adolescents with the HWHtR phenotype were more likely to have hypercholesterolemia (odds ratio (OR) = 7.8, 95 % confidence interval (CI) = 3.5-17.3, P < 0.001), high LDL-C (OR = 9.4, 95 % CI = 2.8-31.2, P < 0.001), low HDL-C (OR = 10.8, 95 % CI = 6.9-17.0, P < 0.001), and high non-HDL-C (OR = 22.9, 95 % CI = 10.0-52.2, P < 0.001) than those adolescents with normal WHtR and normal serum TG concentrations. The present study demonstrates that HWHtR phenotype is a simple marker for identifying adolescents with atherogenic lipid profile. Compared with HW phenotype, HWHtR phenotype is a non-age-dependent index with higher applicability to screen for cardiovascular risk factors in adolescents. • The hypertriglyceridemic waist phenotype is represented by the simultaneous presence of elevated serum triacylglycerol and increased waist circumference. Hypertriglyceridemic waist phenotype can identify adolescents with metabolic syndrome. But the cutoffs of waist circumference are age- and gender-specific standards and are less feasible for non-professional use. • The present study demonstrates that hypertriglyceridemic waist-to-height ratio phenotype is a simple marker for identifying adolescents with atherogenic lipid profile. Compared with hypertriglyceridemic waist phenotype, hypertriglyceridemic waist-to-height ratio phenotype is a non-age-dependent index with higher applicability to screen for cardiovascular risk factors in adolescents.
Facial profile esthetic preferences: perception in two Brazilian states
de Oliveira, Marina Detoni Vieira; da Silveira, Bruno Lopes; Mattos, Cláudia Trindade; Marquezan, Mariana
2015-01-01
OBJECTIVE: The aim of this study was to assess the regional influence on the perception of facial profile esthetics in Rio de Janeiro state (RJ) and Rio Grande do Sul state (RS), Brazil. METHODS: Two Caucasian models, a man and a woman, with balanced facial profiles, had their photographs digitally manipulated so as to produce seven different profiles. First year dental students (laypeople) assessed the images and classified them according to their esthetic preference. RESULTS: The result of the t test for independent samples showed differences among states for certain facial profiles. The female photograph identified with the letter 'G' (mandibular retrusion) received higher scores in RS state (p = 0.006). No differences were found for male photographs (p > 0.007). The evaluators' sex seemed not to influence their esthetic perception (p > 0.007). Considering all evaluators together, ANOVA/Tukey's test showed differences among the profiles (p ≤ 0.05) for both male and female photographs. The female photograph that received the highest score was the one identified with the letter 'F' (dentoalveolar bimaxillary retrusion/ straight profile). For the male profiles, photograph identified with the letter 'E' (dentoalveolar bimaxillary protrusion/ straight profile) received the best score. CONCLUSION: Regional differences were observed regarding preferences of facial profile esthetics. In Rio de Janeiro state, more prominent lips were preferred while in Rio Grande do Sul state, profiles with straight lips were favored. Class III profiles were considered less attractive. PMID:26154461
Diagnosis and therapy of oral squamous cell carcinoma.
Konkimalla, V Badireenath; Suhas, Venkatramana Laxminarayana; Chandra, Nagasuma R; Gebhart, Erich; Efferth, Thomas
2007-03-01
Oral squamous cell carcinoma ranks among the top ten most common cancers worldwide. Despite the success in diagnosis and therapy during the past 30 years, oral squamous cell carcinoma still belongs to the tumor types with a very unfavorable prognosis. In an effort to identify genomic alterations with prognostic relevance, we applied the comparative genomic hybridization technique on oral squamous cell carcinoma. The tumors exhibited from five up to 47 DNA copy number alterations, indicating a considerable degree of genomic imbalance. Out of 35 tumors, 19 showed a gain of chromosome band 7p12. Genomic imbalances were investigated by hierarchical cluster analysis and clustered image mapping to investigate whether genomic profiles correlate with clinical data. Results of the present investigation show that profiling of genomic imbalances in general, and especially of the epidermal growth factor receptor (EGFR) on 7p12, may be suitable as prognostic factors. In order to identify small-molecule inhibitors for EGFR, we established a database of 531 natural compounds derived from medicinal plants used in traditional Chinese medicine. Candidate compounds were identified by correlation analysis using the Kendall tau-test of IC50 values of tumor cell lines and microarray-based EGFR mRNA expression. Further validation was performed by molecular docking studies using the AutoDock program with the crystal structure of EGFR tyrosine kinase domain as docking template. We estimate these results will be a further step toward the ultimate goal of individualized, patient-adapted tumor treatment based on tumor molecular profiling.
Wang, Kehua; Liu, Yanrong; Tian, Jinli; Huang, Kunyong; Shi, Tianran; Dai, Xiaoxia; Zhang, Wanjun
2017-01-01
Perennial ryegrass (Lolium perenne) is one of the most widely used forage and turf grasses in the world due to its desirable agronomic qualities. However, as a cool-season perennial grass species, high temperature is a major factor limiting its performance in warmer and transition regions. In this study, a de novo transcriptome was generated using a cDNA library constructed from perennial ryegrass leaves subjected to short-term heat stress treatment. Then the expression profiling and identification of perennial ryegrass heat response genes by digital gene expression analyses was performed. The goal of this work was to produce expression profiles of high temperature stress responsive genes in perennial ryegrass leaves and further identify the potentially important candidate genes with altered levels of transcript, such as those genes involved in transcriptional regulation, antioxidant responses, plant hormones and signal transduction, and cellular metabolism. The de novo assembly of perennial ryegrass transcriptome in this study obtained more total and annotated unigenes compared to previously published ones. Many DEGs identified were genes that are known to respond to heat stress in plants, including HSFs, HSPs, and antioxidant related genes. In the meanwhile, we also identified four gene candidates mainly involved in C4 carbon fixation, and one TOR gene. Their exact roles in plant heat stress response need to dissect further. This study would be important by providing the gene resources for improving heat stress tolerance in both perennial ryegrass and other cool-season perennial grass plants. PMID:28680431
Free DICOM de-identification tools in clinical research: functioning and safety of patient privacy.
Aryanto, K Y E; Oudkerk, M; van Ooijen, P M A
2015-12-01
To compare non-commercial DICOM toolkits for their de-identification ability in removing a patient's personal health information (PHI) from a DICOM header. Ten DICOM toolkits were selected for de-identification tests. Tests were performed by using the system's default de-identification profile and, subsequently, the tools' best adjusted settings. We aimed to eliminate fifty elements considered to contain identifying patient information. The tools were also examined for their respective methods of customization. Only one tool was able to de-identify all required elements with the default setting. Not all of the toolkits provide a customizable de-identification profile. Six tools allowed changes by selecting the provided profiles, giving input through a graphical user interface (GUI) or configuration text file, or providing the appropriate command-line arguments. Using adjusted settings, four of those six toolkits were able to perform full de-identification. Only five tools could properly de-identify the defined DICOM elements, and in four cases, only after careful customization. Therefore, free DICOM toolkits should be used with extreme care to prevent the risk of disclosing PHI, especially when using the default configuration. In case optimal security is required, one of the five toolkits is proposed. • Free DICOM toolkits should be carefully used to prevent patient identity disclosure. • Each DICOM tool produces its own specific outcomes from the de-identification process. • In case optimal security is required, using one DICOM toolkit is proposed.
Exploring Game Performance in the National Basketball Association Using Player Tracking Data
Calleja-González, Julio; Jiménez Sáiz, Sergio; Schelling i del Alcázar, Xavi; Balciunas, Mindaugas
2015-01-01
Recent player tracking technology provides new information about basketball game performance. The aim of this study was to (i) compare the game performances of all-star and non all-star basketball players from the National Basketball Association (NBA), and (ii) describe the different basketball game performance profiles based on the different game roles. Archival data were obtained from all 2013-2014 regular season games (n = 1230). The variables analyzed included the points per game, minutes played and the game actions recorded by the player tracking system. To accomplish the first aim, the performance per minute of play was analyzed using a descriptive discriminant analysis to identify which variables best predict the all-star and non all-star playing categories. The all-star players showed slower velocities in defense and performed better in elbow touches, defensive rebounds, close touches, close points and pull-up points, possibly due to optimized attention processes that are key for perceiving the required appropriate environmental information. The second aim was addressed using a k-means cluster analysis, with the aim of creating maximal different performance profile groupings. Afterwards, a descriptive discriminant analysis identified which variables best predict the different playing clusters. The results identified different playing profile of performers, particularly related to the game roles of scoring, passing, defensive and all-round game behavior. Coaching staffs may apply this information to different players, while accounting for individual differences and functional variability, to optimize practice planning and, consequently, the game performances of individuals and teams. PMID:26171606
Exploring Game Performance in the National Basketball Association Using Player Tracking Data.
Sampaio, Jaime; McGarry, Tim; Calleja-González, Julio; Jiménez Sáiz, Sergio; Schelling I Del Alcázar, Xavi; Balciunas, Mindaugas
2015-01-01
Recent player tracking technology provides new information about basketball game performance. The aim of this study was to (i) compare the game performances of all-star and non all-star basketball players from the National Basketball Association (NBA), and (ii) describe the different basketball game performance profiles based on the different game roles. Archival data were obtained from all 2013-2014 regular season games (n = 1230). The variables analyzed included the points per game, minutes played and the game actions recorded by the player tracking system. To accomplish the first aim, the performance per minute of play was analyzed using a descriptive discriminant analysis to identify which variables best predict the all-star and non all-star playing categories. The all-star players showed slower velocities in defense and performed better in elbow touches, defensive rebounds, close touches, close points and pull-up points, possibly due to optimized attention processes that are key for perceiving the required appropriate environmental information. The second aim was addressed using a k-means cluster analysis, with the aim of creating maximal different performance profile groupings. Afterwards, a descriptive discriminant analysis identified which variables best predict the different playing clusters. The results identified different playing profile of performers, particularly related to the game roles of scoring, passing, defensive and all-round game behavior. Coaching staffs may apply this information to different players, while accounting for individual differences and functional variability, to optimize practice planning and, consequently, the game performances of individuals and teams.
Latent profiles of perceived time adequacy for paid work, parenting, and partner roles.
Lee, Soomi; Almeida, David M; Davis, Kelly D; King, Rosalind B; Hammer, Leslie B; Kelly, Erin L
2015-10-01
This study examined feelings of having enough time (i.e., perceived time adequacy) in a sample of employed parents (N = 880) in information technology and extended-care industries. Adapting a person-centered latent profile approach, we identified 3 profiles of perceived time adequacy for paid work, parenting, and partner roles: family time protected, family time sacrificed, and time balanced. Drawing upon the conservation of resources theory (Hobfòll, 1989), we examined the associations of stressors and resources with the time adequacy profiles. Parents in the family time sacrificed profile were more likely to be younger, women, have younger children, work in the extended-care industry, and have nonstandard work schedules compared to those in the family time protected profile. Results from multinomial logistic regression analyses revealed that, with the time balanced profile as the reference group, having fewer stressors and more resources in the family context (less parent-child conflict and more partner support), work context (longer company tenure, higher schedule control and job satisfaction), and work-family interface (lower work-to-family conflict) was linked to a higher probability of membership in the family time protected profile. By contrast, having more stressors and fewer resources, in the forms of less partner support and higher work-to-family conflict, predicted a higher likelihood of being in the family time sacrificed profile. Our findings suggest that low work-to-family conflict is the most critical predictor of membership in the family time protected profile, whereas lack of partner support is the most important factor to be included in the family time sacrificed profile. (c) 2015 APA, all rights reserved).
Ritchey, Jamie; Karmaus, Wilfried; Sabo-Attwood, Tara; Steck, Susan E; Zhang, Hongmei
2012-01-01
Objectives Since sex hormone markers are metabolically linked, examining sex steroid hormones singly may account for inconsistent findings by age, race/ethnicity and body mass index (BMI) across studies. First, these markers were statistically combined into profiles to account for the metabolic relationship between markers. Then, the relationships between sex steroid hormone profiles and age, race/ethnicity and BMI were explored in multinomial logistic regression models. Design Cross-sectional survey. Setting The US Third National Health and Nutrition Examination Survey (NHANES III). Participants 1538 Men, >17 years. Primary outcome measure Sex hormone profiles. Results Cluster analysis was used to identify four statistically determined profiles with Blom-transformed T, E, sex hormone binding globulin (SHBG), and 3-α diol G. We used these four profiles with multinomial logistic regression models to examine differences by race/ethnicity, age and BMI. Mexican American men >50 years were associated with the profile that had lowest T, E and 3-α diol G levels compared to other profiles (p<0.05). Non-Hispanic Black, overweight (25–29.9 kg/m2) and obese (>30 kg/m2) men were most likely to be associated with the cluster with the lowest SHBG (p<0.05). Conclusion The associations of sex steroid hormone profiles by race/ethnicity are novel, while the findings by age and BMI groups are largely consistent with observations from single hormone studies. Future studies should validate these hormone profile groups and investigate these profiles in relation to chronic diseases and certain cancers. PMID:23043125
Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa
Näsström, Elin; Parry, Christopher M; Vu Thieu, Nga Tran; Maude, Rapeephan R; de Jong, Hanna K; Fukushima, Masako; Rzhepishevska, Olena; Marks, Florian; Panzner, Ursula; Im, Justin; Jeon, Hyonjin; Park, Seeun; Chaudhury, Zabeen; Ghose, Aniruddha; Samad, Rasheda; Van, Tan Trinh; Johansson, Anders; Dondorp, Arjen M; Thwaites, Guy E; Faiz, Abul; Antti, Henrik; Baker, Stephen
2017-01-01
Salmonella Typhi is the causative agent of typhoid. Typhoid is diagnosed by blood culture, a method that lacks sensitivity, portability and speed. We have previously shown that specific metabolomic profiles can be detected in the blood of typhoid patients from Nepal (Näsström et al., 2014). Here, we performed mass spectrometry on plasma from Bangladeshi and Senegalese patients with culture confirmed typhoid fever, clinically suspected typhoid, and other febrile diseases including malaria. After applying supervised pattern recognition modelling, we could significantly distinguish metabolite profiles in plasma from the culture confirmed typhoid patients. After comparing the direction of change and degree of multivariate significance, we identified 24 metabolites that were consistently up- or down regulated in a further Bangladeshi/Senegalese validation cohort, and the Nepali cohort from our previous work. We have identified and validated a metabolite panel that can distinguish typhoid from other febrile diseases, providing a new approach for typhoid diagnostics. DOI: http://dx.doi.org/10.7554/eLife.15651.001 PMID:28483042
Guthke, Reinhard; Möller, Ulrich; Hoffmann, Martin; Thies, Frank; Töpfer, Susanne
2005-04-15
The immune response to bacterial infection represents a complex network of dynamic gene and protein interactions. We present an optimized reverse engineering strategy aimed at a reconstruction of this kind of interaction networks. The proposed approach is based on both microarray data and available biological knowledge. The main kinetics of the immune response were identified by fuzzy clustering of gene expression profiles (time series). The number of clusters was optimized using various evaluation criteria. For each cluster a representative gene with a high fuzzy-membership was chosen in accordance with available physiological knowledge. Then hypothetical network structures were identified by seeking systems of ordinary differential equations, whose simulated kinetics could fit the gene expression profiles of the cluster-representative genes. For the construction of hypothetical network structures singular value decomposition (SVD) based methods and a newly introduced heuristic Network Generation Method here were compared. It turned out that the proposed novel method could find sparser networks and gave better fits to the experimental data. Reinhard.Guthke@hki-jena.de.
Borges, Cristine Vanz; Amorim, Vanusia Batista de Oliveira; Ramlov, Fernanda; Ledo, Carlos Alberto da Silva; Donato, Marcela; Maraschin, Marcelo; Amorim, Edson Perito
2014-02-15
The banana is an important, widely consumed fruit, especially in areas of rampant undernutrition. Twenty-nine samples were analysed, including 9 diploids, 13 triploids and 7 tetraploids, in the Active Germplasm Bank, at Embrapa Cassava & Fruits, to evaluate the bioactive compounds. The results of this study reveal the presence of a diversity of bioactive compounds, e.g., catechins; they are phenolic compounds with high antioxidant potential and antitumour activity. In addition, accessions with appreciable amounts of pVACs were identified, especially compared with the main cultivars that are currently marketed. The ATR-FTIR, combined with principal components analysis, identified accessions with distinct metabolic profiles in the fingerprint regions of compounds important for human health. Likewise, starch fraction characterisation allowed discrimination of accessions according to their physical, chemical, and functional properties. The results of this study demonstrate that the banana has functional characteristics endowing it with the potential to promote human health. Copyright © 2013 Elsevier Ltd. All rights reserved.
Murine mesenchymal and embryonic stem cells express a similar Hox gene profile.
Phinney, Donald G; Gray, Andrew J; Hill, Katy; Pandey, Amitabh
2005-12-30
Using degenerate oligonucleotide primers targeting the homeobox domain, we amplified by PCR and sequenced 723 clones from five murine cell populations and lines derived from embryonic mesoderm and adult bone marrow. Transcripts from all four vertebrate Hox clusters were expressed by the different populations. Hierarchical clustering of the data revealed that mesenchymal stem cells (MSCs) and the embryonic stem (ES) cell line D3 shared a similar Hox expression profile. These populations exclusively expressed Hoxb2, Hoxb5, Hoxb7, and Hoxc4, transcripts regulating self-renewal and differentiation of other stem cells. Additionally, Hoxa7 transcript quantified by real-time PCR strongly correlated (r2=0.89) with the number of Hoxa7 clones identified by sequencing, validating that data from the PCR screen reflects differences in Hox mRNA abundance between populations. This is the first study to catalogue Hox transcripts in murine MSCs and by comparative analyses identify specific Hox genes that may contribute to their stem cell character.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Apel, William A; Thompson, Vicki S
A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immunemore » complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.« less
Rapid classification of biological components
Thompson, Vicki S.; Barrett, Karen B.; Key, Diane E.
2013-10-15
A method is disclosed for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an illustrative embodiment of the invention, the analyte is a drug, such as marijuana, cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method involves attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein the locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to antigens in the array, thereby forming immune complexes; washing away antibodies that do not form immune complexes; and detecting the immune complexes, thereby forming an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to a subject's identity.
Rapid classification of biological components
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thompson, Vicki S.; Barrett, Karen B.; Key, Diane E.
A method is disclosed for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an illustrative embodiment of the invention, the analyte is a drug, such as marijuana, cocaine, methamphetamine, methyltestosterone, or mesterolone. The method involves attaching antigens to the surface of a solid support in a preselected pattern to form an array wherein the locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to antigens in the array, thereby forming immunemore » complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, thereby forming an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.« less
Protein profile in HBx transfected cells: a comparative iTRAQ-coupled 2D LC-MS/MS analysis.
Feng, Huixing; Li, Xi; Niu, Dandan; Chen, Wei Ning
2010-06-16
The x protein of HBV (HBx) has been involved in the development of hepatocellular carcinoma (HCC), with a possible link to individual genotypes. Nevertheless, the underlying mechanism remains obscure. In this study, we aim to identify the HBx-induced protein profile in HepG2 cells by LC-MS/MS proteomics analysis. Our results indicated that proteins were differentially expressed in HepG2 cells transfected by HBx of various genotypes. Proteins associated with cytoskeleton were found to be either up-regulated (MACF1, HMGB1, Annexin A2) or down-regulated (Lamin A/C). These may in turn result in the decrease of focal adhesion and increase of cell migration in response to HBx. Levels of other cellular proteins with reported impact on the function of extracellular matrix (ECM) proteins and cell migration, including Ca(2+)-binding proteins (S100A11, S100A6, and S100A4) and proteasome protein (PSMA3), were affected by HBx. The differential protein profile identified in this study was also supported by our functional assay which indicated that cell migration was enhanced by HBx. Our preliminary study provided a new platform to establish a comprehensive cellular protein profile by LC-MS/MS proteomics analysis. Further downstream functional assays, including our reported cell migration assay, should provide new insights in the association between HCC and HBx. Copyright 2009 Elsevier B.V. All rights reserved.
Chang, Chunxin; Chen, Minjian; Gao, Jiawei; Luo, Jia; Wu, Keqin; Dong, Tianyu; Zhou, Kun; He, Xiaowei; Hu, Weiyue; Wu, Wei; Lu, Chuncheng; Hang, Bo; Meeker, John D; Wang, Xinru; Xia, Yankai
2017-05-01
Although various pesticides were used globally, the pesticides profiles in human blood serum remain largely unknown. We determined pesticide exposure profiles using solid-phase extraction and gas chromatography tandem with triple quadrupole mass spectrometry in 200 human blood serum samples from the adult population in Jiangsu Province, China. A systematic and comprehensive literature review was carried out to identify the articles investigating pesticide exposure and compare exposure data. Of the 88 pesticides, 76 were found in the blood serum of the population in Jiangsu Province. To the best of our knowledge, 58 pesticides were reported in human blood serum for the first time, and among these pesticides, parathion-methyl, pyrimethanil, fluacrypyrim, simazine, cloquintocet-mexyl and barban were debatable in more than half of the samples. By statistical comparison of the blood serum levels of pesticides between this study and other countries, we found the levels of several organochlorine pesticides were significantly higher in the female population of Jiangsu Province. Health risks related to the pesticide profiling were then revealed, which identified higher carcinogenic toxicity and teratogenic toxicity risk in the female adults of Jiangsu Province caused by organochlorine pesticide exposure. This study not only provides a high-throughput pesticide screening method for future studies of the exposome, but also presents the first human data on exposure to a number of pesticides. It may provide a knowledge database for the risk assessment and management of the pesticides. Copyright © 2017 Elsevier Ltd. All rights reserved.
Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer.
Hannemann, Juliane; Oosterkamp, Hendrika M; Bosch, Cathy A J; Velds, Arno; Wessels, Lodewyk F A; Loo, Claudette; Rutgers, Emiel J; Rodenhuis, Sjoerd; van de Vijver, Marc J
2005-05-20
At present, clinically useful markers predicting response of primary breast carcinomas to either doxorubicin-cyclophosphamide (AC) or doxorubicin-docetaxel (AD) are lacking. We investigated whether gene expression profiles of the primary tumor could be used to predict treatment response to either of those chemotherapy regimens. Within a single-institution, randomized, phase II trial, patients with locally advanced breast cancer received six courses of either AC (n = 24) or AD (n = 24) neoadjuvant chemotherapy. Gene expression profiles were generated from core-needle biopsies obtained before treatment and correlated with the response of the primary tumor to the chemotherapy administered. Additionally, pretreatment gene expression profiles were compared with those in tumors remaining after chemotherapy. Ten (20%) of 48 patients showed a (near) pathologic complete remission of the primary tumor after treatment. No gene expression pattern correlating with response could be identified for all patients or for the AC or AD groups separately. The comparison of the pretreatment biopsy and the tumor excised after chemotherapy revealed differences in gene expression in tumors that showed a partial remission but not in tumors that did not respond to chemotherapy. No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.