Varcasia, O; Garasto, S; Rizza, T
In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...
Many studies in mathematics education research occur with a nonrepresentative sample and are never replicated. To challenge this paradigm, I designed a large-scale study evaluating student conceptions in group theory that surveyed a national, representative sample of students. By replicating questions previously used to build theory around student…
Cook, Bryan G.; Collins, Lauren W.; Cook, Sara C.; Cook, Lysandra
Replication research is essential to scientific knowledge. Reviews of replication studies often electronically search for "replicat*" as a textword, which does not identify studies that replicate previous research but do not self-identify as such. We examined whether the 83 intervention studies published in six non-categorical research…
Parvin Akter Khanam
Full Text Available BIRDEM is the largest referral center of diabetes in the world. It registered more than 300,000 diabetic patients from 1956 to 2005. This retrospective study compared the biophysical characteristics of diabetic patients registered in 1995 to those registered in 2005. Information on social (income, education, clinical (height, weight, blood pressure and oral glucose tolerance (OGTT of patients registered in 1995 and 2005 were retrieved from the BIRDEM registry. The age group ³ 20y was considered eligible. Overall, there were 11489 patients for 1995 and 19580 for 2005. Compared with the registry of 1995, a significant increase of registry for female patients were observed (39.5 vs. 46.7%, p<0.001 and also the rural population (31.9 vs. 47.4%, p<0.001. Likewise, the number of poor social class was also found higher in 2005 (5.2 vs. 25.5%, p<0.001. Young aged (<40y registry was also significantly higher in 2005 (34.4 vs. 37.1%, p<0.001. Compared with the registered patients of 1995, adjusted for sex and area, those of 2005 had a significantly higher BMI, higher FPG and higher 2hPG (for all, p<0.001. In contrast, a significantly lower age, lower height and lower blood pressure were observed in those of 2005. We conclude that the age at registration for diabetes has decreased significantly in 2005 compared to that in 1995 indicating an earlier onset of diabetes. Significantly higher obesity in the year 2005 than 1995 indicates that there has been an increase in obesity that might be an important contributing factor for earlier onset of diabetes. Ibrahim Med. Coll. J. 2008; 2(1: 1-3
Paula de Holanda Mendes
Full Text Available OBJECTIVES: cigarette smoking has been the modifiable risk factor most consistently associated with earlier menopause. This preliminary study based on cross-sectional data aimed to analyze the association between smoking status and age of onset of menopause in a Brazilian population. METHODS: a cross-sectional study was carried out with 1,222 female employees of Rio de Janeiro university campuses aged over 35 years who were at risk of natural menopause. A Cox proportional hazards model was used to investigate the association between smoking status and age at the onset of menopause, adjusting for education, parity and alcohol consumption. RESULTS: current smokers showed a 56% increase in the risk of menopause, being 1.8 years younger at menopause onset compared with women who had never smoked. However, no differences were observed between former smokers and women who had never smoked. The adjusted median age at menopause was 49.5 years for current smokers and 51.3 years for women who had never smoked (p<0.05. CONCLUSIONS: the results suggest a deleterious but potentially reversible effect of smoking on the age of onset of menopause, which should receive greater attention in tobacco control efforts. Longitudinal analyses of this association will be carried out in the future in a follow-up study of this population.
Patil, Prasad; Peng, Roger D; Leek, Jeffrey T
A recent study of the replicability of key psychological findings is a major contribution toward understanding the human side of the scientific process. Despite the careful and nuanced analysis reported, the simple narrative disseminated by the mass, social, and scientific media was that in only 36% of the studies were the original results replicated. In the current study, however, we showed that 77% of the replication effect sizes reported were within a 95% prediction interval calculated using the original effect size. Our analysis suggests two critical issues in understanding replication of psychological studies. First, researchers' intuitive expectations for what a replication should show do not always match with statistical estimates of replication. Second, when the results of original studies are very imprecise, they create wide prediction intervals-and a broad range of replication effects that are consistent with the original estimates. This may lead to effects that replicate successfully, in that replication results are consistent with statistical expectations, but do not provide much information about the size (or existence) of the true effect. In this light, the results of the Reproducibility Project: Psychology can be viewed as statistically consistent with what one might expect when performing a large-scale replication experiment. © The Author(s) 2016.
Anderson, Samantha F; Maxwell, Scott E
Psychology is undergoing a replication crisis. The discussion surrounding this crisis has centered on mistrust of previous findings. Researchers planning replication studies often use the original study sample effect size as the basis for sample size planning. However, this strategy ignores uncertainty and publication bias in estimated effect sizes, resulting in overly optimistic calculations. A psychologist who intends to obtain power of .80 in the replication study, and performs calculations accordingly, may have an actual power lower than .80. We performed simulations to reveal the magnitude of the difference between actual and intended power based on common sample size planning strategies and assessed the performance of methods that aim to correct for effect size uncertainty and/or bias. Our results imply that even if original studies reflect actual phenomena and were conducted in the absence of questionable research practices, popular approaches to designing replication studies may result in a low success rate, especially if the original study is underpowered. Methods correcting for bias and/or uncertainty generally had higher actual power, but were not a panacea for an underpowered original study. Thus, it becomes imperative that 1) original studies are adequately powered and 2) replication studies are designed with methods that are more likely to yield the intended level of power.
David, Daniel; Brown, Richard J
Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.
Kulke, Louisa; von Duhn, Britta; Schneider, Dana; Rakoczy, Hannes
Recently, theory-of-mind research has been revolutionized by findings from novel implicit tasks suggesting that at least some aspects of false-belief reasoning develop earlier in ontogeny than previously assumed and operate automatically throughout adulthood. Although these findings are the empirical basis for far-reaching theories, systematic replications are still missing. This article reports a preregistered large-scale attempt to replicate four influential anticipatory-looking implicit theory-of-mind tasks using original stimuli and procedures. Results showed that only one of the four paradigms was reliably replicated. A second set of studies revealed, further, that this one paradigm was no longer replicated once confounds were removed, which calls its validity into question. There were also no correlations between paradigms, and thus, no evidence for their convergent validity. In conclusion, findings from anticipatory-looking false-belief paradigms seem less reliable and valid than previously assumed, thus limiting the conclusions that can be drawn from them.
Burns, Karen E A; Meade, Maureen O; Lessard, Martin R; Hand, Lori; Zhou, Qi; Keenan, Sean P; Lellouche, Francois
Automated weaning has not been compared with a paper-based weaning protocol in North America. We conducted a pilot randomized trial comparing automated weaning with protocolized weaning in critically ill adults to evaluate clinician compliance and acceptance of the weaning and sedation protocols, recruitment, and impact on outcomes. From August 2007 to October 2009, we enrolled critically ill adults requiring more than 24 hours of mechanical ventilation and at least partial reversal of the condition precipitating respiratory failure at nine Canadian intensive care units. We randomized patients who tolerated at least 30 minutes of pressure support and either failed or were not yet ready to undergo a spontaneous breathing trial to automated or protocolized weaning. Both groups used pressure support, included spontaneous breathing trials, used a common positive end-expiratory pressure-FI(O(2)) chart, sedation protocol, and criteria for extubation, reintubation, and noninvasive ventilation. We recruited 92 patients (49 automated, 43 protocolized) over 26 months. Adherence to assigned weaning protocols and extreme sedation scale scores fell within prespecified thresholds. Combined physician-respiratory therapist and nurse acceptance scores of the study weaning and sedation protocols, respectively, were not significantly different. Automated weaning patients had significantly shorter median times to first successful spontaneous breathing trial (1.0 vs. 4.0 d; P 4.0 d; P = 0.02), and successful extubation (4.0 vs. 5.0 d; P = 0.01), and underwent fewer tracheostomies and episodes of protracted ventilation. Compared with a standardized protocol, automated weaning was associated with promising outcomes that warrant further investigation. Minor protocol modifications may increase compliance, facilitate recruitment, and enhance feasibility. Clinical trial registered with www.controlled-trials.com (ISRCTN43760151).
Ellens, D.J.; Sussenbach, J.S.; Jansz, H.S.
Replicating Ad5 DNA was isolated from nuclei of infected KB cells and studied by electron microscopy. Branched as well as unbranched linear intermediates were observed containing extended regions of single-stranded DNA. The relationship between the branched and unbranched structures was studied
Van Aert, Robbie C M; Van Assen, Marcel A.L.M.
The vast majority of published results in the literature is statistically significant, which raises concerns about their reliability. The Reproducibility Project Psychology (RPP) and Experimental Economics Replication Project (EE-RP) both replicated a large number of published studies in psychology
Bell, William H; Millar, A Paul; Capozza, Luigi; Stockinger, Kurt; Zini, Floriano
Computational grids process large, computationally intensive problems on small data sets. In contrast, data grids process large computational problems that in turn require evaluating, mining and producing large amounts of data. Replication, creating geographically disparate identical copies of data, is regarded as one of the major optimization techniques for reducing data access costs. In this paper, several replication algorithms are discussed. These algorithms were studied using the Grid simulator: OptorSim. OptorSim provides a modular framework within which optimization strategies can be studied under different Grid configurations. The goal is to explore the stability and transient behaviour of selected optimization techniques. We detail the design and implementation of OptorSim and analyze various replication algorithms based on different Grid workloads.
Aberg, Karolina A; Liu, Youfang; Bukszár, Jozsef
768 control subjects from 6 databases and, after quality control 6298 individuals (including 3286 cases) from 1811 nuclear families. MAIN OUTCOMES AND MEASURES Case-control status for SCZ. RESULTS Replication results showed a highly significant enrichment of SNPs with small P values. Of the SNPs...... in an independent family-based replication study that, after quality control, consisted of 8107 SNPs. SETTING Linkage meta-analysis, brain transcriptome meta-analysis, candidate gene database, OMIM, relevant mouse studies, and expression quantitative trait locus databases. PATIENTS We included 11 185 cases and 10...
McCullough, J P; McCune, K J; Kaye, A L; Braith, J A; Friend, R; Roberts, W C; Belyea-Caldwell, S; Norris, S L; Hampton, C
This study replicates an earlier naturalistic-prospective investigation of nontreatment, community DSM-III-R dysthymia subjects. Major goals were to determine spontaneous remission rates and monitor the stability of psychosocial functioning levels over time. Twenty-four dysthymia subjects were followed for 1 year. Three remissions (13%) were diagnosed at the final interview. At a 4-year diagnostic follow-up contact with the remitters only, one remitter had relapsed and two remained in remission. Subjects were monitored for depressive symptom intensity, personality functioning, general medical distress, cognitive functioning, coping stylistics, interpersonal functioning, quality of their social support resources, and general family functioning. Stable levels of psychosocial functioning were maintained across all measures over the 1-year period. Current psychometric findings confirm the conclusions of the earlier nontreatment prospective study that dysthymia is a chronic mood disorder with stable psychosocial features and is unlikely to remit spontaneously over time.
Van Heck, Perugini, Caprara and Froger (1994) report the average generalizability coefficient reflecting the consistent ordering of persons across different situations and different trait markers (items) to be in the order of 0.70. We performed a replication study in which we improved on their
Kafkafi, Neri; Agassi, Joseph; Chesler, Elissa J.; Crabbe, John C.; Crusio, Wim E.; Eilam, David; Gerlai, Robert; Golani, Ilan; Gomez-Marin, Alex; Heller, Ruth; Iraqi, Fuad; Jaljuli, Iman; Karp, Natasha A.; Morgan, Hugh; Nicholson, George; Pfaff, Donald W.; Richter, S. Helene; Stark, Philip B.; Stiedl, Oliver; Stodden, Victoria; Tarantino, Lisa M.; Tucci, Valter; Valdar, William; Williams, Robert W.; Würbel, Hanno; Benjamini, Yoav
The scientific community is increasingly concerned with the proportion of published “discoveries” that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex
van der Vennet, Renee; Serice, Susan
This experimental study replicated Curry and Kasser's (2005) research that tested whether coloring a mandala would reduce anxiety. After inducing an anxious mood via a writing activity, participants were randomly assigned to three groups that colored either on a mandala design, on a plaid design, or on a blank paper. Anxiety level was measured…
Full Text Available The adult height of children with early onset puberty is limited by the premature maturation of hypothalamic-pituitary-gonadal axis. To evaluate the effects of gonadotropin-releasing hormone analog (GnRHa treatment on the final height (FH and bone maturation rate (BMR in girls with early puberty (EP or idiopathic central precocious puberty (ICPP, we examined data from girls who were diagnosed with EP or ICPP and underwent GnRHa (Leuplin Depot: 3.75 mg/month at China Medical University Hospital, in Taiwan, between 2006 and 2015. Patients were observed until the achievement of FH and divided into an "EP group" (T-ep and "ICPP group" (T-icpp according to the age of onset of puberty. Eighty-seven patients were enrolled (T-ep, N = 44, puberty onset at 8-10 years; T-icpp, N = 43, puberty onset before 8 years. The demographic data of girls with EP or IPP was characterized. BMR, change in predicted final height (PFH after GnRHa treatment, target height (TH and FH were measured. After GnRHa treatment, the study groups (T-ep: 160.24±6.18 cm, T-icpp: 158.99±5.92 cm both had higher PFH than at initiation (T-ep: 159.83±7.19 cm, T-icpp: 158.58±5.93 cm. There was deceleration of BMR in both groups (T-ep: 0.57±0.39; T-icpp: 0.97±0.97 and a significant difference between the groups (p = 0.027. The gap in FH standard deviation scores (SDS and TH SDS had a significant difference in T-ep (p = 0.045 but not in T-icpp. Moreover, there was no difference in the gap of PFH SDS between the 1st and final treatment in both groups. We concluded that GnRHa decelerated BMR in girls with earlier puberty. Further prospective clinical studies are warranted.
Rapport, Frances; Shih, Patti; Mitchell, Rebecca; Nikpour, Armin; Bleasel, Andrew; Herkes, Geoffrey; Vagholkar, Sanjyot; Mumford, Virginia
One-third of patients with refractory epilepsy may be candidates for resective surgery, which can lead to positive clinical outcomes if efficiently managed. In Australia, there is currently between a 6-month and 2-year delay for patients who are candidates for respective epilepsy surgery from the point of referral for surgical assessment to the eventual surgical intervention. This is a major challenge for implementation of effective treatment for individuals who could potentially benefit from surgery. This study examines implications of delays following the point of eligibility for surgery, in the assessment and treatment of patients, and the factors causing treatment delays. Mixed methods design: Observations of qualitative consultations, patient and healthcare professional interviews, and health-related quality of life assessments for a group of 10 patients and six healthcare professionals (group 1); quantitative retrospective medical records' reviews examining longitudinal outcomes for 50 patients assessed for, or undergoing, resective surgery between 2014 and 2016 (group 2); retrospective epidemiological study of all individuals hospitalised with a diagnosis of epilepsy in New South Wales (NSW) in the last 5 years (2012-2016; approximately 11 000 hospitalisations per year, total 55 000), examining health services' use and treatment for individuals with epilepsy, including refractory surgery outcomes (group 3). Ethical approval has been granted by the North Sydney Local Health District Human Research Ethics Committee (HREC/17/HAWKE/22) and the NSW Population & Health Services Research Ethics Committee (HREC/16/CIPHS/1). Results will be disseminated through publications, reports and conference presentations to patients and families, health professionals and researchers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Balevre, Park S; Cassells, Julie; Buzaianu, Elena
This expanded (n = 648) replication study examines job-related burnout in practicing nurses in relation to five maladaptive thinking patterns at eight northeast Florida hospitals. Data supported the hypothesis that maladaptive thinking patterns may be related to nurses' burnout thoughts and behaviors. The focus of this research spotlights the individual nurse's thoughts, emotions, and actions and suggests that these burnout tendencies can be mitigated if not changed.
Dragicevic , Pierre; Jansen , Yvonne
International audience; We provide a reappraisal of Tal and Wansink's study "Blinded with Science" , where seemingly trivial charts were shown to increase belief in drug efficacy, presumably because charts are associated with science. Through a series of four replications conducted on two crowdsourcing platforms, we investigate an alternative explanation, namely, that the charts allowed participants to better assess the drug's efficacy. Considered together, our experiments suggest that the ch...
Counsell, S; Swift, S; Tucker, A
Visual Field (VF) tests and corresponding data are commonly used in clinical practices to manage glaucoma. The standard metric used to measure glaucoma severity is the Advanced Glaucoma Intervention Studies (AGIS) metric. We know that time of day when VF tests are applied can influence a patient’s AGIS metric value; a previous study showed that this was the case for a data set of 160 patients. In this paper, we replicate that study using data from 2468 patients obtained from Moorfields Eye Ho...
Bostyn, Dries H; Roets, Arne
The present manuscript addresses how perceived trustworthiness of cooperative partners in a social dilemma context is influenced by the moral judgments those partners make on Trolley-type moral dilemmas; an issue recently investigated by Everett, Pizarro, and Crockett (2016). The present research comprises 2 studies that were conducted independently, simultaneously with, and incognizant of the Everett studies. Whereas the present studies aimed at investigating the same research hypothesis, a different and more elaborate methodology was used, as such providing a conceptual replication opportunity and extension to the Everett et al. Overall, the present studies clearly confirmed the main finding of Everett et al., that deontologists are more trusted than consequentialists in social dilemma games. Study 1 replicates Everett et al.'s effect in the context of trust games. Study 2 generalizes the effect to public goods games, thus demonstrating that it is not specific to the type of social dilemma game used in Everett et al. Finally, both studies build on these results by demonstrating that the increased trust in deontologists may sometimes, but not always, be warranted: deontologists displayed increased cooperation rates but only in the public goods game and not in trust games. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Eshel, Yohanan; Kimhi, Shaul; Lahad, Mooli; Leykin, Dmitry; Goroshit, Marina
The present study was conducted in the context of current concerns about replication in psychological research. It claims that risk factors should be regarded as an integral part of the definition of individual resilience, which should be defined in terms of the balance between individual strength or protective factors, and individual vulnerability or risk factors (IND-SVR). Five independent samples, including 3457 Israeli participants, were employed to determine the effects of resilience promoting and resilience suppressing variables on the IND-SVR index of resilience, and on its two components: recovery from adversity, and distress symptoms. Five path analyses were employed for determining the role of distress symptoms as a measure of psychological resilience, as compared to other indices of this resilience. Results indicated the major role of risk factors (distress symptoms) as an integral component of resilience. This role was generally replicated in the five investigated samples. Risk factors are legitimate, valid, and useful parts of the definition of psychological resilience. Resilience research has shifted away from studying individual risk factors to investigating the process through which individuals overcome the hardships they experience. The present data seem to suggest that this shift should be reexamined.
Mason, Alice; Ludwig, Casimir; Farrell, Simon
Reward is thought to enhance episodic memory formation via dopaminergic consolidation. Bunzeck, Dayan, Dolan, and Duzel [(2010). A common mechanism for adaptive scaling of reward and novelty. Human Brain Mapping, 31, 1380-1394] provided functional magnetic resonance imaging (fMRI) and behavioural evidence that reward and episodic memory systems are sensitive to the contextual value of a reward-whether it is relatively higher or lower-as opposed to absolute value or prediction error. We carried out a direct replication of their behavioural study and did not replicate their finding that memory performance associated with reward follows this pattern of adaptive scaling. An effect of reward outcome was in the opposite direction to that in the original study, with lower reward outcomes leading to better memory than higher outcomes. There was a marginal effect of reward context, suggesting that expected value affected memory performance. We discuss the robustness of the reward memory relationship to variations in reward context, and whether other reward-related factors have a more reliable influence on episodic memory.
Kafkafi, Neri; Agassi, Joseph; Chesler, Elissa J; Crabbe, John C; Crusio, Wim E; Eilam, David; Gerlai, Robert; Golani, Ilan; Gomez-Marin, Alex; Heller, Ruth; Iraqi, Fuad; Jaljuli, Iman; Karp, Natasha A; Morgan, Hugh; Nicholson, George; Pfaff, Donald W; Richter, S Helene; Stark, Philip B; Stiedl, Oliver; Stodden, Victoria; Tarantino, Lisa M; Tucci, Valter; Valdar, William; Williams, Robert W; Würbel, Hanno; Benjamini, Yoav
The scientific community is increasingly concerned with the proportion of published "discoveries" that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues. The general consensus was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, have a key role in identifying specific problems and promoting effective solutions. Replicability is closely related to validity, may affect generalizability and translation of findings, and has important ethical implications. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Full Text Available About 30% of patients with Cystic Fibrosis (CF develop CF-associated liver disease (CFLD. Recent studies have shown that transient elastography (TE, as a method to quantify liver stiffness, allows non-invasive diagnosis of CFLD in adults and children with CF. Within this study we aimed to prospectively identify patients at risk for development of CFLD by longitudinal analysis of liver stiffness and fibrosis scores in a 5-year follow-up. 36 pediatric and 16 adult patients with initial liver stiffness below the cut-off value indicative of CFLD (6.3 kPa were examined by transient elastography for 4-5 years. TE, APRI-, and FIB-4-scores were assessed and compared by Kruskal-Wallis test and receiver operating characteristic (ROC-analysis. Frequencies were compared by Chi2-test. Among the 36 patients participating in this study, a subgroup of 9 patients developed liver stiffness >6.3 kPa after 4-5 years with an increase of ΔTE >0.38 kPa/a (the group with increasing liver stiffness was labelled TEinc. APRI- and FIB-4 scores confirmed the rationale for grouping. The frequency of CFLD assessed by conventional diagnosis was significantly higher in TEinc-group compared to the control group (TEnorm. None of the adult CF patients matched criteria for TEinc-group. For the first time it was shown that the non-invasive longitudinal assessment of TE allows identification of patients with progression of CFLD in a subgroup of juvenile but not in adult CF patients. Comparing TE to conventional fibrosis-scores underlined the strength of the continuous assessment of liver stiffness for the exact diagnosis of progressive CFLD. The newly described cut-off for pathologic increase of liver stiffness, ΔTEcutoff = 0.38kPa/a, might enable to detect developing CFLD using consequent follow up TE measurements before reaching the level of stiffness indicating established CFLD. Nevertheless, the limited size of the analyzed cohort should encourage a prospective, multi
Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François
To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings
Full Text Available To investigate the replication validity of biomedical association studies covered by newspapers.We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking and a non-lifestyle category (e.g. genetic risk. Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses.Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8% and subsequent (58/600 9.7% lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1% than subsequent ones (45/3718 1.2%. Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48 than subsequent ones (29/45 and than lifestyle studies (31/63. Psychiatric studies covered by newspapers were less often confirmed (10/38 than the neurological (26/41 or somatic (40/77 ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim.Journalists preferentially cover initial findings
Smith, Andy; Boraud, Thomas; Gonon, François
Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists
Malhotra, P.K.; Bajaj, S.S.
The twin unit boiling water reactor (BWR) station at TAPS has completed 30 years of power operation and for further extending plant operating life, a fresh extensive exercise involving review of plant operating performance, aging management and review of design bases and safety analysis has been carried out. The review exercise resulted in assessment of acceptability of identified non-conformances and recommendation for compensatory measures in the form of design modification or plant operating procedures. The second part of the exercise is related to safety analysis, which is carried out in view of the plant modifications done and advances taken place in methodologies of analytical techniques. Chiefly, it involves LOCA analysis done for various break sizes at different locations and plant transient studies. It also includes the fatigue analysis of the reactor pressure vessel. The related review approach adopted is presented here
Larsen, Mette Bach; Njor, Sisse; Ingeholm, Peter
program (March 1, 2014 through June 30, 2015). A total of 402,826 residents of Denmark (50-72 years old) were randomly invited to undergo CRC screening within the study period and 956,514 were invited thereafter. We obtained information on CRC diagnosis, date, and stage at diagnosis from the Danish.......6/100,000 not yet invited individuals. CRC incidence increased with age among invited and not yet invited individuals. For invited women compared to not yet invited women, the RR of being diagnosed with stage I CRC was 3.39 (95% CI, 2.61-4.39); with stage II CRC was 2.16 (95% CI, 1.71-2.72); with stage III CRC...
Alahdab, Fares; Farah, Wigdan; Almasri, Jehad; Barrionuevo, Patricia; Zaiem, Feras; Benkhadra, Raed; Asi, Noor; Alsawas, Mouaz; Pang, Yifan; Ahmed, Ahmed T; Rajjo, Tamim; Kanwar, Amrit; Benkhadra, Khalid; Razouki, Zayd; Murad, M Hassan; Wang, Zhen
To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Van Aert, R.C.M.; Van Assen, M.A.L.M.
The unrealistically high rate of positive results within psychology has increased the attention to replication research. However, researchers who conduct a replication and want to statistically combine the results of their replication with a statistically significant original study encounter
Leder, Steven B; Suiter, Debra M; Duffey, Dianne; Judson, Benjamin L
The purpose of this direct replication study was to confirm the incidence of vocal fold immobility (VFI) and its relationship to pharyngeal dysphagia and aspiration. Using a single-group consecutively referred case series, a total of 2,650 participants underwent fiberoptic endoscopic evaluation of swallowing between August 2003 and December 2007. Main outcome measures included overall incidence of VFI and aspiration status, with specific emphasis on age, gender, etiology and pharyngeal phase bolus flow characteristics, and side of VFI (right, left, or bilateral). These data were compared to and then combined with the original study (n = 1,452) for a total of 4,102 participants. Results indicated that the incidence of VFI was 4.3% (112/2,650), i.e., 27% (31/112) unilateral right, 58% (65/112) unilateral left, and 14% (16/112) bilateral. Incidence of aspiration was 22% (580/2,650). Of those with VFI, 40% (45/112) aspirated, i.e., 42% (13/31) unilateral right, 37% (24/65) unilateral left, and 50% (8/16) bilateral. An individual with VFI had 2.50 times the odds of aspirating as someone without VFI (95% CI = 1.86-3.37). For liquid aspiration, the odds ratio (OR) = 2.41 (95% CI = 1.77-3.28), and for puree aspiration, OR = 2.08 (95% CI = 1.47-2.93). Left VFI occurred most frequently due to surgical trauma. Liquid was aspirated more often than a puree. Males exhibited VFI more often than females. Side of VFI and age were not factors that increased the incidence of aspiration significantly. It was confirmed that VFI is not an uncommon finding during dysphagia testing and, when present, increased the odds of aspiration compared to a population already being evaluated for dysphagia.
Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason
To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test
Full Text Available This paper studies the scalability and replicability of smart grid projects. Currently, most smart grid projects are still in the R&D or demonstration phases. The full roll-out of the tested solutions requires a suitable degree of scalability and replicability to prevent project demonstrators from remaining local experimental exercises. Scalability and replicability are the preliminary requisites to perform scaling-up and replication successfully; therefore, scalability and replicability allow for or at least reduce barriers for the growth and reuse of the results of project demonstrators. The paper proposes factors that influence and condition a project’s scalability and replicability. These factors involve technical, economic, regulatory and stakeholder acceptance related aspects, and they describe requirements for scalability and replicability. In order to assess and evaluate the identified scalability and replicability factors, data has been collected from European and national smart grid projects by means of a survey, reflecting the projects’ view and results. The evaluation of the factors allows quantifying the status quo of on-going projects with respect to the scalability and replicability, i.e., they provide a feedback on to what extent projects take into account these factors and on whether the projects’ results and solutions are actually scalable and replicable.
Doabler, Christian T.; Clarke, Ben; Kosty, Derek B.; Kurtz-Nelson, Evangeline; Fien, Hank; Smolkowski, Keith; Baker, Scott K.
The purpose of this closely aligned conceptual replication study was to investigate the efficacy of a Tier 2 kindergarten mathematics intervention. The replication study differed from the initial randomized controlled trial on three important elements: geographical region, timing of the intervention, and instructional context of the…
Tamaru, Yoshiki; Naito, Yasuo; Nishikawa, Takashi
Elderly people are less able to manipulate objects skilfully than young adults. Although previous studies have examined age-related deterioration of hand movements with a focus on the phase after grasping objects, the changes in the reaching phase have not been studied thus far. We aimed to examine whether changes in hand shape patterns during the reaching phase of grasping movements differ between young adults and the elderly. Ten healthy elderly adults and 10 healthy young adults were examined using the Simple Test for Evaluating Hand Functions and kinetic analysis of hand pre-shaping reach-to-grasp tasks. The results were then compared between the two groups. For kinetic analysis, we measured the time of peak tangential velocity of the wrist and the inter-fingertip distance (the distance between the tips of the thumb and index finger) at different time points. The results showed that the elderly group's performance on the Simple Test for Evaluating Hand Functions was significantly lower than that of the young adult group, irrespective of whether the dominant or non-dominant hand was used, indicating deterioration of hand movement in the elderly. The peak tangential velocity of the wrist in either hand appeared significantly earlier in the elderly group than in the young adult group. The elderly group also showed larger inter-fingertip distances with arch-like fingertip trajectories compared to the young adult group for all object sizes. To perform accurate prehension, elderly people have an earlier peak tangential velocity point than young adults. This allows for a longer adjustment time for reaching and grasping movements and for reducing errors in object prehension by opening the hand and fingers wider. Elderly individuals gradually modify their strategy based on previous successes and failures during daily living to compensate for their decline in dexterity and operational capabilities. © 2017 Japanese Psychogeriatric Society.
Balakrishnan, Anjana; Palma, Paolo A; Patenaude, Joshua; Campbell, Lorne
Four replications of Piff and colleagues' study examined the moderating effects of greed attitudes on the relationship between socio-economic status (SES) and unethical behaviour (Study 7). In the original study, the researchers found that both greed and SES predicted increased propensity to engage in unethical behavior. Furthermore, this association was moderated such that the effects of SES on unethical behaviour were no longer present in the greed prime condition versus the neutral condition. In replication 1 of the original study main effects of greed attitudes and SES were found, but no interaction was found. Main effects for greed emerged in replications 3 and 4. However no main effects for SES or interactions emerged for replications 2-4. A meta-analysis was conducted with all replications and the original study, and found no moderating effect of greed on the relationship between SES and unethical behavior.
Banerjee, Rashida; Movahedazarhouligh, Sara; Millen, Kaitlyn; Luckner, John L.
Valid and evidence-informed practices are critical to help young children with disabilities and their families with highly effective interventions and instruction to reach their potentials. Replication research is critical for appraising research and identifying evidence-based practices. The purpose of this study was to replicate the methods used…
Hartman, Sarah; Widaman, Keith F; Belsky, Jay
Manuck, Craig, Flory, Halder, and Ferrell (2011) reported that a theoretically anticipated effect of family rearing on girls' menarcheal age was genetically moderated by two single nucleotide polymorphisms (SNPs) of the estrogen receptor-α gene. We sought to replicate and extend these findings, studying 210 White females followed from birth. The replication was general because a different measure of the rearing environment was used in this inquiry (i.e., maternal sensitivity) than in the prior one (i.e., family cohesion). Extensions of the work included prospective rather than retrospective measurements of the rearing environment, reports of first menstruation within a year of its occurrence rather than decades later, accounting for some heritability of menarcheal age by controlling for maternal age of menarche, and using a new model-fitting approach to competitively compare diathesis-stress versus differential-susceptibility models of Gene × Environment interaction. The replication/extension effort proved successful in the case of both estrogen receptor-α SNPs, with the Gene × Environment interactions principally reflecting diathesis-stress: lower levels of maternal sensitivity predicted earlier age of menarche for girls homozygous for the minor alleles of either SNP but not for girls carrying other genotypes. Results are discussed in light of the new analytic methods adopted.
Full Text Available Abstract Background The capacity of multiple comparisons to produce false positive findings in genetic association studies is abundantly clear. To address this issue, the concept of false positive report probability (FPRP measures "the probability of no true association between a genetic variant and disease given a statistically significant finding". This concept involves the notion of prior probability of an association between a genetic variant and a disease, making it difficult to achieve acceptable levels for the FPRP when the prior probability is low. Increasing the sample size is of limited efficiency to improve the situation. Methods To further clarify this problem, the concept of true report probability (TRP is introduced by analogy to the positive predictive value (PPV of diagnostic testing. The approach is extended to consider the effects of replication studies. The formula for the TRP after k replication studies is mathematically derived and shown to be only dependent on prior probability, alpha, power, and number of replication studies. Results Case-control association studies are used to illustrate the TRP concept for replication strategies. Based on power considerations, a relationship is derived between TRP after k replication studies and sample size of each individual study. That relationship enables study designers optimization of study plans. Further, it is demonstrated that replication is efficient in increasing the TRP even in the case of low prior probability of an association and without requiring very large sample sizes for each individual study. Conclusions True report probability is a comprehensive and straightforward concept for assessing the validity of positive statistical testing results in association studies. By its extension to replication strategies it can be demonstrated in a transparent manner that replication is highly effective in distinguishing spurious from true associations. Based on the generalized TRP
Larsen, Nicolai B; Hickson, Ian D; Mankouri, Hocine W
The high-affinity binding of the Tus protein to specific 21-bp sequences, called Ter, causes site-specific, and polar, DNA replication fork arrest in E coli. The Tus-Ter complex serves to coordinate DNA replication with chromosome segregation in this organism. A number of recent and ongoing studies...... have demonstrated that Tus-Ter can be used as a heterologous tool to generate site-specific perturbation of DNA replication when reconstituted in eukaryotes. Here, we review these recent findings and explore the molecular mechanism by which Tus-Ter mediates replication fork (RF) arrest in the budding...... yeast, S. cerevisiae. We propose that Tus-Ter is a versatile, genetically tractable, and regulatable RF blocking system that can be utilized for disrupting DNA replication in a diverse range of host cells....
Larsen, Nicolai B; Hickson, Ian D; Mankouri, Hocine W
The high-affinity binding of the Tus protein to specific 21-bp sequences, called Ter, causes site-specific, and polar, DNA replication fork arrest in E coli. The Tus-Ter complex serves to coordinate DNA replication with chromosome segregation in this organism. A number of recent and ongoing studies have demonstrated that Tus-Ter can be used as a heterologous tool to generate site-specific perturbation of DNA replication when reconstituted in eukaryotes. Here, we review these recent findings and explore the molecular mechanism by which Tus-Ter mediates replication fork (RF) arrest in the budding yeast, S. cerevisiae. We propose that Tus-Ter is a versatile, genetically tractable, and regulatable RF blocking system that can be utilized for disrupting DNA replication in a diverse range of host cells.
This paper presents an approximate replication of Milton's (2007) study on lexical profiles and learning style. Milton investigated the assumption that more frequent words are acquired before less frequent ones. Using a vocabulary recognition test ("X-Lex") to measure vocabulary size, Milton found that L2 English group profiles show…
Kelly, D.C.; Dimmock, N.J.
The replication of fowl plague virus in BHK and L cells specifically blocked prior to infection with inhibitors of influenza virus replication (actinomycin D and ultraviolet light irradiation) has been studied by the introduction of a metabolically dormant avian erythrocyte nucleus. This permits the synthesis of just the influenza virus nucleoprotein in actinomycin D (but not ultraviolet light) blocked cells. The NP antigen is first detected in the avian erythrocyte nucleus and subsequently in the heterokaryon cytoplasm
Higgins, M.L.; Koch, A.L.; Dicker, D.T.; Daneo-Moore, L.
Analysis of the distribution of autoradiographic grains around cells of Streptococcus faecium which had been either continuously or pulse-labeled with tritiated thymidine (mass doubling time, 90 min) showed a non-Poisson distribution even when the distribution of cell sizes in the populations studied was taken into account. These non-Poisson distributions of grains were assumed to reflect the discontinuous nature of chromosome replication. To study this discontinuous process further, an equation was fitted to the grain distribution observed for the pulse-labeled cells that assumed that in any population of cells there were subpopulations in which there were zero, one, or two replicating chromosomes. This analysis predicted an average time for chromosome replication and for the period between completion of rounds of chromosome replication and division of 55 and 43 min, respectively, which were in excellent agreement with estimates made by other techniques. The present investigation extended past studies in indicating that the initiation and completion of rounds of chromosome replication are poorly phased with increases in cell volume and that the amount of chromosome replication may be different in different cell halves
Replication studies allow for making comparisons and generalizations regarding the effectiveness of an intervention across different populations, versions of a treatment, settings and contexts, and outcomes. One method for making these comparisons across many replication studies is through the use of meta-analysis. A recent innovation in…
Mishra, Sandeep; Lalumière, Martin L; Williams, Robert J
Research suggests that high frequency gambling is a component of the "generality of deviance", which describes the observation that various forms of risky and antisocial behavior tend to co-occur among individuals. Furthermore, risky and antisocial behaviors have been associated with such personality traits as low self-control, and impulsivity, and sensation-seeking. We conducted a replication (and extension) of two previous studies examining whether high frequency gambling is part of the generality of deviance using a large and diverse community sample (n = 328). This study was conducted as a response to calls for more replication studies in the behavioral and psychological sciences (recent systematic efforts suggest that a significant proportion of psychology studies do not replicate). The results of the present study largely replicate those previously found, and in many cases, we observed stronger associations among measures of gambling, risk-taking, and antisocial behavior in this diverse sample. Together, this study provides evidence for the generality of deviance inclusive of gambling (and, some evidence for the replicability of research relating to gambling and individual differences).
Brasch-Andersen, C; Møller, M U; Haagerup, A
replication sample as used in the present study. The aim of the study was to replicate linkage to candidate regions for asthma in an independent Danish sample. METHODS: We performed a replication study investigating linkage to candidate regions for asthma on chromosomes 1p36.31-p36.21, 5q15-q23.2, 6p24.3-p22...... studies have been carried out the results are still conflicting and call for replication experiments. A Danish genome-wide scan has prior reported evidence for candidate regions for asthma susceptibility genes on chromosomes 1p, 5q, 6p, 12q and Xp. Linkage to chromosome 12q was later confirmed in the same.......3, and Xp22.31-p11.4 using additional markers in an independent set of 136 Danish asthmatic sib pair families. RESULTS: Nonparametric multipoint linkage analyses yielded suggestive evidence for linkage to asthma to chromosome Xp21.2 (MLS 2.92) but failed to replicate linkage to chromosomes 1p36.31-p36.21, 5...
Grunnet, L. G.; Hansen, S.; Hjort, L.
and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. RESEARCH DESIGN AND METHODS: We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan...... in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. RESULTS: After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic...... glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI...
Morrissey, Michael B; Hadfield, Jarrod D
Temporal variation in selection is a fundamental determinant of evolutionary outcomes. A recent paper presented a synthetic analysis of temporal variation in selection in natural populations. The authors concluded that there is substantial variation in the strength and direction of selection over time, but acknowledged that sampling error would result in estimates of selection that were more variable than the true values. We reanalyze their dataset using techniques that account for the necessary effect of sampling error to inflate apparent levels of variation and show that directional selection is remarkably constant over time, both in magnitude and direction. Thus we cannot claim that the available data support the existence of substantial temporal heterogeneity in selection. Nonetheless, we conject that temporal variation in selection could be important, but that there are good reasons why it may not appear in the available data. These new analyses highlight the importance of applying techniques that estimate parameters of the distribution of selection, rather than parameters of the distribution of estimated selection (which will reflect both sampling error and "real" variation in selection); indeed, despite availability of methods for the former, focus on the latter has been common in synthetic reviews of the aspects of selection in nature, and can lead to serious misinterpretations. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.
Laceulle, O.M.; Vollebergh, W.A.M.; Ormel, J.
This study aimed to replicate a study by Caspi and colleagues, which proposed that the structure of psychopathology is characterized by a general psychopathology factor, in addition to smaller internalizing and externalizing factors. Our study expanded the approach of the original by using
Full Text Available Genome-wide association studies (GWAS have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate replication rates. The remaining papers replicate significantly worse than expected (p < 10-14, even when adjusting for regression-to-the-mean of effect size between discovery- and replication-cohorts termed the Winner's Curse (p < 10-16. We show this is due in part to misreporting replication cohort-size as a maximum number, rather than per-locus one. In 39 studies accurately reporting per-locus cohort-size for attempted replication of 707 loci in samples with similar ancestry, replication rate matched expectation (predicted 458, observed 457, p = 0.94. In contrast, ancestry differences between replication and discovery (13 studies, 385 loci cause the most highly-powered decile of loci to replicate worse than expected, due to difference in linkage disequilibrium.
Montgomery, Paul; Spreckelsen, Thees F; Burton, Alice; Burton, Jennifer R; Richardson, Alexandra J
Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking. Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA) had beneficial effects on the reading, working memory, and behavior of healthy schoolchildren. Parallel group, fixed-dose, randomized (minimization, 30% random element), double-blind, placebo-controlled trial (RCT). Mainstream primary schools (n = 84) from five counties in the UK in 2012-2015. Healthy children aged 7-9 underperforming in reading (reading, working memory, and behavior, parent-rated and as secondary outcome teacher-rated. 376 children were randomized. Reading, working memory, and behavior change scores showed no consistent differences between intervention and placebo group. Some behavioral subscales showed minor group differences. This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior. Possible reasons are discussed, particularly regarding the replication of complex interventions. www.controlled-trials.com (ISRCTN48803273) and protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw).
Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François
Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability
Mason-Baughman, Mary Beth; Wallace, Sarah E.
Previous studies suggest that people with aphasia have incomplete lexical-semantic representations with decreased low-importance distinctive (LID) feature knowledge. In addition, decreased LID feature knowledge correlates with ability to discriminate among semantically related words. The current study seeks to replicate and extend previous…
Kremer, P.H.; Koeleman, B.P.C.; Rinkel, G.J.; Diekstra, F.P.; Berg, L.H. van den; Veldink, J.H.; Klijn, C.J.M.
BACKGROUND: Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations
Full Text Available Associations between dopamine receptor levels and pro- and antisocial behavior have previously been demonstrated in human subjects using positron emission tomography (PET and self-rated measures of personality traits. So far, only one study has focused on the dopamine D1-receptor (D1-R, finding a positive correlation with the trait social desirability, which is characterized by low dominant and high affiliative behavior, while physical aggression showed a negative correlation. The aim of the present study was to replicate these previous findings using a new independent sample of subjects.Twenty-six healthy males were examined with the radioligand [11C]SCH-23390, and completed the Swedish universities Scales of Personality (SSP which includes measures of social desirability and physical trait aggression. The simplified reference tissue model with cerebellum as reference region was used to calculate BPND values in the whole striatum and limbic striatum. The two regions were selected since they showed strong association between D1-R availability and personality scores in the previous study. Pearson's correlation coefficients and replication Bayes factors were then employed to assess the replicability and robustness of previous results.There were no significant correlations (all p values > 0.3 between regional BPND values and personality scale scores. Replication Bayes factors showed strong to moderate evidence in favor no relationship between D1-receptor availability and social desirability (striatum BF01 = 12.4; limbic striatum BF01 = 7.2 or physical aggression scale scores (limbic striatum BF01 = 3.3, compared to the original correlations.We could not replicate the previous findings of associations between D1-R availability and either pro- or antisocial behavior as measured using the SSP. Rather, there was evidence in favor of failed replications of associations between BPND and scale scores. Potential reasons for these results are restrictive
Galle, Per; Kovacs, L. B.
’ is refined into a method called ‘replication protocol analysis’ (RPA), and discussed from a methodological perspective of design research. It is argued that for the study of real-world design thinking this method offers distinct advantages over traditional ‘design protocol analysis’, which seeks to capture......Given the brief of an architectural competition on site planning, and the design awarded the first prize, the first author (trained as an architect but not a participant in the competition) produced a line of reasoning that might have led from brief to design. In the paper, such ‘design replication...... the designer’s authentic line of reasoning. To illustrate how RPA can be used, the site planning case is briefly presented, and part of the replicated line of reasoning analysed. One result of the analysis is a glimpse of a ‘logic of design’; another is an insight which sheds new light on Darke’s classical...
Galle, Per; Kovacs, L. B.
Given the brief of an architectural competition on site planning, and the design awarded the first prize, the first author (trained as an architect but not a participant in the competition) produced a line of reasoning that might have led from brief to design. In the paper, such ‘design replication......’ is refined into a method called ‘replication protocol analysis’ (RPA), and discussed from a methodological perspective of design research. It is argued that for the study of real-world design thinking this method offers distinct advantages over traditional ‘design protocol analysis’, which seeks to capture...
Munksgaard, Rasmus; Demant, Jakob; Branwen, Gwern
The development of cryptomarkets has gained increasing attention from academics, including growing scientific literature on the distribution of illegal goods using cryptomarkets. Dolliver's 2015 article "Evaluating drug trafficking on the Tor Network: Silk Road 2, the Sequel" addresses this theme by evaluating drug trafficking on one of the most well-known cryptomarkets, Silk Road 2.0. The research on cryptomarkets in general-particularly in Dolliver's article-poses a number of new questions for methodologies. This commentary is structured around a replication of Dolliver's original study. The replication study is not based on Dolliver's original dataset, but on a second dataset collected applying the same methodology. We have found that the results produced by Dolliver differ greatly from our replicated study. While a margin of error is to be expected, the inconsistencies we found are too great to attribute to anything other than methodological issues. The analysis and conclusions drawn from studies using these methods are promising and insightful. However, based on the replication of Dolliver's study, we suggest that researchers using these methodologies consider and that datasets be made available for other researchers, and that methodology and dataset metrics (e.g. number of downloaded pages, error logs) are described thoroughly in the context of web-o-metrics and web crawling. Copyright © 2016 Elsevier B.V. All rights reserved.
Locker Gottfried J
Full Text Available Abstract Background Combining trastuzumab and chemotherapy is standard in her2/neu overexpressing advanced breast cancer. It is not established however, whether trastuzumab treatment should continue after the failure of one earlier combination. In this trial, we report our experience with continued treatment beyond disease progression. Methods Fifty-four patients, median age 46 years, range 25–73 years, were included. We analysed for time to tumour progression (TTP for first, second and beyond second line treatment, response rates and overall survival. Results Median time of observation was 24 months, range 7–51. Response rates for first line treatment were 7.4% complete remission (CR, 35.2% partial remissions (PR, 42.6% stable disease > 6 months (SD and 14.8% of patients experienced disease progression despite treatment (PD. Corresponding numbers for second line were 3.7% CR, 22.2% PR, 42.6% SD and 31.5% PD; numbers for treatment beyond second line (60 therapies, 33 pts 3rd line, 18 pts 4th line, 6 pts 5th line, 2 pts 6th line and 1 patient 7th line were 1.7% CR, 28.3% PR, 28.3% SD and 41.6% PD respectively. Median TTP was 6 months (m in the first line setting, and also 6 m for second line and beyond second line. An asymptomatic drop of left ventricular ejection fraction below 50% was observed in one patient. No case of symptomatic congestive heart failure was observed. Conclusion The data presented clearly strengthen evidence that patients do profit from continued trastuzumab treatment. The fact that TTP did not decrease significantly from first line to beyond second line treatment is especially noteworthy. Still, randomized trials are warranted.
Star, Jon R.
The present issue of "JRME" features three articles--Melhuish (2018; see EJ1167195); Jamil, Larsen, and Hamres (2018; see EJ1167178); and Thanheiser (2018; see EJ1167179)--that involve, at least to some degree, replication of prior published studies. In each of these articles, the authors provide a clear rationale for the importance of…
Mykota, David B.
The purpose of the present study is to conduct an external replication into the multi-dimensionality of social presence as measured by the Computer-Mediated Communication Questionnaire (Tu, 2005). Online social presence is one of the more important constructs for determining the level of interaction and effectiveness of learning in an online…
Verhaagh, S.; Jong, E. de; Goudsmit, J.; Lecollinet, S.; Gillissen, G.; Vries, M. de; Leuven, K. van; Que, I.; Ouwehand, K.; Mintardjo, R.; Weverling, G.J.; Radošević, K.; Richardson, J.; Eloit, M.; Lowik, C.; Quax, P.; Havenga, M.
Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here,
Boesen, Ellen H; Boesen, Sidsel H; Frederiksen, Kirsten
The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malign...... with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate....
Ana Paula Carneiro Salgado
Full Text Available Interfering with cellular signal transduction pathways is a common strategy used by many viruses to create a propitious intracellular environment for an efficient replication. Our group has been studying cellular signalling pathways activated by the orthopoxviruses Vaccinia (VACV and Cowpox (CPXV and their significance to viral replication. In the present study our aim was to investigate whether the GTPase Rac1 was an upstream signal that led to the activation of MEK/ERK1/2, JNK1/2 or Akt pathways upon VACV or CPXV' infections. Therefore, we generated stable murine fibroblasts exhibiting negative dominance to Rac1-N17 to evaluate viral growth and the phosphorylation status of ERK1/2, JNK1/2 and Akt. Our results demonstrated that VACV replication, but not CPXV, was affected in dominant-negative (DN Rac1-N17 cell lines in which viral yield was reduced in about 10-fold. Viral late gene expression, but not early, was also reduced. Furthermore, our data showed that Akt phosphorylation was diminished upon VACV infection in DN Rac1-N17 cells, suggesting that Rac1 participates in the phosphoinositide-3 kinase pathway leading to the activation of Akt. In conclusion, our results indicate that while Rac1 indeed plays a role in VACV biology, perhaps another GTPase may be involved in CPXV replication.
Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei
Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) , a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.
Weissman, M M; McAvay, G; Goldstein, R B; Nunes, E V; Verdeli, H; Wickramaratne, P J
There are few systematic studies of the school-aged offspring of drug-dependent patients, although this information is useful for planning evidence-based prevention programs. We have completed such a study, which we compare to a similar study independently conducted in 1998. In both studies, both the parent and offspring were assessed blindly and independently by direct diagnostic interviews, and parental assessment of offspring was also obtained. The similarity in design and methods between studies provided an opportunity for replication by reanalysis of data. The major findings are a replication in two independently conducted studies of school-aged offspring of opiate- and/or cocaine-addicted mothers of the high rates of any psychiatric disorder (60% in both studies), major depression (20%, 26%), oppositional defiant disorder (ODD) (18%, 23%), conduct disorder (17%, 9%), attention-deficit/hyperactivity disorder (ADHD) (13%, 8%), and substance abuse (5%, 10%) among offspring. Both studies also found high rates of comorbid alcohol abuse, depression, and multiple drugs of abuse in the mothers. We conclude that efforts to replicate findings by analyses of independently conducted studies are an inexpensive way to test the sturdiness of findings that can provide the empirical basis for preventive efforts. Clinically, the data in both studies suggest that both drug dependence and associated psychopathology should be assessed and treated in opiate addicts with young offspring, and the offspring should be monitored for the development of conduct and mood disorders and substance use.
Sandoval, Carolina; Montero, Camila; Jokela, Tero
In this paper, we replicate a study of collaborative mobile phone use to share personal photos in groups of collocated people. The replication study was conducted in a different cultural context to check the generalizability of the findings from the original study in terms of the proposed...
Pechey, Rachel; Couturier, Dominique-Laurent; Hollands, Gareth J; Mantzari, Eleni; Zupan, Zorana; Marteau, Theresa M
Wine glass size may influence perceived volume and subsequently purchasing and consumption. Using a larger glass to serve the same portions of wine was found to increase wine sales by 9.4% (95% CI 1.9, 17.5) in a recent study conducted in one bar. The current study aimed to replicate this previous work in two other bars using a wider range of glass sizes. To match the previous study, a repeated multiple treatment reversal design, during which wine was served in glasses of the same design but different sizes, was used. The study was conducted in two bars in Cambridge, England, using glass sizes of 300, 370, 510 ml (Bar 1) and 300 and 510 ml (Bar 2). Customers purchased their choice of a 750 ml bottle, or standard UK measures of 125, 175 or 250 ml of wine, each of which was served with the same glass. Bar 1 Daily wine volume (ml) purchased was 10.5% (95% CI 1.0, 20.9) higher when sold in 510 ml compared to 370 ml glasses; but sales were not significantly higher with 370 ml versus 300 ml glasses (6.5%, 95% CI -5.2, 19.6). Bar 2 Findings were inconclusive as to whether daily wine purchased differed when using 510 ml versus 300 ml glasses (-1.1%, 95% CI -12.6, 11.9). These results provide a partial replication of previous work showing that introducing larger glasses (without manipulating portion size) increases purchasing. Understanding the mechanisms by which wine glass size influences consumption may elucidate when the effect can be expected and when not. Trial registration This study is a replication study, based on the procedure set out in the trial registration for the study that it attempts to replicate (ISRCTN registry: ISRCTN12018175).
Suhoyo, Yoyo; van Hell, Elisabeth A; Prihatiningsih, Titi S; Kuks, Jan B M; Cohen-Schotanus, Janke
Cultural differences between countries may entail differences in feedback processes. By replicating a Dutch study in Indonesia, we analysed whether differences in processes influenced the perceived instructiveness of feedback. Over a two-week period, Indonesian students (n = 215) recorded feedback moments during clerkships, noting who provided the feedback, whether the feedback was based on observations, who initiated the feedback, and its perceived instructiveness. Data were compared with the earlier Dutch study and analysed with χ(2) tests, t-tests and multilevel techniques. Cultural differences were explored using Hofstede's Model, with Indonesia and the Netherlands differing on "power distance" and "individualism." Perceived instructiveness of feedback did not differ significantly between both countries. However, significant differences were found in feedback provider, observation and initiative. Indonesian students perceived feedback as more instructive if provided by specialists and initiated jointly by the supervisor and student (βresidents = -0.201, p culture. Further research is necessary to unravel other possible influences of culture in implementing feedback procedures in different countries.
Stergiou, George S; Karpettas, Nikos; Atkins, Neil; O'Brien, Eoin
Since 2002 when the European Society of Hypertension International Protocol (ESH-IP) was published it has become the preferred protocol for validating blood pressure monitors worldwide. In 2010, a revised version of the ESH-IP with more stringent criteria was published. This study assesses the impact of applying the revised ESH-IP criteria. A systematic literature review of ESH-IP studies reported between 2002 and 2010 was conducted. The impact of applying the ESH-IP 2010 criteria retrospectively on the data reported in these studies was investigated. The performance of the oscillometric devices in the last decade was also investigated on the basis of the ESH-IP criteria. Among 119 published studies, 112 with sufficient data were analyzed. According to ESH-IP 2002, the test device failed in 19 studies, whereas by applying the ESH-IP 2010 criteria in 28 additional studies increased the failure rate from 17 to 42%. Of these 28 studies, in 20 (71%) the test device failed at part 1 (accuracy per measurement) and in 22 (79%) at part 2 (accuracy per subject). Most of the failures involved the '5 mmHg or less' criterion. In the last decade there has been a consistent trend toward improved performance of oscillometric devices assessed on the basis of the ESH-IP criteria. This retrospective analysis shows that the stricter revised ESH-IP 2010 criteria will noticeably increase the failure rate of devices being validated. Oscillometric devices are becoming more accurate, and the revised ESH-IP by acknowledging this trend will allow more accurate devices to enter the market.
Paganini-Hill, A; Greenia, DE; Perry, S; Sajjadi, SA; Kawas, CH; Corrada, MM
to explore the relationship between risk of falling at age 90+ and prior physical activity at age 60-70s.population-based cohort study (The 90+ Study).California retirement community.of 1596 cohort members, 1536 had both falls and prior activity data. Mean age = 94 years; 78% female; 99% Caucasian.time spent in active physical activity was self-reported in 1980s; medical history, medication, assistive devices, residence type, and falls (outcome) was collected in 2000s. Activity/fall relations...
Kelsey, Meredith; Layzer, Jean
This article describes some of the early implementation challenges faced by nine grantees participating in the Teen Pregnancy Prevention Replication Study and their response to them. The article draws on information collected as part of a comprehensive implementation study. Sources include site and program documents; program officer reports; notes from site investigation, selection and negotiation; ongoing communications with grantees as part of putting the study into place; and semi-structured interviews with program staff. The issues faced by grantees in implementing evidence-based programs designed to prevent teen pregnancy varied by program model. Grantees implementing a classroom-based curriculum faced challenges in delivering the curriculum within the constraints of school schedules and calendars (program length and size of class). Grantees implementing a culturally tailored curriculum faced a series of challenges, including implementing the intervention as part of the regular school curriculum in schools with diverse populations; low attendance when delivered as an after-school program; and resistance on the part of schools to specific curriculum content. The third set of grantees, implementing a program in clinics, faced challenges in identifying and recruiting young women into the program and in retaining young women once they were in the program. The experiences of these grantees reflect some of the complexities that should be carefully considered when choosing to replicate evidence-based programs. The Teen Pregnancy Prevention replication study will provide important context for assessing the effectiveness of some of the more widely replicated evidence-based programs. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.
Brandt, M.J.; IJzerman, H.; Dijksterhuis, Ap; Farach, Frank J.; Geller, Jason; Giner-Sorolla, Roger; Grange, James A.; Perugini, Marco; Spies, Jeffrey R.; van 't Veer, Anna
Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed
Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't
Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed
Gil-Gómez de Liaño, Beatriz; Stablum, Franca; Umiltà, Carlo
The effects of concurrent working memory load in attentional processes have been 1 of the most puzzling issues in cognitive psychology. Studies have shown detrimental effects, no effects, and even beneficial effects of working memory load in different attentional tasks. In the present study we attempted to replicate Kim, Kim, and Chun's (2005, Experiment 3b) findings of beneficial effects of concurrent working memory load in a spatial Stroop-like task. In 3 experiments in which our sample was 3 times larger than that in the original Kim et al. study, we could not replicate their findings. The results are discussed in terms of what may have produced the conflicting results, trying to shed light on how working memory load affects attentional tasks. Also, we emphasize the importance of using adequately large samples in cognitive research. Although we acknowledge the relevance of meta-analyses to analyze conflicting results, in the present article we stress (perhaps more important) the power of an essential trademark in science for research development: replicability. (c) 2015 APA, all rights reserved).
Devolder, T.; Chappert, C.; Bernas, H.
We have developed an irradiation technique that allows us to tune the magnetic properties of Co/Pt multilayers without affecting their roughness. The planarity and the ability to independently control nanostructure size and coercivity make our technique very appealing for magnetic recording. We study the irradiation-induced 1:1 replication of features drilled in a stencil mask. Both the 'gap' G between the magnetic film and the mask, and the aspect ratio (AR) of the mask features are analyzed, in view of the ion straggling in the mask resulting in collateral damages. Optimal gap is such that D<< G<< D/tan(α) (typically 0.1<< G<<25 μm), where the D is the feature size. The replication quality is best for AR≥3. Since the allowed gap interval is wide, we anticipate that mask fast positioning will be possible for the applications to magnetic recording
Full Text Available In a series of four experiments, Topolinski and Sparenberg (2012; TS found support for the conjecture that clockwise movements induce psychological states of temporal progression and an orientation toward the future and novelty. Here we report the results of a preregistered replication attempt of Experiment 2 from TS. Participants turned kitchen rolls either clockwise or counterclockwise while answering items from a questionnaire assessing openness to experience. Data from 102 participants showed that the effect went slightly in the direction opposite to that predicted by TS, and a preregistered Bayes factor hypothesis test revealed that the data were 10.76 times more likely under the null hypothesis than under the alternative hypothesis. Our findings illustrate the theoretical importance and practical advantages of preregistered Bayes factor replication studies, both for psychological science and for empirical work in general.
Full Text Available Generic representation of skeletal remains from burials consists of three dimensions which include physical anthropologists, replication technicians, and promotional educators. For the reason that archaeological excavation is irreversible and disruptive, detail documentation and replication technologies are surely needed for many purposes. Unearthed bones during the process of 3D digital scanning need to go through reverse procedure, 3D scanning, digital model superimposition, rapid prototyping, mould making, and the integrated errors generated from the presentation of colours and textures are important issues for the presentation of replicate skeleton remains among professional decisions conducted by physical anthropologists, subjective determination of makers, and the expectations of viewers. This study presents several cases and examines current issues on display and replication technologies for human skeletal remains of prehistoric burials. This study documented detail colour changes of human skeleton over time for the reference of reproduction. The tolerance errors of quantification and required technical qualification is acquired according to the precision of 3D scanning, the specification requirement of rapid prototyping machine, and the mould making process should following the professional requirement for physical anthropological study. Additionally, the colorimeter is adopted to record and analyse the “colour change” of the human skeletal remains from wet to dry condition. Then, the “colure change” is used to evaluate the “real” surface texture and colour presentation of human skeletal remains, and to limit the artistic presentation among the human skeletal remains reproduction. The“Lingdao man No.1”, is a well preserved burial of early Neolithic period (8300 B.P. excavated from Liangdao-Daowei site, Matsu, Taiwan , as the replicating object for this study. In this study, we examined the reproduction procedures step by
Paganini-Hill, Annlia; Greenia, Dana E; Perry, Shawna; Sajjadi, Seyed Ahmad; Kawas, Claudia H; Corrada, Maria M
to explore the relationship between risk of falling at age 90+ and prior physical activity at age 60-70s. population-based cohort study (The 90+ Study). California retirement community. of 1596 cohort members, 1536 had both falls and prior activity data. Mean age = 94 years; 78% female; 99% Caucasian. time spent in active physical activity was self-reported in 1980s; medical history, medication, assistive devices, residence type, and falls (outcome) was collected in 2000s. Activity/fall relationships were assessed using logistic regression. falls were reported by 52% of participants, recurrent falls by 32%, and severe injury by 21% of fallers. In univariate analyses risk of falling at age 90+ was significantly related to medical history (heart disease, TIA/stroke, arthritis, vision disease, depression, dementia), medication use (hypnotics, anti-psychotics, anti-depressants), use of assistive devices (cane, walker, wheelchair), residence type (living with relatives, sheltered living), and source of information (self-report vs informant). Risks of falling and recurrent falls at age 90+ were 35-45% lower in those reporting 30+ minutes/day of active physical activity at age 60-70s compared with no activity. The odds ratio of falling was 0.65 (95% CI = 0.44-0.97) for 30-45 minutes/day and 0.64 (0.44-0.94) for 1+ hour/day adjusting for age, sex, medical history (stroke/TIA, vision disease, depression), use of assistive devices, and source of information. falls are extremely common among the oldest-old and a significant proportion lead to severe injury. This work is the first to show an association between exercise at age 60-70s and lower risk of falling at age 90+. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: email@example.com
Loewenstein, David A; Curiel, Rosie E; DeKosky, Steven; Rosselli, Monica; Bauer, Russell; Grieg-Custo, Maria; Penate, Ailyn; Li, Chunfei; Lizagarra, Gabriel; Golde, Todd; Adjouadi, Malek; Duara, Ranjan
The rise in incidence of Alzheimer's disease (AD) has led to efforts to advance early detection of the disease during its preclinical stages. To achieve this, the field needs to develop more sensitive cognitive tests that relate to biological markers of disease pathology. Failure to recover from proactive interference (frPSI) is one such cognitive marker that is associated with volumetric reductions in the hippocampus, precuneus, and other AD-prone regions, and to amyloid load in the brain. The current study attempted to replicate and extend our previous findings that frPSI is a sensitive marker of early AD, and related to a unique pattern of volumetric loss in AD prone areas. Three different memory measures were examined relative to volumetric loss and cortical thickness among 45 participants with amnestic mild cognitive impairment. frPSI was uniquely associated with reduced volumes in the hippocampus (r = 0.50) precuneus (r = 0.41), and other AD prone regions, replicating previous findings. Strong associations between frPSI and lower entorhinal cortex volumes and cortical thickness (r≥0.60) and precuneus (r = 0.50) were also observed. Unique and strong associations between volumetric reductions and frPSI as observed by Loewenstein and colleagues were replicated. Together with cortical thickness findings, these results indicate that frPSI is worthy of further study as a sensitive and early cognitive marker of AD.
Matono, Takashi; Nishijima, Takeshi; Teruya, Katsuji; Morino, Eriko; Takasaki, Jin; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Kaku, Mitsuo; Oka, Shinichi
Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.
McCroskey, James C.; And Others
Portions of three earlier studies relating differences in employees to employee satisfaction and one study relating management communication style (MCS) to employee satisfaction were replicated across four organizational contexts. Major findings supported the generalizability of the results revealed in the earlier research. The role of…
Assenberg, R; Delmas, O; Morin, B; Graham, S C; De Lamballerie, X; Laubert, C; Coutard, B; Grimes, J M; Neyts, J; Owens, R J; Brandt, B W; Gorbalenya, A; Tucker, P; Stuart, D I; Canard, B; Bourhy, H
Some mammalian rhabdoviruses may infect humans, and also infect invertebrates, dogs, and bats, which may act as vectors transmitting viruses among different host species. The VIZIER programme, an EU-funded FP6 program, has characterized viruses that belong to the Vesiculovirus, Ephemerovirus and Lyssavirus genera of the Rhabdoviridae family to perform ground-breaking research on the identification of potential new drug targets against these RNA viruses through comprehensive structural characterization of the replicative machinery. The contribution of VIZIER programme was of several orders. First, it contributed substantially to research aimed at understanding the origin, evolution and diversity of rhabdoviruses. This diversity was then used to obtain further structural information on the proteins involved in replication. Two strategies were used to produce recombinant proteins by expression of both full length or domain constructs in either E. coli or insect cells, using the baculovirus system. In both cases, parallel cloning and expression screening at small-scale of multiple constructs based on different viruses including the addition of fusion tags, was key to the rapid generation of expression data. As a result, some progress has been made in the VIZIER programme towards dissecting the multi-functional L protein into components suitable for structural and functional studies. However, the phosphoprotein polymerase co-factor and the structural matrix protein, which play a number of roles during viral replication and drives viral assembly, have both proved much more amenable to structural biology. Applying the multi-construct/multi-virus approach central to protein production processes in VIZIER has yielded new structural information which may ultimately be exploitable in the derivation of novel ways of intervening in viral replication. Copyright 2010 Elsevier B.V. All rights reserved.
Nieuwland, Mante S; Politzer-Ahles, Stephen; Heyselaar, Evelien; Segaert, Katrien; Darley, Emily; Kazanina, Nina; Von Grebmer Zu Wolfsthurn, Sarah; Bartolozzi, Federica; Kogan, Vita; Ito, Aine; Mézière, Diane; Barr, Dale J; Rousselet, Guillaume A; Ferguson, Heather J; Busch-Moreno, Simon; Fu, Xiao; Tuomainen, Jyrki; Kulakova, Eugenia; Husband, E Matthew; Donaldson, David I; Kohút, Zdenko; Rueschemeyer, Shirley-Ann; Huettig, Falk
Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment ('cloze'). In our direct replication study spanning 9 laboratories ( N =334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words. © 2018, Nieuwland et al.
Full Text Available Background: There is a clear difference of opinion amongst researchers on the interrelatedness of the variables trust, commitment, satisfaction, coordination, cooperation and continuity in a business-to-business (B2B environment. The reason is that in previous studies much emphasis has been placed on creating and testing new theories, and not on providing practical generalities. Aim: The aim of this study was to determine how the variable satisfaction is positioned in relation to trust and commitment, and how satisfaction relates to the variables coordination, cooperation and continuity in a South African B2B environment. Setting: This study replicates a similar study conducted in 2013 in a B2B environment in South Africa and hopes to validate the outcome of that study by determining the relationship between the constructs postulated in the current study. The relationships between the different constructs in the proposed model will, therefore, provide a longitudinal perspective which is unique in terms of B2B research in South Africa. Methods: Both the original and replication studies followed a quantitative approach and targeted large companies in South Africa. In the original study, data were collected from 500 large South African companies, while in the replication study data were collected from 250 large companies. Structural equation modelling was used to analyse the data. Results: The findings specifically point to the need for organisations to direct resources towards the establishment of relationships that are founded on trust and commitment. Doing so will help ensure increased satisfaction, which, in turn, will result in greater coordination and cooperation in B2B relationships as well as long-term continuation of the relationship. Conclusion: The foundation for strong B2B relationships is to secure customer satisfaction. Business managers ought to understand that when business customers are dissatisfied, it can result in the
Beare, Brendan K.
Suppose that X and Y are random variables. We define a replicating function to be a function f such that f(X) and Y have the same distribution. In general, the set of replicating functions for a given pair of random variables may be infinite. Suppose we have some objective function, or cost function, defined over the set of replicating functions, and we seek to estimate the replicating function with the lowest cost. We develop an approach to estimating the cheapest replicating function that i...
Full Text Available Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking.Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA had beneficial effects on the reading, working memory, and behavior of healthy schoolchildren.Parallel group, fixed-dose, randomized (minimization, 30% random element, double-blind, placebo-controlled trial (RCT.Mainstream primary schools (n = 84 from five counties in the UK in 2012-2015.Healthy children aged 7-9 underperforming in reading (<20th centile. 1230 invited, 376 met study criteria.600 mg/day DHA (from algal oil, placebo: taste/color matched corn/soybean oil; for 16 weeks.Age-standardized measures of reading, working memory, and behavior, parent-rated and as secondary outcome teacher-rated.376 children were randomized. Reading, working memory, and behavior change scores showed no consistent differences between intervention and placebo group. Some behavioral subscales showed minor group differences.This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior. Possible reasons are discussed, particularly regarding the replication of complex interventions.www.controlled-trials.com (ISRCTN48803273 and protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw.
Bass, Hank W; Wear, Emily E; Lee, Tae-Jin; Hoffman, Gregg G; Gumber, Hardeep K; Allen, George C; Thompson, William F; Hanley-Bowdoin, Linda
The progress of nuclear DNA replication is complex in both time and space, and may reflect several levels of chromatin structure and 3-dimensional organization within the nucleus. To understand the relationship between DNA replication and developmental programmes, it is important to examine replication and nuclear substructure in different developmental contexts including natural cell-cycle progressions in situ. Plant meristems offer an ideal opportunity to analyse such processes in the context of normal growth of an organism. Our current understanding of large-scale chromosomal DNA replication has been limited by the lack of appropriate tools to visualize DNA replication with high resolution at defined points within S phase. In this perspective, we discuss a promising new system that can be used to visualize DNA replication in isolated maize (Zea mays L.) root tip nuclei after in planta pulse labelling with the thymidine analogue, 5-ethynyl-2'-deoxyuridine (EdU). Mixed populations of EdU-labelled nuclei are then separated by flow cytometry into sequential stages of S phase and examined directly using 3-dimensional deconvolution microscopy to characterize spatial patterns of plant DNA replication. Combining spatiotemporal analyses with studies of replication and epigenetic inheritance at the molecular level enables an integrated experimental approach to problems of mitotic inheritance and cellular differentiation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: firstname.lastname@example.org.
Panavas, Tadas; Nagy, Peter D.
Defective interfering (DI) RNA associated with Tomato bushy stunt virus (TBSV), which is a plus-strand RNA virus, requires p33 and p92 proteins of TBSV or the related Cucumber necrosis virus (CNV), for replication in plants. To test if DI RNA can replicate in a model host, we coexpressed TBSV DI RNA and p33/p92 of CNV in yeast. We show evidence for replication of DI RNA in yeast, including (i) dependence on p33 and p92 for DI replication; (ii) presence of active CNV RNA-dependent RNA polymerase in isolated membrane-containing preparations; (iii) increasing amount of DI RNA(+) over time; (iv) accumulation of (-)stranded DI RNA; (v) presence of correct 5' and 3' ends in DI RNA; (vi) inhibition of replication by mutations in the replication enhancer; and (vii) evolution of DI RNA over time, as shown by sequence heterogeneity. We also produced evidence supporting the occurrence of DI RNA recombinants in yeast. In summary, development of yeast as a host for replication of TBSV DI RNA will facilitate studies on the roles of viral and host proteins in replication/recombination
Bringhurst, David L; Watson, Curtis W; Miller, Scott D; Duncan, Barry L
... (Miller, Duncan, Brown, Sparks, AND Claud, 2003). This article reports the findings of an independent replication study evaluating the reliability and concurrent validity of the ORS as studied in a non-clinical sample...
... for Earlier Diagnosis What if we could diagnose Alzheimer's before symptoms started? The hope is, future treatments ... diagnosis is among the most active areas in Alzheimer's science, and funding from the Alzheimer's Association has ...
Munksgaard, Rasmus; Demant, Jakob Johan; Branwen, Gwern
The development of cryptomarkets has gained increasing attention from academics, including growing scientific literature on the distribution of illegal goods using cryptomarkets. Dolliver's 2015 article “Evaluating drug trafficking on the Tor Network: Silk Road 2, the Sequel” addresses this theme...... by evaluating drug trafficking on one of the most well-known cryptomarkets, Silk Road 2.0. The research on cryptomarkets in general—particularly in Dolliver's article—poses a number of new questions for methodologies. This commentary is structured around a replication of Dolliver's original study...
Walsh, Kyle M; Anderson, Erik; Hansen, Helen M; Decker, Paul A; Kosel, Matt L; Kollmeyer, Thomas; Rice, Terri; Zheng, Shichun; Xiao, Yuanyuan; Chang, Jeffrey S; McCoy, Lucie S; Bracci, Paige M; Wiemels, Joe L; Pico, Alexander R; Smirnov, Ivan; Lachance, Daniel H; Sicotte, Hugues; Eckel-Passow, Jeanette E; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R
Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated. We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes. © 2012 WILEY PERIODICALS, INC.
Toledo, Luis; Neelsen, Kai John; Lukas, Jiri
Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA...... breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication...... checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under...
Bjelland, Douglas W.; Howrigan, Daniel P.; Abdellaoui, Abdel; Breen, Gerome; Borglum, Anders; Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Genovese, Giulio; Heilmann-Heimbach, Stefanie; Hoffman, Per; Maier, Wolfgang; Mattheisen, Manuel; Morris, Derek; Mowry, Bryan; Müller-Mhysok, Betram; Neale, Benjamin; Nenadic, Igor; Nöthen, Markus M.; O’Dushlaine, Colm; Rietschel, Marcella; Ruderfer, Douglas M.; Rujescu, Dan; Schulze, Thomas G.; Simonson, Matthew A.; Stahl, Eli; Strohmaier, Jana; Sullivan, Patrick F.; Keller, Matthew C.
It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest. PMID:27792727
Full Text Available Jared R Kohler, Tobias Guennel, Scott L MarshallBioStat Solutions, Inc., Frederick, MD, USAAbstract: In the past decade, the pharmaceutical industry and biomedical research sector have devoted considerable resources to pharmacogenomics (PGx with the hope that understanding genetic variation in patients would deliver on the promise of personalized medicine. With the advent of new technologies and the improved collection of DNA samples, the roadblock to advancements in PGx discovery is no longer the lack of high-density genetic information captured on patient populations, but rather the development, adaptation, and tailoring of analytical strategies to effectively harness this wealth of information. The current analytical paradigm in PGx considers the single-nucleotide polymorphism (SNP as the genomic feature of interest and performs single SNP association tests to discover PGx effects – ie, genetic effects impacting drug response. While it can be straightforward to process single SNP results and to consider how this information may be extended for use in downstream patient stratification, the rate of replication for single SNP associations has been low and the desired success of producing clinically and commercially viable biomarkers has not been realized. This may be due to the fact that single SNP association testing is suboptimal given the complexities of PGx discovery in the clinical trial setting, including: 1 relatively small sample sizes; 2 diverse clinical cohorts within and across trials due to genetic ancestry (potentially impacting the ability to replicate findings; and 3 the potential polygenic nature of a drug response. Subsequently, a shift in the current paradigm is proposed: to consider the gene as the genomic feature of interest in PGx discovery. The proof-of-concept study presented in this manuscript demonstrates that genomic region-based association testing has the potential to improve the power of detecting single SNP or
Catlett, Shelia; Lovan, Sherry R
This qualitative research study, a replication of a study published in 2002, investigated the qualities of a good nurse and the role ethics plays in decision making. After reviewing the limitations of the published work, the current study implemented modifications related to the research questions, sample selection, data collection, and use of software for data analysis. The original study identified seven categories that related to being a good nurse and doing the right thing. In the present study, the use of relational analysis led to the recognition of four categories: (1) personal traits and attributes; (2) technical skills and management of care; (3) work environment and co-workers; and (4) caring and caring behaviors. To understand what it means to be a good nurse and do the right thing is a complex task; however, this research adds to the small amount of empirical data that exists to describe those characteristics.
Full Text Available Abstract Background When developing behaviour measurement tools that use third party assessments, such as parent report, it is important to demonstrate reliability of resulting scales through replication using novel cohorts. The domestic dog has been suggested as a model to investigate normal variation in attention, hyperactivity, and impulsive behaviours impaired in Attention Deficit Hyperactive Disorder (ADHD. The human ADHD Rating Scale, modified for dogs and using owner-directed surveys, was applied in a European sample. We asked whether findings would be replicated utilizing an Internet survey in a novel sample, where unassisted survey completion, participant attitudes and breeds might affect previous findings. Methods Using a slightly modified version of the prior survey, we collected responses (n = 1030, 118 breeds representing 7 breed groups primarily in the United States and Canada. This study was conducted using an Internet survey mechanism. Results Reliability analyses confirmed two scales previously identified for dogs (inattention [IA], hyperactivity-impulsivity [HA-IM]. Models including age, training status, and breed group accounted for very little variance in subscales, with no effect of gender. Conclusions The factor invariance demonstrated in these findings confirms that owner report, using this modified human questionnaire, provides dog scores according to "inattention" and "hyperactivity-impulsivity" axes. Further characterization of naturally occurring variability of attention, activity, and impulsivity in domestic dogs may provide insight into genetic backgrounds underlying behaviours impaired in attention and associated disorders.
E. V. Thomas
Full Text Available Until recently microarray experiments often involved relatively few arrays with only a single representation of each gene on each array. A complete genome microarray with multiple spots per gene (spread out spatially across the array was developed in order to compare the gene expression of a marine cyanobacterium and a knockout mutant strain in a defined artificial seawater medium. Statistical methods were developed for analysis in the special situation of this case study where there is gene replication within an array and where relatively few arrays are used, which can be the case with current array technology. Due in part to the replication within an array, it was possible to detect very small changes in the levels of expression between the wild type and mutant strains. One interesting biological outcome of this experiment is the indication of the extent to which the phosphorus regulatory system of this cyanobacterium affects the expression of multiple genes beyond those strictly involved in phosphorus acquisition.
Siltanen, Susan A.
A study was conducted to replicate and extend an earlier investigation of the persuasive effects of extended, intense concluding sex and death metaphors by using a more controlled design and by mixing metaphors. Fifty-eight high school students completed pretests assessing their attitudes toward a speech topic (legalization of marijuana). Two…
Purpose: Earlier, my colleagues and I showed that children with a history of specific language impairment (H-SLI) are significantly less able to detect audiovisual asynchrony compared with children with typical development (TD; Kaganovich & Schumaker, 2014). Here, I first replicate this finding in a new group of children with H-SLI and TD and…
[EN]: DNA replication and transcription take place on the same DNA template, and the correct interplay between these processes ensures faithful genome duplication. DNA replication must be highly coordinated with other cell cycle events, such as segregation of fully replicated DNA in order to maintain genomic integrity. Transcription generates RNA:DNA hybrids, transient intermediate structures that are degraded by the ribonuclease H (RNaseH) class of enzymes. RNA:DNA hybrids can form R-loops, ...
Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios
In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.
Full Text Available OBJECTIVES: Our aims were to replicate some previously reported associations of single nucleotide polymorphisms (SNPs in five genes (A2BP1, COG5, GDF5, HFE, ESR1 with hand osteoarthritis (OA, and to examine whether genes (BCAP29, DIO2, DUS4L, DVWA, HLA, PTGS2, PARD3B, TGFB1 and TRIB1 associated with OA at other joint sites were associated with hand OA among Finnish women. DESIGN: We examined the bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Data regarding finger joint pain and other risk factors were collected using a questionnaire. We defined two hand OA phenotypes: radiographic OA in at least three joints (ROA and symptomatic DIP OA. The genotypes were determined by PCR-based methods. In statistical analysis, we used SNPStats software, the chi-square test and logistic regression. RESULTS: Of the SNPs, rs716508 in A2BP1 was associated with ROA (OR = 0.7, 95% CI 0.5-0.9 and rs1800470 in TGFB1 with symptomatic DIP OA (1.8, 1.2-2.9. We found an interaction between ESR1 (rs9340799 and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3-6.5. We saw no association among the dentists. We also found that the carriage of the COG5 rs3757713 C allele increased the risk of ROA only among women with the BCAP29 rs10953541 CC genotype (2.6; 1.1-6.1. There was also a suggestive interaction between the HFE rs179945 and the ESR1 rs9340799, and the carriage of the minor allele of either of these SNPs was associated with an increased risk of symptomatic DIP OA (2.1, 1.3-2.5. CONCLUSIONS: Our results support the earlier findings of A2BP1 and TBGF1 being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition.
Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and
Chiba, Toshinori; Matsuo, Hirotaka; Sakiyama, Masayuki; Nakayama, Akiyoshi; Shimizu, Seiko; Wakai, Kenji; Suma, Shino; Nakashima, Hiroshi; Sakurai, Yutaka; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi
Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21-31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. However, no replication study has been performed to confirm this association. Therefore, we first conducted a replication study with clinically defined gout patients in a different population. Linkage disequilibrium (LD) analyzes of the 3 SNPs in ALPK1 revealed that these SNPs are in strong LD in a Japanese population. Among the 3 SNPs of ALPK1, rs11726117 (M861T) is the only missense SNP. Therefore, rs11726117 was genotyped in a Japanese population of 903 clinically defined gout cases and 1,302 controls, and was evaluated for a possible association with gout. The minor allele frequencies of rs11726117 were 0.26 and 0.25 in the case and control groups, respectively. The association analysis has not detected a significant association between rs11726117 and gout susceptibility in a Japanese population (p = 0.44). Because ABCG2, a major causative gene for gout, also locates in the gout-susceptibility locus on chromosome 4q, these findings suggest that among genes in a gout-susceptibility locus, not ALPK1 but ABCG2 could be important as a gout-susceptible gene.
Isella, Valeria; Molteni, Federica; Mapelli, Cristina; Ferrarese, Carlo
In the present study we replicated a previous experiment investigating visuo-spatial short term memory binding in young and older healthy individuals, in the attempt to verify the pattern of impairment that can be observed in normal elderly for short term memory for single items vs short term memory for bindings. Assessing a larger sample size (25 young and 25 older subjects), using a more appropriate measure of accuracy for a change detection task (A'), and adding the evaluation of speed of performance, we confirmed that old normals show a decline in short term memory for bindings of shape and colour that is of comparable extent, and not major, to the decline in memory for single shapes and single colours. The absence of a specific deficit of short term memory for conjunctions of surface features seems to distinguish cognitive ageing from Alzheimer's Disease. Copyright © 2015 Elsevier Inc. All rights reserved.
Toste, Jessica R; Capin, Philip; Williams, Kelly J; Cho, Eunsoo; Vaughn, Sharon
This randomized control trial examined the efficacy of an intervention aimed at improving multisyllabic word reading (MWR) skills among fourth- and fifth-grade struggling readers ( n = 109, 48.6% male), as well as the relative effects of an embedded motivational beliefs training component. This study was a closely aligned replication of our earlier work. The intervention was replicated with a three-condition design: MWR only, MWR with a motivational beliefs component, and business-as-usual control. Students were tutored in small groups for 40 lessons (four 40-min lessons each week). When we combined performance of students in both MWR conditions, intervention students significantly outperformed controls on proximal measures of affix reading and MWR, as well as standardized measures of decoding, spelling, and text comprehension. Furthermore, there was a noted interaction between English learner status and treatment on spelling performance. There were no statistically significant main effects between the MWR groups on proximal or standardized measures of interest. Findings are discussed in terms of their relevance to MWR instruction for students with persistent reading difficulties and considerations for future research related to the malleability of motivation.
Zatorre, R J; Meyer, E; Gjedde, A
Positron emission tomography was used to investigate cerebral blood flow (CBF) changes associated with the processing of speech. In a first experiment, normal right-handed volunteers were scanned under two conditions that required phonetic processing (discrimination of final consonants and phoneme...... monitoring), and one baseline condition of passive listening. Analysis was carried out by paired-image subtraction, with MRI overlay for anatomical localization. Comparison of each phonetic condition with the baseline condition revealed increased CBF in the left frontal lobe, close to the border between...... Broca's area and the motor cortex, and in a left parietal region. A second experiment showed that this area was not activated by a semantic judgement task. Reanalysis of data from an earlier study, in which various baseline conditions were used, confirmed that this region of left frontal cortex...
Full Text Available DNA replication, one of the central events in the cell cycle, is the basis of biological inheritance. In order to be duplicated, a DNA double helix must be opened at defined sites, which are called DNA replication origins (ORIs. Unlike in bacteria, where replication initiates from a single replication origin, multiple origins are utilized in the eukaryotic genome. Among them, the ORIs in budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe have been best characterized. In recent years, advances in DNA microarray and next-generation sequencing technologies have increased the number of yeast species involved in ORIs research dramatically. The ORIs in some nonconventional yeast species such as Kluyveromyces lactis and Pichia pastoris have also been genome-widely identified. Relevant databases of replication origins in yeast were constructed, then the comparative genomic analysis can be carried out. Here, we review several experimental approaches that have been used to map replication origins in yeast and some of the available web resources related to yeast ORIs. We also discuss the sequence characteristics and chromosome structures of ORIs in the four yeast species, which can be utilized to improve the replication origins prediction.
Peng, Chong; Luo, Hao; Zhang, Xi; Gao, Feng
DNA replication, one of the central events in the cell cycle, is the basis of biological inheritance. In order to be duplicated, a DNA double helix must be opened at defined sites, which are called DNA replication origins (ORIs). Unlike in bacteria, where replication initiates from a single replication origin, multiple origins are utilized in the eukaryotic genomes. Among them, the ORIs in budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe have been best characterized. In recent years, advances in DNA microarray and next-generation sequencing technologies have increased the number of yeast species involved in ORIs research dramatically. The ORIs in some non-conventional yeast species such as Kluyveromyces lactis and Pichia pastoris have also been genome-widely identified. Relevant databases of replication origins in yeast were constructed, then the comparative genomic analysis can be carried out. Here, we review several experimental approaches that have been used to map replication origins in yeast and some of the available web resources related to yeast ORIs. We also discuss the sequence characteristics and chromosome structures of ORIs in the four yeast species, which can be utilized to improve yeast replication origins prediction. PMID:25745419
Mohamed, Marwa F; Elyamany, Hany F; Nassar, Hamed M
Replication is considered one of the most important techniques to improve the Quality of Services (QoS) of published Web Services. It has achieved impressive success in managing resource sharing and usage in order to moderate the energy consumed in IT environments. For a robust and successful replication process, attention should be paid to suitable time as well as the constraints and capabilities in which the process runs. The replication process is time-consuming since outsourcing some new replicas into other hosts is lengthy. Furthermore, nowadays, most of the business processes that might be implemented over the Web are composed of multiple Web services working together in two main styles: Orchestration and Choreography. Accomplishing a replication over such business processes is another challenge due to the complexity and flexibility involved. In this paper, we present an adaptive replication framework for regular and orchestrated composite Web services. The suggested framework includes a number of components for detecting unexpected and unhappy events that might occur when consuming the original published web services including failure or overloading. It also includes a specific replication controller to manage the replication process and select the best host that would encapsulate a new replica. In addition, it includes a component for predicting the incoming load in order to decrease the time needed for outsourcing new replicas, enhancing the performance greatly. A simulation environment has been created to measure the performance of the suggested framework. The results indicate that adaptive replication with prediction scenario is the best option for enhancing the performance of the replication process in an online business environment.
Owen, Stewart F; Huggett, Duane B; Hutchinson, Thomas H; Hetheridge, Malcolm J; McCormack, Paul; Kinter, Lewis B; Ericson, Jon F; Constantine, Lisa A; Sumpter, John P
Two studies to examine the effect of waterborne clofibric acid (CA) on growth-rate and condition of rainbow trout were conducted using accepted regulatory tests (Organisation for Economic Co-operation and Development [OECD] 215). The first study (in 2005) showed significant reductions after 21 d of exposure (21-d growth lowest-observed-effect concentration [LOEC] = 0.1 µg/L, 21-d condition LOEC = 0.1 µg/L) that continued to 28 d. Growth rate was reduced by approximately 50% (from 5.27 to 2.67% per day), while the condition of the fish reduced in a concentration-dependant manner. Additionally, in a concentration-dependent manner, significant changes in relative liver size were observed, such that increasing concentrations of CA resulted in smaller livers after 28-d exposure. A no-observed-effect concentration (NOEC) was not achieved in the 2005 study. An expanded second study (in 2006) that included a robust bridge to the 2005 study, with four replicate tanks of eight individual fish per concentration, did not repeat the 2005 findings. In the 2006 study, no significant effect on growth rate, condition, or liver biometry was observed after 21 or 28 d (28-d growth NOEC = 10 µg/L, 28-d condition NOEC = 10 µg/L), contrary to the 2005 findings. We do not dismiss either of these findings and suggest both are relevant and stand for comparison. However, the larger 2006 study carries more statistical power and multiple-tank replication, so probably produced the more robust findings. Despite sufficient statistical power in each study, interpretation of these and similar studies should be conducted with caution, because much significance is placed on the role of limited numbers of individual and tank replicates and the influence of control animals. Copyright © 2010 SETAC.
In this paper, the editor of a recent Cambridge University Press book on research methods discusses replicating previous key studies to throw more light on their reliability and generalizability. Replication research is presented as an accepted method of validating previous research by providing comparability between the original and replicated…
Gspörer, Irene; Schrems, Berta M
The development and evaluation of interventions in long-term care is time-consuming and expensive due to their complexity. To ensure reproducibility and successful implementation, these interventions must be described and published in a comprehensible and qualitative manner. The aim of this study is to analyze intervention studies from the inpatient long-term care setting with regard to their completeness, reporting quality, transparency and thus reproducibility. The completeness and the reporting quality of the interventions described in the publications were examined in the context of a selective literature review by means of intervention studies from the long-term care setting (n=22). To this end, the Template for Intervention Description and Replication (TIDieR) checklist and the Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 (CReDECI2-DE) list were used. Transparency criteria included study registration and access to study protocols. The TIDieR checklist examination revealed that only three studies contained all the information necessary; the CReDECI2 test provided a complete description for only one study. Frequent shortcomings were observed concerning the information on modifications and titrations for the study participants and the location. Protocols were available for eight studies, 14 studies were registered. In terms of science, this means that the reproducibility of scientific findings is limited, which is why they cannot provide secure knowledge. As a result, the practical benefit to be derived from published studies that are accessible to decision-makers is limited as well. As far as publishers are concerned they should pay more attention to the completeness, registration and availability of materials. Copyright © 2018. Published by Elsevier GmbH.
Hurren, Emily; Stewart, Anna; Dennison, Susan
Administrative data are crucial to the "big data" revolution of social science and have played an important role in the development of child maltreatment research. These data are also of value to administrators, policy makers, and clinicians. The focus of this paper is the use of administrative data to produce and replicate longitudinal studies of child maltreatment. Child protection administrative data have several advantages. They are often population-based, and allow longitudinal examination of child maltreatment and complex multi-level analyses. They also allow comparison across subgroups and minority groups, remove burden from individuals to disclose traumatic experiences, and can be less biased than retrospective recall. Finally, they can be linked to data from other agencies to explore comorbidity and outcomes, and are comparatively cost and time effective. The benefits and challenges associated with the use of administrative data for longitudinal child maltreatment research become magnified when these data are used to produce replications. Techniques to address challenges and support future replication efforts include developing a biographical understanding of the systems from which the data are drawn, using multiple data sources to contextualize the data and research results, recognizing and adopting various approaches to replication, and documenting all data coding and manipulation processes. These techniques are illustrated in this paper via a case study of previous replication work.
Swatzyna, Ronald J; Tarnow, Jay D; Roark, Alexandra; Mardick, Jacob
The routine use of stimulants in pediatrics has increased dramatically over the past 3 decades and the long-term consequences have yet to be fully studied. Since 1978 there have been 7 articles identifying electroencephalogram (EEG) abnormalities, particularly epileptiform discharges in children with attention deficit hyperactivity disorder (ADHD). Many have studied the prevalence of these discharges in this population with varying results. An article published in 2011 suggests that EEG technology should be considered prior to prescribing stimulants to children diagnosed with ADHD due to a high prevalence of epileptiform discharges. The 2011 study found a higher prevalence (26%) of epileptiform discharges when using 23-hour and sleep-deprived EEGs in comparison with other methods of activation (hyperventilation or photostimulation) and conventional EEG. We sought to replicate the 2011 results using conventional EEG with the added qEEG technologies of automatic spike detection and low-resolution electromagnetic tomography analysis (LORETA) brain mapping. Our results showed 32% prevalence of epileptiform discharges, which suggests that an EEG should be considered prior to prescribing stimulant medications.
Full Text Available Improving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases. One approach to achieve such an improvement for risk variants identified by the genome wide association study (GWAS approach is to incorporate previously known biology when screening variants across the genome. We developed a simple approach for improving the prioritization of candidate disease genes that incorporates a network diffusion of scores from known disease genes using a protein network and a novel integration with GWAS risk scores, and tested this approach on a large Alzheimer disease (AD GWAS dataset. Using a statistical bootstrap approach, we cross-validated the method and for the first time showed that a network approach improves the expected replication rates in GWAS studies. Several novel AD genes were predicted including CR2, SHARPIN, and PTPN2. Our re-prioritized results are enriched for established known AD-associated biological pathways including inflammation, immune response, and metabolism, whereas standard non-prioritized results were not. Our findings support a strategy of considering network information when investigating genetic risk factors.
Stevens, John; Browne, Graeme; Graham, Iain
The lack of qualified mental health nurses is at critical level with the problem likely to worsen as the aging mental health nursing workforce retires. This study investigates the career preferences of undergraduate nursing students by comparing preferences at the start, middle, and end of the Bachelor of Nursing program. The comparison of the cohorts gave an indication of the change in preferences over the intervening years. It replicates research completed in 1992, 1997, and 2001, and develops a profile of nursing career preferences and the rationale underpinning those preferences in a cohort of students (n = 150) who began their Bachelor of Nursing studies in 2007 and completed in 2009. The main findings included that, like the previous studies, mental health nursing is one of the least desirable career choices for most nurses at the start of their course and remains so as they approach graduation. The reasons change but the outcome remains the same. The current system of using the Bachelor of Nursing award to produce mental health nurses in Australia does not encourage nurses to consider a career in mental health nursing. Which begs the question: where will mental health nurses in the future come from? © 2012 The Authors. International Journal of Mental Health Nursing © 2012 Australian College of Mental Health Nurses Inc.
Swift, D.L.; Cheng, Y.S.; Su, Y.F.; Yeh, H.C.
The size distribution of inhaled radon progeny aerosols is a significant factor in dosimetry. The role of the airways above the trachea is an important determinant of the respiratory distribution of both attached and unattached progeny aerosols. In order to provide information on the effect of particle size and breathing conditions on the overall and local deposition, we have developed a method to produce a replicate airway model from an in vivo magnetic resonance imaging coronal scan. The model consists of a sandwich of methacrylate elements, each element having the thickness of the scan interval. The transition between successive scan outlines traced on the front and back surfaces of each element is handsculpted in the plastic. The hollow model of the nasal passages thus produced has been characterized both morphologically and fluid-mechanically and has a flow resistance typical of a normal adult. The model has several distinct advantages for studies of radon progeny aerosol deposition. After exposure to a radioaerosol (or to an aerosol of an otherwise measurable substance) the individual elements can be separated to determine local deposition. The dimensions of specific upper-airway regions can be changed by replacing a small number of elements. The model has been incorporated in an exposure system for determining overall nandregional deposition of aerosols whose median diameter is approximately 1.7 nm. Measurements at several flow rates are presented to demonstrate use of the model in radon dosimetry. The model should also be useful for determining the airway deposition of other environmental aerosols
Full Text Available The present study explored individual constellations of five personality dimensions (personality types and their internal replicability with a sample of 4- to 14-year-olds (N = 1341. Employing an age- and culture-decentered assessment tool the target participants were rated by their mothers and the procedure by Asendorpf et al. (2001 was followed to derive personality types. Several cluster solutions were investigated with the one representing four personality types appearing the most interpretable. The average type included individuals (26% expressing mean levels of conscientiousness, extraversion, openness/intellect, and neuroticism, and a relatively high level of agreeableness. The reserved children/adolescents (35 % scored below-average in openess/intellect, relatively low in conscientiousness and extraversion, and they were rated relatively high for neuroticism. The wilful participants (30 % were high in openness/intelect and within the average range they appeared relatively extraverted and disagreeable. The resilient type turned out to be the least capacious as it captured extremly conscientious, extraverted, open, emotionally stable and relatively high agreeable individuals. More girls than boys were classified as average and the boys were, in comparison to the girls, more often assigned to the wilful and to the reserved personality types. The wilful type was the most common in early childhood, the reserved type memberhip was the most frequent in middle and late childhood, and early adolesscents were the most frequently classified to the average type.
Pérez, A Patricia; Diaz, Mónica M; Ferraro, Marcela A; Cusminsky, Gabriela C; Zagarese, Horacio E
The role of ultraviolet radiation on shallow, high CDOM (colored dissolved organic matter) lakes was investigated during two consecutive summers (1999 and 2000) in replicated mesocosms (rectangular fiberglass tanks). Each tank (volume: 300 L; depth: 40 cm) was covered with a layer (approximately 3 cm) of sediment from lake El Toro (40 degrees 14' S; 70 degrees 22' W) and filled with filtered water. The experimental design consisted of two treatments: full natural radiation (UV-exposed) and natural radiation without ultraviolet radiation (UV-shielded). UV-exposed and UV-shielded treatments differed in most studied variables as revealed by repeated measures ANOVA. UV-exposed tanks displayed lower CDOM levels (dissolved absorbance) of lower average molecular size (absorbance ratio between 250 and 365 nm), higher bacterial biomass, and lower chlorophyll a concentration. The effect on consumers (rotifers and crustaceans) was less noticeable. The results are consistent with UV stimulation of bacteria production mediated by higher rates of CDOM photobleaching, and the photoinhibition of planktonic algae. Thus, a major effect of UVR in shallow, high CDOM ecosystems appears to be the stimulation of heterotrophic pathways and a simultaneous inhibition of photoautotrophs.
Wood, Louise; Smith, Michael; Miller, Christopher B; O'Carroll, Ronan E
Vaccinations are important preventative health behaviors. The recently developed Vaccination Attitudes Examination (VAX) Scale aims to measure the reasons behind refusal/hesitancy regarding vaccinations. The aim of this replication study is to conduct an independent test of the newly developed VAX Scale in the UK. We tested (a) internal consistency (Cronbach's α); (b) convergent validity by assessing its relationships with beliefs about medication, medical mistrust, and perceived sensitivity to medicines; and (c) construct validity by testing how well the VAX Scale discriminated between vaccinators and nonvaccinators. A sample of 243 UK adults completed the VAX Scale, the Beliefs About Medicines Questionnaire, the Perceived Sensitivity to Medicines Scale, and the Medical Mistrust Index, in addition to demographics of age, gender, education levels, and social deprivation. Participants were asked (a) whether they received an influenza vaccination in the past year and (b) if they had a young child, whether they had vaccinated the young child against influenza in the past year. The VAX (a) demonstrated high internal consistency (α = .92); (b) was positively correlated with medical mistrust and beliefs about medicines, and less strongly correlated with perceived sensitivity to medicines; and (c) successfully differentiated parental influenza vaccinators from nonvaccinators. The VAX demonstrated good internal consistency, convergent validity, and construct validity in an independent UK sample. It appears to be a useful measure to help us understand the health beliefs that promote or deter vaccination behavior.
Bouwmeester, S.; Verkoeijen, P. P.J.L.; Aczel, B.
and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed...... the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned...
Raby, K. Lee; Roisman, Glenn I.; Booth-LaForce, Cathryn
A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin…
Martini, Rose; Polatajko, Helene J.
Replicating a 1994 study, four children with developmental coordination disorder (DCD) were taught a verbal self-guidance strategy (Goal, Plan, Do, Check) by an occupational therapist. All four improved performance in attaining their occupational goals, supporting the possible use of a cognitive strategy with children with DCD. (SK)
Manders, E. M.; Stap, J.; Strackee, J.; van Driel, R.; Aten, J. A.
Like many nuclear processes, DNA replication takes place in distinct domains that are scattered throughout the S-phase nucleus. Recently we have developed a fluorescent double-labeling procedure that allows us to visualize nascent DNA simultaneously with "newborn" DNA that had replicated earlier in
Vlak, J.M.; Rozijn, Th.H.; Sussenbach, J.S.
The replication of adenovirus type 5 DNA occurs by discontinuous chain propagation via short pieces of DNA. These pieces accumulate if the infected cells are treated with hydroxyurea. They have a sedimentation coefficient of 11 S corresponding to a molecular weight of about 700,000, and they contain
Rescorla, Leslie; Nyame, Josephine; Dias, Pedro
Purpose: Our objective was to replicate previous crosslinguistic findings by comparing Portuguese and U.S. children with respect to (a) effects of language, gender, and age on vocabulary size; (b) lexical composition; and (c) late talking. Method: We used the Language Development Survey (LDS; Rescorla, 1989) with children (18-35 months) learning…
Full Text Available Abstract Background A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives. Methods We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13 found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications. Results For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204 showed borderline association (p = 0.006 with hypertension status using recessive model and systolic blood pressure (p = 0.02, but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002. In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant. Conclusions This study highlights the importance of replication to confirm the validity of genome wide
Full Text Available The new probabilistic approaches to the natural language conditional imply that there is a parallel relation between indicative conditionals (ICs “if s then b” and conditional bets (CBs “I bet $1 that if s then b” in two aspects. First, the probability of an IC and the probability of winning a CB are both the conditional probability, P(s|b. Second, both an IC and a CB have a third value “void” (neither true nor false, neither wins nor loses when the antecedent is false (¬s. These aspects of the parallel relation have been found in Western participants. In the present study, we investigated whether this parallel is also present in Eastern participants. We replicated the study of Politzer et al. (2010 with Chinese and Japanese participants and made two predictions. First, Eastern participants will tend to engage in more holistic cognition and take all possible cases, including ¬s, into account when they judge the probability of conditional: Easterners may assess the probability of antecedent s out of all possible cases, P(s, and then may focus on consequent b out of s, P(b|s. Consequently, Easterners may judge the probability of the conditional, and of winning the bet, to be P(s ∗ P(b|s = P(s & b, and false/losing the bet as P(s ∗ P(¬b|s = P(s & ¬b. Second, Eastern participants will tend to be strongly affected by context, and they may not show parallel relationships between ICs and CBs. The results indicate no cultural differences in judging the false antecedent cases: Eastern participants judged false antecedent cases as not making the IC true nor false and as not being winning or losing outcomes. However, there were cultural differences when asked about the probability of a conditional. Consistent with our hypothesis, Eastern participants had a greater tendency to take all possible cases into account, especially in CBs. We discuss whether these results can be explained by a hypothesized tendency for Eastern people to think
Burgers, Peter M J; Kunkel, Thomas A
This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.
Leicher, Veronika; Mulder, Regina H.
Purpose: The purpose of this replication study is to identify relevant individual and contextual factors influencing learning from errors at work and to determine if the predictors for learning activities are the same for the domains of nursing and retail banking. Design/methodology/approach: A cross-sectional replication study was carried out in…
Annette W M Spithoven
Full Text Available Gene-by-environment interaction (GxEs studies have gained popularity over the last decade, but the robustness of such observed interactions has been questioned. The current study contributes to this debate by replicating the only study on the interaction between the serotonin transporter gene (5-HTTLPR and perceived parental support on adolescents' peer-related loneliness. A total of 1,111 adolescents (51% boys with an average age of 13.70 years (SD = 0.93 participated and three annual waves of data were collected. At baseline, adolescent-reported parental support and peer-related loneliness were assessed and genetic information was collected. Assessment of peer-related loneliness was repeated at Waves 2 and 3. Using a cohort-sequential design, a Latent Growth Curve Model was estimated. Overall, a slight increase of loneliness over time was found. However, the development of loneliness over time was found to be different for boys and girls: girls' levels of loneliness increased over time, whereas boys' levels of loneliness decreased. Parental support was inversely related to baseline levels of loneliness, but unrelated to change of loneliness over time. We were unable to replicate the main effect of 5-HTTLPR or the 5-HTTLPR x Support interaction effect. In the Discussion, we examine the implications of our non-replication.
Mitchell, Roxanne M.; Tarter, C. John
This study replicated an earlier study conducted by Tarter and Hoy (2004) in which an open systems model was used to test a series of hypotheses that explained elements of school performance. Four internal system elements (structure, individual, culture, and politics) of the school were used to explain two sets of school outcomes (student…
Van Meter, Anna; Youngstrom, Eric A.; Demeter, Christine; Findling, Robert L.
DSM-IV-TR defines four subtypes of bipolar disorder (BP): bipolar I, bipolar II, cyclothymic disorder and bipolar not otherwise specified (NOS). However, cyclothymic disorder in children is rarely researched, or often subsumed in an "NOS" category. The present study tests the replicability of findings from an earlier study, and expands on the…
Orozco, Gisela; Alizadeh, Behrooz Z.; Delgado-Vega, Angelica M.; Gonzalez-Gay, Miguel A.; Balsa, Alejandro; Pascual-Salcedo, Dora; Fernandez-Gutierrez, Benjamin; Gonzalez-Escribano, Maria F.; Petersson, Ingemar F.; van Riel, Piet L. C. M.; Barrera, Pilar; Coenen, Marieke J. H.; Radstake, Timothy R. D. J.; van Leeuwen, Miek A.; Wijmenga, Cisca; Koeleman, Bobby P. C.; Alarcon-Riquelme, Marta; Martin, Javier
Objective. This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. Methods.
Michel G Gauthier
Full Text Available In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.
Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A
In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (approximately 3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in checkpoint
Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A
Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in
Full Text Available Abstract Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU, which limits the pool of deoxyribonucleoside triphosphates (dNTPs and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR or cds1 (which encodes the fission yeast homologue of Chk2. Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3% behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild
Honan, Linda; Shealy, Sarah; Fennie, Kristopher; Duffy, Thomas C; Friedlaender, Linda; Del Vecchio, Megan
Development of perceptual aptitude is a critical yet complex skill that requires the effective organization and interpretation of data using visual and auditory clinical observation. Educators face challenges in creating pedagogy that consistently demonstrates reliability and validity in fostering clinical skills. We have dependably used the arts as a means to improve students' auditory and visual skills, and this article will describe replication of our work with accelerated nursing students in a bachelor's program in their last semester of nursing school (n=23). Our results reveal that auscultative and observational abilities of soon-to-be registered nurses are in need of improvement. The use of art in a museum improves observational and assessment abilities, and music training increases auscultative interpretive skills significantly. Copyright © 2016 Elsevier Inc. All rights reserved.
It is now understood that X-ray binaries dominate the hard X-ray emission from normal star-forming galaxies. Thanks to the deepest (2-4 Ms) Chandra surveys, such galaxies are now being studied in X-rays out to z approximates 4. Interesting X-ray stacking results (based on 30+ galaxies per redshift bin) suggest that the mean rest-frame 2-10 keV luminosity from z=3-4 Lyman break galaxies (LBGs), is comparable to the most powerful starburst galaxies in the local Universe. This result possibly indicates a similar production mechanism for accreting binaries over large cosmological timescales. To understand and constrain better the production of X-ray binaries in high-redshift LBGs, we have utilized XMM-Newton observations of a small sample of z approximates 0.1 GALEX-selected Ultraviolet-Luminous Galaxies (UVLGs); local analogs to high-redshift LBGs. Our observations enable us to study the X-ray emission from LBG-like galaxies on an individual basis, thus allowing us to constrain object-to-object variances in this population. We supplement these results with X-ray stacking constraints using the new 3.2 Ms Chandra Deep Field-South (completed spring 2010) and LBG candidates selected from HST, Swift UVOT, and ground-based data. These measurements provide new X-ray constraints that sample well the entire z=0-4 baseline
Peycelon, M; Rossignol, G; Muller, C O; Carricaburu, E; Philippe-Chomette, P; Paye-Jaouen, A; El Ghoneimi, A
The absence of a testis occurs for various reasons in children, but testicular prosthesis implantation in children is uncommon. The optimal time for prosthesis placement is still unclear, and its complication rate has been poorly studied in children. The aim of this study was to determine the risk factors of complications in cases of testicular prosthesis implantation in children. A monocentric, retrospective review was performed of children implanted with a testicular prosthesis between 2008 and 2014. All implantations were performed through an inguinal incision with a standardized procedure. Children were divided into two groups depending on the interval after orchiectomy: (A) early implantation (delay between surgeries prosthesis implantation at the mean age of 14.7 years (range 9-18) (A, 14.3; B, 14.6) with a mean delay of 36.1 months (A, 1.3; B, 80.3). Indications were mainly spermatic cord torsion (27%), bilateral anorchia (27%), and testicular atrophy after cryptorchidism surgery (19.2%). Complications (10.5%) included two cases of extrusion, one infection and one migration. Patient 1 had a history of acute lymphoblastic leukemia with testicle relapse 2 years after induction therapy. High-dose chemotherapy, total body irradiation and bilateral orchiectomies were performed, and bilateral prostheses were implanted 12 years after the end of chemotherapy. Complications happened 85 days after surgery. Patient 2 was followed-up for a proximal hypospadias. The tunica vaginalis flap, which was used during a redo urethroplasty, lead to testicular atrophy. Thirteen years after the last penile surgery, a testicular prosthesis was placed through an inguinal incision, and extrusion occurred 203 days after surgery. Bacterial cultures of the prostheses were sterile and histological review showed no sign of granuloma or graft rejection. The complication rate was significantly higher if the delay between the two surgeries exceeded 1 year (P = 0.01). Indications of
Hayes, Sidney; Horbay, Monique A.; Hayes, Connie
Several earlier studies have described an unusual exclusion phenotype exhibited by cells with plasmids carrying a portion of the replication region of phage lambda. Cells exhibiting this inhibition phenotype (IP) prevent the plating of homo-immune and hybrid hetero-immune lambdoid phages. We have attempted to define aspects of IP, and show that it is directed to repλ phages. IP was observed in cells with plasmids containing a λ DNA fragment including oop, encoding a short OOP micro RNA, and part of the lambda origin of replication, oriλ, defined by iteron sequences ITN1-4 and an adjacent high AT-rich sequence. Transcription of the intact oop sequence from its promoter, pO is required for IP, as are iterons ITN3–4, but not the high AT-rich portion of oriλ. The results suggest that IP silencing is directed to theta mode replication initiation from an infecting repλ genome, or an induced repλ prophage. Phage mutations suppressing IP, i.e., Sip, map within, or adjacent to cro or in O, or both. Our results for plasmid based IP suggest the hypothesis that there is a natural mechanism for silencing early theta-mode replication initiation, i.e. the buildup of λ genomes with oop + oriλ+ sequence. PMID:22590552
Jayanthi, Madhavi; Dimino, Joseph; Gersten, Russell; Taylor, Mary Jo; Haymond, Kelly; Smolkowski, Keith; Newman-Gonchar, Rebecca
The purpose of this replication study was to examine the impact of the Teacher Study Group (TSG) professional development in vocabulary on first-grade teachers' knowledge of vocabulary instruction and observed teaching practice, and on students' vocabulary knowledge. Sixty-two schools from 16 districts in four states were randomly assigned to…
Nogueira Yeda L.
Full Text Available Several studies have recently shown the use of recombinant rabies virus as potential vector-viral vaccine for HIV-1. The sequence homology between gp 120 and rabies virus glycoprotein has been reported. The McCoy cell line has therefore been used to show CD4+ or CD4+ like receptors. Samples of HIV-1 were isolated, when plasma of HIV-1 positive patients was inoculated in the McCoy cell line. The virus infection was then studied during successive virus passages. The proteins released in the extra cellular medium were checked for protein activity, by exposure to SDS Electrophoresis and blotting to nitro-cellulose filter, then reacting with sera of HIV positive and negative patients. Successive passages were performed, and showed viral replication, membrane permeabilization, the syncytium formation, and the cellular lysis (cytopathic effect. Flow cytometry analysis shows clear evidence that CD4+ receptors are present in this cell line, which enhances the likelihood of easy isolation and replication of HIV. The results observed allow the use of this cell line as a possible model for isolating HIV, as well as for carrying out studies of the dynamics of viral infection in several situations, including exposure to drugs in pharmacological studies, and possibly studies and analyses of the immune response in vaccine therapies.
Leder, Steven B; Suiter, Debra M; Agogo, George O; Cooney, Leo M
United States census data project dramatic increases in the geriatric population ageing demographics by 2060 with concomitant health-care consequences. The purpose of this replication and continuation study was to collect new 2014 demographic data relative to ageing, swallow evaluation referral rates, and oral feeding status in geriatric-hospitalized patients for comparison with published data from 2000 to 2007. This was a planned data acquisition study of consecutive hospitalized patients referred for swallow assessments. Swallow evaluation referral rates for 2014 were described according to inpatient discharges, age range 60-105 years grouped by decade, gender, admitting diagnostic category, results of swallow evaluations, and oral feeding status. Determination of aspiration risk status was made with the Yale Swallow Protocol and diagnosis of dysphagia made with fiberoptic endoscopic evaluation of swallowing (FEES). There were 1348 referrals and 961 patients ≥60 years of age participated. Overall swallow evaluation referral rates increased an average of 63 % between the comparison years 2007 and 2014 with consistent increases corresponding to the decades, i.e., 60-69 (46 %), 70-79 (68 %), 80-89 (53 %), and 90+ (222 %). A total of 75 % of participants resumed oral alimentation and oral medications. Swallow evaluation referral rates increased by 63 % for 60-90+ year-old acute care geriatric-hospitalized participants despite only a 23 % increase in inpatient discharges for the years 2007 versus 2014. This corroborated previously reported increases for individual years from 2000 to 2007. For timely, safe, and successful initiation of oral alimentation, it is important to perform a reliable swallow screen for aspiration risk assessment with the Yale Swallow Protocol and, if failed, instrumental testing with FEES. More dysphagia specialists are needed through 2060 and beyond due to projections of continued population ageing resulting in ever increasing
Lahne, Jacob; Collins, Thomas S; Heymann, Hildegarde
In consumer food-sensory studies, sorting and closely related methods (for example, projective mapping) have often been applied to large product sets which are complex and fatiguing for panelists. Analysis of sorting by Multi-Dimensional Scaling (MDS) is common, but this method discards relevant individual decisions; analysis by DISTATIS, which accounts for individual differences, is gaining acceptance. This research posits that replication can improve DISTATIS analysis by stabilizing consumer sensory maps, which are often extremely unstable. As a case study a fatiguing product set was sorted: 10 American whiskeys-5 bourbons and 5 ryes-were sorted into groups by 21 consumers over 2 replications. These products were chosen because American whiskeys are some of the most important distilled beverages in today's market; in particular, "bourbon" (mashbill more than 50% corn) and "rye" (more than 50% rye) whiskeys are important and assumed to be products with distinct sensory attributes. However, there is almost no scientific information about their sensory properties. Data were analyzed using standard and aggregated DISTATIS and MDS. No significant relationship between mashbill and consumer categorization in whiskeys was found; instead, there was evidence of producer and aging effects. aggregated DISTATIS was found to provide more stable results than without replication, and DISTATIS results provided a number of benefits over MDS, including bootstrapped confidence intervals for product separation. In addition, this is the first published evidence that mashbill does not determine sensory properties of American whiskey: bourbons and ryes, while legally distinct, were not separated by consumers. © 2016 Institute of Food Technologists®
Talati, Ardesheer; Pantazatos, Spiro P.; Schneier, Franklin R.; Weissman, Myrna M; Hirsch, Joy
Background Despite increasing evidence that neuroanatomical abnormalities underlie pathological anxiety, social anxiety disorder (SAD), although among the most common of anxiety disorders, has received little attention. Using Magnetic Resonance Imaging, we (1) examined grey matter (GM) differences between generalized SAD and healthy control groups; (2) retested the findings in an independent clinical sample; and (3) tested for specificity by contrasting the SAD group to a separate group of panic disorder (PD) subjects. Methods The primary SAD group (N=16) was required to meet DSM-IV criteria for SAD, with onset by age 30; controls (N=20) had no lifetime history of anxiety. The replication sample included 17 generalized SAD and 17 control subjects. The PD comparison group (N=16) was required to have no lifetime SAD. Images were acquired on a 1.5Tesla GE Signa MRI scanner using a 3D T1-weighted spoiled gradient recalled pulse sequence. Morphological differences were determined using voxel based morphometry, in SPM8. Results After adjusting for age, gender, and total intracranial volume, SAD (as compared to control) subjects had greater GM in the left parahippocampal and middle occipital, and bilateral supramarginal and angular cortices, and left cerebellum; and lower GM in bilateral temporal poles and left lateral orbitofrontal cortex. Cerebellar, parahippocampal, and temporal pole differences were observed in both samples, survived whole brain corrections, and were not observed in the PD group, pointing to relative specificity to SAD. Conclusions These findings parallel the functional literature on SAD, and suggest structural abnormalities underlying the functional disturbances. PMID:22748614
Cruz V, V.L.
The sister chromatid exchanges (SCE) frequency determination has been used as index of damage to DNA, however the biological meaning of this event is still ignored. Different models in order to explain the mechanism of their formation have been proposed and they could be contained in two categories: a) those that consider that the SCE is produced by means of discreet lesions to the DNA and that they occur in the place of the lesion, and b) those that propose that the SCE is caused by a group of lesions and that therefore the place in which they occur could not be associated with a lesion in particular. The model of Painter (1980) belongs to this last group. It suggests that the region of the DNA where the clusters are united, is the only place in which the exchange of double chain could happen during the synthesis of the DNA and makes the prediction that since the x rays retard the beginning of the duplication, the pretreatment with ionizing radiation would reduce the frequency of SCE induced by agents capable to block the lengthening of the chain of DNA, that are the most efficient SCE inducers. The objective of the present work was to establish the validity of this replicative model for the SCE formation, based in its prediction. The effect of the unilateral preexposition of mouse to gamma radiation was determined on the SCE induction by Mitomycin C (MMC), in cells of the femoral bone marrow In vivo. This strategy allows to determine the effect of the pretreatment in the same organism, minimizing the variability of the response between individuals. There was not a significant variability between the frequencies of SCE, basal and induced by gamma radiation or MMC in the same organism. The animals that received the gamma radiation pretreatment, showed a reduction of approximately the 30 % in the frequency of SCE, assuming an additive effect of the radiation with the MMC. These results coincide with the prediction of the model of Painter, however it is not
This report describes the design of a Replication Framework that facilitates the implementation and com-parison of database replication techniques. Furthermore, it discusses the implementation of a Database Replication Prototype and compares the performance measurements of two replication techniques based on the Atomic Broadcast communication primitive: pessimistic active replication and optimistic active replication. The main contributions of this report can be split into four parts....
A positive correlation between elderly dependency ratios and elderly suicide rates has been observed using one-year cross-sectional data on elderly suicide rates. A cross-national study designed to replicate this positive correlation between elderly dependency ratios and elderly suicide rates was undertaken by: (i) using one-year average of five years data on suicide rates; and (ii) using more recent data on both elderly suicide rates and elderly dependency ratios. Data on elderly suicide rates, and the total number of elderly and young people was ascertained from the World Health Organization website. The main findings were of significant positive correlations between elderly dependency ratios and suicide rates in both sexes in both the elderly age-bands (65-74 years and 75+ years). The replication of the positive correlations between elderly dependency ratios and elderly suicide rates by using one-year average of five years data on suicide rates suggests that this relationship is robust and accurate.
Abstract: Background: A positive correlation between elderly dependency ratios and elderly suicide rates has been observed using one-year cross-sectional data on elderly suicide rates. Methods: A cross-national study designed to replicate this positive correlation between elderly dependency ratios and elderly suicide rates was undertaken by: (i) using one-year average of five years data on suicide rates; and (ii) using more recent data on both elderly suicide rates and elderly dependency ratios. Data on elderly suicide rates, and the total number of elderly and young people was ascertained from the World Health Organization website. Results: The main findings were of significant positive correlations between elderly dependency ratios and suicide rates in both sexes in both the elderly age-bands (65-74 years and 75+ years). Conclusions: The replication of the positive correlations between elderly dependency ratios and elderly suicide rates by using one-year average of five years data on suicide rates suggests that this relationship is robust and accurate. PMID:21483194
This research thesis addresses the synthesis, measurement and study of the biological impact of radio-induced DNA double damages. In the first part, the author reports the study of the reactivity and fate of the 5-(2'-desoxy-uridilyl)methyl radical which is one of the intermediates formed by oxidizing photo-sensitisation of thymine. The next part reports results of the formation and measurement of double damages of isolated and cellular DNA, notably in the case of γ irradiation. The third part reports the study of in vitro replication of one of the double damages. The behaviour of different polymerases with respect to the damage is reported. Finally, the modified oligonucleotide has been used as a substrate to highlight possible activities of enzymatic repair for this type of cross-link damages by purified proteins or proteins present within cellular extracts [fr
Tsurimoto, T.; Matsubara, K.
In this paper results of studies on the mechanism of bacteriophage lambda replication using molecular biological and biochemical approaches are reported. The purification of the initiator proteins, O and P, and the role of the O and P proteins in the initiation of lambda DNA replication through interactions with specific DNA sequences are described. 47 references, 15 figures
Shen, Li; Liu, Ruiping; Zhang, Hui; Huang, Yong; Sun, Rongbin; Tang, Peifu
Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are common systemic autoimmune diseases with genetic and environmental predisposing factors. Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by interleukin-12, interleukin-23 and interferon-γ, which are key cytokines and play important roles in the development of autoimmune diseases. Previous studies confirmed the STAT4 rs7574865 G/T locus to be associated with RA. Thus we conducted a replication study to investigate STAT4 rs7574865 G/T polymorphism and RA/AS susceptibility in a Chinese population. We studied STAT4 rs7574865 G/T gene polymorphism in 520 patients with RA, 100 AS patients and 520 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the STAT4 rs7574865 GG homozygote genotype was used as the reference group, the GT or GT/TT genotypes were associated with the risk for RA. After stratification analyses, a significantly increased risk for RA associated with the STAT4 rs7574865 GT genotype was evident among the rheumatoid factor (RF)-positive patients, patients with higher erythrocyte sedimentation rate (ESR) level and patients with higher RA disease activity score (DAS28) compared with the STAT4 rs7574865 GG genotype. A significantly increased risk for RA associated with the STAT4 rs7574865 TT genotype was evident among older patients and RF-negative patients compared with the STAT4 rs7574865 GG genotype. STAT4 rs7574865 G/T was not associated with susceptibility to AS. This replication study confirmed that STAT4 rs7574865 G/T polymorphism was associated with the risk of RA. STAT4 polymorphisms are associated with rheumatoid arthritis risk. Copyright © 2013 Elsevier B.V. All rights reserved.
We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association
Sundqvist, J; Xu, H; Vodolazkaia, A; Fassbender, A; Kyama, C; Bokor, A; Gemzell-Danielsson, K; D'Hooghe, T M; Falconer, H
Is it possible to replicate the previously identified genetic association of four single-nucleotide polymorphisms (SNPs), rs12700667, rs7798431, rs1250248 and rs7521902, with endometriosis in a Caucasian population? A borderline association was observed for rs1250248 and endometriosis (P = 0.049). However, we could not replicate the other previously identified endometriosis-associated SNPs (rs12700667, rs7798431 and rs7521902) in the same population. Endometriosis is considered a complex disease, influenced by several genetic and environmental factors, as well as interactions between them. Previous studies have found genetic associations with endometriosis for SNPs at the 7p15 and 2q35 loci in a Caucasian population. Allele frequencies of SNPs were investigated in patients with endometriosis and controls. Blood samples and peritoneal biopsies were taken from a Caucasian female population consisting of 1129 patients with endometriosis and 831 controls. DNA was extracted for genotyping. The study was performed at a University hospital and research laboratories. A weak association with endometriosis (all stages) was observed for rs1250248 (P = 0.049). No significant associations were observed for the SNPs rs12700667, rs7798431 and rs7521902. A non-significant trend towards the association of rs1250248 with moderate/severe endometriosis was observed (odds ratio 1.18, 95% confidence interval 0.97-1.44). The inability to confirm all previous findings may result from differences between populations and type II errors. Our result demonstrates the difficulty of identifying common genetic variants in complex diseases. This study was supported by grants from the Karolinska Institutet and Stockholm City County/Karolinska Institutet (ALF), Stockholm, Sweden, Swedish Medical Research Council (K2007-54X-14212-06-3, K2010-54X-14212-09-3), Stockholm, Sweden, Leuven University Research Council (Onderzoeksraad KU Leuven), the Leuven University Hospitals Clinical Research Foundation
Chen, X; Lee, G; Maher, B S
We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed...... bioinformatic prioritization for all the markers with P-values ¿0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE...... in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11¿380 cases and 15¿021 controls), we...
Menéndez, Cammie Chaumont; Amick, Benjamin C.; Robertson, Michelle; Bazzani, Lianna; DeRango, Kelly; Rooney, Ted; Moore, Anne
Objective Examine the effects of two office ergonomics interventions in reducing visual symptoms at a private sector worksite. Methods A quasi-experimental study design evaluated the effects of a highly adjustable chair with office ergonomics training intervention (CWT group) and the training only (TO group) compared with no intervention (CO group). Data collection occurred 2 and 1 month(s) pre-intervention and 2, 6 and 12 months post-intervention. During each data collection period, a work environment and health questionnaire (covariates) and daily health diary (outcomes) were completed. Multilevel statistical models tested hypotheses. Results Both the training only intervention (p office ergonomics training alone and coupled with a highly adjustable chair reduced visual symptoms. In replicating results from a public sector worksite at a private sector worksite the external validity of the interventions is strengthened, thus broadening its generalizability. PMID:22030069
Menéndez, Cammie Chaumont; Amick, Benjamin C; Robertson, Michelle; Bazzani, Lianna; DeRango, Kelly; Rooney, Ted; Moore, Anne
Examine the effects of two office ergonomics interventions in reducing visual symptoms at a private sector worksite. A quasi-experimental study design evaluated the effects of a highly adjustable chair with office ergonomics training intervention (CWT group) and the training only (TO group) compared with no intervention (CO group). Data collection occurred 2 and 1 month(s) pre-intervention and 2, 6 and 12 months post-intervention. During each data collection period, a work environment and health questionnaire (covariates) and daily health diary (outcomes) were completed. Multilevel statistical models tested hypotheses. Both the training only intervention (poffice ergonomics training alone and coupled with a highly adjustable chair reduced visual symptoms. In replicating results from a public sector worksite at a private sector worksite the external validity of the interventions is strengthened, thus broadening its generalizability. Published by Elsevier Ltd.
Sparks, Richard L; Philips, Lois G; Javorsky, James
This replication study examined whether 158 college students classified as learning disabled (LD) who were granted course substitutions for the foreign language (FL) requirement would display significant cognitive and academic achievement differences when grouped by levels of IQ-achievement and achievement-achievement discrepancy and by level of performance on an FL aptitude test (Modern Language Aptitude Test; MLAT), phonological/orthographic processing measures, and in FL courses. The results showed that there were few differences among groups with differing levels of IQ-achievement or achievement-achievement discrepancy (i.e., 1.50 SD) on MLAT and American College Testing (ACT) scores, graduating grade point average (GPA), or college FL GPA. The results also showed that between groups who scored at or above versus below the 15th percentile (i.e., or = 1.0 SD) for classification as LD. These findings suggest that many traditional assumptions about LD and FL learning are likely to be false.
Full Text Available BACKGROUND: The development of CRS is believed to be the result of combined interactions between the genetic background of the affected subject and environmental factors. OBJECTIVES: To replicate and extend our recent findings from genetic association studies in chronic rhinosinusitis (CRS performed in a Canadian Caucasian population in a Chinese population. METHODS: In a case-control replication study, DNA samples were obtained from CRS with (n = 306; CRSwNP and without (n = 332; CRSsNP nasal polyps, and controls (n = 315 in a Chinese population. A total of forty-nine single nucleotide polymorphisms (SNPs selected from previous identified SNPs associated with CRS in Canadian population, and SNPs from the CHB HapMap dataset were individually genotyped. RESULTS: We identified two SNPs respectively in RYBP (rs4532099, p = 2.15E-06, OR = 2.59 and AOAH (rs4504543, p = 0.0001152, OR = 0.58 significantly associated with whole CRS cohort. Subgroup analysis for the presence of nasal polyps (CRSwNP and CRSsNP displayed significant association in CRSwNP cohorts regarding to one SNP in RYBP (P = 3.24(E-006, OR = 2.76. Evidence of association in the CRSsNP groups in terms of 2 SNPs (AOAH_rs4504543 and RYBP_rs4532099 was detected as well. Stratifying analysis by gender demonstrated that none of the selected SNPs were associated with CRSwNP as well as CRSsNP. Meanwhile 3 SNPs (IL1A_rs17561, P = 0.005778; IL1A_rs1800587, P = 0.009561; IRAK4_rs4251513, P = 0.03837 were associated with serum total IgE level. CONCLUSIONS: These genes are biologically plausible, with roles in regulation of transcription (RYBP and inflammatory response (AOAH. The present data suggests the potential common genetic basis in the development of CRS in Chinese and Caucasian population.
Liu, Xiaohua; Kelsoe, John R; Greenwood, Tiffany A
Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10(-8) for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10(-6) for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10(-7) and 4.3×10(-6), respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness. Copyright © 2015 Elsevier B.V. All rights reserved.
Honorato, Talita C; Haadsma, Maaike L; Land, Jolande A; Boezen, Marike H; Hoek, Annemieke; Groen, Henk
OBJECTIVE: Cigarette smoking is a risk factor for earlier menopause. Animal studies show that in-utero smoke exposure is toxic to developing ovaries. Our aim was to evaluate whether in-utero smoke exposed women reach menopause earlier compared with nonexposed women. METHODS: This is a cohort study
Full Text Available In response to concerns about the validity of empirical findings in psychology, some scientists use replication studies as a way to validate good science and to identify poor science. Such efforts are resource intensive and are sometimes controversial (with accusations of researcher incompetence when a replication fails to show a previous result. An alternative approach is to examine the statistical properties of the reported literature to identify some cases of poor science. This review discusses some details of this process for prominent findings about racial bias, where a set of studies seems too good to be true. This kind of analysis is based on the original studies, so it avoids criticism from the original authors about the validity of replication studies. The analysis is also much easier to perform than a new empirical study. A variation of the analysis can also be used to explore whether it makes sense to run a replication study. As demonstrated here, there are situations where the existing data suggest that a direct replication of a set of studies is not worth the effort. Such a conclusion should motivate scientists to generate alternative experimental designs that better test theoretical ideas.
Ohtsuki, Hisashi; Nowak, Martin A.
Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic acti...
Vinson, Bonita M.; Reardon, Robert C.; Bertoch, Sara C.
This study examines career planning programs and career services offices at colleges and universities in the United States as viewed by senior student affairs officers (SSAOs). Findings from a 1979 study of career services offices (CSOs) were compared to the current findings. Additionally, new areas of research were examined in order to provide…
Full Text Available Background TNF-α mediated inflammation is thought to play a key role in the respiratory and systemic features of Chronic Obstructive Pulmonary Disease. The aim of the present study was to replicate and extend recent findings in Taiwanese and Caucasian populations of associations between COPD susceptibility and variants of the TNFA gene in a Spanish cohort. Methods The 3 reported SNPs were complemented with nine tag single nucleotide polymorphisms (SNP of the TNFA and LTA genes and genotyped in 724 individuals (202 COPD patients, 90 smokers without COPD and 432 healthy controls. Pulmonary function parameters and serum inflammatory markers were also measured in COPD patients. Results The TNFA rs1800630 (-863C/A SNP was associated with a lower COPD susceptibility (ORadj = 0.50, 95% CI = 0.33-0.77, p = 0.001. The -863A allele was also associated with less severe forms of the disease (GOLD stages I and II (ORadj = 0.303, 95%CI = 0.14-0.65, p = 0.014 and with lower scores of the BODE index (1 percent predicted (p = 0.004 and a lower BODE index (p = 0.003 over a 2 yrs follow-up period. None of the TNFA or LTA gene variants correlated with the serum inflammatory markers in COPD patients (p > 0.05. Conclusions We replicated the previously reported association between the TNFA -863 SNP and COPD. TNFA -863A allele may confer a protective effect to the susceptibility to the disease in the Spanish population.
Rose, David; Horne, Sharon; Rose, John L.; Hastings, Richard P.
Background: Hastings, R. P. ["American Journal on Mental Retardation" (2002) Vol. 107, pp. 455-467] hypothesized that staff negative emotional reactions to challenging behaviour might accumulate over time to affect staff well-being. Only one previous study (Mitchell, G.& Hastings, R. P. ["American Journal on Mental…
Bao, Yingying; Chen, G.; Hauff, C.; Hu, X.; Barnes, T.; Hershkovitz, A.; Paquette, L.
Massive Open Online Courses (MOOCs) are a promising form of online education. However, the occurrence of academic dishonesty has been threatening MOOC certificates’ effectiveness as a serious tool for recruiters and employers. Recently, a large-scale study on the log traces from more than one
Schaefer, A.S.; Bochenek, G.; Manke, T.; Nothnagel, M.; Graetz, C.; Thien, A.; Jockel-Schneider, Y.; Harks, I.; Staufenbiel, I.; Wijmenga, C.; Eberhard, J.; Guzeldemir-Akcakanat, E.; Cine, N.; Folwaczny, M.; Noack, B.; Meyle, J.; Eickholz, P.; Trombelli, L.; Scapoli, C.; Nohutcu, R.; Bruckmann, C.; Doerfer, C.; Jepsen, S.; Loos, B.G.; Schreiber, S.
Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441
Schaefer, Arne S.; Bochenek, Gregor; Manke, Thomas; Nothnagel, Michael; Graetz, Christian; Thien, Anneke; Jockel-Schneider, Yvonne; Harks, Inga; Staufenbiel, Ingmar; Wijmenga, Cisca; Eberhard, Joerg; Guzeldemir-Akcakanat, Esra; Cine, Naci; Folwaczny, Mathias; Noack, Barbara; Meyle, Joerg; Eickholz, Peter; Trombelli, Leonardo; Scapoli, Chiara; Nohutcu, Rahime; Bruckmann, Corinna; Doerfer, Christof; Jepsen, Soren; Loos, Bruno G.; Schreiber, Stefan
Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441
Zimmer, Robert; Koernig, Stephen K.; Greene, Scott
For almost three decades, the AACSB and business leaders have sought increased emphasis on internationalizing students' perspectives. Recent studies demonstrate mixed results in the extent to which business schools have globalized their curricula. With decreasing student interest in the marketing major, Introductory Marketing emerges as a critical…
Orozco, G.; Alizadeh, B.Z.; Delgado-Vega, A.M.; Gonzalez-Gay, M.A.; Balsa, A.; Pascual-Salcedo, D.; Fernandez-Gutierrez, B.; Gonzalez-Escribano, M.F.; Petersson, I.F.; Riel, P.L.C.M. van; Barrera, P.; Coenen, M.J.H.; Radstake, T.R.D.J.; Leeuwen, M.A. van; Wijmenga, C.; Koeleman, B.P.; Alarcon-Riquelme, M.E.; Martin, J.
OBJECTIVE: This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. METHODS:
Ding, Hongliu; Sarokhan, Alison K.; Roderick, Sarah S.; Bakshi, Rachit; Maher, Nancy E.; Ashourian, Paymon; Kan, Caroline G.; Chang, Sunny; Santarlasci, Andrea; Swords, Kyleen E.; Ravina, Bernard M.; Hayes, Michael T.; Sohur, U. Shivraj; Wills, Anne-Marie; Flaherty, Alice W.; Unni, Vivek K.; Hung, Albert Y.; Selkoe, Dennis J.; Schwarzschild, Michael A.; Schlossmacher, Michael G.; Sudarsky, Lewis R.; Growdon, John H.; Ivinson, Adrian J.; Hyman, Bradley T.; Scherzer, Clemens R.
Background Mutations in the α-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson’s disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies. Methods Here we genotyped a prioritized non-coding variant in SNCA intron-4 in 344 patients with Parkinson’s and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study. Results The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio = 1.40, P value = 0.0032). Conclusions This result increases confidence in the notion that in many clinically well-characterized patients genetic variation in SNCA contributes to “sporadic” disease. PMID:21953863
Full Text Available BACKGROUND: Genome-wide association studies (GWAS have identified three loci (rs17401966 in KIF1B, rs7574865 in STAT4, rs9275319 in HLA-DQ as being associated with hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC in a Chinese population, two loci (rs2596542 in MICA, rs9275572 located between HLA-DQA and HLA-DQB with hepatitis C virus-related HCC (HCV-related HCC in a Japanese population. In the present study, we sought to determine whether these SNPs are predictive for HBV-related HCC development in other Chinese population as well. METHOD AND FINDINGS: We genotyped 4 SNPs, rs2596542, rs9275572, rs17401966, rs7574865, in 506 HBV-related HCC patients and 772 chronic hepatitis B (CHB patients in Han Chinese by TaqMan methods. Odds ratio(ORand 95% confidence interval (CI were calculated by logistic regression. In our case-control study, significant association between rs9275572 and HCC were observed (P = 0.02, OR = 0.73, 95% CI = 0.56-0.95. In the further haplotype analysis between rs2596542 at 6p21.33 and rs9275572 at 6p21.3, G-A showed a protective effect on HBV-related HCC occurrence (P<0.001, OR = 0.66, 95% CI = 0.52-0.84. CONCLUSION: These findings provided convincing evidence that rs9275572 significantly associated with HBV-related HCC.
Chen, Kangmei; Shi, Weimei; Xin, Zhenhui; Wang, Huifen; Zhu, Xilin; Wu, Xiaopan; Li, Zhuo; Li, Hui; Liu, Ying
Genome-wide association studies (GWAS) have identified three loci (rs17401966 in KIF1B, rs7574865 in STAT4, rs9275319 in HLA-DQ) as being associated with hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) in a Chinese population, two loci (rs2596542 in MICA, rs9275572 located between HLA-DQA and HLA-DQB) with hepatitis C virus-related HCC (HCV-related HCC) in a Japanese population. In the present study, we sought to determine whether these SNPs are predictive for HBV-related HCC development in other Chinese population as well. We genotyped 4 SNPs, rs2596542, rs9275572, rs17401966, rs7574865, in 506 HBV-related HCC patients and 772 chronic hepatitis B (CHB) patients in Han Chinese by TaqMan methods. Odds ratio(OR)and 95% confidence interval (CI) were calculated by logistic regression. In our case-control study, significant association between rs9275572 and HCC were observed (P = 0.02, OR = 0.73, 95% CI = 0.56-0.95). In the further haplotype analysis between rs2596542 at 6p21.33 and rs9275572 at 6p21.3, G-A showed a protective effect on HBV-related HCC occurrence (P<0.001, OR = 0.66, 95% CI = 0.52-0.84). These findings provided convincing evidence that rs9275572 significantly associated with HBV-related HCC.
Chiba, Toshinori; Matsuo, Hirotaka; Sakiyama, Masayuki; Nakayama, Akiyoshi; Shimizu, Seiko; Wakai, Kenji; Suma, Shino; Nakashima, Hiroshi; Sakurai, Yutaka; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi
Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21?31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. Howeve...
Full Text Available Schizophrenia (SCZ is a severe psychiatric disorder associated with many different risk factors, both genetic and environmental. A recent genome-wide association study (GWAS of Han Chinese identified three single-nucleotide polymorphisms (SNPs rs11038167, rs11038172, and rs835784 in the tetraspanins gene TSPAN18 as possible susceptibility loci for schizophrenia. Hoping to validate these findings, we conducted a case-control study of Han Chinese with 1093 schizophrenia cases and 1022 healthy controls. Using the LDR-PCR method to genotype polymorphisms in TSPAN18, we found no significant differences (P>0.05 between patients and controls in either the allele or genotype frequency of the SNPs rs11038167 and rs11038172. We did find, however, that the frequency of the 'A' allele of SNP rs835784 is significantly higher in patients than in controls. We further observed a significant association (OR= 1.197, 95%CI= 1.047-1.369 between risk for SCZ and this 'A' allele. These results confirm the significant association, in Han Chinese populations, of increased SCZ risk and the variant of the TSPAN18 gene containing the 'A' allele of SNP rs835784.
Developmental psychologists have shown interest in the development of psychological essentialism among children; that is, a belief that certain psychological characteristics (such as personality) are relatively stable and unchanging. Although previous studies have shown that children are essentialistic about human traits, and the coherence among various essentialism dimensions increases with age, moderating cultural factors in the development of essentialism, especially among Asian children, have received little attention. Using the methodologies of Gelman, Heyman, and Legare (2007), levels of psychological essentialism among Korean children and adults were measured, and compared with the original US data. Results demonstrated cross-cultural similarity in the development of coherence in essentialistic thought, and difference in the level of essentialism among adult participants. The present findings imply that different cultural values between Asians and Westerners can play a role in the developmental trajectory of psychological essentialism.
Carolyn S. Gentle-Genitty
Full Text Available The purpose of this paper is multifold.Key aspects discussed include exploring the extent of theory discussion and progression in social work journals for the year 2004; discussing the necessity of theory in social work research and practice; reviewing previous research literature regarding evaluation of theory discussion and progression; proposing criteria for defining theory in social work journals; and presenting findings from the current study concerning theory discussion and progression in social work journals. Results: Of the 1,168 articles reviewed from 37 journals, 71 (approximately 6% met the criteria for theory development with empirical base. Thus, a minimal number of articles (3 out of 71 or 4.2% evaluated, based on the criteria in the theory quality scale (Table 1, received high quality ratings. Conclusion: Based on the results yielded by the analysis, we assert that social workers need to make a conscious effort to include theory in practice decisions.
Stephan, Yannick; Maiano, Christophe
Few researchers have considered the relationship between global self-esteem and the reflected appraisal of others in one's life, or how reflected appraisals and global self-esteem may change as a result of interpersonal feedback. In this study, the authors collected data from 110 undergraduate students on (a) their global self-esteem and the reflected appraisals of multiple others in their lives and (b) how these dimensions changed in hypothetical interpersonal-feedback situations. Results showed that participants' global self-esteem was related to the reflected appraisals of their fathers, teachers, and friends. The results also indicated that others' reflected appraisals and the individual's global self-esteem fluctuated according to the nature (i.e., positive vs. negative) of the hypothetical interpersonal feedback. Overall, the findings emphasize the social nature and regulation of global self-esteem.
Full Text Available The present paper attempted to investigate whether there is any significant relationship between participants' brain laterality and L2 proficiency level. To carry out the experiment, 30 participants administered in the present study. Fifteen of them did not have any English language learning experience and were at the start of language learning, while the rest had attended L2 learning classes for about 2 years in a popular English language center, located in Bandar-e Anzali, Iran. Finally, the researchers concluded that the activity of the right hemisphere went up by the increase in language proficiency among bilinguals. Thereupon, the result of the paper was at variance with Albert and Obler's (1978 early work on hemispheric differentiation, which indicated that bilinguals were less hemispheric dominant than monolinguals.
Orozco, Gisela; Alizadeh, Behrooz Z; Delgado-Vega, Angélica M; González-Gay, Miguel A; Balsa, Alejandro; Pascual-Salcedo, Dora; Fernández-Gutierrez, Benjamín; González-Escribano, María F; Petersson, Ingemar F; van Riel, Piet L C M; Barrera, Pilar; Coenen, Marieke J H; Radstake, Timothy R D J; van Leeuwen, Miek A; Wijmenga, Cisca; Koeleman, Bobby P C; Alarcón-Riquelme, Marta; Martín, Javier
This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. Three different cohorts were included in the study: 923 RA patients and 1,296 healthy controls from Spain, 273 RA patients and 285 healthy controls from Sweden, and 876 RA patients and 893 healthy controls from The Netherlands. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the STAT4 single-nucleotide polymorphism rs7574865 using a TaqMan 5'-allele discrimination assay. The chi-square test was performed to compare allele and genotype distributions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We observed a significantly increased frequency of the minor T allele in RA patients compared with healthy controls in the Spanish population (24.8% versus 20.8%; P = 0.001, OR 1.26 [95% CI 1.09-1.45]). This association was confirmed in both the Swedish population (P = 0.03, OR 1.35 [95% CI 1.03-1.77]) and the Dutch population (P = 0.03, OR 1.45 [95% CI 1.21-1.73]). The overall P value for all 3 populations was 9.79 x 10(-6) (OR 1.25 [95% CI 1.13-1.37]). No association between rs7574865 and the presence of rheumatoid factor or anti-cyclic citrullinated peptide autoantibodies was observed. A meta-analysis of all published STAT4 associations revealed an OR of 1.25 (95% CI 1.19-1.33) (P = 1 x 10(-5)). Our findings indicate an association between the STAT4 polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data.
Franciscatto, André Cerutti; Ludwig, Fernanda S; Matte, Ursula S; Mota, Simone; Stefani, Marco A
The aim of this study was to reproducibly determine if any of the polymorphisms were associated with the susceptibility to brain arteriovenous malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation. We recruited 63 BAVM patients and 96 controls. The polymorphisms selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B -31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219), endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795). In the single analysis, we observed statistically signiﬁcant differences in the allele distributions for IL1B -31T>C (rs1143627) between the BAVM patients and control subjects (P = 0.02). There was a trend toward significance for the association between the IL1B 511C>T (rs16944) allele and BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism was significantly associated with the risk of BAVM. No polymorphisms were associated with hemorrhage presentation according to both single and multivariable analyses. In our sample from a south Brazil population, we found no association between the risks of BAVM and ICH presentation with any of the selected polymorphisms.
Yamada, Hiroki; Penney, Kathryn L; Takahashi, Hiroyuki; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin; Freedman, Matthew L
Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.
Full Text Available A fundamental stage in viral infection is the internalization of viral genomes in host cells. Although extensively studied, the mechanisms and factors responsible for the genome internalization process remain poorly understood. Here we report our observations, derived from diverse imaging methods on genome internalization of the large dsDNA Paramecium bursaria chlorella virus-1 (PBCV-1. Our studies reveal that early infection stages of this eukaryotic-infecting virus occurs by a bacteriophage-like pathway, whereby PBCV-1 generates a hole in the host cell wall and ejects its dsDNA genome in a linear, base-pair-by-base-pair process, through a membrane tunnel generated by the fusion of the virus internal membrane with the host membrane. Furthermore, our results imply that PBCV-1 DNA condensation that occurs shortly after infection probably plays a role in genome internalization, as hypothesized for the infection of some bacteriophages. The subsequent perforation of the host photosynthetic membranes presumably enables trafficking of viral genomes towards host nuclei. Previous studies established that at late infection stages PBCV-1 generates cytoplasmic organelles, termed viral factories, where viral assembly takes place, a feature characteristic of many large dsDNA viruses that infect eukaryotic organisms. PBCV-1 thus appears to combine a bacteriophage-like mechanism during early infection stages with a eukaryotic-like infection pathway in its late replication cycle.
Rafael Aguiar Maciel
Full Text Available Objectives: At present, data are limited on the comorbidity profiles associated with aging people with HIV in the developing world, where most such people live. The aim of this study was to compare the disease burden between older HIV-positive subjects and HIV-negative matched controls in Brazil. Methods: This was a cross-sectional analysis of the South Brazilian HIV Cohort. Individuals aged 50 years and older were enrolled at Hospital de Clínicas de Porto Alegre and matched with HIV-negative controls from the primary practice unit of the same hospital. Multimorbidity (the presence of two or more comorbid conditions and the number of non-infectious comorbidities were compared. Poisson regression was used to identify factors associated with multimorbidity. Results: A total of 208 HIV-positive subjects were matched to 208 HIV-negative controls. Overall, the median age was 57 years and 56% were male. The prevalence of multimorbidity was higher in HIV-positive subjects than in HIV-negative controls (63% vs. 43%, p < 0.001, and the median number of comorbidities was 2, compared to 1 in controls (p < 0.001. The duration of HIV infection (p = 0.02 and time on treatment in years (p = 0.015 were associated with greater multimorbidity in HIV-positive persons. Conclusions: In this large cohort from the developing world, multimorbidity was found to be more common in HIV-positive subjects than in HIV-negative controls. The duration of HIV and time on antiretrovirals were associated with multimorbidity. Keywords: HIV, AIDS, Multimorbidity, Comorbidities, Aging, Developing countries, Brazil
Maciel, Rafael Aguiar; Klück, Helena Moreira; Durand, Madeleine; Sprinz, Eduardo
At present, data are limited on the comorbidity profiles associated with aging people with HIV in the developing world, where most such people live. The aim of this study was to compare the disease burden between older HIV-positive subjects and HIV-negative matched controls in Brazil. This was a cross-sectional analysis of the South Brazilian HIV Cohort. Individuals aged 50 years and older were enrolled at Hospital de Clínicas de Porto Alegre and matched with HIV-negative controls from the primary practice unit of the same hospital. Multimorbidity (the presence of two or more comorbid conditions) and the number of non-infectious comorbidities were compared. Poisson regression was used to identify factors associated with multimorbidity. A total of 208 HIV-positive subjects were matched to 208 HIV-negative controls. Overall, the median age was 57 years and 56% were male. The prevalence of multimorbidity was higher in HIV-positive subjects than in HIV-negative controls (63% vs. 43%, p<0.001), and the median number of comorbidities was 2, compared to 1 in controls (p<0.001). The duration of HIV infection (p=0.02) and time on treatment in years (p=0.015) were associated with greater multimorbidity in HIV-positive persons. In this large cohort from the developing world, multimorbidity was found to be more common in HIV-positive subjects than in HIV-negative controls. The duration of HIV and time on antiretrovirals were associated with multimorbidity. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Wang, K; Pearson, G D
We have studied the in vivo replication properties of plasmids carrying deletion mutations within cloned adenovirus terminal sequences. Deletion mapping located the adenovirus DNA replication origin entirely within the first 67 bp of the adenovirus inverted terminal repeat. This region could be further subdivided into two functional domains: a minimal replication origin and an adjacent auxillary region which boosted the efficiency of replication by more than 100-fold. The minimal origin occup...
H. Noppers, E.; Keizer, K.; Bockarjova, M.; Steg, L.
We investigated motivations of potential earlier and later adopters for adopting sustainable innovations. A large questionnaire study revealed that potential earlier adopters of innovative cars evaluated the symbolic attributes of electric cars, but not the instrumental and environmental attributes,
Full Text Available In pain patients, comorbid emotional problems have been linked to negative outcomes, including suboptimal treatment gains. Developing parsimonious and accessible treatment options is therefore important. The overarching aim of this study was to test an internet delivered therapist guided transdiagnostic treatment with telephone support. An adapted version of the Unified Protocol for Transdiagnostic Treatments of Emotional Disorders was used as an intervention for pain patients with residual pain problems and comorbid emotional problems after having received a multimodal pain rehabilitation. The study used a replicated AB single case experimental design (N = 5; 3 females. Outcome measures were depressive and general anxiety symptoms, pain intensity, pain coping problems, and diagnostic status. Feasibility measures (completion and compliance and patient satisfaction were also assessed. Scores on Nonoverlap of All Pairs (NAP indicate a decrease of anxiety for three participants and a decrease of depression for four participants. Decreases were small and did not always reach statistical significance. Also, Tau-U scores could only confirm a reliable trend for one participant. Two out of four patients who were diagnosed with psychiatric disorders before treatment did no longer fulfill diagnostic criteria posttreatment. No improvements could be seen on pain problems. The treatment was feasible and patient satisfaction was high. Hence, while an internet delivered transdiagnostic treatment with telephone support may be a feasible and accepted secondary intervention for pain patients with comorbid emotional problems, the effects are unclear. The gap between high patient satisfaction and small changes in symptomatology should be explored further.
Bruder, Gerard E; Haggerty, Agnes; Siegle, Greg J
There are no commonly used clinical indicators of whether an individual will benefit from cognitive therapy (CT) for depression. A prior study found right ear (left hemisphere) advantage for perceiving dichotic words predicted CT response. This study replicates this finding at a different research center in clinical trials that included clinically representative samples and community therapists. Right-handed individuals with unipolar major depressive disorder who subsequently received 12-14 weeks of CT at the University of Pittsburgh were tested on dichotic fused words and complex tones tests. Responders to CT showed twice the mean right ear advantage in dichotic fused words performance than non-responders. Patients with a right ear advantage greater than the mean for healthy controls had an 81% response rate to CT, whereas those with performance lower than the mean for controls had a 46% response rate. Individuals with a right ear advantage, indicative of strong left hemisphere language dominance, may be better at utilizing cognitive processes and left frontotemporal cortical regions critical for success of CT for depression. Findings at two clinical research centers suggest that verbal dichotic listening may be a clinically disseminative brief, inexpensive and easily automated test prognostic for response to CT across diverse clinical settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Molina, Vicente; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Hornero, Roberto; Cea-Cañas, Benjamín; Valcárcel, César; Haidar, Mahmoun-Karim; Poza, Jesús
Spectral entropy (SE) is a measurement from information theory field that provides an estimation of EEG regularity and may be useful as a summary of its spectral properties. Previous studies using small samples reported a deficit of EEG entropy modulation in schizophrenia during cognitive activity. The present study is aimed at replicating this finding in a larger sample, to explore its cognitive and clinical correlates and to discard antipsychotic treatment as the main source of that deficit. We included 64 schizophrenia patients (21 first episodes, FE) and 65 healthy controls. We computed SE during performance of an odd-ball paradigm, at the windows prior (-300 to 0ms) and following (150 to 450ms) stimulus presentation. Modulation of SE was defined as the difference between post- and pre-stimulus windows. In comparison to controls, patients showed a deficit of SE modulation over frontal and central regions, also shown by FE patients. Baseline SE did not differ between patients and controls. Modulation deficit was directly associated with cognitive deficits and negative symptoms, and inversely with positive symptoms. SE modulation was not related to antipsychotic doses. Patients also showed a smaller change of median frequency (i.e., smaller slowing of oscillatory activity) of the EEG from pre- to post-stimulus windows. These results support that a deficit of fast modulation contributes to cognitive deficits and symptoms in schizophrenia patients. Copyright © 2017. Published by Elsevier B.V.
Ester M M Klaassen
Full Text Available The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined.To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma.In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring study were followed until the age of six. At that age a classification (transient wheeze or asthma was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis.In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97 p = 0.04 and no association with preschool wheeze.Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.
Doest, ter L.; Jonge, de J.
This study re-evaluated causal relationships between job characteristics (demands, autonomy, social support) and employee well-being (job satisfaction, emotional exhaustion) in a methodological replication of De Jonge et al.'s (2001) two-wave panel study. The principal difference was the 2-year time
Crane, Paul K; Foroud, Tatiana; Montine, Thomas J; Larson, Eric B
The Alzheimer's Disease Sequencing Project (ADSP) used different criteria for assigning case and control status from the discovery and replication phases of the project. We considered data from a community-based prospective cohort study with autopsy follow-up where participants could be categorized as case, control, or neither by both definitions and compared the two sets of criteria. We used data from the Adult Changes in Thought (ACT) study including Diagnostic and Statistical Manual-IV criteria for dementia status, McKhann et al. criteria for clinical Alzheimer's disease, and Braak and Consortium to Establish a Registry for AD findings on neurofibrillary tangles and neuritic plaques to categorize the 621 ACT participants of European ancestry who died and came to autopsy. We applied ADSP discovery and replication definitions to identify controls, cases, and people who were neither controls nor cases. There was some agreement between the discovery and replication definitions. Major areas of discrepancy included the finding that only 40% of the discovery sample controls had sufficiently low levels of neurofibrillary tangles and neuritic plaques to be considered controls by the replication criteria and the finding that 16% of the replication phase cases were diagnosed with non-AD dementia during life and thus were excluded as cases for the discovery phase. These findings should inform interpretation of genetic association findings from the ADSP. Differences in genetic association findings between the two phases of the study may reflect these different phenotype definitions from the discovery and replication phase of the ADSP. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Senkevich, Tatiana G; Bruno, Daniel; Martens, Craig; Porcella, Stephen F; Wolf, Yuri I; Moss, Bernard
Poxviruses reproduce in the host cytoplasm and encode most or all of the enzymes and factors needed for expression and synthesis of their double-stranded DNA genomes. Nevertheless, the mode of poxvirus DNA replication and the nature and location of the replication origins remain unknown. A current but unsubstantiated model posits only leading strand synthesis starting at a nick near one covalently closed end of the genome and continuing around the other end to generate a concatemer that is subsequently resolved into unit genomes. The existence of specific origins has been questioned because any plasmid can replicate in cells infected by vaccinia virus (VACV), the prototype poxvirus. We applied directional deep sequencing of short single-stranded DNA fragments enriched for RNA-primed nascent strands isolated from the cytoplasm of VACV-infected cells to pinpoint replication origins. The origins were identified as the switching points of the fragment directions, which correspond to the transition from continuous to discontinuous DNA synthesis. Origins containing a prominent initiation point mapped to a sequence within the hairpin loop at one end of the VACV genome and to the same sequence within the concatemeric junction of replication intermediates. These findings support a model for poxvirus genome replication that involves leading and lagging strand synthesis and is consistent with the requirements for primase and ligase activities as well as earlier electron microscopic and biochemical studies implicating a replication origin at the end of the VACV genome.
Full Text Available Research has identified appetitive aggression, i.e., the perception of committed, violent acts as appealing, exciting and fascinating, as a common phenomenon within populations living in precarious and violent circumstances. Investigating demobilized soldiers in the Democratic Republic of Congo demonstrated that violent offending is associated with appetitive aggression but not necessarily with symptoms of posttraumatic stress. In the present study we sought to replicate these results in an independent and larger sample of demobilized soldiers from Burundi. As with the Congolese ex-combatants, random forest regression revealed that the number of lifetime perpetrated violent acts is the most important predictor of appetitive aggression and the number of lifetime experienced traumatic events is the main predictor for posttraumatic stress. Perpetrated violent acts with salient cues of hunting (pursuing the victim, the sight of blood, etc. were most predictive for perceiving violent cues appealingly after demobilization. Moreover, the association of violent acts and appetitive aggression as well as traumatic events and posttraumatic stress remains strong even years after demobilization. Patterns of traumatic events and perpetrated acts as predictors for posttraumatic stress and appetitive aggression seem to be robust among different samples of ex-combatants who fought in civil wars. Psychotherapeutic interventions that address these complementary facets of combat-related disorders -- namely, posttraumatic stress and appetitive aggression -- are indispensable for a successful reintegration of those who fought in armed conflicts and to achieve a successful transition to peace.
Lay See eOng
Full Text Available We report the results of three high-powered replications of Troisi and Gabriel’s (2011 idea that writing about comfort food reduces feelings of loneliness amongst securely attached individuals after a belongingness threat. We conducted our studies amongst a large group of participants (Total N = 649 amongst American (MTurk, Dutch (Tilburg University; TiU, and Singaporean (Singapore Management University; SMU samples. Participants first completed an attachment style scale, followed by writing two essays for manipulating a sense of belongingness and salience of comfort food, and then reporting their loneliness levels. We did not confirm the overall effect over all three countries. However, exploratory results provide the preliminary suggestion that 1 the comfort food explanation likely holds amongst the American samples (including Troisi & Gabriel’s, but not amongst the TiU and SMU samples, and potentially that 2 the TiU and SMU participants self-regulate through warmer (vs. colder temperature foods. Both of these should be regarded with great caution as these analyses were exploratory, and because the Ns for the different temperature foods were small. We suspect we have uncovered first cross-cultural differences in self-regulation through food, but further confirmatory work is required to understand the cultural significance of comfort food for self-regulation.
Yao, Qiucheng; Ma, Jian; Wang, Xuefeng; Guo, Miaomiao; Li, Yanfei; Wang, Xiaojun
Tetherin (BST-2) is an important host restriction factor that can inhibit the release of a diverse array of enveloped viruses from infected cells. Conversely, to facilitate their release and spread, many viruses have evolved various strategies to overcome the antiviral effect of tetherin in a species-specific manner. During the development of an attenuated equine infectious anemia virus (EIAV) vaccine in our laboratory, we found that serial passage of a field-isolated virulent EIAV strains in horse and donkey as well as the cultivated donkey cells, produces several typical EIAV strains, including EIAV DV , EIAV DLV , and EIAV FDDV , which exhibit distinct virulence and replication features in vivo and in vitro. However, the role of host restriction factors in EIAV evolution during the serial passage is not well understood. This study aimed to evaluate whether these newly generated strains adapt differently to donkey tetherin (do-tetherin) based on their virulence. We found that do-tetherin exerts an inhibition on the release of the viral particles produced by all three strains, albeit with varying intensity: EIAV DV EIAV DLV > EIAV FDDV . These results indicate that donkey tetherin is involved in shaping of EIAV evolution during serial passage. Copyright © 2016 Elsevier Ltd. All rights reserved.
Brittany M Ashlock
Full Text Available Kaposi's sarcoma (KS is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV. KS tumors are composed of KSHV-infected spindle cells of vascular origin with aberrant neovascularization and erythrocyte extravasation. KSHV genes expressed during both latent and lytic replicative cycles play important roles in viral oncogenesis. Animal models able to recapitulate both viral and host biological characteristics of KS are needed to elucidate oncogenic mechanisms, for developing targeted therapies, and to trace cellular components of KS ontogeny. Herein, we describe two new murine models of Kaposi's sarcoma. We found that murine bone marrow-derived cells, whether established in culture or isolated from fresh murine bone marrow, were infectable with rKSHV.219, formed KS-like tumors in immunocompromised mice and produced mature herpesvirus-like virions in vivo. Further, we show in vivo that the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat enhanced viral lytic reactivation. We propose that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of Kaposi's sarcoma. Furthermore, our isolation of bone marrow-derived cell populations containing a cell type that, when infected with KSHV, renders a tumorigenic KS-like spindle cell, should facilitate systematic identification of KS progenitor cells.
Andersen, Vibeke; Ernst, Anja; Sventoraityte, Jurgita; Kupcinskas, Limas; Jacobsen, Bent A; Krarup, Henrik B; Vogel, Ulla; Jonaitis, Laimas; Denapiene, Goda; Kiudelis, Gediminas; Balschun, Tobias; Franke, Andre
Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).No SNP reached genome
Full Text Available Abstract Background Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS (Franke et al., 2010, for 1 association with UC in the Nordic countries, 2 for population heterogeneity between the Nordic countries and the rest of Europe, and, 3 eventually, to drive some of the previous findings towards overall genome-wide significance. Methods Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD and Cochran-Mantel-Haenszel (CMH tests were used for association analyses and heterogeneity testing. Results The rs5771069 (IL17REL SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02. No association was found between rs7809799 (SMURF1/KPNA7 and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10 or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7 in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs. Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001, rs12518307 (P = 0.007, and rs2395609 (TCP11 (P = 0
Soeur, L; Desmoineaux, P; Devillier, A; Pujol, N; Beaufils, P
When managed conservatively, lateral epicondylitis often subsides only after considerable time, during which social and occupational activities are severely disrupted. If conservative management fails, a recently introduced option is arthroscopic release of the extensor carpi radialis brevis (ECRB). The primary objective of this study was to compare clinical outcomes of this procedure according to preoperative symptom duration. Earlier arthroscopic release is associated with better functional outcomes. Consecutive patients with arthroscopically managed lateral epicondylitis were included in a retrospective study. Arthroscopy was performed only after at least 6 months of conservative treatment. The criteria to evaluate the clinical outcomes were the Nirschl and Quick-DASH scores, muscle strength, time to pain relief, and percentage of functional recovery. Thirty-five patients were evaluated at a median of 4 years (range: 1-12 years) after surgery. Mean preoperative symptom duration was 18 months (range: 6-106 months) with a mean sick leave duration of 2.3±4.9 months. Postoperatively, mean time to recovery was 37.5 days (range: 7 days to 5 years) and mean sick leave duration was 2.4±2.4 months. The mean Quick-DASH score was 15.9±19.1. The Nirschl score improved significantly, from 26.4±7.9 to 66.3±16.3. The initial muscle strength deficit was 10.1±33.2% and muscle strength at last follow-up was increased by 4.3±30.3%. Symptom duration showed no correlations with any of the clinical outcome measures. Outcomes after arthroscopic release were not associated with symptom duration in this study. Nevertheless, the good clinical outcomes support treatment with arthroscopic release after only 6 months of conservative management. IV, retrospective study. Copyright © 2016. Published by Elsevier Masson SAS.
Sebastiaan M Bol
Full Text Available HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART, macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages.Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96 or high (n = 96 p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16 × 10(-5. While the association was not genome-wide significant (p<1 × 10(-7, we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034. Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84 × 10(-6. In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048.These findings suggest that the kinase DYRK1A is involved in the replication of HIV-1, in vitro in macrophages
Bol, Sebastiaan M.; Moerland, Perry D.; Limou, Sophie; van Remmerden, Yvonne; Coulonges, Cédric; van Manen, Daniëlle; Herbeck, Joshua T.; Fellay, Jacques; Sieberer, Margit; Sietzema, Jantine G.; van 't Slot, Ruben; Martinson, Jeremy; Zagury, Jean-François; Schuitemaker, Hanneke; van 't Wout, Angélique B.
Background HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages. Methodology/Principal Findings Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96) or high (n = 96) p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16×10−5). While the association was not genome-wide significant (p<1×10−7), we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034). Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84×10−6). In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048). Conclusions/Significance These findings suggest that
This paper reports on the findings of a case study in a company in the financial services sector in which we replicated the use of a previously published approach to systematically balance the contextual uncertainties in the estimation of Enterprise Resource Planning (ERP) projects. The approach is
Smith, Stephen W.; Daunic, Ann P.; Aydin, Burak; Van Loan, Christopher L.; Barber, Brian R.; Taylor, Gregory G.
Social-emotional learning curricula to prevent student problematic behaviors should play a prominent role in public school instruction. While social-emotional curricula have been shown to be effective, there are few replication studies that substantiate their capacity to improve outcomes for students who exhibit problem behaviors. Thus, we…
Kapoutsis, Ilias; Papalexandris, Alexandros; Nikolopoulos, Andreas; Hochwarter, Wayne A.; Ferris, Gerald R.
We developed a two-study, cross-national, constructive replication to examine the role of organizational politics perceptions as a contextual moderator of the political skill-job performance relationship. Specifically, we hypothesized that high levels of political skill would demonstrate its strongest positive effects on job performance when…
Klaassen, Ester M M; Penders, John; Jöbsis, Quirijn; van de Kant, Kim D G; Thijs, Carel; Mommers, Monique; van Schayck, Constant P; van Eys, Guillaume; Koppelman, Gerard H; Dompeling, Edward
The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a pchildhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.
Liu, Feng; Ren, Chao; Li, Hao; Zhou, Pingkun; Bo, Xiaochen; Shu, Wenjie
The de novo identification of the initiation and termination zones-regions that replicate earlier or later than their upstream and downstream neighbours, respectively-remains a key challenge in DNA replication. Building on advances in deep learning, we developed a novel hybrid architecture combining a pre-trained, deep neural network and a hidden Markov model (DNN-HMM) for the de novo identification of replication domains using replication timing profiles. Our results demonstrate that DNN-HMM can significantly outperform strong, discriminatively trained Gaussian mixture model-HMM (GMM-HMM) systems and other six reported methods that can be applied to this challenge. We applied our trained DNN-HMM to identify distinct replication domain types, namely the early replication domain (ERD), the down transition zone (DTZ), the late replication domain (LRD) and the up transition zone (UTZ), using newly replicated DNA sequencing (Repli-Seq) data across 15 human cells. A subsequent integrative analysis revealed that these replication domains harbour unique genomic and epigenetic patterns, transcriptional activity and higher-order chromosomal structure. Our findings support the 'replication-domain' model, which states (1) that ERDs and LRDs, connected by UTZs and DTZs, are spatially compartmentalized structural and functional units of higher-order chromosomal structure, (2) that the adjacent DTZ-UTZ pairs form chromatin loops and (3) that intra-interactions within ERDs and LRDs tend to be short-range and long-range, respectively. Our model reveals an important chromatin organizational principle of the human genome and represents a critical step towards understanding the mechanisms regulating replication timing. Our DNN-HMM method and three additional algorithms can be freely accessed at https://github.com/wenjiegroup/DNN-HMM The replication domain regions identified in this study are available in GEO under the accession ID GSE53984. email@example.com or boxc
Jacobsen, Kari Stougaard; Nielsen, Kirstine Overgaard; Nordmann Winther, Thilde
expressed microRNAs with liver-specific target genes in plasma from children with chronic hepatitis B. To further understand the biological role of these microRNAs in the pathogenesis of chronic hepatitis B, we have used the human liver cell line HepG2, with and without HBV replication, after transfection...
Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan
Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112
Dec 13, 2010 ... the production of new seedless wampee cultivars in recent years were operated. ... increase burliness rate in hybridization. In order to earlier ... methods is greatly limited due to a long juvenile phase of ... Plant materials .... This fragment may be linked ... reduce high temperature which affected pollen germi-.
Moran, Lauren V; Masters, Grace A; Pingali, Samira; Cohen, Bruce M; Liebson, Elizabeth; Rajarethinam, R P; Ongur, Dost
A childhood history of attention deficit hyperactivity disorder (ADHD) is common in psychotic disorders, yet prescription stimulants may interact adversely with the physiology of these disorders. Specifically, exposure to stimulants leads to long-term increases in dopamine release. We therefore hypothesized that individuals with psychotic disorders previously exposed to prescription stimulants will have an earlier onset of psychosis. Age of onset of psychosis (AOP) was compared in individuals with and without prior exposure to prescription stimulants while controlling for potential confounding factors. In a sample of 205 patients recruited from an inpatient psychiatric unit, 40% (n = 82) reported use of stimulants prior to the onset of psychosis. Most participants were prescribed stimulants during childhood or adolescence for a diagnosis of ADHD. AOP was significantly earlier in those exposed to stimulants (20.5 vs. 24.6 years stimulants vs. no stimulants, p drugs of abuse, and family history of a first-degree relative with psychosis, the association between stimulant exposure and earlier AOP remained significant. There was a significant gender × stimulant interaction with a greater reduction in AOP for females, whereas the smaller effect of stimulant use on AOP in males did not reach statistical significance. In conclusion, individuals with psychotic disorders exposed to prescription stimulants had an earlier onset of psychosis, and this relationship did not appear to be mediated by IQ or cannabis. Copyright © 2015 Elsevier Ltd. All rights reserved.
Jennifer Pontius; Richard Hallett
Forested ecosystems are threatened by invasive pests, pathogens, and unusual climatic events brought about by climate change. Earlier detection of incipient forest health problems and a quantitatively rigorous assessment method is increasingly important. Here, we describe a method that is adaptable across tree species and stress agents and practical for use in the...
Pestel, Gunther J; Fukui, Kimiko; Kimberger, Oliver; Hager, Helmut; Kurz, Andrea; Hiltebrand, Luzius B
Untreated hypovolemia results in impaired outcome. This study tests our hypothesis whether general hemodynamic parameters detect acute blood loss earlier than monitoring parameters of regional tissue beds. Eight pigs (23-25 kg) were anesthetized and mechanically ventilated. A pulmonary artery catheter and an arterial catheter were inserted. Tissue oxygen tension was measured with Clark-type electrodes in the jejunal and colonic wall, in the liver, and subcutaneously. Jejunal microcirculation was assessed by laser Doppler flowmetry (LDF). Intravascular volume was optimized using difference in pulse pressure (dPP) to keep dPP below 13%. Sixty minutes after preparation, baseline measurements were taken. At first, 5% of total blood volume was withdrawn, followed by another 5% increment, and then in 10% increments until death. After withdrawal of 5% of estimated blood volume, dPP increased from 6.1% +/- 3.0% to 20.8% +/- 2.7% (P < 0.01). Mean arterial pressure (MAP), mean pulmonary artery pressure (PAP) and pulmonary artery occlusion pressure (PAOP) decreased with a blood loss of 10% (P < 0.01). Cardiac output (CO) changed after a blood loss of 20% (P < 0.05). Tissue oxygen tension in central organs, and blood flow in the jejunal muscularis decreased (P < 0.05) after a blood loss of 20%. Tissue oxygen tension in the skin, and jejunal mucosa blood flow decreased (P < 0.05) after a blood loss of 40% and 50%, respectively. In this hemorrhagic pig model systemic hemodynamic parameters were more sensitive to detect acute hypovolemia than tissue oxygen tension measurements or jejunal LDF measurements. Acute blood loss was detected first by dPP. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Coyne, Michael D.; Cook, Bryan G.; Therrien, William J.
Special education researchers conduct studies that can be considered replications. However, they do not often refer to them as replication studies. The purpose of this article is to consider the potential benefits of conceptualizing special education intervention research within a framework of systematic, conceptual replication. Specifically, we…
Sandholt, Camilla Helene; Mogensen, Mette S; Borch-Johnsen, Knut
The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case-control stud......The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case......-control studies and analyses of obesity-related quantitative traits. Moreover, since environmental and genetic factors may modulate the impact of a genetic variant, we wanted to perform such interaction analyses. We focused on physical activity as an environmental risk factor, and on the GWA identified obesity...
Taplin, Stephanie; Mattick, Richard P
Although a high level of involvement with the child protection system has been identified in families where parental substance use is a feature, not all such parents abuse or neglect their children or have contact with the child protection system. Identifying parents with substance-use histories who are able to care for their children without intervention by the child protection system, and being able to target interventions to the families who need them the most is important. This study interviewed a relatively large sample of mothers about their histories, their children and their involvement with the child protection system. We hypothesized that mothers in opioid pharmacological treatment who are involved with child protection services are different in characteristics to those mothers who are not involved. One hundred and seventy-one women, with at least one child aged under 16 years, were interviewed at nine treatment clinics providing pharmacological treatment for opioid dependence across Sydney, Australia. Just over one-third of the women were involved with child protection services at the time of interview, mostly with children in out-of-home care. Logistic regression analyses revealed that factors which significantly increased the likelihood of the mother being involved with the child protection system were: (1) having a greater number of children, (2) being on psychiatric medication, and (3) having less than daily contact with her own parents. This study replicates and extends the work of Grella, Hser, and Huang (2006) and the limited literature published to date examining the factors which contribute to some substance-using mothers becoming involved with the child protection system while others do not. The finding that mental health problems and parental supports (along with the number of children) were significantly associated with child protection system involvement in this study, indicates a need for improved interventions and the provision of
Leonardo da Silva Boia
decline for short distances.------------------------------Cite this article as: Boia LS, Junior J, Menezes AF, Silva AX. Computational system to create an entry file for replicating I-125 seeds simulating brachytherapy case studies using the MCNPX code. Int J Cancer Ther Oncol 2014; 2(2:02023.DOI: http://dx.doi.org/10.14319/ijcto.0202.3
Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard
A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways...... causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy....
Several oxidative processes induce the formation of DNA lesions. In order to evaluate the biological and structural significance of such damage, several DNA lesions were inserted into synthetic oligonucleotides at defined sites. The research work aimed at describing the preparation of oligonucleotides t hat contained DNA damage and the evaluation of the biological properties of the lesions. A first part described the incorporation of radiation-induced lesions, namely (5'S,6S)-5',6-cyclo-5,6-dihydro-2'-deoxyuridine and (5'S,5S,6S)-5',6-cyclo-5-hydroxy-5,6-dihydro-2'-desoxyuridine into oligonucleotides. The modified DNA fragments were characterised by several spectroscopic and biochemical analyses including ESI MS, MALDI-TOF MS, CLHP and enzymatic digestions. During in vitro DNA synthesis by Taq DNA polymerase and Klenow exo fragment, the pyrimidine cyclo-nucleosides were found to block the progression of the enzymes. Then, repair studies by ADN N glycosylases, operating in the base excision repair pathway, have shown that the anhydro-nucleoside lesions were not recognised nor excised by Fpg, endo III, endo VIII, yNtg1 yNtg2 and yOgg1. Interestingly, the Latococcus lactis Fpg protein recognises (formation of a non covalent complex) but do not excise the damage. The incorporation into oligonucleotides of the (5R*) and (5S*) diastereoisomers of 1-[2-deoxy-β-D-erythro-pentofuranosyl]-5-hydroxy-hydantoin, generated by several oxidative processes was then described. In vitro DNA replication assays using modified oligonucleotides matrix showed a lethal potential of the latter base damage. Repair studies by ADN N-glycosylases showed that the damage was substrate for Fpg, endo III, endo VIII, Ntg1, Ntg2 and Fpg-L1. The rates of excision as inferred from the determination of the Michaelis kinetics constants were found to be affected by the presence of the damage. MALDI-TOF MS was used in order to gain insights into mechanistic aspects of oligonucleotides cleavage by the
Moran, Lauren V.; Masters, Grace A.; Pingali, Samira; Cohen, Bruce M.; Liebson, Elizabeth; Rajarethinam, R.P.; Ongur, Dost
A childhood history of attention deficit hyperactivity disorder (ADHD) is common in psychotic disorders, yet prescription stimulants may interact adversely with the physiology of these disorders. Specifically, exposure to stimulants leads to long-term increases in dopamine release. We therefore hypothesized that individuals with psychotic disorders previously exposed to prescription stimulants will have an earlier onset of psychosis. Age of onset of psychosis (AOP) was compared in individuals...
DeLong, Kristine L.; Flannery, Jennifer A.; Maupin, Christopher R.; Poore, Richard Z.; Quinn, Terrence M.
This study examined the variations in the ratio of strontium-to-calcium (Sr/Ca) for two Atlantic corals (Montastraea faveolata and Siderastrea siderea) from the Dry Tortugas National Park (centered on 24.7°N, 82.8°W) in the Gulf of Mexico. Cores from coral colonies in close proximity (10s of meters) and with the same environmental conditions (i.e., depth and water chemistry) were micro-sampled with approximately monthly resolution and the resulting Sr/Ca variations were calibrated with local sea surface temperature (SST) records. Replication tests for coral Sr/Ca variations found high agreement between intra-colony variations and between individual colonies of S. siderea (a single M. faveolata colony was sampled). Regression analysis of monthly variations in coral Sr/Ca and local SST revealed significant correlation on monthly and inter-annual timescales. Verification of the calibration on different timescales found coral Sr/Ca–SST reconstructions in S. siderea were more accurate than those from M. faveolata, especially on inter-annual timescales. Sr/Ca–SST calibration equations for the two species are significantly different (cf., Sr/Ca = -0.042 SST + 10.070, S. siderea; Sr/Ca = -0.027 SST + 9.893, M. faveolata). Mean linear extension for M. faveolata is approximately twice that of S. siderea (4.63, 4.31, and 8.31 mm year−1, A1, F1, and B3, respectively); however, seasonal Sr/Ca variability in M. faveolata is less than S. siderea (0.323, 0.353, and 0.254 mmol mol−1, A1, F1, and B3, respectively). The reduced slope for M. faveolata is attributed to physical sampling issues associated with complex time-skeletal structure of M. faveolata, i.e., a sampling effect, and not a growth effect since the faster growing M. faveolata has the reduced Sr/Ca variability.
Lee, Ying C; Nielsen, Jens Høiriis
Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...
Emily A. McKinney
Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.
Kolesnikov, T D; Andreenkova, N G; Beliaeva, E S; Goncharov, F P; Zykova, T Iu; Boldyreva, L V; Pokholkova, g V; Zhimulev, I F
About 240 specific regions that are replicated at the very end of the S-phase have been identified in D. melanogaster polytene chromosomes. These regions have a repressive chromatine state, low gene density, long intergenic distances and are enriched in tissue specific genes. In polytene chromosomes, about a quarter of these regions have no enough time to complete replication. As a result, underreplication zones represented by fewer DNA copy number, appear. We studied 60 chromosome regions that demonstrated the most pronounced under-replication. By comparing the location of these regions on a molecular map with syntenic blocks found earlier for Drosophila species by von Grotthuss et al., 2010, we have shown that across the genus Drosophila, these regions tend to have conserved gene order. This forces us to assume the existence of evolutionary mechanisms aimed at maintaining the integrity of these regions.
Agogo, George O; van der Voet, Hilko; van't Veer, Pieter; Ferrari, Pietro; Leenders, Max; Muller, David C; Sánchez-Cantalejo, Emilio; Bamia, Christina; Braaten, Tonje; Knüppel, Sven; Johansson, Ingegerd; van Eeuwijk, Fred A; Boshuizen, Hendriek
In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.
Ingason, Andrés; Giegling, Ina; Cichon, Sven
The Abelson helper integration site 1 (AHI1) gene locus on chromosome 6q23 is among a group of candidate loci for schizophrenia susceptibility that were initially identified by linkage followed by linkage disequilibrium mapping, and subsequent replication of the association in an independent sample....... Here, we present results of a replication study of AHI1 locus markers, previously implicated in schizophrenia, in a large European sample (in total 3907 affected and 7429 controls). Furthermore, we perform a meta-analysis of the implicated markers in 4496 affected and 18,920 controls. Both...... as the neighbouring phosphodiesterase 7B (PDE7B)-may be considered candidates for involvement in the genetic aetiology of schizophrenia....
Varvara A Khoroshko
Full Text Available Late-replicating domains (intercalary heterochromatin in the Drosophila genome display a number of features suggesting their organization is quite unique. Typically, they are quite large and encompass clusters of functionally unrelated tissue-specific genes. They correspond to the topologically associating domains and conserved microsynteny blocks. Our study aims at exploring further details of molecular organization of intercalary heterochromatin and has uncovered surprising heterogeneity of chromatin composition in these regions. Using the 4HMM model developed in our group earlier, intercalary heterochromatin regions were found to host chromatin fragments with a particular epigenetic profile. Aquamarine chromatin fragments (spanning 0.67% of late-replicating regions are characterized as a class of sequences that appear heterogeneous in terms of their decompactization. These fragments are enriched with enhancer sequences and binding sites for insulator proteins. They likely mark the chromatin state that is related to the binding of cis-regulatory proteins. Malachite chromatin fragments (11% of late-replicating regions appear to function as universal transitional regions between two contrasting chromatin states. Namely, they invariably delimit intercalary heterochromatin regions from the adjacent active chromatin of interbands. Malachite fragments also flank aquamarine fragments embedded in the repressed chromatin of late-replicating regions. Significant enrichment of insulator proteins CP190, SU(HW, and MOD2.2 was observed in malachite chromatin. Neither aquamarine nor malachite chromatin types appear to correlate with the positions of highly conserved non-coding elements (HCNE that are typically replete in intercalary heterochromatin. Malachite chromatin found on the flanks of intercalary heterochromatin regions tends to replicate earlier than the malachite chromatin embedded in intercalary heterochromatin. In other words, there exists a
Fan, Bihang; Guo, Li; Li, Ning; Chen, Jin; Lin, Henry; Zhang, Xiaoyang; Shen, Miaogen; Rao, Yuhan; Wang, Cong; Ma, Lei
The observed decline of spring dust storms in Northeast Asia since the 1950s has been attributed to surface wind stilling. However, spring vegetation growth could also restrain dust storms through accumulating aboveground biomass and increasing surface roughness. To investigate the impacts of vegetation spring growth on dust storms, we examine the relationships between recorded spring dust storm outbreaks and satellite-derived vegetation green-up date in Inner Mongolia, Northern China from 1982 to 2008. We find a significant dampening effect of advanced vegetation growth on spring dust storms (r = 0.49, p = 0.01), with a one-day earlier green-up date corresponding to a decrease in annual spring dust storm outbreaks by 3%. Moreover, the higher correlation (r = 0.55, p storm outbreak ratio (the ratio of dust storm outbreaks to times of strong wind events) indicates that such effect is independent of changes in surface wind. Spatially, a negative correlation is detected between areas with advanced green-up dates and regional annual spring dust storms (r = -0.49, p = 0.01). This new insight is valuable for understanding dust storms dynamics under the changing climate. Our findings suggest that dust storms in Inner Mongolia will be further mitigated by the projected earlier vegetation green-up in the warming world.
Richard A. Klein
Full Text Available This dataset is from the Many Labs Replication Project in which 13 effects were replicated across 36 samples and over 6,000 participants. Data from the replications are included, along with demographic variables about the participants and contextual information about the environment in which the replication was conducted. Data were collected in-lab and online through a standardized procedure administered via an online link. The dataset is stored on the Open Science Framework website. These data could be used to further investigate the results of the included 13 effects or to study replication and generalizability more broadly.
Ahmad, Muhammad Khairi; Tabana, Yasser M; Ahmed, Mowaffaq Adam; Sandai, Doblin Anak; Mohamed, Rafeezul; Ismail, Ida Shazrina; Zulkiflie, Nurulisa; Yunus, Muhammad Amir
A norovirus maintains its viability, infectivity and virulence by its ability to replicate. However, the biological mechanisms of the process remain to be explored. In this work, the NanoLuc™ Luciferase gene was used to develop a reporter-tagged replicon system to study norovirus replication. The NanoLuc™ Luciferase reporter protein was engineered to be expressed as a fusion protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A (FMDV2A) sequence was inserted between the 3'end of the reporter gene and the VP2 start sequence to allow co-translational 'cleavage' of fusion proteins during intracellular transcript expression. Amplification of the fusion gene was performed using a series of standard and overlapping polymerase chain reactions. The resulting amplicon was then cloned into three readily available backbones of MNV-1 cDNA clones. Restriction enzyme analysis indicated that the NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA clone. The insertion was further confirmed by using DNA sequencing. NanoLuc™ Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such clones can be exploited to develop robust experimental assays for in vitro assessments of viral RNA replication.
Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)
Rapp, Jordan B.; Ansbach, Alison B.; Noguchi, Chiaki; Noguchi, Eishi
Replication of chromosomes involves a variety of replication proteins including DNA polymerases, DNA helicases, and other accessory factors. Many of these proteins are known to localize at replication forks and travel with them as components of the replisome complex. Other proteins do not move with replication forks but still play an essential role in DNA replication. Therefore, in order to understand the mechanisms of DNA replication and its controls, it is important to examine localization ...
Vogelauer, Maria; Rubbi, Liudmilla; Lucas, Isabelle; Brewer, Bonita J; Grunstein, Michael
The temporal firing of replication origins throughout S phase in yeast depends on unknown determinants within the adjacent chromosomal environment. We demonstrate here that the state of histone acetylation of surrounding chromatin is an important regulator of temporal firing. Deletion of RPD3 histone deacetylase causes earlier origin firing and concurrent binding of the replication factor Cdc45p to origins. In addition, increased acetylation of histones in the vicinity of the late origin ARS1412 by recruitment of the histone acetyltransferase Gcn5p causes ARS1412 alone to fire earlier. These data indicate that histone acetylation is a direct determinant of the timing of origin firing.
Girard, D E; Carlton, B E
There are important measurements of alcoholism that are poorly understood by physicians. Professional attitudes toward alcoholic patients are often counterproductive. Americans spend about $30 billion on alcohol a year and most adults drink alcohol. Even though traditional criteria allow for recognition of the disease, diagnosis is often made late in the natural course, when intervention fails. Alcoholism is a major health problem and accounts for 10 percent of total health care costs. Still, this country's 10 million adult alcoholics come from a pool of heavy drinkers with well defined demographic characteristics. These social, cultural and familial traits, along with subtle signs of addiction, allow for earlier diagnosis. Although these factors alone do not establish a diagnosis of alcoholism, they should alert a physician that significant disease may be imminent. Focus must be directed to these aspects of alcoholism if containment of the problem is expected.
These studies describe the isolation and characterization of early minicircle replication intermediates from Crithidia fasciculata, and Leishmania tarentolae, the mitochondrial localization of a type II topoisomerase (TIImt) in C. fasciculata, and the implication of the aforementioned TIImt in minicircle replication in L. tarentolae. Early minicircle replication intermediates from C. fasciculata were identified and characterized using isolated kinetoplasts to incorporate radiolabeled nucleotides into its DNA. The pulse-label in an apparent theta-type intermediate chase into two daughter molecules. A uniquely gapped, ribonucleotide primed, knotted molecule represents the leading strand in the model proposed, and a highly gapped molecule represents the lagging strand. This theta intermediate is repaired in vitro to a doubly nicked catenated dimer which was shown to result from the replication of a single parental molecule. Very similar intermediates were found in the heterogeneous population of minicircles of L. tarentolae. The sites of the Leishmania specific discontinuities were mapped and shown to lie within the universally conserved sequence blocks in identical positions as compared to C. fasciculata and Trypanosoma equiperdum
Zsofia A Kiss
Full Text Available Criniviruses comprise one of the genera within the family Closteroviridae. Members in this family are restricted to the phloem and rely on whitefly vectors of the genera Bemisia and/or Trialeurodes for plant-to-plant transmission. All criniviruses have bipartite, positive-sense ssRNA genomes, although there is an unconfirmed report of one having a tripartite genome. Lettuce infectious yellows virus (LIYV is the type species of the genus, the best studied so far of the criniviruses and the first for which a reverse genetics system was available. LIYV RNA 1 encodes for proteins predicted to be involved in replication, and alone is competent for replication in protoplasts. Replication results in accumulation of cytoplasmic vesiculated membranous structures which are characteristic of most studied members of the Closteroviridae. These membranous structures, often referred to as BYV-type vesicles, are likely sites of RNA replication. LIYV RNA 2 is replicated in trans when co-infecting cells with RNA 1, but is temporally delayed relative to RNA1. Efficient RNA 2 replication also is dependent on the RNA 1-encoded RNA binding protein, P34. No LIYV RNA 2-encoded proteins have been shown to affect RNA replication, but at least four, CP, CPm, Hsp70h, and p59 are virion structural components and CPm is a determinant of whitefly transmissibility. Roles of other LIYV RNA 2-encoded proteins are largely as yet unknown, but P26 is a non-virion protein that accumulates in cells as characteristic plasmalemma deposits which in plants are localized within phloem parenchyma and companion cells over plasmodesmata connections to sieve elements. The two remaining crinivirus-conserved RNA 2-encoded proteins are P5 and P9. P5 is 39 amino acid protein and is encoded at the 5’ end of RNA 2 as ORF1 and is part of the hallmark closterovirus gene array. The orthologous gene in BYV has been shown to play a role in cell-to-cell movement and indicated to be localized to the
Standing, Lionel G.; Grenier, Manuel; Lane, Erica A.; Roberts, Meigan S.; Sykes, Sarah J.
It is suggested that replication projects may be valuable in teaching research methods, and also address the current need in psychology for more independent verification of published studies. Their use in an undergraduate methods course is described, involving student teams who performed direct replications of four well-known experiments, yielding…
Prasad, Alka; Remick, Jill; Zeichner, Steven L
A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.
Full Text Available The late detection of the kick (the entrance of underground fluids into oil wells leads to oil well blowouts. It causes human life loss and imposes a great deal of expenses on the petroleum industry. This paper presents the application of adaptive neuro-fuzzy inference system designed for an earlier kick detection using measurable drilling parameters. In order to generate the initial fuzzy inference system, subtractive clustering is utilized. The training set contains 50 data samples and there are 362 data samples for testing the proposed method. Also, ANFIS structure is examined at different radii (the parameter of subtractive clustering. Different conformations are tested to get the earliest detection and the lowest false alarms while facing kick. Eventually, ANFIS verifies the danger exposure depth of about 28.6 meters before the depth that the kick was sensed by crew. Such an assessment gives the rig crew enough time to prepare for the danger and stop the operation before being exposed to high pressure zones.
van Tilborg, Theodora C.; Broekmans, Frank J.; Pijpe, Anouk; Schrijver, Lieske H.; Mooij, Thea M.; Oosterwijk, Jan C.; Verhoef, Senno; Garcia, Encarna B. Gomez; van Zelst-Stams, Wendy A.; Adank, Muriel A.; van Asperen, Christi J.; van Doorn, Helena C.; van Os, Theo A.; Bos, Anna M.; Rookus, Matti A.; Ausems, Margreet G.
Objective: It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature.
Duffy, J. F.; Dijk, D. J.; Klerman, E. B.; Czeisler, C. A.
The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.
Full Text Available Lettuce infectious yellows virus (LIYV is the type member of the genus Crinivirus in the family Closteroviridae. Like many other positive-strand RNA viruses, LIYV infections induce a number of cytopathic changes in plant cells, of which the two most characteristic are: Beet yellows virus-type inclusion bodies composed of vesicles derived from cytoplasmic membranes; and conical plasmalemma deposits (PLDs located at the plasmalemma over plasmodesmata pit fields. The former are not only found in various closterovirus infections, but similar structures are known as ‘viral factories’ or viroplasms in cells infected with diverse types of animal and plant viruses. These are generally sites of virus replication, virion assembly and in some cases are involved in cell-to-cell transport. By contrast, PLDs induced by the LIYV-encoded P26 non-virion protein are not involved in replication but are speculated to have roles in virus intercellular movement. These deposits often harbor LIYV virions arranged to be perpendicular to the plasma membrane over plasmodesmata, and our recent studies show that P26 is required for LIYV systemic plant infection. The functional mechanism of how LIYV P26 facilitates intercellular movement remains unclear, however, research on other plant viruses provides some insights on the possible ways of viral intercellular movement through targeting and modifying plasmodesmata via interactions between plant cellular components and viral-encoded factors. In summary, beginning with LIYV, we review the studies that have uncovered the biological determinants giving rise to these cytopathological effects and their importance in viral replication, virion assembly and intercellular movement during the plant infection by closteroviruses, and compare these findings with those for other positive-strand RNA viruses.
Alexey A. Leontovich
Full Text Available Metabolic memory (MM is defined as the persistence of diabetic (DM complications even after glycemic control is pharmacologically achieved. Using a zebrafish diabetic model that induces a MM state, we previously reported that, in this model, tissue dysfunction was of a heritable nature based on cell proliferation studies in limb tissue and this correlated with epigenetic DNA methylation changes that paralleled alterations in gene expression. In the current study, control, DM, and MM excised fin tissues were further analyzed by MeDIP sequencing and microarray techniques. Bioinformatics analysis of the data found that genes of the DNA replication/DNA metabolism process group (with upregulation of the apex1, mcm2, mcm4, orc3, lig1, and dnmt1 genes were altered in the DM state and these molecular changes continued into MM. Interestingly, DNA methylation changes could be found as far as 6–13 kb upstream of the transcription start site for these genes suggesting potential higher levels of epigenetic control. In conclusion, DNA methylation changes in members of the DNA replication/repair process group best explain the heritable nature of cell proliferation impairment found in the zebrafish DM/MM model. These results are consistent with human diabetic epigenetic studies and provide one explanation for the persistence of long term tissue complications as seen in diabetes.
Theilade, Uffe Arlø; Hansen, Hans Nørgaard
topography is transcribed onto the plastic part through complex mechanisms. This replication, however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... molding of surface microstructures. The fundamental problem of surface microstructure replication has been studied. The research is based on specific microstructures as found in lab-on-a-chip products and on rough surfaces generated from EDM (electro discharge machining) mold cavities. Emphasis is put...... on the ability to replicate surface microstructures under normal injection-molding conditions, i.e., with commodity materials within typical process windows. It was found that within typical process windows the replication quality depends significantly on several process parameters, and especially the mold...
Cao, Shuai; Realegeno, Susan; Pant, Anil; Satheshkumar, Panayampalli S; Yang, Zhilong
Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV), the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.
Full Text Available Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV, the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.
He, Chong; Zhou, Chuankai; Kennedy, Brian K
It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.
Yao, Nina Y.; O'Donnell, Mike E.
The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some “gears” of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the “replisome” machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus. PMID:27160337
Kopiske, Karl K; Bruno, Nicola; Hesse, Constanze; Schenk, Thomas; Franz, Volker H
It has often been suggested that visual illusions affect perception but not actions such as grasping, as predicted by the "two-visual-systems" hypothesis of Milner and Goodale (1995, The Visual Brain in Action, Oxford University press). However, at least for the Ebbinghaus illusion, relevant studies seem to reveal a consistent illusion effect on grasping (Franz & Gegenfurtner, 2008. Grasping visual illusions: consistent data and no dissociation. Cognitive Neuropsychology). Two interpretations are possible: either grasping is not immune to illusions (arguing against dissociable processing mechanisms for vision-for-perception and vision-for-action), or some other factors modulate grasping in ways that mimic a vision-for perception effect in actions. It has been suggested that one such factor may be obstacle avoidance (Haffenden Schiff & Goodale, 2001. The dissociation between perception and action in the Ebbinghaus illusion: nonillusory effects of pictorial cues on grasp. Current Biology, 11, 177-181). In four different labs (total N = 144), we conducted an exact replication of previous studies suggesting obstacle avoidance mechanisms, implementing conditions that tested grasping as well as multiple perceptual tasks. This replication was supplemented by additional conditions to obtain more conclusive results. Our results confirm that grasping is affected by the Ebbinghaus illusion and demonstrate that this effect cannot be explained by obstacle avoidance. Copyright © 2016 Elsevier Ltd. All rights reserved.
Etienne P LeBel
Full Text Available In recent years, there has been a growing concern regarding the replicability of findings in psychology, including a mounting number of prominent findings that have failed to replicate via high-powered independent replication attempts. In the face of this replicability “crisis of confidence”, several initiatives have been implemented to increase the reliability of empirical findings. In the current article, I propose a new replication norm that aims to further boost the dependability of findings in psychology. Paralleling the extant social norm that researchers should peer review about three times as many articles that they themselves publish per year, the new replication norm states that researchers should aim to independently replicate important findings in their own research areas in proportion to the number of original studies they themselves publish per year (e.g., a 4:1 original-to-replication studies ratio. I argue this simple approach could significantly advance our science by increasing the reliability and cumulative nature of our empirical knowledge base, accelerating our theoretical understanding of psychological phenomena, instilling a focus on quality rather than quantity, and by facilitating our transformation toward a research culture where executing and reporting independent direct replications is viewed as an ordinary part of the research process. To help promote the new norm, I delineate (1 how each of the major constituencies of the research process (i.e., funders, journals, professional societies, departments, and individual researchers can incentivize replications and promote the new norm and (2 any obstacles each constituency faces in supporting the new norm.
Hua, Brian L.; Orr-Weaver, Terry L.
Proper control of DNA replication is critical to ensure genomic integrity during cell proliferation. In addition, differential regulation of the DNA replication program during development can change gene copy number to influence cell size and gene expression. Drosophila melanogaster serves as a powerful organism to study the developmental control of DNA replication in various cell cycle contexts in a variety of differentiated cell and tissue types. Additionally, Drosophila has provided several developmentally regulated replication models to dissect the molecular mechanisms that underlie replication-based copy number changes in the genome, which include differential underreplication and gene amplification. Here, we review key findings and our current understanding of the developmental control of DNA replication in the contexts of the archetypal replication program as well as of underreplication and differential gene amplification. We focus on the use of these latter two replication systems to delineate many of the molecular mechanisms that underlie the developmental control of replication initiation and fork elongation. PMID:28874453
Dewar, James M; Walter, Johannes C
A recent study has uncovered a new mechanism that attenuates DNA replication during periods of heightened gene expression to avoid collisions between replication and transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.
This proposal has focused on a broad host range plasmid, RK2, as a model system to study how a pair of initiation proteins encoded by the plasmid for DNA replication function when replication occurs...
Elbaz, Alexis; Nelson, Lorene M; Payami, Haydeh; Ioannidis, John P A; Fiske, Brian K; Annesi, Grazia; Belin, Andrea Carmine; Factor, Stewart A; Ferrarese, Carlo; Hadjigeorgiou, Georgios M; Higgins, Donald S; Kawakami, Hideshi; Krüger, Rejko; Marder, Karen S; Mayeux, Richard P; Mellick, George D; Nutt, John G; Ritz, Beate; Samii, Ali; Tanner, Caroline M; Van Broeckhoven, Christine; Van Den Eeden, Stephen K; Wirdefeldt, Karin; Zabetian, Cyrus P; Dehem, Marie; Montimurro, Jennifer S; Southwick, Audrey; Myers, Richard M; Trikalinos, Thomas A
Summary Background A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson’s disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. Methods Investigators from three Michael J Fox Foundation for Parkinson’s Research-funded genetics consortia—comprising 14 teams—contributed DNA samples from 5526 patients with Parkinson’s disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. Findings In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0·89 to 1·09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0·95 to 1.08); there was little heterogeneity except for SNP rs7520966. Interpretation Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson’s disease. PMID:17052658
Morris, T.J. [Univ. of Nebraska, Lincoln, NE (United States). School of Biological Sciences; Jackson, A.O. [Univ. of California, Berkeley, CA (United States). Dept. of Plant Biology
Tomato bushy stunt virus (TBSV) is a small icosahedral virus with a very broad host-range. The symptoms of systemic infection range from mild mosaic to severe necrosis that often results in death. The genome of TBSV is composed of a single plus stranded RNA molecule with five genes. Two 5 inch genes are translated from the viral RNA, and the remaining three are translated from two subgenomic RNAs. Prior to the DOE supported studies, TBSV gene function had been assigned solely on the basis of sequence similarity with other virus genes of known function. The two 5 inch proximal genes (p33 and p92) were thought to be involved in viral replication, the middle gene encoded the capsid protein (p41), but no clear function was assigned to two nested 3 inch genes (p19 and p22), although it was suggested that at least one could be involved in movement. This research has determined the roles of each of the viral genes in the infection process, and the authors have obtained considerable genetic information pertinent to the contributions of the coat protein and the nested genes to the disease phenotypes observed in several host plants. They have also identified another genetic element with a short open reading frame in the 3 inch-noncoding region of the genome that provides a host-dependent replication function.
Full Text Available Influenza A and B viruses (IAV and IBV, respectively cause annual seasonal human respiratory disease epidemics. In addition, IAVs have been implicated in occasional pandemics with inordinate health and economic consequences. Studying influenza viruses in vitro or in vivo requires the use of laborious secondary methodologies to identify infected cells. To circumvent this requirement, replication-competent infectious influenza viruses expressing an easily traceable fluorescent reporter protein can be used. Timer is a fluorescent protein that undergoes a time-dependent color emission conversion from green to red. The rate of spectral change is independent of Timer protein concentration and can be used to chronologically measure the duration of its expression. Here, we describe the generation of replication-competent IAV and IBV where the viral non-structural protein 1 (NS1 was fused to the fluorescent dynamic Timer protein. Timer-expressing IAV and IBV displayed similar plaque phenotypes and growth kinetics to wild-type viruses in tissue culture. Within infected cells, Timer's spectral shift can be used to measure the rate and cell-to-cell spread of infection using fluorescent microscopy, plate readers, or flow cytometry. The progression of Timer-expressing IAV infection was also evaluated in a mouse model, demonstrating the feasibility to characterize IAV cell-to-cell infections in vivo. By providing the ability to chronologically track viral spread, Timer-expressing influenza viruses are an excellent option to evaluate the in vitro and in vivo dynamics of viral infection.
Vera, Julie; Brulez, Anne-Catherine; Contraires, Elise; Larochette, Mathieu; Trannoy-Orban, Nathalie; Pignon, Maxime; Mauclair, Cyril; Valette, Stéphane; Benayoun, Stéphane
In recent years, there has been increased interest in producing and providing high-precision plastic parts that can be manufactured by microinjection molding: gears, pumps, optical grating elements, and so on. For all of these applications, the replication quality is essential. This study has two goals: (1) fabrication of high-precision parts using the conventional injection molding machine; (2) identification of robust parameters that ensure production quality. Thus, different technological solutions have been used: cavity vacuuming and the use of a mold coated with DLC or CrN deposits. AFM and SEM analyses were carried out to characterize the replication profile. The replication quality was studied in terms of the process parameters, coated and uncoated molds and crystallinity of the polymer. Specific studies were processed to quantify the replicability of injection molded parts (ABS, PC and PP). Analysis of the Taguchi experimental designs permits prioritization of the impact of each parameter on the replication quality. A discussion taking into account these new parameters and the thermal and spreading properties on the coatings is proposed. It appeared that, in general, increasing the mold temperature improves the molten polymer fill in submicron features except for the steel insert (for which the presence of a vacuum is the most important factor). Moreover, the DLC coating was the best coating to increase the quality of the replication. This result could be explained by the lower thermal diffusivity of this coating. We noted that the viscosity of the polymers is not a primordial factor of the replication quality.
Kessler, R C; Aguilar-Gaxiola, S; Alonso, J; Bromet, E J; Gureje, O; Karam, E G; Koenen, K C; Lee, S; Liu, H; Pennell, B-E; Petukhova, M V; Sampson, N A; Shahly, V; Stein, D J; Atwoli, L; Borges, G; Bunting, B; de Girolamo, G; Gluzman, S F; Haro, J M; Hinkov, H; Kawakami, N; Kovess-Masfety, V; Navarro-Mateu, F; Posada-Villa, J; Scott, K M; Shalev, A Y; Ten Have, M; Torres, Y; Viana, M C; Zaslavsky, A M
Although earlier trauma exposure is known to predict posttraumatic stress disorder (PTSD) after subsequent traumas, it is unclear whether this association is limited to cases where the earlier trauma led to PTSD. Resolution of this uncertainty has important implications for research on pretrauma vulnerability to PTSD. We examined this issue in the World Health Organization (WHO) World Mental Health (WMH) Surveys with 34 676 respondents who reported lifetime trauma exposure. One lifetime trauma was selected randomly for each respondent. DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) PTSD due to that trauma was assessed. We reported in a previous paper that four earlier traumas involving interpersonal violence significantly predicted PTSD after subsequent random traumas (odds ratio (OR)=1.3-2.5). We also assessed 14 lifetime DSM-IV mood, anxiety, disruptive behavior and substance disorders before random traumas. We show in the current report that only prior anxiety disorders significantly predicted PTSD in a multivariate model (OR=1.5-4.3) and that these disorders interacted significantly with three of the earlier traumas (witnessing atrocities, physical violence victimization and rape). History of witnessing atrocities significantly predicted PTSD after subsequent random traumas only among respondents with prior PTSD (OR=5.6). Histories of physical violence victimization (OR=1.5) and rape after age 17 years (OR=17.6) significantly predicted only among respondents with no history of prior anxiety disorders. Although only preliminary due to reliance on retrospective reports, these results suggest that history of anxiety disorders and history of a limited number of earlier traumas might usefully be targeted in future prospective studies as distinct foci of research on individual differences in vulnerability to PTSD after subsequent traumas.Molecular Psychiatry advance online publication, 19 September 2017; doi:10.1038/mp.2017.194.
Comparative study between Federer and Gomez method for number of replication in complete randomized design using simulation: study of Areca Palm (Areca catechu) as organic waste for producing handicraft paper
Ihwah, A.; Deoranto, P.; Wijana, S.; Dewi, I. A.
The part of Areca Palm (Areca catechu) that economical is the seed. It is commercially available in dried, cured and fresh forms, while the fibre is usually thrown away. Cellulose fibers from agricultural waste can be utilized as raw material for handicraft paper. Laboratory research showed that Areca palm fibre contained 70.2% of cellulose, 10.92% of water, and 6.02% of ash. This indicated that Areca palm fibre is very potential to be processed as handicraft paper. Handicraft paper is made of wastepaper or plants which cointain celluloce to produce rough-textured paper. In order to obtain preferred sensory quality of handicraft paper such as color, fiber appearance and texture as well as good physical quantity such as tensile strength, tear resistance and grammage, the addition of wastepaper to provide secondary fibre and sometimes adhesive are needed in making handicraft paper. Handicraft paper making was one alternative to treat the solid waste and to reduce the use of wood fiber as paper raw material. The aim of this study is to compare the two most famous method, i.e. Federer and Gomez Method, for calculate the number of replications. This study is preliminary research before do the research in order to get the best treatment to produce handicraft paper. The Gomez method calculates fewer replications than the Federer method. Based on data simulation the error generated using 3 replicates of 0.0876 while using 2 replicates of 0.1032.
Brook, Judith S.; Zhang, Chenshu; Brook, David W.; Leukefeld, Carl G.
This longitudinal study examined the association between psychosocial antecedents, including illicit drug use, and adult compulsive buying (CB) across a 29-year time period from mean age 14 to mean age 43. Participants originally came from a community-based random sample of residents in two upstate New York counties. Multivariate linear regression analysis was used to study the relationship between the participant’s earlier psychosocial antecedents and adult CB in the fifth decade of life. The results of the multivariate linear regression analyses showed that gender (female), earlier adult impulse buying (IB), depressive mood, illicit drug use, and concurrent ADHD symptoms were all significantly associated with adult CB at mean age 43. It is important that clinicians treating CB in adults should consider the role of drug use, symptoms of ADHD, IB, depression, and family factors in CB. PMID:26165963
Brook, Judith S; Zhang, Chenshu; Brook, David W; Leukefeld, Carl G
This longitudinal study examined the association between psychosocial antecedents, including illicit drug use, and adult compulsive buying (CB) across a 29-year time period from mean age 14 to mean age 43. Participants originally came from a community-based random sample of residents in two upstate New York counties. Multivariate linear regression analysis was used to study the relationship between the participant's earlier psychosocial antecedents and adult CB in the fifth decade of life. The results of the multivariate linear regression analyses showed that gender (female), earlier adult impulse buying (IB), depressive mood, illicit drug use, and concurrent ADHD symptoms were all significantly associated with adult CB at mean age 43. It is important that clinicians treating CB in adults should consider the role of drug use, symptoms of ADHD, IB, depression, and family factors in CB. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.
Xu, Kai; Nagy, Peter D
Membranous structures derived from various organelles are important for replication of plus-stranded RNA viruses. Although the important roles of co-opted host proteins in RNA virus replication have been appreciated for a decade, the equally important functions of cellular lipids in virus replication have been gaining full attention only recently. Previous work with Tomato bushy stunt tombusvirus (TBSV) in model host yeast has revealed essential roles for phosphatidylethanolamine and sterols in viral replication. To further our understanding of the role of sterols in tombusvirus replication, in this work we showed that the TBSV p33 and p92 replication proteins could bind to sterols in vitro The sterol binding by p33 is supported by cholesterol recognition/interaction amino acid consensus (CRAC) and CARC-like sequences within the two transmembrane domains of p33. Mutagenesis of the critical Y amino acids within the CRAC and CARC sequences blocked TBSV replication in yeast and plant cells. We also showed the enrichment of sterols in the detergent-resistant membrane (DRM) fractions obtained from yeast and plant cells replicating TBSV. The DRMs could support viral RNA synthesis on both the endogenous and exogenous templates. A lipidomic approach showed the lack of enhancement of sterol levels in yeast and plant cells replicating TBSV. The data support the notion that the TBSV replication proteins are associated with sterol-rich detergent-resistant membranes in yeast and plant cells. Together, the results obtained in this study and the previously published results support the local enrichment of sterols around the viral replication proteins that is critical for TBSV replication. IMPORTANCE One intriguing aspect of viral infections is their dependence on efficient subcellular assembly platforms serving replication, virion assembly, or virus egress via budding out of infected cells. These assembly platforms might involve sterol-rich membrane microdomains, which are
Di Rienzi, Sara C; Collingwood, David; Raghuraman, M K; Brewer, Bonita J
Genome rearrangements are mediators of evolution and disease. Such rearrangements are frequently bounded by transfer RNAs (tRNAs), transposable elements, and other repeated elements, suggesting a functional role for these elements in creating or repairing breakpoints. Though not well explored, there is evidence that origins of replication also colocalize with breakpoints. To investigate a potential correlation between breakpoints and origins, we analyzed evolutionary breakpoints defined between Saccharomyces cerevisiae and Kluyveromyces waltii and S. cerevisiae and a hypothetical ancestor of both yeasts, as well as breakpoints reported in the experimental literature. We find that origins correlate strongly with both evolutionary breakpoints and those described in the literature. Specifically, we find that origins firing earlier in S phase are more strongly correlated with breakpoints than are later-firing origins. Despite origins being located in genomic regions also bearing tRNAs and Ty elements, the correlation we observe between origins and breakpoints appears to be independent of these genomic features. This study lays the groundwork for understanding the mechanisms by which origins of replication may impact genome architecture and disease.
Xu, Leilei; Sun, Weixiang; Qin, Xiaodong; Qiu, Yong; Zhu, Zezhang
The transforming growth factor beta-1 (TGFB1) gene was recently reported to be a new susceptible gene of adolescent idiopathic scoliosis (AIS) in Russian population. This study aimed to replicate the relationship between the TGFB1 gene and the susceptibility of AIS in a Chinese population, and to further describe its association with the curve severity. A total of 1251 female AIS patients and 994 age-matched healthy controls were included in this study. The rs1800469 of TGFB1 gene was genotyped for all participants using the PCR-based Invader assay. The differences of genotype and allele distributions between AIS patients and healthy controls were assessed using the Chi-square test. One-way ANOVA test was used to compare the mean Cobb angles among patients with different genotypes. There was no significant difference in terms of the genotype and the allele frequency between the patients and the controls. The mean Cobb angle was 34.7 ± 11.9° (range 25-61°). Case-only analysis showed that rs1800469 was significantly associated with the curve severity. Patients with genotype TT had remarkably higher curve magnitude (39.1 ± 12.8°) than those with genotype CT (34.8 ± 11.1°) or CC (32.1 ± 10.6°). The TGFB1 gene may not be a predisposition gene of AIS in the Chinese population. However, it can play a role in the curve progression of AIS. Replication studies in other ethnic groups are warranted to understand the implication of TGFB1 gene in AIS.
Kikkert, Martijn J; Driessen, Ellen; Peen, Jaap; Barber, Jacques P; Bockting, Claudi; Schalkwijk, Frans; Dekker, Jeff; Dekker, Jack J M
Barber and Muenz (1996) reported that cognitive behavior therapy (CBT) was more effective than interpersonal therapy (IPT) for depressed patients with elevated levels of avoidant personality disorder, while IPT was more effective than CBT in patients with elevated levels of obsessive-compulsive personality disorder. These findings may have important clinical implications, but have not yet been replicated. We conducted a study using data from a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy in the outpatient treatment of depression. We found no evidence indicating that avoidant patients may benefit more from CBT compared to short-term psychodynamic supportive therapy (SPSP). Our results indicate that treatment effect does not depend on the level of avoidance, or obsessive-compulsiveness personality disorders further examine the influence of personality disorders on the effectiveness of CBT or psychodynamic therapy in the treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.
Dewar, James M; Walter, Johannes C
Genome duplication is carried out by pairs of replication forks that assemble at origins of replication and then move in opposite directions. DNA replication ends when converging replication forks meet. During this process, which is known as replication termination, DNA synthesis is completed, the replication machinery is disassembled and daughter molecules are resolved. In this Review, we outline the steps that are likely to be common to replication termination in most organisms, namely, fork convergence, synthesis completion, replisome disassembly and decatenation. We briefly review the mechanism of termination in the bacterium Escherichia coli and in simian virus 40 (SV40) and also focus on recent advances in eukaryotic replication termination. In particular, we discuss the recently discovered E3 ubiquitin ligases that control replisome disassembly in yeast and higher eukaryotes, and how their activity is regulated to avoid genome instability.
Park, Yonghan; Chaparro, Erin A.; Preciado, Jorge; Cummings, Kelli D.
Research Findings: The goal of the present study was to provide empirical evidence for the importance of mastering reading fluency in early schooling. Study participants were 1,322 students in 3rd grade in 42 schools in a northwestern state. These students were assessed using a battery of reading skill tests as well as comprehensive tests of more…
Alsairi, Meshari A.
Various studies have been carried out in order to find out the suitable age for foreign language acquisition. Every research study has had a different Critical Period (CP) and most of them have not been really close together in terms of years. Critical Period refers to the actual time frame during which foreign language acquisition should take…
Brewer, B J; Fangman, W L
The replicon hypothesis, first proposed in 1963 by Jacob and Brenner, states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an assessment of their activity. Two-dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms.
Alabert, Constance; Groth, Anja
Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization. During cell division the entire genome must be accurately replicated and the chromatin landscape reproduced on new DNA. Chromatin and nuclear structure influence where and when DNA replication...... initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...
Farahmand, Alireza; AghaKouchak, Amir; Teixeira, Joao
Each year, droughts cause significant economic and agricultural losses across the world. The early warning and onset detection of drought is of particular importance for effective agriculture and water resource management. Previous studies show that the Standard Precipitation Index (SPI), a measure of precipitation deficit, detects drought onset earlier than other indicators. Here we show that satellite-based near surface air relative humidity data can further improve drought onset detection and early warning. This paper introduces the Standardized Relative Humidity Index (SRHI) based on the NASA Atmospheric Infrared Sounder (AIRS) observations. The results indicate that the SRHI typically detects the drought onset earlier than the SPI. While the AIRS mission was not originally designed for drought monitoring, we show that its relative humidity data offers a new and unique avenue for drought monitoring and early warning. We conclude that the early warning aspects of SRHI may have merit for integration into current drought monitoring systems.
Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.
Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…
Arlø, Uffe Rolf; Hansen, Hans Nørgaard; Kjær, Erik Michael
The surface micro topography of injection moulded plastic parts can be important for aesthetical and technical reasons. The quality of replication of mould surface topography onto the plastic surface depends among other factors on the process conditions. A study of this relationship has been...... carried out with rough EDM (electrical discharge machining) mould surfaces, a PS grade, and by applying established three-dimensional topography parameters. Significant quantitative relationships between process parameters and topography parameters were established. It further appeared that replication...
Woolley, Kaitlin; Fishbach, Ayelet
Can immediate (vs. delayed) rewards increase intrinsic motivation? Prior research compared the presence versus absence of rewards. By contrast, this research compared immediate versus delayed rewards, predicting that more immediate rewards increase intrinsic motivation by creating a perceptual fusion between the activity and its goal (i.e., the reward). In support of the hypothesis, framing a reward from watching a news program as more immediate (vs. delayed) increased intrinsic motivation to watch the program (Study 1), and receiving more immediate bonus (vs. delayed, Study 2; and vs. delayed and no bonus, Study 3) increased intrinsic motivation in an experimental task. The effect of reward timing was mediated by the strength of the association between an activity and a reward, and was specific to intrinsic (vs. extrinsic) motivation-immediacy influenced the positive experience of an activity, but not perceived outcome importance (Study 4). In addition, the effect of the timing of rewards was independent of the effect of the magnitude of the rewards (Study 5). (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Full Text Available Abstract Background Replicative phenotypic HIV resistance testing (rPRT uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS. We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA Results Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09. Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15. Conclusions In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.
Aller, Pierre; Duclos, Stéphanie; Wallace, Susan S.; Doublié, Sylvie (Vermont)
Thymine glycol (Tg) is the most common oxidation product of thymine and is known to be a strong block to replicative DNA polymerases. A previously solved structure of the bacteriophage RB69 DNA polymerase (RB69 gp43) in complex with Tg in the sequence context 5'-G-Tg-G shed light on how Tg blocks primer elongation: The protruding methyl group of the oxidized thymine displaces the adjacent 5'-G, which can no longer serve as a template for primer elongation [Aller, P., Rould, M. A., Hogg, M, Wallace, S. S. and Doublie S. (2007). A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycol. Proc. Natl. Acad. Sci. USA, 104, 814-818.]. Several studies showed that in the sequence context 5'-C-Tg-purine, Tg is more likely to be bypassed by Klenow fragment, an A-family DNA polymerase. We set out to investigate the role of sequence context in Tg bypass in a B-family polymerase and to solve the crystal structures of the bacteriophage RB69 DNA polymerase in complex with Tg-containing DNA in the three remaining sequence contexts: 5'-A-Tg-G, 5'-T-Tg-G, and 5'-C-Tg-G. A combination of several factors - including the associated exonuclease activity, the nature of the 3' and 5' bases surrounding Tg, and the cis-trans interconversion of Tg - influences Tg bypass. We also visualized for the first time the structure of a well-ordered exonuclease complex, allowing us to identify and confirm the role of key residues (Phe123, Met256, and Tyr257) in strand separation and in the stabilization of the primer strand in the exonuclease site.
Kim, Lyoung Hyo; Cheong, Hyun Sub; Namgoong, Suhg; Kim, Ji On; Kim, Jeong-Hyun; Park, Byung Lae; Cho, Sung Won; Park, Neung Hwa; Cheong, Jae Youn; Koh, InSong; Shin, Hyoung Doo; Kim, Yoon-Jun
A recent genome-wide association study (GWAS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) identified two loci (rs7574865 in STAT4 and rs9275319 in HLA-DQ) in a Chinese population. We attempted to replicate the associations between the two SNP loci and the risk of HCC in a Korean population. The rs7574865 in STAT4 and rs9275319 in HLA-DQ were genotyped in a total of 3838 Korean subjects composed of 287 HBV-related hepatocellular carcinoma patients, 671 chronic hepatitis B virus (CHB) patients, and 2880 population controls using TaqMan genotyping assay. Gene expression was measured by microarray. A logistic regression analysis revealed that rs7574865 in STAT4 and rs9275319 in HLA-DQ were associated with the risk of CHB (OR = 1.25, P = 0.0002 and OR = 1.57, P= 1.44 × 10(-10), respectively). However, these loci were no association with the risk of HBV-related HCC among CHB patients. In the gene expression analyses, although no significant differences in mRNA expression of nearby genes according to genotypes were detected, a significantly decreased mRNA expression in HCC subjects was observed in STAT4, HLA-DQA1, and HLA-DQB1. Although the genetic effects of two HCC susceptibility loci were not replicated, the two loci were found to exert susceptibility effects on the risk of CHB in a Korean population. In addition, the decreased mRNA expression of STAT4, HLA-DQA1, and HLA-DQB1 in HCC tissue might provide a clue to understanding their role in the progression to HCC. Copyright © 2015 Elsevier B.V. All rights reserved.
Chen, X.; Lee, G.; Maher, B. S.; Fanous, A. H.; Chen, J.; Zhao, Z.; Guo, A.; van den Oord, E.; Sullivan, P. F.; Shi, J.; Levinson, D. F.; Gejman, P. V.; Sanders, A.; Duan, J.; Owen, M. J.; Craddock, N. J.; O'Donovan, M. C.; Blackman, J.; Lewis, D.; Kirov, G. K.; Qin, W.; Schwab, S.; Wildenauer, D.; Chowdari, K.; Nimgaonkar, V.; Straub, R. E.; Weinberger, D. R.; O'Neill, F. A.; Walsh, D.; Bronstein, M.; Darvasi, A.; Lencz, T.; Malhotra, A. K.; Rujescu, D.; Giegling, I.; Werge, T.; Hansen, T.; Ingason, A.; Nöethen, M. M.; Rietschel, M.; Cichon, S.; Djurovic, S.; Andreassen, O. A.; Cantor, R. M.; Ophoff, R.; Corvin, A.; Morris, D. W.; Gill, M.; Pato, C. N.; Pato, M. T.; Macedo, A.; Gurling, H. M. D.; McQuillin, A.; Pimm, J.; Hultman, C.; Lichtenstein, P.; Sklar, P.; Purcell, S. M.; Scolnick, E.; St Clair, D.; Blackwood, D. H. R.; Kendler, K. S.; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez; O'Donovan, Michael C.; Kirov, George K.; Craddock, Nick J.; Holmans, Peter A.; Williams, Nigel M.; Georgieva, Lyudmila; Nikolov, Ivan; Norton, N.; Williams, H.; Toncheva, Draga; Milanova, Vihra; Owen, Michael J.; Hultman, Christina M.; Lichtenstein, Paul; Thelander, Emma F.; Sullivan, Patrick; Morris, Derek W.; O'Dushlaine, Colm T.; Kenny, Elaine; Quinn, Emma M.; Gill, Michael; Corvin, Aiden; McQuillin, Andrew; Choudhury, Khalid; Datta, Susmita; Pimm, Jonathan; Thirumalai, Srinivasa; Puri, Vinay; Krasucki, Robert; Lawrence, Jacob; Quested, Digby; Bass, Nicholas; Gurling, Hugh; Crombie, Caroline; Fraser, Gillian; Kuan, Soh Leh; Walker, Nicholas; St Clair, David; Blackwood, Douglas H. R.; Muir, Walter J.; McGhee, Kevin A.; Pickard, Ben; Malloy, Pat; Maclean, Alan W.; van Beck, Margaret; Wray, Naomi R.; Macgregor, Stuart; Visscher, Peter M.; Pato, Michele T.; Medeiros, Helena; Middleton, Frank; Carvalho, Celia; Morley, Christopher; Fanous, Ayman; Conti, David; Knowles, James A.; Ferreira, Carlos Paz; Macedo, Antonio; Azevedo, M. Helena; Pato, Carlos N.; Stone, Jennifer L.; Ruderfer, Douglas M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Purcell, Shaun M.; Sklar, Pamela; Chambert, Kimberly; Kuruvilla, Finny; Gabriel, Stacey B.; Ardlie, Kristin; Moran, Jennifer L.; Scolnick, Edward M.
We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed
Barr, Elissa M.; Moore, Michele J.; Johnson, Tammie; Forrest, Jamie; Jordan, Melissa
Background: Numerous studies document support for sexuality education to be taught in high school, and often, in middle school. However, little research has been conducted addressing support for sexuality education in elementary schools. Methods: As part of the state Behavioral Risk Factor Surveillance System (BRFSS) Survey administration, the…
Full Text Available Fuchs endothelial corneal dystrophy (FECD is a common, late-onset disorder of the corneal endothelium. Although progress has been made in understanding the genetic basis of FECD by studying large families in which the phenotype is transmitted in an autosomal dominant fashion, a recently reported genome-wide association study identified common alleles at a locus on chromosome 18 near TCF4 which confer susceptibility to FECD. Here, we report the findings of our independent validation study for TCF4 using the largest FECD dataset to date (450 FECD cases and 340 normal controls. Logistic regression with sex as a covariate was performed for three genetic models: dominant (DOM, additive (ADD, and recessive (REC. We found significant association with rs613872, the target marker reported by Baratz et al.(2010, for all three genetic models (DOM: P = 9.33×10(-35; ADD: P = 7.48×10(-30; REC: P = 5.27×10(-6. To strengthen the association study, we also conducted a genome-wide linkage scan on 64 multiplex families, composed primarily of affected sibling pairs (ASPs, using both parametric and non-parametric two-point and multipoint analyses. The most significant linkage region localizes to chromosome 18 from 69.94cM to 85.29cM, with a peak multipoint HLOD = 2.5 at rs1145315 (75.58cM under the DOM model, mapping 1.5 Mb proximal to rs613872. In summary, our study presents evidence to support the role of the intronic TCF4 single nucleotide polymorphism rs613872 in late-onset FECD through both association and linkage studies.
Ferreri, J. C.; Carmen, A. del
A numerical study of the dynamics of pattern evolution in reaction-diffusion systems is performed, although limited to one spatial dimension. The diffusion coefficients are nonlinear, based on powers of the scalar variables. The system keeps the dynamics of previous studies in the literature, but the presence of nonlinear diffusion generates a field of strong nonlinear interactions due to the presence of receding travelling waves. This field is limited by the plane of symmetry of the space domain and the last born outgoing travelling wave. These effects are discussed. (author). 10 refs., 7 figs
Treadway, Darren C; Ferris, Gerald R; Hochwarter, Wayne; Perrewé, Pamela; Witt, L A; Goodman, Joseph M
This research examined the interaction of organizational politics perceptions and employee age on job performance in 3 studies. On the basis of conservation of resources theory, the authors predicted that perceptions of politics would demonstrate their most detrimental effects on job performance for older workers. Results across the 3 studies provided strong support for the hypothesis that increases in politics perceptions are associated with decreases in job performance for older employees and that perceptions of politics do not affect younger employees' performance. Implications of these results, strengths and limitations, and directions for future research are discussed. Copyright 2005 APA, all rights reserved.
Full Text Available Regularly conducted exercise programs effectively influence affective states. Studies suggest that this is also true for short bouts of physical activity of ten minutes or less. Accordingly, everyday life activities of short duration might be used to regulate affective states. However, this association has rarely been studied in reference to unstructured activities in ongoing real-life situations. The current study examined the influence of various everyday life activities on three dimensions of mood (valence, calmness, energetic arousal in a predominantly inactive sample. Ambulatory Assessment (AA was used to investigate the association between actual physical activity (aPA and affective states during the course of one day. Seventy-seven students ages 19 - 30 participated in the study. aPA was assessed with accelerometers, and affective state assessments were conducted hourly using an e-diary with a six-item mood scale that was specially designed for AA. Multilevel analyses indicated that the mood dimensions energetic arousal (p = .001 and valence (p = .005 were positively influenced by the intensity of the activity carried out in the ten minutes prior to the assessment. As their activity increased, the participants’ positive feelings and energetic arousal increased. However, the students’ calmness was not affected by their activity levels. The findings highlight the importance of integrating short activity intervals of 10 minutes or less into everyday life routines to improve affective states.
Joanna M Biernacka
Full Text Available Genome-wide association studies (GWAS have revealed many single nucleotide polymorphisms (SNPs associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017. Because the GWAS study that originally reported association of alcohol dependence with this SNP  included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI = 0.80 (0.66, 0.95; women: OR (95%CI = 0.83 (0.66, 1.03. We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081, and independently in the alcohol-dependent cases (p = 0.046. Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.
Stanton, Sarah; Moroz, Sarah; Balzarini, Rhonda; Dobson, Kiersten; Hahn, Christian; Kohut, Taylor; Campbell, Lorne
Across three studies, Murray et al. (2002) found that low self-esteem individuals responded in a negative manner compared to those high in self-esteem in the face of relationship threat, perceiving their partners and relationships less positively. This was the first empirical support for the hypothesized dynamics of a dependency regulation perspective, and has had a significant impact on the field of relationship science. In the present research, we sought to reproduce the methods and procedu...
Diaz-Gallo, Lina Marcela; Palomino-Morales, Rogelio J; Gómez-García, María; Cardeña, Carlos; Rodrigo, Luis; Nieto, Antonio; Alcain, Guillermo; Cueto, Ignacio; López-Nevot, Miguel A; Martin, Javier
Recently, the signal transducer and activator of transcription 4 (STAT4) gene has been associated with multiple autoimmune diseases. Interestingly, a recent work showed that the T allele of the rs7574865 STAT4 SNP was associated with inflammatory bowel disease (IBD) in a Spanish population. The aim of the present study was to reevaluate the role of the STAT4 rs7574865 polymorphism on IBD. The present case-control study included 498 Crohn's disease (CD) patients, 402 ulcerative colitis (UC) patients, and 1296 healthy matched controls. Genotyping was performed using a PCR system with a pre-developed TaqMan allelic discrimination assay for the rs7574865 STAT4 SNP. Moreover, a meta-analysis was performed with the previous work in a Spanish population and the current study, including a final sample size of 1574 IBD patients (820 with CD and 754 with UC) and 2012 healthy controls. No evidence of association was found for the current case-control study (CD: p = 0.23, OR = 0.9, 95% CI = 0.75-1.1; UC: p = 0.17, OR = 1.14, 95% CI = 0.95-1.38). However, the meta-analysis showed that the STAT4 rs7574865 T allele was significantly associated with susceptibility to UC (p = 0.012 pooled; OR = 1.20, 95% CI = 1.04-1.39) but not CD (p = 0.71 pooled; OR = 0.93, 95% CI = 0.65-1.34). Our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for UC but not CD in the Spanish population. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Duncan, Greg J; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J
Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key results are robust across estimation methods, data sets, and demographic subgroups. This article makes the case for prioritizing both explicit replications and, especially, within-study robustness checks in developmental psychology. It provides evidence on variation in effect sizes in developmental studies and documents strikingly different replication and robustness-checking practices in a sample of journals in developmental psychology and a sister behavioral science-applied economics. Our goal is not to show that any one behavioral science has a monopoly on best practices, but rather to show how journals from a related discipline address vital concerns of replication and generalizability shared by all social and behavioral sciences. We provide recommendations for promoting graduate training in replication and robustness-checking methods and for editorial policies that encourage these practices. Although some of our recommendations may shift the form and substance of developmental research articles, we argue that they would generate considerable scientific benefits for the field. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Jonsson, Anna; Foss, Nicolai Juul
Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to ada......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator.......Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to adapt...
Kallionpaa, Maria; Gasselseder, Hans-Peter
, for example, the acoustics of the concert hall, the instrumentation, the qualities of the concert instrument, or the technologies used. Today´s electroacoustic repertoires frequently contain manipulation of (either physical or virtual) space or acoustic qualities, which sets new requirements...... to the capabilities of the performers. This leads to a question what these requirements may be and how can the performers and composers best deal with them? Can the space itself form part of the structure of a composition and/or performance? This chapter explores the topic through a composition case study “Climb...
Barr, Elissa M; Moore, Michele J; Johnson, Tammie; Forrest, Jamie; Jordan, Melissa
Numerous studies document support for sexuality education to be taught in high school, and often, in middle school. However, little research has been conducted addressing support for sexuality education in elementary schools. As part of the state Behavioral Risk Factor Surveillance System (BRFSS) Survey administration, the Florida Department of Health conducted the Florida Child Health Survey (FCHS) by calling back parents who had children in their home and who agreed to participate (N = 1715). Most parents supported the following sexuality education topics being taught specifically in elementary school: communication skills (89%), human anatomy/reproductive information (65%), abstinence (61%), human immunodeficiency virus (HIV)/sexually transmitted infections (STIs) (53%), and gender/sexual orientation issues (52%). Support was even greater in middle school (62-91%) and high school (72-91%) for these topics and for birth control and condom education. Most parents supported comprehensive sexuality education (40.4%), followed by abstinence-plus (36.4%) and abstinence-only (23.2%). Chi-square results showed significant differences in the type of sexuality education supported by almost all parent demographic variables analyzed including sex, race, marital status, and education. Results add substantial support for age-appropriate school-based sexuality education starting at the elementary school level, the new National Sexuality Education Standards, and funding to support evidence-based abstinence-plus or comprehensive sexuality education. © 2013, American School Health Association.
Tremblay, Line; Roy-Vaillancourt, Mélina; Chebbi, Brahim; Bouchard, Stéphane; Daoust, Michael; Dénommée, Jessica; Thorpe, Moriah
It is well documented that anti-fat attitudes influence the interactions individuals have with overweight people. However, testing attitudes through self-report measures is challenging. In the present study, we explore the use of a haptic virtual reality environment to physically interact with overweight virtual human (VH). We verify the hypothesis that duration and strength of virtual touch vary according to the characteristics of VH in ways similar to those encountered from interaction with real people in anti-fat attitude studies. A group of 61 participants were randomly assigned to one of the experimental conditions involving giving a virtual hug to a female or a male VH of either normal or overweight. We found significant associations between body image satisfaction and anti-fat attitudes and sex differences on these measures. We also found a significant interaction effect of the sex of the participants, sex of the VH, and the body size of the VH. Female participants hugged longer the overweight female VH than overweight male VH. Male participants hugged longer the normal-weight VH than the overweight VH. We conclude that virtual touch is a promising method of measuring attitudes, emotion and social interactions.
Abas, Norzaida; Daud, Zalina M.; Yusof, Fadhilah
A stochastic rainfall model is presented for the generation of hourly rainfall data in an urban area in Malaysia. In view of the high temporal and spatial variability of rainfall within the tropical rain belt, the Spatial-Temporal Neyman-Scott Rectangular Pulse model was used. The model, which is governed by the Neyman-Scott process, employs a reasonable number of parameters to represent the physical attributes of rainfall. A common approach is to attach each attribute to a mathematical distribution. With respect to rain cell intensity, this study proposes the use of a mixed exponential distribution. The performance of the proposed model was compared to a model that employs the Weibull distribution. Hourly and daily rainfall data from four stations in the Damansara River basin in Malaysia were used as input to the models, and simulations of hourly series were performed for an independent site within the basin. The performance of the models was assessed based on how closely the statistical characteristics of the simulated series resembled the statistics of the observed series. The findings obtained based on graphical representation revealed that the statistical characteristics of the simulated series for both models compared reasonably well with the observed series. However, a further assessment using the AIC, BIC and RMSE showed that the proposed model yields better results. The results of this study indicate that for tropical climates, the proposed model, using a mixed exponential distribution, is the best choice for generation of synthetic data for ungauged sites or for sites with insufficient data within the limit of the fitted region.
to aid the binding of proto-tRNAs and proto-mRNAs, allowing the reduction of base pairs between them (ultimately resulting in the triplet anticodon/codon pair, thus further saving the replication cost. In this context, the replication cost saved would allow the appearance of more and longer functional peptides and, finally, proteins. The hypothesis could be called "DRT-RP" ("RP" for "replication parsimony". Testing the hypothesis The scenario described here is open for experimental work at some key scenes, including the compact DRT mechanism, the development of adaptors from aa-aptamers, the synthesis of peptides by proto-tRNAs and proto-mRNAs without the participation of proto-rRNAs, etc. Interestingly, a recent computer simulation study has demonstrated the plausibility of one of the evolving processes driven by replication parsimony in the scenario. Implication of the hypothesis An RNA-based proto-translation system could arise gradually from the DRT mechanism according to the principle of "replication parsimony" --- to save the replication cost of RNA templates for functional peptides. A surprising side deduction along the logic of the hypothesis is that complex, biosynthetic amino acids might have entered the genetic code earlier than simple, prebiotic amino acids, which is opposite to the common sense. Overall, the present discussion clarifies the blurry scenario concerning the origin of translation with a major clue, which shows vividly how life could "manage" to exploit potential chemical resources in nature, eventually in an efficient way over evolution. Reviewers This article was reviewed by Eugene V. Koonin, Juergen Brosius, and Arcady Mushegian.
Campbell, Rebecca; Bybee, Deborah; Townsend, Stephanie M; Shaw, Jessica; Karim, Nidal; Markowitz, Jenifer
To address the underreporting and underprosecution of adult sexual assaults, communities throughout the United States have implemented multidisciplinary interventions to improve postassault care for victims and the criminal justice system response. One such model is the Sexual Assault Nurse Examiner (SANE) Program, whereby specially trained nurses provide comprehensive psychological, medical, and forensic services for sexual assault. In this study, we conducted a multisite evaluation of six SANE programs (two rural programs, two serving midsized communities, two urban) to assess how implementation of SANE programs affects adult sexual assault prosecution rates. At each site, most sexual assaults reported to law enforcement were never referred by police to prosecutors or were not charged by the prosecutor's office (80%-89%). Individually, none of the sites had a statistically significant increase in prosecution rates pre-SANE to post-SANE. However, when the data were aggregated across sites, thereby increasing statistical power, there was a significant effect such that cases were more likely to be prosecuted post-SANE as compared with pre-SANE. These findings suggest that the SANE intervention model does have a positive impact on sexual assault case progression in the criminal justice system. Nevertheless, there is still a pressing need for improvement as the vast majority of both pre-SANE and post-SANE resulted in nonreferral/no charges filed. © The Author(s) 2014.
Birman, Dina; Trickett, Edison; Buchanan, Rebecca M
While a great deal of research has been conducted to understand acculturation and its relationship to adaptation in the new country, surprisingly little attention has been paid to the ways in which the characteristics of the local community impact these processes. The present study addresses this gap in the literature by exploring the potential role of community differences in the acculturation and adaptation processes of 269 refugee and immigrant adolescents from the former Soviet Union who resettled in two different community contexts. Specifically, a prior study on acculturation and adjustment among high school students (D. Birman, E. J. Trickett, & A. Vinokurov, 2002) was replicated with the same émigré population in a contrasting community within the same state. The contrast between these communities allowed us to test hypotheses emerging from an ecological perspective concerning (1) patterns of acculturation, (2) levels of discrimination and its effect on acculturative outcomes, and (3) community differences in the relationship between acculturation and outcomes. In addition to the focus on community differences, the study also employs a multidimensional measure of acculturation and assesses acculturation to both American and Russian culture. Furthermore, adaptation is assessed across different life domains; including peer relationships, family relationships, school adaptation, and psychological adaptation. Findings support the general ecological perspective, suggesting the importance of studying acculturation and adaptation as a reflexive process in which culture and context are very much intertwined.
Brumbach, Michael T.; Mirabal, Alex James; Kalan, Michael; Trujillo, Ana B; Hale, Kevin
Replicating compounds are used to cast reproductions of surface features on a variety of materials. Replicas allow for quantitative measurements and recordkeeping on parts that may otherwise be difficult to measure or maintain. In this study, the chemistry and replicating capability of several replicating compounds was investigated. Additionally, the residue remaining on material surfaces upon removal of replicas was quantified. Cleaning practices were tested for several different replicating compounds. For all replicating compounds investigated, a thin silicone residue was left by the replica. For some compounds, additional inorganic species could be identified in the residue. Simple solvent cleaning could remove some residue.
Antonopoulos, Chrissi A.; Dillon, Heather E.; Baechler, Michael C.
This study presents findings from survey and interview data investigating replication efforts of Commercial Building Partnership (CBP) partners that worked directly with the Pacific Northwest National Laboratory (PNNL). PNNL partnered directly with 12 organizations on new and retrofit construction projects, which represented approximately 28 percent of the entire U.S. Department of Energy (DOE) CBP program. Through a feedback survey mechanism, along with personal interviews, PNNL gathered quantitative and qualitative data relating to replication efforts by each organization. These data were analyzed to provide insight into two primary research areas: 1) CBP partners’ replication efforts of technologies and approaches used in the CBP project to the rest of the organization’s building portfolio (including replication verification), and, 2) the market potential for technology diffusion into the total U.S. commercial building stock, as a direct result of the CBP program. The first area of this research focused specifically on replication efforts underway or planned by each CBP program participant. Factors that impact replication include motivation, organizational structure and objectives firms have for implementation of energy efficient technologies. Comparing these factors between different CBP partners revealed patterns in motivation for constructing energy efficient buildings, along with better insight into market trends for green building practices. The second area of this research develops a diffusion of innovations model to analyze potential broad market impacts of the CBP program on the commercial building industry in the United States.
Full Text Available AIMS: East Asian genome-wide association studies (GWAS for type 2 diabetes identified 8 loci with genome-wide significance, and 2 loci with a borderline association. However, the associations of these loci except MAEA locus with type 2 diabetes have not been evaluated in independent East Asian cohorts. We performed a replication study to investigate the association of these susceptibility loci with type 2 diabetes in an independent Japanese population. METHODS: We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and 2,064 controls for each of the 9 single nucleotide polymorphisms (SNPs, rs7041847 in GLIS3, rs6017317 in FITM2-R3HDML-HNF4A, rs6467136 near GCCI-PAX4, rs831571 near PSMD6, rs9470794 in ZFAND3, rs3786897 in PEPD, rs1535500 in KCNK16, rs16955379 in CMIP, and rs17797882 near WWOX. Because the sample size in this study was not sufficient to replicate single SNP associations, we constructed a genetic risk score (GRS by summing a number of risk alleles of the 9 SNPs, and examined the association of the GRS with type 2 diabetes using logistic regression analysis. RESULTS: With the exception of rs1535500 in KCNK16, all SNPs had the same direction of effect (odds ratio [OR]>1.0 as in the original reports. The GRS constructed from the 9 SNPs was significantly associated with type 2 diabetes in the Japanese population (p = 4.0 × 10(-4, OR = 1.05, 95% confidence interval: 1.02-1.09. In quantitative trait analyses, rs16955379 in CMIP was nominally associated with a decreased homeostasis model assessment of β-cell function and with increased fasting plasma glucose, but neither the individual SNPs nor the GRS showed a significant association with the glycemic traits. CONCLUSIONS: These results indicate that 9 loci that were identified in the East Asian GWAS meta-analysis have a significant effect on the susceptibility to type 2 diabetes in the Japanese population.
Chappell, Sally L
Abstract Background Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. Methods We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. Results Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. Conclusions These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.
Chang, Pei-Ching [Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan (China); Kung, Hsing-Jien, E-mail: firstname.lastname@example.org [Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan (China); Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616 (United States); UC Davis Cancer Center, University of California, Davis, CA 95616 (United States); Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (China)
Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.
Pattengale, Nicholas D; Alipour, Masoud; Bininda-Emonds, Olaf R P; Moret, Bernard M E; Stamatakis, Alexandros
Phylogenetic bootstrapping (BS) is a standard technique for inferring confidence values on phylogenetic trees that is based on reconstructing many trees from minor variations of the input data, trees called replicates. BS is used with all phylogenetic reconstruction approaches, but we focus here on one of the most popular, maximum likelihood (ML). Because ML inference is so computationally demanding, it has proved too expensive to date to assess the impact of the number of replicates used in BS on the relative accuracy of the support values. For the same reason, a rather small number (typically 100) of BS replicates are computed in real-world studies. Stamatakis et al. recently introduced a BS algorithm that is 1 to 2 orders of magnitude faster than previous techniques, while yielding qualitatively comparable support values, making an experimental study possible. In this article, we propose stopping criteria--that is, thresholds computed at runtime to determine when enough replicates have been generated--and we report on the first large-scale experimental study to assess the effect of the number of replicates on the quality of support values, including the performance of our proposed criteria. We run our tests on 17 diverse real-world DNA--single-gene as well as multi-gene--datasets, which include 125-2,554 taxa. We find that our stopping criteria typically stop computations after 100-500 replicates (although the most conservative criterion may continue for several thousand replicates) while producing support values that correlate at better than 99.5% with the reference values on the best ML trees. Significantly, we also find that the stopping criteria can recommend very different numbers of replicates for different datasets of comparable sizes. Our results are thus twofold: (i) they give the first experimental assessment of the effect of the number of BS replicates on the quality of support values returned through BS, and (ii) they validate our proposals for
Gerretsen, Philip; Voineskos, Aristotle N; Graff-Guerrero, Ariel; Menon, Mahesh; Pollock, Bruce G; Mamo, David C; Mulsant, Benoit H; Rajji, Tarek K
Impaired insight into illness in schizophrenia is associated with illness severity and deficits in premorbid intellectual function, executive function, and memory. A previous study of patients aged 60 years and older found that illness severity and premorbid intellectual function accounted for variance in insight impairment. As such, we aimed to test whether similar relationships would be observed in earlier life. A retrospective analysis was performed on 1 large sample of participants (n = 171) with a DSM-IV-TR diagnosis of schizophrenia aged 19 to 79 years acquired from 2 studies: (1) a psychosocial intervention trial for older persons with schizophrenia (June 2008 to May 2014) and (2) a diffusion tensor imaging and genetics study of psychosis across the life span (February 2007 to December 2013). We assessed insight into illness using the Positive and Negative Syndrome Scale (PANSS) item G12 and explored its relationship to illness severity (PANSS total modified), premorbid intellectual function (Wechsler Test of Adult Reading [WTAR]), and cognition. Insight impairment was more severe in later life (≥ 60 years) than in earlier years (t = -3.75, P insight was explained by PANSS total modified (Exp[B] = 1.070, P insight, they did not independently contribute to its variance. However, the relationships between impaired insight and illness severity and between impaired insight and cognition, particularly working memory, were stronger in later life than in earlier life. These results suggest an opportunity for intervention may exist with cognitive-enhancing neurostimulation or medications to improve insight into illness in schizophrenia across the life span. Original study registered on ClinicalTrials.gov (identifier: NCT00832845). © Copyright 2017 Physicians Postgraduate Press, Inc.
Saayman, Xanita; Ramos-Pérez, Cristina; Brown, Grant W
Profiling of DNA replication during progression through S phase allows a quantitative snap-shot of replication origin usage and DNA replication fork progression. We present a method for using deep sequencing data to profile DNA replication in S. cerevisiae.
Full Text Available Misinterpretations of the p value and the introduction of bias through arbitrary analytical choices have been discussed in the literature for decades. Nonetheless, they seem to have persisted in empirical research, and criticisms of p value misuses have increased in the recent past due to the non-replicability of many studies. Unfortunately, the critical concerns that have been raised in the literature are scattered over many disciplines, often linguistically confusing, and differing in their main reasons for criticisms. Misuses and misinterpretations of the p value are currently being discussed intensely under the label “replication crisis” in many academic disciplines and journals, ranging from specialized scientific journals to Nature and Science. In a drastic response to the crisis, the editors of the journal Basic and Applied Social Psychology even decided to ban the use of p values from future publications at the beginning of 2015, a fact that has certainly added fuel to the discussions in the relevant scientific forums. Finally, in early March, the American Statistical Association released a brief formal statement on p values that explicitly addresses misuses and misinterpretations. In this context, we systematize the most serious flaws related to the p value and discuss suggestions of how to prevent them and reduce the rate of false discoveries in the future.
Scientific inquiry requires the replication of results in experimental studies. Recent studies draw a severe picture on the need of replication and the difficulties in replicating already published studies. As replicated confirmation of results is the basis of scientific and medical research, there may be a need to introduce the topic of…
Kenza Lahkim Bennani-Belhaj
Full Text Available Bloom's syndrome (BS displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU, which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.
Hendro Nindito; Evaristus Didik Madyatmadja; Albert Verasius Dian Sano
The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MyS...
Giroux, S; Elfassihi, L; Cole, D E C; Rousseau, F
Replication is a critical step to validate positive genetic associations. In this study, we tested two previously reported positive associations. The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated. This result is in line with results from large consortiums such as Genomos. However, the estrogen-related receptor alpha (ESRRA) repeat in the promoter is not replicated although the polymorphism studied was functional and could have been a causative variant. We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample. For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels. We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645). The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.
Lawrence, David Wyndham; Richards, Doug; Comper, Paul; Hutchison, Michael G
To determine whether earlier time to initiation of aerobic exercise following acute concussion is associated with time to full return to (1) sport and (2) school or work. A retrospective stratified propensity score survival analysis of acute (≤14 days) concussion was used to determine whether time (days) to initiation of aerobic exercise post-concussion was associated with, both, time (days) to full return to (1) sport and (2) school or work. A total of 253 acute concussions [median (IQR) age, 17.0 (15.0-20.0) years; 148 (58.5%) males] were included in this study. Multivariate Cox regression models identified that earlier time to aerobic exercise was associated with faster return to sport and school/work adjusting for other covariates, including quintile propensity strata. For each successive day in delay to initiation of aerobic exercise, individuals had a less favourable recovery trajectory. Initiating aerobic exercise at 3 and 7 days following injury was associated with a respective 36.5% (HR, 0.63; 95% CI, 0.53-0.76) and 73.2% (HR, 0.27; 95% CI, 0.16-0.45) reduced probability of faster full return to sport compared to within 1 day; and a respective 45.9% (HR, 0.54; 95% CI, 0.44-0.66) and 83.1% (HR, 0.17; 95% CI, 0.10-0.30) reduced probability of faster full return to school/work. Additionally, concussion history, symptom severity, LOC deleteriously influenced concussion recovery. Earlier initiation of aerobic exercise was associated with faster full return to sport and school or work. This study provides greater insight into the benefits and safety of aerobic exercise within the first week of the injury.
Holman, Benjamin W B; Collins, Damian; Kilgannon, Ashleigh K; Hopkins, David L
The Nix Pro Colour Sensor™ (NIX) can be potentially used to measure meat colour, but procedural guidelines that assure measurement reproducibility and repeatability (precision) must first be established. Technical replicate number (r) will minimise response variation, measureable as standard error of predicted mean (SEM), and contribute to improved precision. Consequently, we aimed to explore the effects of r on NIX precision when measuring aged beef colour (colorimetrics; L*, a*, b*, hue and chroma values). Each colorimetric SEM declined with increasing r to indicate improved precision and followed a diminishing rate of improvement that allowed us to recommend r=7 for meat colour studies using the NIX. This definition was based on practical limitations and a* variability, as additional r would be required if other colorimetrics or advanced levels of precision are necessary. Beef ageing and display period, holding temperature, loin and sampled portion were also found to contribute to colorimetric variation, but were incorporated within our definition of r. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.
Smith, Shawn H; Steenhof, Karen; McClure, Christopher J W; Heath, Julie A
Warming temperatures cause temporal changes in growing seasons and prey abundance that drive earlier breeding by birds, especially dietary specialists within homogeneous habitat. Less is known about how generalists respond to climate-associated shifts in growing seasons or prey phenology, which may occur at different rates across land cover types. We studied whether breeding phenology of a generalist predator, the American kestrel (Falco sparverius), was associated with shifts in growing seasons and, presumably, prey abundance, in a mosaic of non-irrigated shrub/grasslands and irrigated crops/pastures. We examined the relationship between remotely-sensed normalized difference vegetation index (NDVI) and abundance of small mammals that, with insects, constitute approximately 93% of kestrel diet biomass. We used NDVI to estimate the start of the growing season (SoGS) in irrigated and non-irrigated lands from 1992 to 2015 and tested whether either estimate of annual SoGS predicted the timing of kestrel nesting. Finally, we examined relationships among irrigated SoGS, weather and crop planting. NDVI was a useful proxy for kestrel prey because it predicted small mammal abundance and past studies showed that NDVI predicts insect abundance. NDVI-estimated SoGS advanced significantly in irrigated lands (β = -1·09 ± 0·30 SE) but not in non-irrigated lands (β = -0·57 ± 0·53). Average date of kestrel nesting advanced 15 days in the past 24 years and was positively associated with the SoGS in irrigated lands, but not the SoGS in non-irrigated lands. Advanced SoGS in irrigated lands was related to earlier planting of crops after relatively warm winters, which were more common in recent years. Despite different patterns of SoGS change between land cover types, kestrel nesting phenology shifted with earlier prey availability in irrigated lands. Kestrels may preferentially track prey in irrigated lands over non-irrigated lands because of higher quality prey on
Nagaraja M Phani
Full Text Available Several genetic variants for type 2 diabetes (T2D have been identified through genome wide association studies (GWAS from Caucasian population; however replication studies were not consistent across various ethnicities. Objective of the current study is to examine the possible correlation of 9 most significant GWAS single nucleotide polymorphisms (SNPs for T2D susceptibility as well as the interactive effect of these variants on the risk of T2D in an Indian population.Case-control cohorts of 1156 individuals were genotyped for 9 SNPs from an Indian population. Association analyses were performed using logistic regression after adjusting for covariates. Multifactor dimensionality reduction (MDR analysis was adopted to determine gene-gene interactions and discriminatory power of combined SNP effect was assessed by grouping individuals based on the number of risk alleles and by calculating area under the receiver-operator characteristic curve (AUC.We confirm the association of TCF7L2 (rs7903146 and SLC30A8 (rs13266634 with T2D. MDR analysis showed statistically significant interactions among four SNPs of SLC30A8 (rs13266634, IGF2BP2 (rs4402960, HHEX (rs1111875 and CDKN2A (rs10811661 genes. Cumulative analysis showed an increase in odds ratio against the baseline group of individuals carrying 5 to 6 risk alleles and discriminatory power of genetic test based on 9 variants showed higher AUC value when analyzed along with body mass index (BMI.These results provide a strong evidence for independent association between T2D and SNPs for in TCF7L2 and SLC30A8. MDR analysis demonstrates that independently non-significant variants may interact with one another resulting in increased disease susceptibility in the population tested.
Kruschwitz, J D; Waller, L; Daedelow, L S; Walter, H; Veer, I M
One hallmark example of a link between global topological network properties of complex functional brain connectivity and cognitive performance is the finding that general intelligence may depend on the efficiency of the brain's intrinsic functional network architecture. However, although this association has been featured prominently over the course of the last decade, the empirical basis for this broad association of general intelligence and global functional network efficiency is quite limited. In the current study, we set out to replicate the previously reported association between general intelligence and global functional network efficiency using the large sample size and high quality data of the Human Connectome Project, and extended the original study by testing for separate association of crystallized and fluid intelligence with global efficiency, characteristic path length, and global clustering coefficient. We were unable to provide evidence for the proposed association between general intelligence and functional brain network efficiency, as was demonstrated by van den Heuvel et al. (2009), or for any other association with the global network measures employed. More specifically, across multiple network definition schemes, ranging from voxel-level networks to networks of only 100 nodes, no robust associations and only very weak non-significant effects with a maximal R 2 of 0.01 could be observed. Notably, the strongest (non-significant) effects were observed in voxel-level networks. We discuss the possibility that the low power of previous studies and publication bias may have led to false positive results fostering the widely accepted notion of general intelligence being associated to functional global network efficiency. Copyright © 2018 Elsevier Inc. All rights reserved.
Farsalinos, Konstantinos E; Kistler, Kurt A; Pennington, Alexander; Spyrou, Alketa; Kouretas, Dimitris; Gillman, Gene
A recent study identified high aldehyde emissions from e-cigarettes (ECs), that when converted to reasonable daily human EC liquid consumption, 5 g/day, gave formaldehyde exposure equivalent to 604-3257 tobacco cigarettes. We replicated this study and also tested a new-generation atomizer under verified realistic (no dry puff) conditions. CE4v2 atomizers were tested at 3.8 V and 4.8 V, and a Nautilus Mini atomizer was tested at 9.0 W and 13.5 W. All measurements were performed in a laboratory ISO-accredited for EC aerosol collection and aldehyde measurements. CE4v2 generated dry puffs at both voltage settings. Formaldehyde levels were >10-fold lower, acetaldehyde 6-9-fold lower and acrolein 16-26-fold lower than reported in the previous study. Nautilus Mini did not generate dry puffs, and minimal aldehydes were emitted despite >100% higher aerosol production per puff compared to CE4v2 (formaldehyde: 16.7 and 16.5 μg/g; acetaldehyde: 9.6 and 10.3 μg/g; acrolein: 8.6 and 11.7 μg/g at 9.0 W and 13.5 W, respectively). EC liquid consumption of 5 g/day reduces aldehyde exposure by 94.4-99.8% compared to smoking 20 tobacco cigarettes. Checking for dry puffs is essential for EC emission testing. Under realistic conditions, new-generation ECs emit minimal aldehydes/g liquid at both low and high power. Validated methods should be used when analyzing EC aerosol. Copyright © 2017 Elsevier Ltd. All rights reserved.
Oras, Paola; Thernström Blomqvist, Ylva; Hedberg Nyqvist, Kerstin; Gradin, Maria; Rubertsson, Christine; Hellström-Westas, Lena; Funkquist, Eva-Lotta
This study investigated the effects of skin-to-skin contact on breastfeeding attainment, duration and infant growth in preterm infants, as this has not been sufficiently explored. A prospective longitudinal study on Kangaroo mother care was carried out, comprising 104 infants with a gestational age of 28 + 0 to 33 + 6 and followed up to one year of corrected age. Parents and staff recorded the duration of skin-to skin contact during the stay in the neonatal intensive care unit (NICU). Medical data were collected through patient records, and follow-up questionnaires were filled in by parents. The 53 infants who attained full breastfeeding in the NICU did so at a median (range) of 35 + 0 (32 + 1 to 37 + 5) weeks of postmenstrual age, and skin-to-skin contact was the only factor that influenced earlier attainment in the regression analysis (R(2) 0.215 p skin-to-skin contact during the stay in the NICU did not affect the duration of breastfeeding or infant growth after discharge. Furthermore, infant growth was not affected by the feeding strategy of exclusive, partial breastfeeding or no breastfeeding. A longer daily duration of skin-to-skin contact in the NICU was associated with earlier attainment of exclusive breastfeeding. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Harkema, S.; Schäffer, E.; Morariu, M.D.; Steiner, U
The dewetting of a polymer film in a confined geometry was employed in a pattern-replication process. The instability of dewetting films is pinned by a structured confining surface, thereby replicating its topographic pattern. Depending on the surface energy of the confining surface, two different
Rhim, Lauren Morando
"Replication" is the practice of a single charter school board or management organization opening several more schools that are each based on the same school model. The most rapid strategy to increase the number of new high-quality charter schools available to children is to encourage the replication of existing quality schools. This policy guide…
Bonifazi, F; Carbone, A; D'Apice, A; Dell'Agnello, L; Re, G L; Martelli, B; Ricci, P P; Sapunenko, V; Vitlacil, D; Perez, E D; Duellmann, D; Girone, M; Peco, G; Vagnoni, V
Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements
Bonifazi, F; Perez, E D; D'Apice, A; dell'Agnello, L; Düllmann, D; Girone, M; Re, G L; Martelli, B; Peco, G; Ricci, P P; Sapunenko, V; Vagnoni, V; Vitlacil, D
Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.
Weissman, David G; Schriber, Roberta A; Fassbender, Catherine; Atherton, Olivia; Krafft, Cynthia; Robins, Richard W; Hastings, Paul D; Guyer, Amanda E
Early adolescent onset of substance use is a robust predictor of future substance use disorders. We examined the relation between age of substance use initiation and resting state functional connectivity (RSFC) of the core reward processing (nucleus accumbens; NAcc) to cognitive control (prefrontal cortex; PFC) brain networks. Adolescents in a longitudinal study of Mexican-origin youth reported their substance use annually from ages 10 to 16 years. At age 16, 69 adolescents participated in a resting state functional magnetic resonance imaging scan. Seed-based correlational analyses were conducted using regions of interest in bilateral NAcc. The earlier that adolescents initiated substance use, the stronger the connectivity between bilateral NAcc and right dorsolateral PFC, right dorsomedial PFC, right pre-supplementary motor area, right inferior parietal lobule, and left medial temporal gyrus. The regions that demonstrated significant positive linear relationships between the number of adolescent years using substances and connectivity with NAcc are nodes in the right frontoparietal network, which is central to cognitive control. The coupling of reward and cognitive control networks may be a mechanism through which earlier onset of substance use is related to brain function over time, a trajectory that may be implicated in subsequent substance use disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Ffrench-Constant, Richard H; Somers-Yeates, Robin; Bennie, Jonathan; Economou, Theodoros; Hodgson, David; Spalding, Adrian; McGregor, Peter K
The ecological impact of night-time lighting is of concern because of its well-demonstrated effects on animal behaviour. However, the potential of light pollution to change plant phenology and its corresponding knock-on effects on associated herbivores are less clear. Here, we test if artificial lighting can advance the timing of budburst in trees. We took a UK-wide 13 year dataset of spatially referenced budburst data from four deciduous tree species and matched it with both satellite imagery of night-time lighting and average spring temperature. We find that budburst occurs up to 7.5 days earlier in brighter areas, with the relationship being more pronounced for later-budding species. Excluding large urban areas from the analysis showed an even more pronounced advance of budburst, confirming that the urban 'heat-island' effect is not the sole cause of earlier urban budburst. Similarly, the advance in budburst across all sites is too large to be explained by increases in temperature alone. This dramatic advance of budburst illustrates the need for further experimental investigation into the impact of artificial night-time lighting on plant phenology and subsequent species interactions. As light pollution is a growing global phenomenon, the findings of this study are likely to be applicable to a wide range of species interactions across the world. © 2016 The Authors.
Syed A Ali
Full Text Available There remains a need for newer therapeutic approaches to combat HIV/AIDS. Viral capsid protein p24 plays important roles in HIV pathogenesis. Peptides and small molecule inhibitors targeting p24 have shown to inhibit virus replication in treated cell. High specificity and biological stability of monoclonal antibodies (mAbs make them an attractive contender for in vivo treatments. However, mAbs do not enter into cells, thus are restricted to target surface molecules. This also makes targeting intracellular HIV-1 p24 a challenge. A mAb specific to p24 that can internalize into the HIV-infected cells is hypothesized to inhibit the virus replication. We selected a mAb that has previously shown to inhibit p24 polymerization in an in vitro assay and chemically conjugated it with cell penetrating peptides (CPP to generate cell internalizing anti-p24 mAbs. Out of 8 CPPs tested, κFGF-MTS -conjugated mAbs internalized T cells most efficiently. At nontoxic concentration, the κFGF-MTS-anti-p24-mAbs reduced the HIV-1 replication up to 73 and 49% in T-lymphocyte and PBMCs respectively. Marked inhibition of HIV-1 replication in relevant cells by κFGF-MTS-anti-p24-mAbs represents a viable strategy to target HIV proteins present inside the cells.
Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic
Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Tamaru, Yutaka; Ogata, Shin; Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi
Spatiotemporal regulation of DNA replication in the S-phase nucleus has been extensively studied in mammalian cells because it is tightly coupled with the regulation of other nuclear processes such as transcription. However, little is known about the replication dynamics in nonmammalian cells. Here, we analyzed the DNA replication processes of zebrafish (Danio rerio) cells through the direct visualization of replicating DNA in the nucleus and on DNA fiber molecules isolated from the nucleus. We found that zebrafish chromosomal DNA at the nuclear interior was replicated first, followed by replication of DNA at the nuclear periphery, which is reminiscent of the spatiotemporal regulation of mammalian DNA replication. However, the relative duration of interior DNA replication in zebrafish cells was longer compared to mammalian cells, possibly reflecting zebrafish-specific genomic organization. The rate of replication fork progression and ori-to-ori distance measured by the DNA combing technique were ∼ 1.4 kb/min and 100 kb, respectively, which are comparable to those in mammalian cells. To our knowledge, this is a first report that measures replication dynamics in zebrafish cells.
Kitao, Hiroyuki; Iimori, Makoto; Kataoka, Yuki; Wakasa, Takeshi; Tokunaga, Eriko; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko
DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss the underlying mechanism of cancer therapy from the aspect of DRS. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Manturov, Alexey O.; Grigoryev, Anton V.
In the present work we discuss the features of the DNA replication kinetics at the case of multiplicity of simultaneously elongated DNA fragments. The interaction between replicated DNA fragments is carried out by free protons that appears at the every nucleotide attachment at the free end of elongated DNA fragment. So there is feedback between free protons concentration and DNA-polymerase activity that appears as elongation rate dependence. We develop the numerical model based on a cellular automaton, which can simulate the elongation stage (growth of DNA strands) for DNA elongation process with conditions pointed above and we study the possibility of the DNA polymerases movement synchronization. The results obtained numerically can be useful for DNA polymerase movement detection and visualization of the elongation process in the case of massive DNA replication, eg, under PCR condition or for DNA "sequencing by synthesis" sequencing devices evaluation.
We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r(2)>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10 × 10(-3) and rs2274736, P=1.21 × 10(-3)). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45 × 10(-3) and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29 × 10(-3)). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43 × 10(-3)). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736\\/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.
One of the most important and high-profile issues in public education reform today is the replication of successful public charter school programs. With more than 5,000 failing public schools in the United States, there is a tremendous need for strong alternatives for parents and students. Replicating successful charter school models is an…
The kinetic equations of DNA replication are shown to be exactly solved in terms of iterated function systems, running along the template sequence and giving the statistical properties of the copy sequences, as well as the kinetic and thermodynamic properties of the replication process. With this method, different effects due to sequence heterogeneity can be studied, in particular, a transition between linear and sublinear growths in time of the copies, and a transition between continuous and fractal distributions of the local velocities of the DNA polymerase along the template. The method is applied to the human mitochondrial DNA polymerase γ without and with exonuclease proofreading.
Full Text Available When a replicative DNA polymerase stalls upon encountering a lesion on the template strand, it is relieved by other low-processivity polymerase(s, which insert nucleotide(s opposite the lesion, extend by a few nucleotides, and dissociate from the 3′-OH. The replicative polymerase then resumes DNA synthesis. This process, termed translesion replication (TLS or replicative bypass, may involve at least five different polymerases in mammals, although the participating polymerases and their roles have not been entirely characterized. Using siRNAs originally designed and an alkaline sucrose density gradient sedimentation technique, we verified the involvement of several polymerases in ultraviolet (UV light-induced TLS in HeLa cells. First, siRNAs to Rev3 or Rev7 largely abolished UV-TLS, suggesting that these 2 gene products, which comprise Polζ, play a main role in mutagenic TLS. Second, Rev1-targeted siRNA also abrogated UV-TLS, indicating that Rev1 is also indispensable to mutagenic TLS. Third, Polη-targeted siRNA also prevented TLS to a greater extent than our expectations. Forth, although siRNA to Polι had no detectable effect, that to Polκ delayed UV-TLS. To our knowledge, this is the first study reporting apparent evidence for the participation of Polκ in UV-TLS.
El Khoury, Louis; Ribbans, William J; Raleigh, Stuart M
Variants within the MMP3 (rs679620) and TIMP2 (rs4789932) genes have been associated with the risk of Achilles tendon pathology (ATP) in populations from South Africa and Australia. This study aimed to determine whether these variants were associated with the risk of ATP in British Caucasians. We recruited 118 cases with ATP, including a subset of 25 individuals with Achilles tendon rupture (RUP) and 131 controls. DNA samples were isolated from saliva and genotyped using qPCR. For the TIMP2 rs4789932 variant we found a significant (p = 0.038) difference in the genotype distribution frequency between males with ATP (CC, 39.4%; CT, 43.7%; TT, 16.9%) compared to male controls (CC, 20.7%; CT, 59.8%; TT, 19.5%). We also observed a difference in the TIMP2 rs4789932 genotype distribution between males with rupture compared to male controls (p = 0.038). The MMP3 rs679620 GG genotype was found to be overrepresented in the Achilles tendon rupture (RUP) group (AA, 24.0%; AG, 32.0%; GG, 44.0%) compared to controls (AA, 26.7%; AG, 54.2%; GG, 19.1%). In conclusion, the CT genotype of the TIMP2 rs4789932 variant was associated with lower risk of ATP in males. Furthermore, while we revealed differences for both variants in genotype distribution between the RUP and control groups, the sample size of the RUP group was small and confirmation would be required in additional cohorts. Finally, although both the TIMP2 rs4789932 and MMP3 rs679620 variants tentatively associated with ATP, there were differences in the direction of association compared to earlier work.
Milbredt, Sarah; Farmani, Neda; Sobetzko, Patrick; Waldminghaus, Torsten
The standard outline of bacterial genomes is a single circular chromosome with a single replication origin. From the bioengineering perspective, it appears attractive to extend this basic setup. Bacteria with split chromosomes or multiple replication origins have been successfully constructed in the last few years. The characteristics of these engineered strains will largely depend on the respective DNA replication patterns. However, the DNA replication has not been investigated systematically in engineered bacteria with multiple origins or split replicons. Here we fill this gap by studying a set of strains consisting of (i) E. coli strains with an extra copy of the native replication origin (oriC), (ii) E. coli strains with an extra copy of the replication origin from the secondary chromosome of Vibrio cholerae (oriII), and (iii) a strain in which the E. coli chromosome is split into two linear replicons. A combination of flow cytometry, microarray-based comparative genomic hybridization (CGH), and modeling revealed silencing of extra oriC copies and differential timing of ectopic oriII copies compared to the native oriC. The results were used to derive construction rules for future multiorigin and multireplicon projects.
Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L
Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory
Severini, Alberto; Sevenhuysen, Claire; Garbutt, Michael; Tipples, Graham A.
We have studied the structure of the replicative intermediates of human herpesvirus 6 (HHV-6) using pulsed-field gel electrophoresis, partial digestion, two-dimensional gel electrophoresis, and sedimentation centrifugation. The results show that DNA replication of HHV-6 produces head-to-tail concatemeric intermediates as well as approximately equal amounts of circular monomers or oligomers. Unlike the situation in herpes simplex virus, the intermediates of human herpesvirus 6 replication are not highly branched, suggesting a difference in the mechanism of replication or a lower frequency of homologous recombination in human herpesvirus 6 compared to herpes simplex virus
Zarski, Lila M; High, Emily A; Nelli, Rahul K; Bolin, Steven R; Williams, Kurt J; Hussey, Gisela
Equine herpesvirus 5 (EHV-5) infection is associated with pulmonary fibrosis in horses, but further studies on EHV-5 persistence in equine cells are needed to fully understand viral and host contributions to disease pathogenesis. Our aim was to develop a quantitative PCR (qPCR) assay to measure EHV-5 viral copy number in equine cell cultures, blood lymphocytes, and nasal swabs of horses. Furthermore, we used a recently developed equine primary respiratory cell culture system to study EHV-5 pathogenesis at the respiratory tract. PCR primers and a probe were designed to target gene E11 of the EHV-5 genome. Sensitivity and repeatability were established, and specificity was verified by testing multiple isolates of EHV-5, as well as DNA from other equine herpesviruses. Four-week old fully differentiated (mature), newly seeded (immature) primary equine respiratory epithelial cell (ERECs), and equine dermal cell cultures were inoculated with EHV-5 and the cells and supernatants collected daily for 14days. Blood lymphocytes and nasal swabs were collected from horses experimentally infected with equine herpesvirus 1 (EHV-1). The qPCR assay detected EHV-5 at stable concentrations throughout 14days in inoculated mature EREC and equine dermal cell cultures (peaking at 202 and 5861 viral genomes per 10 6 cellular β actin, respectively). EHV-5 copies detected in the immature EREC cultures increased over 14days and reached levels greater than 10,000 viral genomes per 10 6 cellular β actin. Moreover, EHV-5 was detected in the lymphocytes of 76% of horses and in the nasal swabs of 84% of horses experimentally infected with EHV-1 pre-inoculation with EHV-1. Post-inoculation with EHV-1, EHV-5 was detected in lymphocytes of 52% of horses while EHV-5 levels in nasal swabs were not significantly different from pre-inoculation levels. In conclusion, qPCR was a reliable technique to investigate viral load in in vivo and in vitro samples, and EHV-5 replication in equine epithelial cells
Stroebe, Wolfgang; Strack, Fritz
There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a replication crisis in psychology. Psychologists are encouraged to conduct more exact
Margot, Kelly C.; Rinn, Anne N.
To provide further generalizability for the results garnered by two previous studies, the authors conducted a methodological replication. In addition to adding to the body of replication research done with gifted students, the purpose of this study was to examine perfectionism differences among gifted adolescents in regards to gender, birth order,…
Duran, Anyelo; Valero, Nereida; Mosquera, Jesús; Fuenmayor, Edgard; Alvarez-Mon, Melchor
The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. Increased DENV2 replication and anti-viral cytokine production (IFN-α/β, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.
Hedberg, Thomas D; Hartman, Nathan W; Rosche, Phil; Fischer, Kevin
Design for Manufacturing (DFM), especially the use of manufacturing knowledge to support design decisions, has received attention in the academic domain. However, industry practice has not been studied enough to provide solutions that are mature for industry. The current state of the art for DFM is often rule-based functionality within Computer-Aided Design (CAD) systems that enforce specific design requirements. That rule-based functionality may or may not dynamically affect geometry definition. And, if rule-based functionality exists in the CAD system, it is typically a customization on a case-by-case basis. Manufacturing knowledge is a phrase with vast meanings, which may include knowledge on the effects of material properties decisions, machine and process capabilities, or understanding the unintended consequences of design decisions on manufacturing. One of the DFM questions to answer is how can manufacturing knowledge, depending on its definition, be used earlier in the product lifecycle to enable a more collaborative development environment? This paper will discuss the results of a workshop on manufacturing knowledge that highlights several research questions needing more study. This paper proposes recommendations for investigating the relationship of manufacturing knowledge with shape, behavior, and context characteristics of product to produce a better understanding of what knowledge is most important. In addition, the proposal includes recommendations for investigating the system-level barriers to reusing manufacturing knowledge and how model-based manufacturing may ease the burden of knowledge sharing. Lastly, the proposal addresses the direction of future research for holistic solutions of using manufacturing knowledge earlier in the product lifecycle.
van Tilborg, Theodora C; Broekmans, Frank J; Pijpe, Anouk; Schrijver, Lieske H; Mooij, Thea M; Oosterwijk, Jan C; Verhoef, Senno; Gómez Garcia, Encarna B; van Zelst-Stams, Wendy A; Adank, Muriel A; van Asperen, Christi J; van Doorn, Helena C; van Os, Theo A; Bos, Anna M; Rookus, Matti A; Ausems, Margreet G
It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. Cross-sectional assessment from an ongoing nationwide cohort study among members of BRCA1/2 mutated families. Information was obtained by a standardized questionnaire. Kaplan-Meier curves were constructed, and Cox regression was used to assess the association between BRCA1/2 mutation status and ANM. Adjustments were made for birth cohort, family, smoking, use of hormonal contraceptives, and parity. A total of 1,208 BRCA1/2 mutation carriers and 2,211 proven noncarriers were included. Overall, no association was found between BRCA1/2 mutation status and ANM (adjusted hazard ratio [HR] = 1.06 [95% CI, 0.87-1.30]). We examined if the null finding was due to informative censoring by uptake of risk-reducing salpingo-oophorectomy. Indeed, within the oldest birth cohort, in which the percentage of surgical menopause events was lowest and comparable between carriers and noncarriers, the HR for earlier natural menopause in carriers was 1.45 (95% CI, 1.09-1.94). The second oldest birth cohort, however, demonstrated a decreased HR (0.67 [95% CI, 0.46-0.98]), and thus no trend over birth cohorts was found. Various types of selection bias hamper the comparison of ANM between BRCA1/2 mutation carriers and noncarriers, genetically tested in the clinic.
Full Text Available Introduction. Human polyomavirus BK (BKV is worldwide distributed, with a seroprevalence rate of 70–90% in the adults. Following primary infection, BK remains latent in the renourinary tract as the epidemiologically most relevant latency site, and in B cell, brain, spleen and probably other tissues. Reactivation may occur in both immunocompetent subjects and immunocompromised patients. In renal transplantation, in the context of intense immunosuppression, viral replication may determine BKV-associated nephropathy (BKVAN with interstitial nephritis and/or ureteral stenosis in 1–10% of the patients and leading to graft failure and return to haemodialysis in 30 to 80% of the cases (5. Screening of BKV replication represents the basic strategy to predict early the onset of BKVAN and may allow for earlier intervention with reduced allograft loss (3, 4. Nowadays, replication of BKV is monitored by quantification of BKV-DNA in serum and urine (2. The aim of this study was to evaluated the role of BKV VP1 mRNA in urine as a marker of viral replication in renal transplant recipients.
de Boer, E.J.; den Tonkelaar, I.; Burger, C.W.; van Leeuwen, F.E.
Objective: To study whether women diagnosed with unexplained subfertility reach the menopause transition and natural menopause earlier than women with tubal subfertility, in an in vitro fertilization (FVF)-treated population, and to examine the influence of the number of FVT cycles on the occurrence
Soliman, Sameh E; Eldomiaty, Wesam; Goweida, Mohamed B; Dowidar, Amgad
To evaluate the clinical presentation of retinoblastoma in Alexandria, Egypt, correlate the timing of accurate diagnosis with the presence of advanced disease and identify causes of delayed presentation. Retrospective noncomparative single institution study reviews demographic and clinical data of all new children with retinoblastoma presenting to Alexandria Main University ocular oncology clinic (OOC) from January 2012 to June 2014. Diagnosis time was from initial parental complaint to retinoblastoma diagnosis and referral time was from retinoblastoma diagnosis to presentation to the Alexandria OCC. Delayed Diagnosis and referral were counted if >2 weeks. Advanced presentation is defined as clinical TNMH (8th edition) staging of cT2 or cT3 (international intraocular retinoblastoma classification group D or E) in at least one eye or the presence of extra-ocular disease (cT4). Seventy eyes of 47 children were eligible: 52% unilateral, 7% with family history and 96% presented with leukocorea. Sixty-four percent of children had advanced intraocular disease and none had extra-ocular disease. Delayed presentation occurred in 58% of children and was significantly associated with advanced disease in both unilaterally and bilaterally affected children (p = 0.003, 0.002 respectively). The delay in diagnosis was more in unilateral cases while the delay in referral was more in bilateral cases. The main cause of delayed presentation in unilateral retinoblastoma was misdiagnosis (30%) while parental shopping for second medical opinion (30%) was the main cause in bilateral children. Delayed diagnosis is a problem affecting retinoblastoma management. Better medical education and training, health education and earlier screening are recommended to achieve earlier diagnosis.
DNA replication in ultraviolet-irradiated HeLa cells was studied by two different techniques: measurements of the kinetics of semiconservative DNA synthesis, and DNA fiber autoradiography. In examining the kinetics of semiconservative DNA synthesis, density label was used to avoid measuring the incorporation due to repair replication. The extent of inhibition varied with time. After doses of less than 10 J/m 2 the rate was initially depressed but later showed some recovery. After higher doses, a constant, low rate of synthesis was seen for at least the initial 6 h. An analysis of these data indicated that the inhibition of DNA synthesis could be explained by replication forks halting at pyrimidine dimers. DNA fiber autoradiography was used to further characterize replication after ultraviolet irradiation. The average length of labeled segments in irradiated cells increased in the time immediately after irradiation, and then leveled off. This is the predicted pattern if DNA synthesis in each replicon continued at its previous rate until a lesion is reached, and then halted. The frequency of lesions that block synthesis is approximately the same as the frequency of pyrimidine dimers
Forst, C V
A general system of high-order differential equations describing complex dynamics of replicating biomolecules is given. Symmetry relations and coordinate transformations of general replication systems leading to topologically equivalent systems are derived. Three chaotic attractors observed in Lotka-Volterra equations of dimension n = 3 are shown to represent three cross-sections of one and the same chaotic regime. Also a fractal torus in a generalized three-dimensional Lotka-Volterra Model has been linked to one of the chaotic attractors. The strange attractors are studied in the equivalent four-dimensional catalytic replicator network. The fractal torus has been examined in adapted Lotka-Volterra equations. Analytic expressions are derived for the Lyapunov exponents of the flow in the replicator system. Lyapunov spectra for different pathways into chaos has been calculated. In the generalized Lotka-Volterra system a second inner rest point--coexisting with (quasi)-periodic orbits--can be observed; with an abundance of different bifurcations. Pathways from chaotic tori, via quasi-periodic tori, via limit cycles, via multi-periodic orbits--emerging out of periodic doubling bifurcations--to "simple" chaotic attractors can be found.
The invention relates to a replication tool (1, 1a, 1b) for producing a part (4) with a microscale textured replica surface (5a, 5b, 5c, 5d). The replication tool (1, 1a, 1b) comprises a tool surface (2a, 2b) defining a general shape of the item. The tool surface (2a, 2b) comprises a microscale...... energy directors on flange portions thereof uses the replication tool (1, 1a, 1b) to form an item (4) with a general shape as defined by the tool surface (2a, 2b). The formed item (4) comprises a microscale textured replica surface (5a, 5b, 5c, 5d) with a lateral arrangement of polydisperse microscale...
Wiktor, J.M.; Lesterlin, Christian; Sherratt, David J.; Dekker, C.
Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is
Porte, Graeme; Richards, Keith
This paper discusses the meaning and range of replication in L2 research from both quantitative and qualitative perspectives. In the first half of the paper, it will be argued that key quantitative studies need to be replicated to have their robustness and generalizability tested and that this is a requirement of scientific inquiry. Such research…
Holy, V.; Darhuber, A.A.; Stangl, J.; Bauer, G.; Nützel, J.-F.; Abstreiter, G.
The replication of the interface roughness in SiGe/Si multilayers grown on miscut Si(001) substrates has been studied by means of x-ray reflectivity reciprocal space mapping. The interface profiles were found to be highly correlated and the direction of the maximal replication was inclined with
Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.
-1 (FCN1) gene is associated with an earlier onset of type 1 diabetes mellitus in children and adolescents from northeast Brazil. ZILMA PEREIRA DOS ANJOSA MANUELLA MARIA SILVA SANTOS NATASSIA JAVORSKI RODRIGUES ...
Toledo, Luis Ignacio; Altmeyer, Matthias; Rask, Maj-Britt; Lukas, Claudia; Larsen, Dorthe Helena; Povlsen, Lou Klitgaard; Bekker-Jensen, Simon; Mailand, Niels; Bartek, Jiri; Lukas, Jiri
ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.
Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...
Jones, Martin H.; McMichael, Stephanie N.
Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…
Gamon, John A.; Huemmrich, K. Fred; Stone, Robert S.; Tweedie, Craig E.
In the Arctic, earlier snowmelt and longer growing seasons due to warming have been hypothesized to increase vegetation productivity. Using the Normalized Difference Vegetation Index (NDVI) from both field and satellite measurements as an indicator of vegetation phenology and productivity, we monitored spatial and temporal patterns of vegetation growth for a coastal wet sedge tundra site near Barrow, Alaska over three growing seasons (2000-2002). Contrary to expectation, earlier snowmelt did not lead to increased productivity. Instead, productivity was associated primarily with precipitation and soil moisture, and secondarily with growing degree days, which, during this period, led to reduced growth in years with earlier snowmelt. Additional moisture effects on productivity and species distribution, operating over a longer time scale, were evident in spatial NDVI patterns associated with microtopography. Lower, wetter regions dominated by graminoids were more productive than higher, drier locations having a higher percentage of lichens and mosses, despite the earlier snowmelt at the more elevated sites. These results call into question the oft-stated hypothesis that earlier arctic growing seasons will lead to greater vegetation productivity. Rather, they agree with an emerging body of evidence from recent field studies indicating that early-season, local environmental conditions, notably moisture and temperature, are primary factors determining arctic vegetation productivity. For this coastal arctic site, early growing season conditions are strongly influenced by microtopography, hydrology, and regional sea ice dynamics, and may not be easily predicted from snowmelt date or seasonal average air temperatures alone. Our comparison of field to satellite NDVI also highlights the value of in-situ monitoring of actual vegetation responses using field optical sampling to obtain detailed information on surface conditions not possible from satellite observations alone.
Andersen, Vibeke; Ernst, Anja; Sventoraityte, Jurgita
the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively). No SNP reached genome-wide significance in the combined analyses of all the panels. Conclusions......Background: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome...... wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. Methods...
Vilaplana, Cristina; Prats, Clara; Marzo, Elena; Barril, Carles; Vegué, Marina; Diaz, Jorge; Valls, Joaquim; López, Daniel; Cardona, Pere-Joan
The temporo-spatial relationship between the three organs (lung, spleen and lymph node) involved during the initial stages of Mycobacterium tuberculosis infection has been poorly studied. As such, we performed an experimental study to evaluate the bacillary load in each organ after aerosol or intravenous infection and developed a mathematical approach using the data obtained in order to extract conclusions. The results showed that higher bacillary doses result in an earlier IFN-γ response, that a certain bacillary load (BL) needs to be reached to trigger the IFN-γ response, and that control of the BL is not immediate after onset of the IFN-γ response, which might be a consequence of the spatial dimension. This study may have an important impact when it comes to designing new vaccine candidates as it suggests that triggering an earlier IFN-γ response might not guarantee good infection control, and therefore that additional properties should be considered for these candidates.
Full Text Available In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.
Acosta, Alberto; Adams, Reginald B; Albohn, Daniel N; Allard, Eric S; Beek, Titia; Benning, Stephen D; Blouin- Hudon, Eve-Marie; Bulnes, Luis Carlo; Caldwell, Tracy L; Calin-Jageman, Robert J; Capaldi, Colin A; Carfagno, Nicholas S; Chasten, Kelsie T; Cleeremans, Axel; Connell, Louise; DeCicco, Jennifer M.; Dijkhoff, Laura; Dijkstra, Katinka; Fischer, Agneta H; Foroni, Francesco; Gronau, Quentin F; Hess, Ursula; Holmes, Kevin J; Jones, Jacob L H; Klein, Olivier; Koch, Christopher; Korb, Sebastian; Lewinski, Peter; Liao, Julia D; Lund, Sophie; Lupiáñez, Juan; Lynott, Dermot; Nance, Christin N; Oosterwijk, Suzanne; Özdog˘ru, Asil Ali; Pacheco-Unguetti, Antonia Pilar; Pearson, Bethany; Powis, Christina; Riding, Sarah; Roberts, Tomi-Ann; Rumiati, Raffaella I; Senden, Morgane; Shea-Shumsky, Noah B; Sobocko, Karin; Soto, Jose A; Steiner, Troy G; Talarico, Jennifer M; vanAllen, Zack M; Wagenmakers, E-J; Vandekerckhove, Marie; Wainwright, Bethany; Wayand, Joseph F; Zeelenberg, Rene; Zetzer, Emily E; Zwaan, Rolf A
According to the facial feedback hypothesis, people's affective responses can be influenced by their own facial expression (e.g., smiling, pouting), even when their expression did not result from their emotional experiences. For example, Strack, Martin, and Stepper (1988) instructed participants to rate the funniness of cartoons using a pen that they held in their mouth. In line with the facial feedback hypothesis, when participants held the pen with their teeth (inducing a "smile"), they rated the cartoons as funnier than when they held the pen with their lips (inducing a "pout"). This seminal study of the facial feedback hypothesis has not been replicated directly. This Registered Replication Report describes the results of 17 independent direct replications of Study 1 from Strack et al. (1988), all of which followed the same vetted protocol. A meta-analysis of these studies examined the difference in funniness ratings between the "smile" and "pout" conditions. The original Strack et al. (1988) study reported a rating difference of 0.82 units on a 10-point Likert scale. Our meta-analysis revealed a rating difference of 0.03 units with a 95% confidence interval ranging from -0.11 to 0.16. © The Author(s) 2016.
Huttel, Hans; Srba, Jiri
We use some recent techniques from process algebra to draw several conclusions about the well studied class of ping-pong protocols introduced by Dolev and Yao. In particular we show that all nontrivial properties, including reachability and equivalence checking wrt. the whole van Glabbeek's spect...... of messages in the sense of Amadio, Lugiez and Vanackere. We conclude by showing that reachability analysis for a replicative variant of the protocol becomes decidable....
Newsom, Doug A.; And Others
Replicates a 1972 survey of students, educators, and Public Relations Society of America members regarding who the public relations counselor really serves. Finds that, in 1992, most respondents thought primary responsibility was to the client, then to the client's relevant publics, then to self, then to society, and finally to media. Compares…
Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.
Ebersberger, Bernd; Galia, Fabrice; Laursen, Keld
innovation survey data for France, Germany and the UK, we conduct a ‘large-scale’ replication using the Bayesian averaging approach of classical estimators. Our method tests a wide range of determinants of innovation suggested in the prior literature, and establishes a robust set of findings on the variables...
Full Text Available Throughout the world, iconic rock art is preceded by non-iconic rock art. Cupules (manmade, roughly semi-hemispherical depressions on rocks form the major bulk of the early non-iconic rock art globally. The antiquity of cupules extends back to the Lower Paleolithic in Asia and Africa, hundreds of thousand years ago. When one observes these cupules, the inquisitive mind poses so many questions with regard to understanding their technology, reasons for selecting the site, which rocks were used to make the hammer stones used, the skill and cognitive abilities employed to create the different types of cupules, the objective of their creation, their age, and so on. Replication of the cupules can provide satisfactory answers to some of these questions. Comparison of the hammer stones and cupules produced by the replication process with those obtained from excavation can provide support to observations. This paper presents a manual of cupule replication technology based on our experience of cupule replication on hard quartzite rock near Daraki-Chattan in the Chambal Basin, India.
Stroebe, Wolfgang; Strack, Fritz
There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a "replication crisis" in psychology. Psychologists are encouraged to conduct more "exact" replications of published studies to assess the reproducibility of psychological research. This article argues that the alleged "crisis of replicability" is primarily due to an epistemological misunderstanding that emphasizes the phenomenon instead of its underlying mechanisms. As a consequence, a replicated phenomenon may not serve as a rigorous test of a theoretical hypothesis because identical operationalizations of variables in studies conducted at different times and with different subject populations might test different theoretical constructs. Therefore, we propose that for meaningful replications, attempts at reinstating the original circumstances are not sufficient. Instead, replicators must ascertain that conditions are realized that reflect the theoretical variable(s) manipulated (and/or measured) in the original study. © The Author(s) 2013.
Yokoi, Fumiaki; Yang, Guang; Li, Jindong; DeAndrade, Mark P; Zhou, Tong; Li, Yuqing
DYT1 early-onset generalized torsion dystonia is an inherited movement disorder caused by mutations in DYT1 coding for torsinA with ∼30% penetrance. Most of the DYT1 dystonia patients exhibit symptoms during childhood and adolescence. On the other hand, DYT1 mutation carriers without symptoms during these periods mostly do not exhibit symptoms later in their life. Little is known about what controls the timing of the onset, a critical issue for DYT1 mutation carriers. DYT11 myoclonus-dystonia is caused by mutations in SGCE coding for ε-sarcoglycan. Two dystonia patients from a single family with double mutations in DYT1 and SGCE exhibited more severe symptoms. A recent study suggested that torsinA contributes to the quality control of ε-sarcoglycan. Here, we derived mice carrying mutations in both Dyt1 and Sgce and found that these double mutant mice showed earlier onset of motor deficits in beam-walking test. A novel monoclonal antibody against mouse ε-sarcoglycan was developed by using Sgce knock-out mice to avoid the immune tolerance. Western blot analysis suggested that functional deficits of torsinA and ε-sarcoglycan may independently cause motor deficits. Examining additional mutations in other dystonia genes may be beneficial to predict the onset in DYT1 mutation carriers.
Knowles, J. F.; Molotch, N. P.; Trujillo, E.; Litvak, M. E.
Future projections of declining snowpack and increasing potential evaporation associated with climate warming are predicted to advance the timing of snowmelt in mountain ecosystems globally. This scenario has direct implications for snowmelt-driven forest productivity, but the net effect of temporally shifting moisture dynamics is unknown with respect to the annual carbon balance. Accordingly, this study uses both satellite- and tower-based observations to document the forest productivity response to snowpack and potential evaporation variability between 1989 and 2012 throughout the southern Rocky Mountain ecoregion, USA. These results show that a combination of low snow accumulation and record high potential evaporation in 2012 resulted in the 34-year minimum ecosystem productivity that could be indicative of future conditions. Moreover, early and late season productivity were significantly and inversely related, suggesting that future shifts toward earlier or reduced snowmelt could increase late-season moisture stress to vegetation and thus restrict productivity despite a longer growing season. This relationship was further subject to modification by summer precipitation, and the controls on the early/late season productivity ratio are explored within the context of ecosystem carbon storage in the future. Any perturbation to the carbon cycle at this scale represents a potential feedback to climate change since snow-covered forests represent an important global carbon sink.
Steltzer, Heidi; Landry, Chris; Painter, Thomas H; Anderson, Justin; Ayres, Edward
Dust deposition to mountain snow cover, which has increased since the late 19(th) century, accelerates the rate of snowmelt by increasing the solar radiation absorbed by the snowpack. Snowmelt occurs earlier, but is decoupled from seasonal warming. Climate warming advances the timing of snowmelt and early season phenological events (e.g., the onset of greening and flowering); however, earlier snowmelt without warmer temperatures may have a different effect on phenology. Here, we report the results of a set of snowmelt manipulations in which radiation-absorbing fabric and the addition and removal of dust from the surface of the snowpack advanced or delayed snowmelt in the alpine tundra. These changes in the timing of snowmelt were superimposed on a system where the timing of snowmelt varies with topography and has been affected by increased dust loading. At the community level, phenology exhibited a threshold response to the timing of snowmelt. Greening and flowering were delayed before seasonal warming, after which there was a linear relationship between the date of snowmelt and the timing of phenological events. Consequently, the effects of earlier snowmelt on phenology differed in relation to topography, which resulted in increasing synchronicity in phenology across the alpine landscape with increasingly earlier snowmelt. The consequences of earlier snowmelt from increased dust deposition differ from climate warming and include delayed phenology, leading to synchronized growth and flowering across the landscape and the opportunity for altered species interactions, landscape-scale gene flow via pollination, and nutrient cycling.
DNA replication in ultraviolet light irradiated Chinese hamster cells was studied using techniques of DNA fiber autoradiography and alkaline sucrose sedimentation. Bidirectionally growing replicons were observed in the autoradiograms independent of the irradiation conditions. After a dose of 5 J/m 2 at 254 nm the rate of fork progression was the same as in unirradiated cells, while the rate of replication was reduced by 50%. After a dose of 10J/m 2 the rate of fork progression was reduced 40%, while the replication rate was only 25% of normal. Therefore, at low doses of ultraviolet light irradiation, the inhibition of DNA replication is due to reduction in the number of functioning replicons, while at higher doses the rate of fork progression is also slowed. Those replicons which no longer function after irradiation are blocked in fork movement rather than replicon initiation. After irradiation, pulse label was first incorporated into short nascent strands, the average size of which was approximately equal to the distance between pyrimidine dimers. Under conditions where post-replication repair occurs these short strands were eventually joined into larger pieces. Finally, the data show that slowing post-replication repair with caffeine does not slow fork movement. The results presented here support the post-replication repair model of 'gapped synthesis' and rule out a major role for 'replicative bypass'. (author)
Stoeck, Ina Karen; Lee, Ji-Young; Tabata, Keisuke; Romero-Brey, Inés; Paul, David; Schult, Philipp; Lohmann, Volker; Kaderali, Lars; Bartenschlager, Ralf
endomembrane system to produce a membranous replication organelle (RO). The underlying mechanisms are far from being elucidated fully. In this report, we provide evidence that HCV RNA replication depends on functional lipid transport along the endosomal-lysosomal pathway that is mediated by several lipid transfer proteins, such as the Niemann-Pick type C1 (NPC1) protein. Pharmacological inhibition of NPC1 function reduced viral replication, impaired the transport of cholesterol to the viral replication organelle, and altered organelle morphology. Besides NPC1, our study reports the importance of additional endosomal and lysosomal lipid transfer proteins required for viral replication, thus contributing to our understanding of how HCV manipulates their function in order to generate a membranous replication organelle. These results might have implications for the biogenesis of replication organelles of other positive-strand RNA viruses. Copyright © 2017 American Society for Microbiology.
Full Text Available Oncogenes induce cell proliferation leading to replicative stress, DNA damage and genomic instability. A wide variety of cellular stresses activate c-Jun N-terminal kinase (JNK proteins, but few studies have directly addressed the roles of JNK isoforms in tumor development. Herein, we show that jnk2 knockout mice expressing the Polyoma Middle T Antigen transgene developed mammary tumors earlier and experienced higher tumor multiplicity compared to jnk2 wildtype mice. Lack of jnk2 expression was associated with higher tumor aneuploidy and reduced DNA damage response, as marked by fewer pH2AX and 53BP1 nuclear foci. Comparative genomic hybridization further confirmed increased genomic instability in PyV MT/jnk2-/- tumors. In vitro, PyV MT/jnk2-/- cells underwent replicative stress and cell death as evidenced by lower BrdU incorporation, and sustained chromatin licensing and DNA replication factor 1 (CDT1 and p21(Waf1 protein expression, and phosphorylation of Chk1 after serum stimulation, but this response was not associated with phosphorylation of p53 Ser15. Adenoviral overexpression of CDT1 led to similar differences between jnk2 wildtype and knockout cells. In normal mammary cells undergoing UV induced single stranded DNA breaks, JNK2 localized to RPA (Replication Protein A coated strands indicating that JNK2 responds early to single stranded DNA damage and is critical for subsequent recruitment of DNA repair proteins. Together, these data support that JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.
Panni, Roheena Z; Ashfaq, Awais; Amanullah, Muhammad M
Congenital heart disease (CHD) accounts for a major proportion of disease in the pediatric age group. The objective of the study was to estimate the cost of illness associated with CHD pre, intra and postoperatively; among patients referred to a tertiary care hospital in Karachi, Pakistan. This is the first study conducted to estimate the cost of managing CHD in Pakistan. A prevalence based cost of illness study design was used to estimate the cost of cardiac surgery (corrective & palliative) for congenital heart defects in children ≤ 5 years of age from June 2006 to June 2009. A total of 120 patients were enrolled after obtaining an informed consent and the data was collected using a pre-tested questionnaire. The mean age at the time of surgery in group A (1-12 mo age) was 6.08 ± 2.80 months and in group B (1-5 yrs) was 37.10 ± 19.94 months. The cost of surgical admission was found to be significantly higher in the older group, p = 0.001. The total number and cost of post-operative outpatient visits was also higher in group B, p = 0.003. Pre and post operative hospital admissions were not found to be significantly different among the two groups, p = 0.166 and 0.627, respectively. The number of complications were found to be different between the two groups (p = 0.019). Majority of these were contributed by hemorrhage and post-operative seizures. This study concluded that significant expenditure is incurred by people with CHD; with the implication that resources could be saved by earlier detection and awareness campaigns.
Pandey, Manjula; Elshenawy, Mohamed; Jergic, Slobodan; Takahashi, Masateru; Dixon, Nicholas E.; Hamdan, Samir; Patel, Smita S.
The Escherichia coli replication terminator protein (Tus) binds to Ter sequences to block replication forks approaching from one direction. Here, we used single molecule and transient state kinetics to study responses of the heterologous phage T7
Calaon, M.; Tosello, G.; Garnaes, J.
The present study investigates the capabilities of the two employed processes, injection molding (IM) and injection compression molding (ICM) on replicating different channel cross sections. Statistical design of experiment was adopted to optimize replication quality of produced polymer parts wit...
Full Text Available The GTG-banding and 5-BrdU incorporation patterns of the late-replicating X-chromosome were studied in female dogs and cattle, and compared to human female patterns. The replication patterns of the short arm of the X-chromosomes did not show any difference between human, dog and cattle females. As to the long arm, some bands showed differences among the three studied species regarding the replication kinetics pattern. These differences were observed in a restricted region of the X-chromosome, delimited by Xq11 -> q25 in humans, by Xq1 -> q8 in dogs, and by Xq12 -> q32 in cattle. In an attempt to find out if these differences in the replication kinetics could be a reflection of differences in the localization of genes in that region of the X-chromosome, we used the probe for the human androgen receptor gene (AR localized at Xq12, which is in the region where we observed differences among the three studied species. We did not, however, observe hybridization signals. Our study goes on, using other human probes for genes located in the region Xq11 -> Xq25.
DeBar, Lynn L.; Striegel-Moore, Ruth H.; Wilson, G. Terence; Perrin, Nancy; Yarborough, Bobbi Jo; Dickerson, John; Lynch, Frances; Rosselli, Francine; Kraemer, Helena C.
Objective The aim of this study was to replicate and extend results of a previous blended efficacy and effectiveness trial of a low-intensity, manual-based guided self-help form of cognitive-behavioral therapy (CBT-GSH) for the treatment of binge eating disorders in a large health maintenance organization (HMO) and to compare them with usual care. Methods To extend earlier findings, the investigators modified earlier recruitment and assessment approaches and conducted a randomized clinical trial to better reflect procedures that may be reasonably carried out in real-world practices. The intervention was delivered by master’s-level interventionists to 160 female members of a health maintenance organization who met diagnostic criteria for recurrent binge eating. Data collected at baseline, immediately posttreatment, and at six- and 12-month follow-ups were used in intent-to-treat analyses. Results At the 12-month follow-up, CBT-GSH resulted in greater remission from binge eating (35%, N=26) than usual care (14%, N=10) (number needed to treat=5). The CBT-GSH group also demonstrated greater improvements in dietary restraint (d=.71) and eating, shape, and weight concerns (d=1.10, 1.24, and .98, respectively) but not weight change. Conclusions Replication of the pattern of previous findings suggests that CBT-GSH is a robust treatment for patients with recurrent binge eating. The magnitude of changes was significantly smaller than in the original study, however, suggesting that patients recruited and assessed with less intensive procedures may respond differently from their counterparts enrolled in trials requiring more comprehensive procedures. PMID:21459987
Full Text Available Climate changes will have an impact on food production and will require costly adaptive responses. Adapting to a changing environment will be particularly challenging in sub-Saharan Africa where climate change is expected to have a major impact. However, one important phenomenon that is often overlooked and is poorly documented is the ability of agro-systems to rapidly adapt to environmental variations. Such an adaptation could proceed by the adoption of new varieties or by the adaptation of varieties to a changing environment. In this study, we analyzed these two processes in one of the driest agro-ecosystems in Africa, the Sahel. We performed a detailed study in Niger where pearl millet is the main crop and covers 65% of the cultivated area. To assess how the agro-system is responding to recent recurrent drought, we analyzed samples of pearl millet landraces collected in the same villages in 1976 and 2003 throughout the entire cultivated area of Niger. We studied phenological and morphological differences in the 1976 and 2003 collections by comparing them over three cropping seasons in a common garden experiment. We found no major changes in the main cultivated varieties or in their genetic diversity. However, we observed a significant shift in adaptive traits. Compared to the 1976 samples, samples collected in 2003 displayed a shorter lifecycle, and a reduction in plant and spike size. We also found that an early flowering allele at the PHYC locus increased in frequency between 1976 and 2003. The increase exceeded the effect of drift and sampling, suggesting a direct effect of selection for earliness on this gene. We conclude that recurrent drought can lead to selection for earlier flowering in a major Sahelian crop. Surprisingly, these results suggest that diffusion of crop varieties is not the main driver of short term adaptation to climatic variation.
Feng, Wenyi; Di Rienzi, Sara C; Raghuraman, M K; Brewer, Bonita J
Chromosome breakage as a result of replication stress has been hypothesized to be the direct consequence of defective replication fork progression, or "collapsed" replication forks. However, direct and genome-wide evidence that collapsed replication forks give rise to chromosome breakage is still lacking. Previously we showed that a yeast replication checkpoint mutant mec1-1, after transient exposure to replication impediment imposed by hydroxyurea (HU), failed to complete DNA replication, accumulated single-stranded DNA (ssDNA) at the replication forks, and fragmented its chromosomes. In this study, by following replication fork progression genome-wide via ssDNA detection and by direct mapping of chromosome breakage after HU exposure, we have tested the hypothesis that the chromosome breakage in mec1 cells occurs at collapsed replication forks. We demonstrate that sites of chromosome breakage indeed correlate with replication fork locations. Moreover, ssDNA can be detected prior to chromosome breakage, suggesting that ssDNA accumulation is the common precursor to double strand breaks at collapsed replication forks.
Hattori, Yusuke; Ishibashi, Kohei; Noda, Takashi; Okamura, Hideo; Kanzaki, Hideaki; Anzai, Toshihisa; Yasuda, Satoshi; Kusano, Kengo
We describe the case of a 37-year-old woman who presented with complete right bundle branch block and right axis deviation. She was admitted to our hospital due to severe heart failure and was dependent on inotropic agents. Cardiac resynchronization therapy was initiated but did not improve her condition. After the optimization of the pacing timing, we performed earlier right ventricular pacing, which led to an improvement of her heart failure. Earlier right ventricular pacing should be considered in patients with complete right bundle branch block and right axis deviation when cardiac resynchronization therapy is not effective.
Chonis, Taylor Steven
In the upcoming era of extremely large ground-based astronomical telescopes, the design of wide-field spectroscopic survey instrumentation has become increasingly complex due to the linear growth of instrument pupil size with telescope diameter for a constant spectral resolving power. The upcoming Visible Integral field Replicable Unit Spectrograph (VIRUS), a baseline array of 150 copies of a simple integral field spectrograph that will be fed by 3:36 x 104 optical fibers on the upgraded Hobby-Eberly Telescope (HET) at McDonald Observatory, represents one of the first uses of large-scale replication to break the relationship between instrument pupil size and telescope diameter. By dividing the telescope's field of view between a large number of smaller and more manageable instruments, the total information grasp of a traditional monolithic survey spectrograph can be achieved at a fraction of the cost and engineering complexity. To highlight the power of this method, VIRUS will execute the HET Dark Energy Experiment (HETDEX) and survey & 420 degrees2 of sky to an emission line flux limit of ˜ 10-17 erg s-1 cm -2 to detect ˜ 106 Lyman-alpha emitting galaxies (LAEs) as probes of large-scale structure at redshifts of 1:9 production of the suite of volume phase holographic (VPH) diffraction gratings for VIRUS is presented, which highlights the challenge and success associated with producing of a very large number of highly customized optical elements whose performance is crucial to meeting the efficiency requirements of the spectrograph system. To accommodate VIRUS, the HET is undergoing a substantial wide-field upgrade to increase its field of view to 22' in diameter. The previous HET facility Low Resolution Spectrograph (LRS), which was directly fed by the telescope's previous spherical aberration corrector, must be removed from the prime focus instrument package as a result of the telescope upgrades and instead be fiber-coupled to the telescope focal plane. For a
Windgassen, Tricia A; Wessel, Sarah R; Bhattacharyya, Basudeb
Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT). PMID:29202195
Wiktor, Jakub; Lesterlin, Christian; Sherratt, David J; Dekker, Cees
Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is accurately regulated by the DnaA protein, which promotes the unwinding of DNA at oriC We demonstrate that the binding of CRISPR/dCas9 to any position within origin or replication blocks the initiation of replication. Serial-dilution plating, single-cell fluorescence microscopy, and flow-cytometry experiments show that ongoing rounds of chromosome replication are finished upon CRISPR/dCas9 binding, but no new rounds are initiated. Upon arrest, cells stay metabolically active and accumulate cell mass. We find that elevating the temperature from 37 to 42°C releases the CRISR/dCas9 replication inhibition, and we use this feature to recover cells from the arrest. Our simple and robust method of controlling the bacterial cell cycle is a useful asset for synthetic biology and DNA-replication studies in particular. The inactivation of CRISPR/dCas9 binding at elevated temperatures may furthermore be of wide interest for CRISPR/Cas9 applications in genomic engineering. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
Eugeny L. Furman
Full Text Available The replication casting process gives the open-cell aluminum foams that can be used in many industrial applications as well as in filtering technology. The essential requirement for filters is the uniformity of filtering degree which is defined by the minimal pore size. However the structure of replication castings is often inhomogeneous and the minimal pore radius is decreasing in the direction of melt infiltration. The objective of this investigation is to study the dynamics of melt impregnation of the porous medium by vacuum suction to identify the possibility of reducing the anisotropy. Theoretical data illustrate the processes at the boundary between melt and gas medium. The experiments were carried out using the replication aluminum samples produced according to commercial technology. It was found that the permeability coefficient varies throughout the height of castings. A method for estimation of pressure on the line of melt movement was proposed. The resistance of NaCl layer and circular vents of the mold causes the inhomogeneity of castings. Finally the ways of minimizing the anisotropy were offered.
Patel, Avnish; Roy, Polly
The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses which are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at a molecular and structural level. The complex nature of the virion structure has been well characterised at high resolution along with the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell as well as the protein and genome sequestration required for it; and the role of host proteins in virus entry and virus release. More recent developments of Reverse Genetics and Cell-Free Assembly systems have allowed integration of the accumulated structural and molecular knowledge to be tested at meticulous level, yielding higher insight into basic molecular virology, from which the rational design of safe efficacious vaccines has been possible. This article is centred on the molecular dissection of BTV with a view to understanding the role of each protein in the virus replication cycle. These areas are important in themselves for BTV replication but they also indicate the pathways that related viruses, which includes viruses that are pathogenic to man and animals, might also use providing an informed starting point for intervention or prevention. Copyright © 2014 Elsevier B.V. All rights reserved.
Cantner, Uwe; Savin, Ivan; Vannuccini, Simone
The pure model of replicator dynamics though providing important insights in the evolution of markets has not found much of empirical support. This paper extends the model to the case of firms vertically integrated in value chains. We show that i) by taking value chains into account, the replicator...... dynamics may revert its effect. In these regressive developments of market selection, firms with low fitness expand because of being integrated with highly fit partners, and the other way around; ii) allowing partner's switching within a value chain illustrates that periods of instability in the early...... stage of industry life-cycle may be the result of an 'optimization' of partners within a value chain providing a novel and simple explanation to the evidence discussed by Mazzucato (1998); iii) there are distinct differences in the contribution to market selection between the layers of a value chain...
Puri, Sapna; Roy, Nilotpal; Russ, Holger A; Leonhardt, Laura; French, Esra K; Roy, Ritu; Bengtsson, Henrik; Scott, Donald K; Stewart, Andrew F; Hebrok, Matthias
Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal β cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that β-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult β cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal β that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the β cell reverts to a less functional one in response to proliferative cues.
Alabert, Constance; Jasencakova, Zuzana; Groth, Anja
Inheritance of the DNA sequence and its proper organization into chromatin is fundamental for genome stability and function. Therefore, how specific chromatin structures are restored on newly synthesized DNA and transmitted through cell division remains a central question to understand cell fate...... choices and self-renewal. Propagation of genetic information and chromatin-based information in cycling cells entails genome-wide disruption and restoration of chromatin, coupled with faithful replication of DNA. In this chapter, we describe how cells duplicate the genome while maintaining its proper...... organization into chromatin. We reveal how specialized replication-coupled mechanisms rapidly assemble newly synthesized DNA into nucleosomes, while the complete restoration of chromatin organization including histone marks is a continuous process taking place throughout the cell cycle. Because failure...
The main goal of the research proposal was to develop an assay system for studying the specific genetic elements, if any, involved in the initiation of DNA replication in mammalian cells as outlined in Task 1...
Virtual machines offer a fair degree of system state encapsulation, which promotes practical advances in fault tolerance, system debugging, profiling and security applications. This work investigates deterministic replay and semi-active replication for system paravirtualization, a software discipline trading guest kernel binar compatibility for reduced dependency on costly trap-and-emulate techniques. A primary contribution is evidence that trace capturing under a piecewise deterministic exec...
Poliovirus is a member of the Picornaviridae whose genome is a single stranded RNA molecule of positive polarity surrounded by a proteinaceous capsid. Replication of poliovirus occurs via negative strand intermediates in infected cells using a virally encoded RNA-dependent RNA polymerase and host cell proteins. The authors have exploited the fact that complete cDNA copies of the viral genome when transfected onto susceptible cells generate virus. Utilizing the bacteriophage SP6 DNA dependent RNA polymerase system to synthesize negative strands in vitro and using these in an in vitro reaction the authors have generated full length infectious plus strands. Mutagenesis of the 5' and 3' ends of the negative and positive strands demonstrated that replication could occur either de novo or be extensions of the templates from their 3' ends or from nicks occurring during replication. The appearance of dimeric RNA molecules generated in these reactions was not dependent upon the same protein required for de novo initiation. Full length dimeric RNA molecules using a 5' 32 P end-labelled oligo uridylic acid primer and positive strand template were demonstrated in vitro containing only the 35,000 Mr host protein and the viral RNA-dependent RNA polymerase. A model for generating positive strands without protein priming by cleavage of dimeric RNA molecules was proposed
Lim, Chin Tat; Goodman, Stuart B; Huddleston, James I; Harris, Alex H S; Bhowmick, Subhrojyoti; Maloney, William J; Amanatullah, Derek F
Smoking is associated with early postoperative complications, increased length of hospital stay, and an increased risk of revision after total knee arthroplasty (TKA). However, the effect of smoking on time to revision TKA is unknown. A total of 619 primary TKAs referred to an academic tertiary center for revision TKA were retrospectively stratified according to the patient smoking status. Smoking status was then analyzed for associations with time to revision TKA using a Chi square test. The association was also analyzed according to the indication for revision TKA. Smokers (37/41, 90%) have an increased risk of earlier revision for any reason compared to non-smokers (274/357, 77%, p=0.031). Smokers (37/41, 90%) have an increased risk of earlier revision for any reason compared to ex-smokers (168/221, 76%, p=0.028). Subgroup analysis did not reveal a difference in indication for revision TKA (p>0.05). Smokers are at increased risk of earlier revision TKA when compared to non-smokers and ex-smokers. The risk for ex-smokers was similar to that of non-smokers. Smoking appears to have an all-or-none effect on earlier revision TKA as patients who smoked more did not have higher risk of early revision TKA. These results highlight the need for clinicians to urge patients not to begin smoking and encourage smokers to quit smoking prior to primary TKA. Copyright © 2017 Elsevier B.V. All rights reserved.
Gundlund, Anna; Fosbøl, Emil Loldrup; Kim, Sunghee
BACKGROUND: We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. METHODS: Using the ORBIT-AF, we compared symptoms and disease...
Coenen, T; Lundgren, J; Lazarus, Jeff
The articles in this supplement were developed from a recent pan-European conference entitled 'HIV in Europe 2007: Working together for optimal testing and earlier care', which took place on 26-27 November in Brussels, Belgium. The conference, organized by a multidisciplinary group of experts rep...
Chenevez, Jérôme; Beckmann, V.; Kuulkers, E.
The recently reported outburst from the supergiant fast X-ray transient XTE J1739-302/IGR J17391-3021 (ATEL #1466) began already about five hours earlier than the Swift/BAT trigger on 2008-04-08. The INTEGRAL/JEM-X monitor detected a flare starting at 16:18 (UTC) on the same day during recent Gal...
McGrath, Rachel T; Glastras, Sarah J; Hocking, Samantha; Fulcher, Gregory R
The use of metformin in gestational diabetes is safe and effective, yet some women require additional insulin therapy to achieve glycaemic targets. We found a significant association between earlier gestational age at initiation of metformin therapy and the necessity for supplemental insulin in women treated with metformin during pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Full Text Available The current outbreak of Ebola virus (EBOV in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.
Merritt, A.; Helmreich, R. L. (Principal Investigator)
Survey data collected from 9,400 male commercial airline pilots in 19 countries were used in a replication study of Hofstede's indexes of national culture. The analysis that removed the constraint of item equivalence proved superior, both conceptually and empirically, to the analysis using Hofstede's items and formulae as prescribed, and rendered significant replication correlations for all indexes (Individualism-Collectivism .96, Power Distance .87, Masculinity-Femininity .75, and Uncertainty Avoidance .68). The successful replication confirms that national culture exerts an influence on cockpit behavior over and above the professional culture of pilots, and that "one size fits all" training is inappropriate.
In June 1992, an ICP-MS instrument (Inductively Coupled Plasma-Mass Spectrometry) was commissioned for use with radioactive sample solutions at Studsvik Nuclear's Hot Cell Laboratory. For conventional environmental samples the instrument permits the simultaneous analysis of many trace elements, but the software used in evaluation of the mass spectra is based on a library of isotopic compositions relevant only for elements in the lithosphere. Fission products and actinides, however, have isotopic compositions which are significantly different from the natural elements, and which also vary with the burnup of the nuclear fuel specimen. Consequently, a spread-sheet had to be developed which could evaluate the mass spectra with these isotopic compositions. Following these preparations, a large number of samples (about 200) from SKB's experimental programme for the study of spent fuel corrosion have been analyzed by the ICP-MS technique. Many of these samples were archive solutions of samples which had been taken earlier in the programme. This report presents a comparison of the analytical results for uranium, plutonium, cesium, strontium and technetium by both the ICP-MS technique, and the previously used analytical methods. For three products, a satisfactory agreement between the results from the various methods was obtained, but for uranium and plutonium the ICP-MS method gave results which were 10-20% higher than the conventional methods. The comparison programme has also shown, not unexpectedly, that significant losses of plutonium from solution had occurred, by precipitation and/or absorption, in the archive solutions during storage. It can be expected that such losses also occur for the other actinides, and consequently, all the analytical results for actinides in older archive solutions must be treated with great caution. 9 refs
Baerug, Anne; Sletner, Line; Laake, Petter; Fretheim, Atle; Løland, Beate Fossum; Waage, Christin W; Birkeland, Kåre I; Jenum, Anne Karen
It has previously been shown that breastfeeding may reduce the risk of type 2 diabetes in mothers with recent gestational diabetes mellitus (GDM). This study compared the cessation of predominant breastfeeding in mothers with and without recent GDM in a multi-ethnic population. From May 2008 to May 2010, healthy pregnant women attending antenatal care provided by community health services in Eastern Oslo, Norway were recruited. We included 616 women-58% non-Western-and interviewed and examined them at a mean of 15 and 28 weeks of gestation and 14 weeks' postpartum. Cox regression models examined the association between GDM, as assessed by the 2013 World Health Organization criteria, and breastfeeding cessation. Overall, 190 of the 616 (31%) mothers had GDM and they ended predominant breastfeeding earlier than mothers without GDM, with an adjusted hazard ratio (aHR) of 1.33 and 95% confidence interval (95% CI) of 1.01-1.77. Mothers of South Asian origin ended predominant breastfeeding earlier than Western European mothers in the adjusted analysis (aHR 1.53, 95% CI: 1.04-2.25), but Middle Eastern mothers did not. Recent gestational diabetes was associated with earlier cessation of predominant breastfeeding in Western European and non-Western women. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Abrams, Joseph Y; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu
To assess if observed higher observed risks of cardiac complications for patients with Kawasaki disease (KD) treated earlier may reflect bias due to confounding from initial disease severity, as opposed to any negative effect of earlier treatment. We used data from Japanese nationwide KD surveys from 1997 to 2004. Receipt of additional intravenous immunoglobulin (IVIG) (data available all years) or any additional treatment (available for 2003-2004) were assessed as proxies for initial disease severity. We determined associations between earlier or later IVIG treatment (defined as receipt of IVIG on days 1-4 vs days 5-10 of illness) and cardiac complications by stratifying by receipt of additional treatment or by using logistic modeling to control for the effect of receiving additional treatment. A total of 48 310 patients with KD were included in the analysis. In unadjusted analysis, earlier IVIG treatment was associated with a higher risk for 4 categories of cardiac complications, including all major cardiac complications (risk ratio, 1.10; 95% CI, 1.06-1.15). Stratifying by receipt of additional treatment removed this association, and earlier IVIG treatment became protective against all major cardiac complications when controlling for any additional treatment in logistic regressions (OR, 0.90; 95% CI, 0.80-1.00). Observed higher risks of cardiac complications among patients with KD receiving IVIG treatment on days 1-4 of the illness are most likely due to underlying higher initial disease severity, and patients with KD should continue to be treated with IVIG as early as possible. Published by Elsevier Inc.
Full Text Available Some of the experimental designs can be composed of replicated response measures in which the replications cannot be identified exactly and may have uncertainty different than randomness. Then, the classical regression analysis may not be proper to model the designed data because of the violation of probabilistic modeling assumptions. In this case, fuzzy regression analysis can be used as a modeling tool. In this study, the replicated response values are newly formed to fuzzy numbers by using descriptive statistics of replications and golden ratio. The main aim of the study is obtaining the most suitable fuzzy model for replicated response measures through fuzzification of the replicated values by taking into account the data structure of the replications in statistical framework. Here, the response and unknown model coefficients are considered as triangular type-1 fuzzy numbers (TT1FNs whereas the inputs are crisp. Predicted fuzzy models are obtained according to the proposed fuzzification rules by using Fuzzy Least Squares (FLS approach. The performances of the predicted fuzzy models are compared by using Root Mean Squared Error (RMSE criteria. A data set from the literature, called wheel cover component data set, is used to illustrate the performance of the proposed approach and the obtained results are discussed. The calculation results show that the combined formulation of the descriptive statistics and the golden ratio is the most preferable fuzzification rule according to the well-known decision making method, called TOPSIS, for the data set.
Kwasniewska, Jolanta; Kus, Arita; Swoboda, Monika; Braszewska-Zalewska, Agnieszka
The temporal and spatial properties of DNA replication in plants related to DNA damage and mutagenesis is poorly understood. Experiments were carried out to explore the relationships between DNA replication, chromatin structure and DNA damage in nuclei from barley root tips. We quantitavely analysed the topological organisation of replication foci using pulse EdU labelling during the S phase and its relationship with the DNA damage induced by mutagenic treatment with maleic hydrazide (MH), nitroso-N-methyl-urea (MNU) and gamma ray. Treatment with mutagens did not change the characteristic S-phase patterns in the nuclei; however, the frequencies of the S-phase-labelled cells after treatment differed from those observed in the control cells. The analyses of DNA replication in barley nuclei were extended to the micronuclei induced by mutagens. Replication in the chromatin of the micronuclei was rare. The results of simultanous TUNEL reaction to identify cells with DNA strand breaks and the labelling of the S-phase cells with EdU revealed the possibility of DNA replication occurring in damaged nuclei. For the first time, the intensity of EdU fluorescence to study the rate of DNA replication was analysed. Copyright Â© 2016 Elsevier B.V. All rights reserved.
Background In patients with ST-elevation myocardial infarction (STEMI) reperfusion therapy should be initiated as soon as possible. This study evaluated whether use of a helicopter for transportation of patients is associated with earlier initiation of reperfusion therapy. Material and methods A prospective study was conducted, including patients with STEMI and symptom duration less than 12 hours, who had primary percutaneous coronary intervention (PPCI) performed at Aarhus University Hospital in Skejby. Patients with a health care system delay (time from emergency call to first coronary intervention) of more than 360 minutes were excluded. The study period ran from 1.1.2011 until 31.12.2011. A Western Denmark Helicopter Emergency Medical Service (HEMS) project was initiated 1.6.2011 for transportation of patients with time-critical illnesses, including STEMI. Results The study population comprised 398 patients, of whom 376 were transported by ambulance Emergency Medical Service (EMS) and 22 by HEMS. Field-triage directly to the PCI-center was used in 338 of patients. The median system delay was 94 minutes among those field-triaged, and 168 minutes among those initially admitted to a local hospital. Patients transported by EMS and field-triaged were stratified into four groups according to transport distance from the scene of event to the PCI-center: ≤25 km., 26–50 km., 51–75 km. and > 75 km. For these groups, the median system delay was 78, 89, 99, and 141 minutes. Among patients transported by HEMS and field-triaged the estimated median transport distance by ground transportation was 115 km, and the observed system delay was 107 minutes. Based on second order polynomial regression, it was estimated that patients with a transport distance of >60 km to the PCI-center may benefit from helicopter transportation, and that transportation by helicopter is associated with a system delay of less than 120 minutes even at a transport distance up to 150 km
Henderson, C W; Johnson, C L; Lodhi, S A; Bilimoria, S L
The boll weevil, Anthonomus grandis Boheman, is a devastating pest of cotton. Chemical pesticides are problematic due to relative lack of target specificity and resistance. Microbial pesticides may provide viable alternatives because of their narrow host range. Chilo iridescent virus (CIV) is the type species for genus Iridovirus, family Iridoviridae: large, icosahedral cytoplasmic viruses containing a double-stranded DNA genome. Earlier work suggested that CIV replicated in the boll weevil; however, efficiency or production of infectious virus was not established. We showed that CIV undergoes a productive cycle in A. grandis. CIV DNA levels in boll weevil pupae increased significantly from 0 to 3 days post infection. Moreover, virogenic stromata and complete virus particles were observed in the cytoplasm by 7 days. An endpoint dilution assay using viral DNA replication as indicator suggested a 10(5)-fold increase in infectious virus titer over 7 days. This is the first such demonstration in larval infections with genus Iridovirus. Our study establishes that CIV undergoes a productive cycle in the boll weevil and provides an important and useful model system for replication at the organismal level. These results have important implications for the potential of CIV and its components in boll weevil control.
Peters, Scott J.; Pereira, Nielsen
Even as the importance of replication research has become more widely understood, the field of gifted education is almost completely devoid of replication studies. An area in which replication is a particular problem is in student identification research, since instrument validity is a necessary prerequisite for any sound psychometric decision. To…
Adams, R. C.
Precipitated by questions of using Q methodology in television market segmentation and of the replicability of such research, this paper reports on both a reexamination of 1968 research by Joseph M. Foley and an attempt to replicate Foley's study. By undertaking a reanalysis of the Foley data, the question of replication in Q method is addressed.…
Menberu, Meseret Walle; Marttila, Hannu; Tahvanainen, Teemu; Kotiaho, Janne S.; Hokkanen, Reijo; Kløve, Bjørn; Ronkanen, Anna-Kaisa
Drainage is known to affect peatland natural hydrology and water quality, but peatland restoration is considered to ameliorate peatland degradation. Using a replicated BACIPS (Before-After-Control-Impact Paired Series) design, we investigated 24 peatlands, all drained for forestry and subsequently restored, and 19 pristine control boreal peatlands with high temporal and spatial resolution data on hydroclimate and pore water quality. In drained conditions, total nitrogen (Ntot), total phosphorus (Ptot), and dissolved organic carbon (DOC) in pore water were several-fold higher than observed at pristine control sites, highlighting the impacts of long-term drainage on pore water quality. In general, pore water DOC and Ntot decreased after restoration measures but still remained significantly higher than at pristine control sites, indicating long time lags in restoration effects. Different peatland classes and trophic levels (vegetation gradient) responded differently to restoration, primarily due to altered hydrology and varying acidity levels. Sites that were hydrologically overrestored (inundated) showed higher Ptot, Ntot, and DOC than well-restored or insufficiently restored sites, indicating the need to optimize natural-like hydrological regimes when restoring peatlands drained for forestry. Rich fens (median pH 6.2-6.6) showed lower pore water Ptot, Ntot, and DOC than intermediate and poor peats (pH 4.0-4.6) both before and after restoration. Nutrients and DOC in pore water increased in the first year postrestoration but decreased thereafter. The most important variables related to pore water quality were trophic level, peatland class, water table level, and soil and air temperature.
Haryanto, Joko Tri; Astuti S.A., Esther Sri
In many countries, relationship between decentralization of government activities and the extent of rent extraction by private parties is an important element in the recent debate on institutional design. The topic of corruption was actively, openly and debated in Indonesia by government, its development partners, and a broadly based group of political and civil society leaders are engaged in meetings and exchange on a daily basis. In the ongoing debate on corruption a lot of attention is pai...
Hansen, Hans Nørgaard; Hocken, R.J.; Tosello, Guido
The paper describes the state-of-the-art in replication of surface texture and topography at micro and nano scale. The description includes replication of surfaces in polymers, metals and glass. Three different main technological areas enabled by surface replication processes are presented......: manufacture of net-shape micro/nano surfaces, tooling (i.e. master making), and surface quality control (metrology, inspection). Replication processes and methods as well as the metrology of surfaces to determine the degree of replication are presented and classified. Examples from various application areas...... are given including replication for surface texture measurements, surface roughness standards, manufacture of micro and nano structured functional surfaces, replicated surfaces for optical applications (e.g. optical gratings), and process chains based on combinations of repeated surface replication steps....
Goldar, A.; Arneodo, A.; Audit, B.; Argoul, F.; Rappailles, A.; Guilbaud, G.; Petryk, N.; Kahli, M.; Hyrien, O.
We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.
Hüttel, Hans; Haagensen, Bjørn
Parametrised replication and replication are common ways of expressing infinite computation in process calculi. While parametrised constants can be encoded using replication in the π-calculus, this changes in the presence of spatial mobility as found in e.g. the distributed π- calculus...... of the distributed π-calculus with parametrised constants and replication are incomparable. On the other hand, we shall see that there exists a simple encoding of recursion in mobile ambients....
... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Replication. 910.64 Section 910.64 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.64 Replication. Replication means the process of using modern methods...
Dobbelstein, Matthias; Sørensen, Claus Storgaard
DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...
Fabien Le Floc’h
Full Text Available The popular replication formula to price variance swaps assumes continuity of traded option strikes. In practice, however, there is only a discrete set of option strikes traded on the market. We present here different discrete replication strategies and explain why the continuous replication price is more relevant.
Full Text Available Abstract Background The evolution of complexity is among the most important questions in biology. The evolution of complexity is often observed as the increase of genetic information or that of the organizational complexity of a system. It is well recognized that the formation of biological organization – be it of molecules or ecosystems – is ultimately instructed by the genetic information, whereas it is also true that the genetic information is functional only in the context of the organization. Therefore, to obtain a more complete picture of the evolution of complexity, we must study the evolution of both information and organization. Results Here we investigate the evolution of complexity in a simulated RNA-like replicator system. The simplicity of the system allows us to explicitly model the genotype-phenotype-interaction mapping of individual replicators, whereby we avoid preconceiving the functionality of genotypes (information or the ecological organization of replicators in the model. In particular, the model assumes that interactions among replicators – to replicate or to be replicated – depend on their secondary structures and base-pair matching. The results showed that a population of replicators, originally consisting of one genotype, evolves to form a complex ecosystem of up to four species. During this diversification, the species evolve through acquiring unique genotypes with distinct ecological functionality. The analysis of this diversification reveals that parasitic replicators, which have been thought to destabilize the replicator's diversity, actually promote the evolution of diversity through generating a novel "niche" for catalytic replicators. This also makes the current replicator system extremely stable upon the evolution of parasites. The results also show that the stability of the system crucially depends on the spatial pattern formation of replicators. Finally, the evolutionary dynamics is shown to
Fried, Eiko I.; Eidhof, Marloes B.; Palic, Sabina
. This renders network structures in clinical data, and the extent to which networks replicate across data sets, unknown. To overcome these limitations, the present cross-cultural multisite study estimated regularized partial correlation networks of 16 PTSD symptoms across four data sets of traumatized patients...... discuss the importance of future replicability efforts to improve clinical psychological science and provide code, model output, and correlation matrices to make the results of this article fully reproducible....
Zhao, Kui; Li, Jida; He, Wenqi; Song, Deguang; Zhang, Ximu; Zhang, Di; Zhou, Yanlong; Gao, Feng
Background Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the f...
Conclusions: The decline of (18F-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.
The objective of this paper is to provide practical assistance on judging the safety of a nuclear power plant, on the basis of a comparison with current safety standards and operational practices. For nuclear power plants built to earlier standards for which there are questions about the adequacy of the maintenance of the plant design and operational practices, a safety review against current standards and practices can be considered a high priority. The objective of reviewing nuclear power plants built to earlier standards against current standards and practices is to determine whether there are any deviations which would have an impact on plant safety. The safety significance of the issues identified should be judged according to their implications for plant design and operation in terms of basic safety concepts such as defence in depth and safety culture. In addition, this paper provides assistance on the prioritization of corrective measures and their implementation so as to approach an acceptable level of safety
Ates, Ihsan; Kaplan, Mustafa; Demirci, Selim; Altiparmak, Emin
Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Hepatitis B virus infection is one of the most important etilogical factors of HCC. In this case report, a patient with HCC previously infected and having ongoing immunity against hepatitis B virus will be discussed. Ates I, Kaplan M, Demirci S, Altiparmak E. A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B Virus Earlier. Euroasian J Hepato-Gastroenterol 2016;6(1):82-83.
Stilp, Christian E; Assgari, Ashley A
Speech perception is heavily influenced by surrounding sounds. When spectral properties differ between earlier (context) and later (target) sounds, this can produce spectral contrast effects (SCEs) that bias perception of later sounds. For example, when context sounds have more energy in low-F 1 frequency regions, listeners report more high-F 1 responses to a target vowel, and vice versa. SCEs have been reported using various approaches for a wide range of stimuli, but most often, large spectral peaks were added to the context to bias speech categorization. This obscures the lower limit of perceptual sensitivity to spectral properties of earlier sounds, i.e., when SCEs begin to bias speech categorization. Listeners categorized vowels (/ɪ/-/ɛ/, Experiment 1) or consonants (/d/-/g/, Experiment 2) following a context sentence with little spectral amplification (+1 to +4 dB) in frequency regions known to produce SCEs. In both experiments, +3 and +4 dB amplification in key frequency regions of the context produced SCEs, but lesser amplification was insufficient to bias performance. This establishes a lower limit of perceptual sensitivity where spectral differences across sounds can bias subsequent speech categorization. These results are consistent with proposed adaptation-based mechanisms that potentially underlie SCEs in auditory perception. Recent sounds can change what speech sounds we hear later. This can occur when the average frequency composition of earlier sounds differs from that of later sounds, biasing how they are perceived. These "spectral contrast effects" are widely observed when sounds' frequency compositions differ substantially. We reveal the lower limit of these effects, as +3 dB amplification of key frequency regions in earlier sounds was enough to bias categorization of the following vowel or consonant sound. Speech categorization being biased by very small spectral differences across sounds suggests that spectral contrast effects occur
David G. Weissman
Discussion: The regions that demonstrated significant positive linear relationships between the number of adolescent years using substances and connectivity with NAcc are nodes in the right frontoparietal network, which is central to cognitive control. The coupling of reward and cognitive control networks may be a mechanism through which earlier onset of substance use is related to brain function over time, a trajectory that may be implicated in subsequent substance use disorders.
Dawson, S.P.; Hasslacher, B.; Pearson, J.E.
We use the lattice gas cellular automation (LGCA) developed to simulate a process of pattern-formation recently observed in reaction-diffusion systems. We study the reaction mechanism, which is an extension of the Selkov model for glycolytic oscillations. We are able to reproduce the self-replicating domains observed in this work. We use the LGCA simulation to estimate the smallest length-scale on which this process can occur under conditions encountered in the cell. These estimates are similar to those obtained for Turing patterns in the same setting
Dawson, S.P.; Hasslacher, B.; Pearson, J.E.
We use the lattice gas cellular automation (LGCA) developed to simulate a process of pattern-formation recently observed in reaction-diffusion systems. We study the reaction mechanism, which is an extension of the Selkov model for glycolytic oscillations. We are able to reproduce the self-replicating domains observed in this work. We use the LGCA simulation to estimate the smallest length-scale on which this process can occur under conditions encountered in the cell. These estimates are similar to those obtained for Turing patterns in the same setting.
Raghuraman, M K; Winzeler, E A; Collingwood, D; Hunt, S; Wodicka, L; Conway, A; Lockhart, D J; Davis, R W; Brewer, B J; Fangman, W L
Oligonucleotide microarrays were used to map the detailed topography of chromosome replication in the budding yeast Saccharomyces cerevisiae. The times of replication of thousands of sites across the genome were determined by hybridizing replicated and unreplicated DNAs, isolated at different times in S phase, to the microarrays. Origin activations take place continuously throughout S phase but with most firings near mid-S phase. Rates of replication fork movement vary greatly from region to region in the genome. The two ends of each of the 16 chromosomes are highly correlated in their times of replication. This microarray approach is readily applicable to other organisms, including humans.
The chromosomal DNA replication of higher plant cells has been investigated by DNA fiber autoradiography. The nuclear DNA fibers of Vicia root meristematic cells are organized into many tandem arrays of replication units or replicons which exist as clusters with respect to replication. DNA is replicated bidirectionally from the initiation points at the average rate of 0.15 μm/min at 20 0 C, and the average interinitiation interval is about 16 μm. The manner of chromosomal DNA replication in this higher plant is similar to that found in other eukaryotic cells at a subchromosomal level. (auth.)
Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia
Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose...... RAD52 facilitates repair of collapsed DNA replication forks in cancer cells....
Slor, H.; Cleaver, J.E.
Ultraviolet light induces more pyrimidine dimers and more repair replication in DNA that replicates within 2 to 3 h of irradiation than in DNA that does not replicate during this period. This difference may be due to special conformational changes in DNA and chromatin that might be associated with semiconservative DNA replication.
Zhao, Kui; Li, Jida; He, Wenqi; Song, Deguang; Zhang, Ximu; Zhang, Di; Zhou, Yanlong; Gao, Feng
Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored. Suppression subtractive hybridization (SSH) technique was applied to identify genes differentially expressed in the ORFV-infected MDBK cells at an early phase of infection. Cellular CypB was confirmed to be significantly up-regulated by quantitative reverse transcription-PCR (qRT-PCR) analysis and Western blotting. The role of CypB in ORFV infection was further determined using Cyclosporin A (CsA) and RNA interference (RNAi). Effect of CypB gene silencing on ORFV replication by 50% tissue culture infectious dose (TCID 50 ) assay and qRT-PCR detection. In the present study, CypB was found to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection. Cyclosporin A (CsA) exhibited suppressive effects on ORFV replication through the inhibition of CypB. Silencing of CypB gene inhibited the replication of ORFV in MDBK cells. In conclusion, these data suggest that CypB is critical for the efficient replication of the ORFV genome. Cellular CypB was confirmed to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection, which could effectively facilitate the replication of ORFV.
Lee, Y.C.; Byfield, J.E.; Bennett, L.R.; Chan, P.Y.M.
Repair replication has been studied in detail in mouse L1210 leukemia cells. A method of identifying and quantitating repair replication using a pre- and postradiation block of normal replication with cytosine arabinoside is illustrated. The method derived does not require isolation of DNA per se and appears to be satisfactory for screening for inhibitors of repair replication. Repair replication can be demonstrated at doses in the 1000-rad range in bromouridine deoxyriboside-substituted cells and at slightly higher doses in nonsubstituted cells. Drugs that are known to bind to DNA inhibit this x-ray-induced repair replication. Drugs with these properties may be identified by the methods described and compared quantitatively in their ability to inhibit this type of x-ray damage. Since these phenomena can be demonstrated for low radiation doses and at drug concentrations attainable in vivo during human cancer chemotherapy this class of anticancer agent may be worthy of closer study. Application to the L1210 leukemia system should permit comparison of in vitro and in vivo drug effects in the context of the extensive in vivo pharmacological data already available for L1210 cells. (U.S.)
Cotobal, Cristina; Segurado, Mónica; Antequera, Francisco
DNA replication origins (ORI) in Schizosaccharomyces pombe colocalize with adenine and thymine (A+T)-rich regions, and earlier analyses have established a size from 0.5 to over 3 kb for a DNA fragment to drive replication in plasmid assays. We have asked what are the requirements for ORI function in the chromosomal context. By designing artificial ORIs, we have found that A+T-rich fragments as short as 100 bp without homology to S. pombe DNA are able to initiate replication in the genome. On the other hand, functional dissection of endogenous ORIs has revealed that some of them span a few kilobases and include several modules that may be as short as 25–30 contiguous A+Ts capable of initiating replication from ectopic chromosome positions. The search for elements with these characteristics across the genome has uncovered an earlier unnoticed class of low-efficiency ORIs that fire late during S phase. These results indicate that ORI specification and dynamics varies widely in S. pombe, ranging from very short elements to large regions reminiscent of replication initiation zones in mammals. PMID:20094030
Gaunt, Eleanor R; Cheung, Winsome; Richards, James E; Lever, Andrew; Desselberger, Ulrich
Recently the recruitment of lipid droplets (LDs) to sites of rotavirus (RV) replication was reported. LDs are polymorphic organelles that store triacylglycerols, cholesterol and cholesterol esters. The neutral fats are derived from palmitoyl-CoA, synthesized via the fatty acid biosynthetic pathway. RV-infected cells were treated with chemical inhibitors of the fatty acid biosynthetic pathway, and the effects on viral replication kinetics were assessed. Treatment with compound C75, an inhibitor of the fatty acid synthase enzyme complex (FASN), reduced RV infectivity 3.2-fold (P = 0.07) and modestly reduced viral RNA synthesis (1.2-fold). Acting earlier in the fatty acid synthesis pathway, TOFA [5-(Tetradecyloxy)-2-furoic acid] inhibits the enzyme acetyl-CoA carboxylase 1 (ACC1). TOFA reduced the infectivity of progeny RV 31-fold and viral RNA production 6-fold. The effect of TOFA on RV infectivity and RNA replication was dose-dependent, and infectivity was reduced by administering TOFA up to 4 h post-infection. Co-treatment of RV-infected cells with C75 and TOFA synergistically reduced viral infectivity. Knockdown by siRNA of FASN and ACC1 produced findings similar to those observed by inhibiting these proteins with the chemical compounds. Inhibition of fatty acid synthesis using a range of approaches uniformly had a more marked impact on viral infectivity than on viral RNA yield, inferring a role for LDs in virus assembly and/or egress. Specific inhibitors of fatty acid metabolism may help pinpoint the critical structural and biochemical features of LDs that are essential for RV replication, and facilitate the development of antiviral therapies.
Clark, J.M.; Hanawalt, P.C.
The authors have used Simian virus 40 (SV40) as a probe to study the replication of UV-damaged DNA in mammalian cells. Viral DNA replication in infected monkey kidney cells was synchronized by incubating a mutant of SV40 (tsA58) temperature-sensitive for the initiation of DNA synthesis at the restrictive temperature and then adding aphidicolin to temporarily inhibit DNA synthesis at the permissive temperature while permitting pre-replicative events to occur. After removal of the drug, the infected cells were irradiated at 100 J/m 2 (254 nm) to produce 6-7 pyrimidine dimers per SV40 genome, and returned to the restrictive temperature to prevent reinitiation of replication from the SV40 origin. Replicative intermediates (RI) were labeled with [ 3 H]thymidine. The size distribution of daughter DNA strands in RI isolated shortly after irradiation was skewed towards lengths less than the interdimer spacing in parental DNA; this bias persisted for at least 1 h after irradiation, but disappeared within 3 h by which time the size of the newly-synthesized DNA exceeded the interdimer distance. Evidence was obtained for the generation at late times after irradiation, of Form I molecules in which the daughter DNA strand contain dimers. Thus DNA strand exchange as well as trans-dimer synthesis may be involved in the generation of supercoiled Form I DNA from 0V-damaged SV40 replicative intermediates. (Auth.)
Sullivan, Rachel T; Frommelt, Peter C; Hill, Garick D
The association between Down syndrome and pulmonary hypertension could contribute to more severe pulmonary regurgitation after tetralogy of Fallot repair and possibly earlier pulmonary valve replacement. We compared cardiac magnetic resonance measures of pulmonary regurgitation and right ventricular dilation as well as timing of pulmonary valve replacement between those with and without Down syndrome after tetralogy of Fallot repair. Review of our surgical database from 2000 to 2015 identified patients with tetralogy of Fallot with pulmonary stenosis. Those with Down syndrome were compared to those without. The primary outcome of interest was time from repair to pulmonary valve replacement. Secondary outcomes included pulmonary regurgitation and indexed right ventricular volume on cardiac magnetic resonance imaging. The cohort of 284 patients included 35 (12%) with Down syndrome. Transannular patch repair was performed in 210 (74%). Down syndrome showed greater degree of pulmonary regurgitation (55 ± 14 vs. 37 ± 16%, p = 0.01) without a significantly greater rate of right ventricular dilation (p = 0.09). In multivariable analysis, Down syndrome (HR 2.3, 95% CI 1.2-4.5, p = 0.02) and transannular patch repair (HR 5.5, 95% CI 1.7-17.6, p = 0.004) were significant risk factors for valve replacement. Those with Down syndrome had significantly lower freedom from valve replacement (p = 0.03). Down syndrome is associated with an increased degree of pulmonary regurgitation and earlier pulmonary valve replacement after tetralogy of Fallot repair. These patients require earlier assessment by cardiac magnetic resonance imaging to determine timing of pulmonary valve replacement and evaluation for and treatment of preventable causes of pulmonary hypertension.
Li Xuequn; Chen Shi; Li Xinbang
The authors analysed the production and treatment of low- and intermediate-level radwastes (L/ILW) in China. Some problems and situation in this field are introduced. Over the past ten years, preliminary efforts have been made by CNNC (China National Nuclear Corporation) in policy, law and rules, developing program, management system, siting, engineering techniques, and safety assessment for radwaste disposal. The investment of the earlier stage work of L/ILW disposal site construction is estimated, the program and assumption to disposal site construction of the L/ILW are reviewed
Curby, Timothy W; Rimm-Kaufman, Sara E; Abry, Tashia
Many teachers believe that providing greater emotional and organizational supports in the beginning of the year strengthens their ability to teach effectively as the year progresses. Some interventions, such as the Responsive Classroom (RC) approach, explicitly embed this sequence into professional development efforts. We tested the hypothesis that earlier emotional and organizational supports set the stage for improved instruction later in the year in a sample of third- and fourth-grade teachers enrolled in a randomized controlled trial of the RC approach. Further, we examined the extent to which the model generalized for teachers using varying levels of RC practices as well as whether or not teachers were in the intervention or control groups. Teachers' emotional, organizational, and instructional interactions were observed using the Classroom Assessment Scoring System (Pianta, La Paro, & Hamre, 2008) on five occasions throughout the year. Results indicated a reciprocal relation between emotional and instructional supports. Specifically, higher levels of emotional support earlier in the year predicted higher instructional support later in the year. Also, higher levels of instructional support earlier in the year predicted higher emotional support later in the year. Classroom organization was not found to have longitudinal associations with the other domains across a year. This pattern was robust when controlling for the use of RC practices as well as across intervention and control groups. Further, teachers' use of RC practices predicted higher emotional support and classroom organization throughout the year, suggesting the malleability of this teacher characteristic. Discussion highlights the connection between teachers' emotional and instructional supports and how the use of RC practices improves teachers' emotionally supportive interactions with students. Copyright © 2013 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights
Parajuli, Shankar; Teasley, Daniel C; Murali, Bhavna; Jackson, Jessica; Vindigni, Alessandro; Stewart, Sheila A
Faithful DNA replication is essential for genome stability. To ensure accurate replication, numerous complex and redundant replication and repair mechanisms function in tandem with the core replication proteins to ensure DNA replication continues even when replication challenges are present that could impede progression of the replication fork. A unique topological challenge to the replication machinery is posed by RNA-DNA hybrids, commonly referred to as R-loops. Although R-loops play important roles in gene expression and recombination at immunoglobulin sites, their persistence is thought to interfere with DNA replication by slowing or impeding replication fork progression. Therefore, it is of interest to identify DNA-associated enzymes that help resolve replication-impeding R-loops. Here, using DNA fiber analysis, we demonstrate that human ribonuclease H1 (RNH1) plays an important role in replication fork movement in the mammalian nucleus by resolving R-loops. We found that RNH1 depletion results in accumulation of RNA-DNA hybrids, slowing of replication forks, and increased DNA damage. Our data uncovered a role for RNH1 in global DNA replication in the mammalian nucleus. Because accumulation of RNA-DNA hybrids is linked to various human cancers and neurodegenerative disorders, our study raises the possibility that replication fork progression might be impeded, adding to increased genomic instability and contributing to disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H
DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.
Grow, Laura L; Kodak, Tiffany; Carr, James E
Previous research has demonstrated that the conditional-only method (starting with a multiple-stimulus array) is more efficient than the simple-conditional method (progressive incorporation of more stimuli into the array) for teaching receptive labeling to children with autism spectrum disorders (Grow, Carr, Kodak, Jostad, & Kisamore,). The current study systematically replicated the earlier study by comparing the 2 approaches using progressive prompting with 2 boys with autism. The results showed that the conditional-only method was a more efficient and reliable teaching procedure than the simple-conditional method. The results further call into question the practice of teaching simple discriminations to facilitate acquisition of conditional discriminations. © Society for the Experimental Analysis of Behavior.
Li Fang; Liu Xingdang; Lu Zhihui; Liu Congjin
Objective: To investigate the difference between the early phases and delay phase of three-phase bone scintigraphy on hemiplegic patients with earlier complex regional pain syndrome (CRPS). Methods: Twenty-nine stroke patients with hemiplegia complicating CRPS received three-phase bone scintigraphy after intravenous injection of 99 Tc m -methylene diphosphonate (MDP). The region of interest (ROI) technique was used to obtain the radioactive counts of involved joints and contralateral sites on wrists, metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints. The total counts of these four sites in each patient were then obtained and the total uptake ratios of involved joints/contralateral joints for each phase were calculated to compare the difference among the three phases. Wilcoxon test and ANOVA were used in data analyses. Results: The involved joints of hemiplegic side displayed higher tracer uptake. There were significant differences of the radioactive counts between involved joints and uninvolved ones in the perfusion, pool and delay phase (Wilcoxon test, Z: -4.73 to -2.10, P<0.05). There was no significant difference of total uptake ratios of involved joints/contralateral joints among the three phases (ANOVA, F = 0. 807, P < 0.05). Conclusions: Due to higher bone seeking agent accumulation on three-phase bone scintigraphy, both early phases and delay phase imaging showed similar value in stroke patients with hemiplegia complicating earlier CRPS. (authors)
Rosenberg, Noah A; Vanliere, Jenna M
The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence.
Sigurdson, Alice J; Brenner, Alina V; Roach, James A; Goudeva, Lilia; Müller, Jörg A; Nerlich, Kai; Reiners, Christoph; Schwab, Robert; Pfeiffer, Liliane; Waldenberger, Melanie; Braganza, Melissa; Xu, Li; Sturgis, Erich M; Yeager, Meredith; Chanock, Stephen J; Pfeiffer, Ruth M; Abend, Michael; Port, Matthias
Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case-control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genotyped 422 PTC and 130 FTC cases and 752 controls recruited from three German clinical centers. We used polytomous logistic regression to simultaneously estimate PTC and FTC associations for 79 SNPs based on log-additive models. We assessed effect modification by body mass index (BMI), gender and age for all SNPs, and selected SNP by SNP interactions. We confirmed associations with PTC and SNPs in FOXE1/HEMGN, SERPINA5 (rs2069974), FTO (rs8047395), EVPL (rs2071194), TICAM1 (rs8120) and SCARB1 (rs11057820) genes. We found associations with SNPs in FOXE1, SERPINA5, FTO, TICAM1 and HSPA6 and FTC. We found two significant interactions between FTO (rs8047395) and BMI (P = 0.0321) and between TICAM1 (rs8120) and FOXE1 (rs10984377) (P = 0.0006). Besides the known associations with FOXE1 SNPs, we confirmed additional PTC SNP associations reported previously. We also found several new associations with FTC risk and noteworthy interactions. We conclude that multiple variants and host factors might interact in complex ways to increase risk of PTC and FTC. Published by Oxford University Press 2016.
Allahverdyan, Armen E.; Galstyan, Aram
The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.
Smits, Veronique A J; Freire, Raimundo
DNA replication is both highly conserved and controlled. Problematic DNA replication can lead to genomic instability and therefore carcinogenesis. Numerous mechanisms work together to achieve this tight control and increasing evidence suggests that post-translational modifications (phosphorylation, ubiquitination, SUMOylation) of DNA replication proteins play a pivotal role in this process. Here we discuss such modifications in the light of a recent article that describes a novel role for the deubiquitinase (DUB) USP7/HAUSP in the control of DNA replication. USP7 achieves this function by an unusual and novel mechanism, namely deubiquitination of SUMOylated proteins at the replication fork, making USP7 also a SUMO DUB (SDUB). This work extends previous observations of increased levels of SUMO and low levels of ubiquitin at the on-going replication fork. Here, we discuss this novel study, its contribution to the DNA replication and genomic stability field and what questions arise from this work. © 2016 WILEY Periodicals, Inc.
Arlø, Uffe Rolf
Thermoplastic injection moulding is a widely used industrial process that involves surface generation by replication. The surface topography of injection moulded plastic parts can be important for aesthetical or technical reasons. With the emergence of microengineering and nanotechnology additional...... importance of surface topography follows. In general the replication is not perfect and the topography of the plastic part differs from the inverse topography of the mould cavity. It is desirable to be able to control the degree of replication perfection or replication quality. This requires an understanding...... of the physical mechanisms of replication. Such understanding can lead to improved process design and facilitate in-line process quality control with respect to surface properties. The purpose of the project is to identify critical factors that affect topography replication quality and to obtain an understanding...
Chromatin serves structural and functional roles crucial for genome stability and correct gene expression. This organization must be reproduced on daughter strands during replication to maintain proper overlay of epigenetic fabric onto genetic sequence. Nucleosomes constitute the structural...... framework of chromatin and carry information to specify higher-order organization and gene expression. When replication forks traverse the chromosomes, nucleosomes are transiently disrupted, allowing the replication machinery to gain access to DNA. Histone recycling, together with new deposition, ensures...
McNeill, Donald F.; Budd, Ann F.; Borne, Pamela F.
An integrated stratigraphic study of reefal deposits on the Caribbean side of the Isthmus of Panama (Limon, Costa Rica) has discovered a significantly earlier first appearance of the major reef-building coral Acropora palmata. A. palmata is here reported from the early late Pliocene, constrained in age to within the Gauss chron (ca. 3.6 2.6 Ma). This coral was previously thought to have originated in the earliest Pleistocene and has subsequently been used as a Quaternary marker throughout the Caribbean and the Bahamas. An earlier appearance in the southern Caribbean implies a diachronous first appearance datum relative to the northern Caribbean. This older age also places A. palmata well within the transition phase of a Pliocene (4 1 Ma) faunal turnover that was marked by widespread extinction and origination of Caribbean coral species. An early late Pliocene origination is coincident with formation of the Isthmus, climate reorganization, and frequent sea-level changes associated with onset of Northern Hemisphere glaciations. The rapid growth and accumulation rates that characterize A. palmata may therefore be adaptive to these fluctuating environmental conditions, enabling its success during the subsequent Pleistocene glacial cycles.
Vassos, Evangelos; Steinberg, Stacy; Cichon, Sven
Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric ...... phenotypes, including major depression and schizophrenia....
Arsenault, Benoit J.; Boekholdt, S. Matthijs; Dubé, Marie-Pierre; Rhéaume, Eric; Wareham, Nicholas J.; Khaw, Kay-Tee; Sandhu, Manjinder S.; Tardif, Jean-Claude
Although a previous study has suggested that a genetic variant in the LPA region was associated with the presence of aortic valve stenosis (AVS), no prospective study has suggested a role for lipoprotein(a) levels in the pathophysiology of AVS. Our objective was to determine whether lipoprotein(a)
Stayton, M.M.; Bertsch, L.; Biswas, S.
In this paper we discuss the process of recognition of the complementary-strand origin with emphasis on RNA polymerase action in priming M13 DNA replication, the role of primase in G4 DNA replication, and the function of protein n, a priming protein, during primosome assembly. These phage systems do not require several of the bacterial DNA replication enzymes, particularly those involved in the regulation of chromosome copy number of the initiatiion of replication of duplex DNA. 51 references, 13 figures, 1 table
Kobayashi, M; Takatori, T; Nakajima, M; Sakurada, K; Hatanaka, K; Ikegaya, H; Matsuda, Y; Iwase, H
Rigor mortis is thought to be related to falling ATP levels in muscles postmortem. We measured rigor mortis as tension determined isometrically in three rat leg muscles in liquid paraffin kept at 37 degrees C or 25 degrees C--two red muscles, red gastrocnemius (RG) and soleus (SO) and one white muscle, white gastrocnemius (WG). Onset, half and full rigor mortis occurred earlier in RG and SO than in WG both at 37 degrees C and at 25 degrees C even though RG and WG were portions of the same muscle. This suggests that rigor mortis directly reflects the postmortem intramuscular ATP level, which decreases more rapidly in red muscle than in white muscle after death. Rigor mortis was more retarded at 25 degrees C than at 37 degrees C in each type of muscle.
Eiko I., Fried; Eidhof, Marloes B.; Palic, Sabina
The growing literature conceptualizing mental disorders like Posttraumatic Stress Disorder (PTSD) as networks of interacting symptoms faces three key challenges. Prior studies predominantly used (a) small samples with low power for precise estimation, (b) non-clinical samples, and (c) single...... samples. This renders network structures in clinical data, and the extent to which networks replicate across datasets, unknown. To overcome these limitations, the present cross-cultural multisite study estimated regularized partial correlation networks of 16 PTSD symptoms across four datasets...... of traumatized patients receiving treatment for PTSD (total N=2,782). Despite differences in culture, trauma-type and severity of the samples, considerable similarities emerged, with moderate to high correlations between symptom profiles (0.43-0.82), network structures (0.62-0.74), and centrality estimates (0...
Pugliese, Cara E.; Kenworthy, Lauren; Bal, Vanessa Hus; Wallace, Gregory L.; Yerys, Benjamin E.; Maddox, Brenna B.; White, Susan W.; Popal, Haroon; Armour, Anna Chelsea; Miller, Judith; Herrington, John D.; Schultz, Robert T.; Martin, Alex; Anthony, Laura Gutermuth
Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised…
Button, Le; Peter, Beate; Stoel-Gammon, Carol; Raskind, Wendy H.
The purpose of this study was to address the hypothesis that childhood apraxia of speech (CAS) is influenced by an underlying deficit in sequential processing that is also expressed in other modalities. In a sample of 21 adults from five multigenerational families, 11 with histories of various familial speech sound disorders, 3 biologically…
Wang, Xiaoling; Pan, Yue; Zhu, Haidong; Hao, Guang; Huang, Yisong; Barnes, Vernon; Shi, Huidong; Snieder, Harold; Pankow, James; North, Kari; Grove, Megan; Guan, Weihua; Demerath, Ellen; Dong, Yanbin; Su, Shaoyong
Background: We conducted an epigenome-wide association study (EWAS) on obesity in healthy youth and young adults and further examined to what extent identified signals influenced gene expression and were independent of cell type composition and obesity-related cardio-metabolic risk factors.
Grill, Jacques; Lamfers, Martine L. M.; van Beusechem, Victor W.; Dirven, Clemens M.; Pherai, D. Shareen; Kater, Mathijs; van der Valk, Paul; Vogels, Ronald; Vandertop, W. Peter; Pinedo, Herbert M.; Curiel, David T.; Gerritsen, Winald R.
The use of adenoviruses for gene transfer and as oncolytic agents is currently receiving widespread attention. As specific constraints to adenovirus distribution and spread cannot be studied in cell cultures, there is a need for an in vitro three-dimensional (3D) model mimicking the in vivo biology
Derikx, M.H.; Kovacs, P.; Scholz, M.; Masson, E.; Chen, J.M.; Ruffert, C.; Lichtner, P.; Morsche, R.H. Te; Cavestro, G.M.; Ferec, C.; Drenth, J.P.H.; Witt, H.; Rosendahl, J.
OBJECTIVE: Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci
V.J.M. Verhoeven (Virginie); P.G. Hysi (Pirro); S-M. Saw (Seang-Mei); V. Vitart (Veronique); A. Mirshahi (Alireza); J. Guggenheim (Jean); M.F. Cotch (Mary Frances); K. Yamashiro (Kenji); P.N. Baird (Paul); D.A. Mackey (David); R. Wojciechowski (Robert); M.K. Ikram (Kamran); A.W. Hewit (Alex); P. Duggal (Priya); S. Janmahasatian (Sarayut); C.C. Khor; Q. Fan (Qiao); X. Zhou (Xinying); T.L. Young (Terri); E.S. Tai (Shyong); L.-K. Goh; Y.J. Li (Yi); T. Aung (Tin); E.N. Vithana (Eranga); Y.Y. Teo (Yik Ying); W.-T. Tay; X. Sim (Xueling); I. Rudan (Igor); C. Hayward (Caroline); A.F. Wright (Alan); O. Polasek (Ozren); H. Campbell (Harry); J.F. Wilson (James); B. Fleck (Brian); I. Nakata (Isao); N. Yoshimura; R. Yamada (Ryo); F. Matsuda (Fumihiko); K. Ohno-Matsui (Kyoko); A. Nag (Abhishek); G. Mcmahon (George); B. St Pourcain (Beate); Y. Lu (Yi); J.S. Rahi (Jugnoo); P. Cumberland (Phillippa); S. Bhattacharya (Shoumo); C.L. Simpson (Claire); L.D. Atwood (Larry); X. Li (Xiaohui); L.J. Raffel (Leslie); D. Murgia (Daniela); L. Portas (Laura); D.D.G. Despriet (Dominique); L.M.E. van Koolwijk (Leonieke); C. Wolfram (Christian); K.J. Lackner (Karl); A. Tönjes (Anke); R. Mägi (Reedik); T. Lehtimäki (Terho); M. Kähönen (Mika); T. Esko (Tõnu); A. Metspalu (Andres); T. Rantanen (Taina); O. Pärssinen (Olavi); B.E.K. Klein (Barbara); T. Meitinger (Thomas); T.D. Spector (Timothy); B.A. Oostra (Ben); G.D. Smith; P.T.V.M. de Jong (Paulus); A. Hofman (Albert); N. Amin (Najaf); L.C. Karssen (Lennart); F. Rivadeneira Ramirez (Fernando); J.R. Vingerling (Hans); G. Eiriksdottir (Gudny); V. Gudnason (Vilmundur); A. Döring (Angela); T. Bettecken (Thomas); A.G. Uitterlinden (André); C. Williams (Cathy); T. Zeller (Tanja); R. Castagne (Raphaële); K. Oexle (Konrad); C.M. van Duijn (Cornelia); S.K. Iyengar (Sudha); P. Mitchell (Paul); J.J. Wang (Jie Jin); R. Höhn (René); A.F.H. Pfeiffer (Andreas); J.E. Bailey-Wilson (Joan); D.E. Stambolian (Dwight); T.Y. Wong (Tien Yin); C.J. Hammond (Christopher); C.C.W. Klaver (Caroline)
textabstractMyopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and
Verhoeven, Virginie J. M.; Hysi, Pirro G.; Saw, Seang-Mei; Vitart, Veronique; Mirshahi, Alireza; Guggenheim, Jeremy A.; Cotch, Mary Frances; Yamashiro, Kenji; Baird, Paul N.; Mackey, David A.; Wojciechowski, Robert; Ikram, M. Kamran; Hewitt, Alex W.; Duggal, Priya; Janmahasatian, Sarayut; Khor, Chiea-Chuen; Fan, Qiao; Zhou, Xin; Young, Terri L.; Tai, E.-Shyong; Goh, Liang-Kee; Li, Yi-Ju; Aung, Tin; Vithana, Eranga; teo, Yik-Ying; Tay, Wanting; Sim, Xueling; Rudan, Igor; Hayward, Caroline; Wright, Alan F.; Polasek, Ozren; Campbell, Harry; Wilson, James F.; Fleck, Brian W.; Nakata, Isao; Yoshimura, Nagahisa; Yamada, Ryo; Matsuda, Fumihiko; Ohno-Matsui, Kyoko; Nag, Abhishek; McMahon, George; St Pourcain, Beate; Lu, Yi; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Bhattacharya, Shomi; Simpson, Claire L.; Atwood, Larry D.; Li, Xiaohui; Raffel, Leslie J.; Murgia, Federico; Portas, Laura; Despriet, Dominiek D. G.; van Koolwijk, Leonieke M. E.; Wolfram, Christian; Lackner, Karl J.; Tönjes, Anke; Mägi, Reedik; Lehtimäki, Terho; Kähönen, Mika; Esko, Tõnu; Metspalu, Andres; Rantanen, Taina; Pärssinen, Olavi; Klein, Barbara E.; Meitinger, Thomas; Spector, Timothy D.; Oostra, Ben A.; Smith, Albert V.; de Jong, Paulus T. V. M.; Hofman, Albert; Amin, Najaf; Karssen, Lennart C.; Rivadeneira, Fernando; Vingerling, Johannes R.; Eiríksdóttir, Guðný; Gudnason, Vilmundur; Döring, Angela; Bettecken, Thomas; Uitterlinden, André G.; Williams, Cathy; Zeller, Tanja; Castagné, Raphaële; Oexle, Konrad; van Duijn, Cornelia M.; Iyengar, Sudha K.; Mitchell, Paul; Wang, Jie Jin; Höhn, René; Pfeiffer, Norbert; Bailey-Wilson, Joan E.; Stambolian, Dwight; Wong, Tien-Yin; Hammond, Christopher J.; Klaver, Caroline C. W.
Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis
Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.
We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.
Full Text Available Dissection of the genetic architecture of complex traits persists as a major challenge in biology; despite considerable efforts, much remains unclear including the role and importance of genetic interactions. This study provides empirical evidence for a strong and persistent contribution of both second- and third-order epistatic interactions to long-term selection response for body weight in two divergently selected chicken lines. We earlier reported a network of interacting loci with large effects on body weight in an F(2 intercross between these high- and low-body weight lines. Here, most pair-wise interactions in the network are replicated in an independent eight-generation advanced intercross line (AIL. The original report showed an important contribution of capacitating epistasis to growth, meaning that the genotype at a hub in the network releases the effects of one or several peripheral loci. After fine-mapping of the loci in the AIL, we show that these interactions were persistent over time. The replication of five of six originally reported epistatic loci, as well as the capacitating epistasis, provides strong empirical evidence that the originally observed epistasis is of biological importance and is a contributor in the genetic architecture of this population. The stability of genetic interaction mechanisms over time indicates a non-transient role of epistasis on phenotypic change. Third-order epistasis was for the first time examined in this study and was shown to make an important contribution to growth, which suggests that the genetic architecture of growth is more complex than can be explained by two-locus interactions only. Our results illustrate the importance of designing studies that facilitate exploration of epistasis in populations for obtaining a comprehensive understanding of the genetics underlying a complex trait.
Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.
Boudreaux, Crystal E.; Kelly, Deborah F.; McDonald, Sarah M.
Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally, using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process. - Highlights: • Rotaviruses replicate their genomes in tandem with early virion assembly. • Little is known about rotavirus assembly-replication intermediates. • Assembly-replication intermediates were imaged using electron microscopy
Boudreaux, Crystal E.; Kelly, Deborah F. [Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, VA (United States); McDonald, Sarah M., E-mail: email@example.com [Virginia Tech Carilion School of Medicine and Research Institute, Roanoke, VA (United States); Department of Biomedical Sciences and Pathobiology, Virginia—Maryland Regional College of Veterinary Medicine, Blacksburg, VA (United States)
Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally, using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process. - Highlights: • Rotaviruses replicate their genomes in tandem with early virion assembly. • Little is known about rotavirus assembly-replication intermediates. • Assembly-replication intermediates were imaged using electron microscopy.
Full Text Available BACKGROUND: During S. pombe S-phase, initiation of DNA replication occurs at multiple sites (origins that are enriched with AT-rich sequences, at various times. Current studies of genome-wide DNA replication profiles have focused on the DNA replication timing and origin location. However, the replication and/or firing efficiency of the individual origins on the genomic scale remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using the genome-wide ORF-specific DNA microarray analysis, we show that in S. pombe, individual origins fire with varying efficiencies and at different times during S-phase. The increase in DNA copy number plotted as a function of time is approximated to the near-sigmoidal model, when considering the replication start and end timings at individual loci in cells released from HU-arrest. Replication efficiencies differ from origin to origin, depending on the origin's firing efficiency. We have found that DNA replication is inefficient early in S-phase, due to inefficient firing at origins. Efficient replication occurs later, attributed to efficient but late-firing origins. Furthermore, profiles of replication timing in cds1Delta cells are abnormal, due to the failure in resuming replication at the collapsed forks. The majority of the inefficient origins, but not the efficient ones, are found to fire in cds1Delta cells after HU removal, owing to the firing at the remaining unused (inefficient origins during HU treatment. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that efficient DNA replication/firing occurs late in S-phase progression in cells after HU removal, due to efficient late-firing origins. Additionally, checkpoint kinase Cds1p is required for maintaining the efficient replication/firing late in S-phase. We further propose that efficient late-firing origins are essential for ensuring completion of DNA duplication by the end of S-phase.
Mudrik, Liad; Shalgi, Shani; Lamy, Dominique; Deouell, Leon Y
Whether contextual regularities facilitate perceptual stages of scene processing is widely debated, and empirical evidence is still inconclusive. Specifically, it was recently suggested that contextual violations affect early processing of a scene only when the incongruent object and the scene are presented a-synchronously, creating expectations. We compared event-related potentials (ERPs) evoked by scenes that depicted a person performing an action using either a congruent or an incongruent object (e.g., a man shaving with a razor or with a fork) when scene and object were presented simultaneously. We also explored the role of attention in contextual processing by using a pre-cue to direct subjects׳ attention towards or away from the congruent/incongruent object. Subjects׳ task was to determine how many hands the person in the picture used in order to perform the action. We replicated our previous findings of frontocentral negativity for incongruent scenes that started ~ 210 ms post stimulus presentation, even earlier than previously found. Surprisingly, this incongruency ERP effect was negatively correlated with the reaction times cost on incongruent scenes. The results did not allow us to draw conclusions about the role of attention in detecting the regularity, due to a weak attention manipulation. By replicating the 200-300 ms incongruity effect with a new group of subjects at even earlier latencies than previously reported, the results strengthen the evidence for contextual processing during this time window even when simultaneous presentation of the scene and object prevent the formation of prior expectations. We discuss possible methodological limitations that may account for previous failures to find this an effect, and conclude that contextual information affects object model selection processes prior to full object identification, with semantic knowledge activation stages unfolding only later on. Copyright © 2014 Elsevier Ltd. All rights reserved.
Pugliese, Cara E.; Kenworthy, Lauren; Bal, Vanessa Hus; Wallace, Gregory L; Yerys, Benjamin E; Maddox, Brenna B.; White, Susan W.; Popal, Haroon; Armour, Anna Chelsea; Miller, Judith; Herrington, John D.; Schultz, Robert T.; Martin, Alex; Anthony, Laura Gutermuth
Recent updates have been proposed to the Autism Diagnostic Observation Schedule-2 Module 4 diagnostic algorithm. This new algorithm, however, has not yet been validated in an independent sample without intellectual disability (ID). This multi-site study compared the original and revised algorithms in individuals with ASD without ID. The revised algorithm demonstrated increased sensitivity, but lower specificity in the overall sample. Estimates were highest for females, individuals with a verb...
Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard
A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.
Full Text Available This study aims to compare the suicide risk over the past decade following recent onset psychosis to findings from the eighties and nineties in the same catchment area and to identify predictors of suicide in the context of the Psychosis Recent Onset Groningen-Survey (PROGR-S. A medical file search was carried out to determine the current status of all patients admitted between 2000 and 2009. The suicide rate was compared with a study executed in 1973-1988 in the same catchment area. Predictors of suicide were investigated using Cox regression. The status of 424 of the 614 patients was known in July 2014. Suicide occurred in 2.4% of patients with psychosis disorders (n = 10; mean follow-up 5.6 years; 6 out of 10 suicides took place within two years. Within two decades, the suicide rate dropped from 11% (follow-up 15 years, 8.5% after 5 years to 2.4%. The Standardized Mortality Rate (SMR of suicides compared with the general population was 41.6. A higher age was the only significant predictor for suicide. Neuroticism, living situation, disorganized and negative symptoms, and passive coping style all showed a trend for significance. A significant reduction in the suicide rate was found for people with psychosis over the past decades. Given the high SMR, suicide research should be given the highest priority. Identifying predictors may contribute to further reduction of suicide among patients with psychosis.
Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.
Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…
Button, Le; Peter, Beate; Stoel-Gammon, Carol; Raskind, Wendy H
The purpose of this study was to address the hypothesis that childhood apraxia of speech (CAS) is influenced by an underlying deficit in sequential processing that is also expressed in other modalities. In a sample of 21 adults from five multigenerational families, 11 with histories of various familial speech sound disorders, 3 biologically related adults from a family with familial CAS showed motor sequencing deficits in an alternating motor speech task. Compared with the other adults, these three participants showed deficits in tasks requiring high loads of sequential processing, including nonword imitation, nonword reading and spelling. Qualitative error analyses in real word and nonword imitations revealed group differences in phoneme sequencing errors. Motor sequencing ability was correlated with phoneme sequencing errors during real word and nonword imitation, reading and spelling. Correlations were characterized by extremely high scores in one family and extremely low scores in another. Results are consistent with a central deficit in sequential processing in CAS of familial origin.
Full Text Available Single-nucleotide polymorphisms (SNPs in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC, rs28493229 and caspase-3 (CASP3, rs113420705 are associated with susceptibility to KD in Japanese and Taiwanese populations. This study was conducted to investigate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG resistance and coronary artery lesion (CAL in Taiwanese population. A total of 340 KD patients were subjected to assess by the identification of 2-locus genes model. A combinatorial association between ITPKC (rs28493229 and CASP3 (rs113420705 was found in CAL formation (P = 0.0227, OR: 3.06. KD patients with high-risk genotype had a trend of overrepresentation in IVIG resistance compared with individual SNPs. Our findings suggest the existence of genetic factors affecting patients' risk for CAL formation and IVIG responsiveness in a Taiwanese population.
Rohmer, Stanimira; Mainka, Astrid; Knippertz, Ilka; Hesse, Andrea; Nettelbeck, Dirk M
Key to the realization of gene therapy is the development of efficient and targeted gene transfer vectors. Therapeutic gene transfer by replication-deficient or more recently by conditionally replication-competent/oncolytic adenoviruses has shown much promise. For specific applications, however, it will be advantageous to provide vectors that allow for external control of gene expression. The efficient cellular heat shock system in combination with available technology for focused and controlled hyperthermia suggests heat-regulated transcription control as a promising tool for this purpose. We investigated the feasibility of a short fragment of the human hsp70B' promoter, with and without upstream insulator elements, for the regulation of transgene expression by replication-deficient or oncolytic adenoviruses. Two novel adenoviral vectors with an insulated hsp70B' promoter were developed and showed stringent heat-inducible gene expression with induction ratios up to 8000-fold. In contrast, regulation of gene expression from the hsp70B' promoter without insulation was suboptimal. In replication-competent/oncolytic adenoviruses regulation of the hsp70B' promoter was lost specifically during late replication in permissive cells and could not be restored by the insulators. We developed novel adenovirus gene transfer vectors that feature improved and stringent regulation of transgene expression from the hsp70B' promoter using promoter insulation. These vectors have potential for gene therapy applications that benefit from external modulation of therapeutic gene expression or for combination therapy with hyperthermia. Furthermore, our study reveals that vector replication can deregulate inserted cellular promoters, an observation which is of relevance for the development of replication-competent/oncolytic gene transfer vectors. (c) 2008 John Wiley & Sons, Ltd.
Dellas, Nikki; Snyder, Jamie C; Bolduc, Benjamin; Young, Mark J
The Archaea-and their viruses-remain the most enigmatic of life's three domains. Once thought to inhabit only extreme environments, archaea are now known to inhabit diverse environments. Even though the first archaeal virus was described over 40 years ago, only 117 archaeal viruses have been discovered to date. Despite this small number, these viruses have painted a portrait of enormous morphological and genetic diversity. For example, research centered around the various steps of the archaeal virus life cycle has led to the discovery of unique mechanisms employed by archaeal viruses during replication, maturation, and virion release. In many instances, archaeal virus proteins display very low levels of sequence homology to other proteins listed in the public database, and therefore, structural characterization of these proteins has played an integral role in functional assignment. These structural studies have not only provided insights into structure-function relationships but have also identified links between viruses across all three domains of life.
Derikx, Monique H; Kovacs, Peter; Scholz, Markus; Masson, Emmanuelle; Chen, Jian-Min; Ruffert, Claudia; Lichtner, Peter; Te Morsche, Rene H M; Cavestro, Giulia Martina; Férec, Claude; Drenth, Joost P H; Witt, Heiko; Rosendahl, Jonas
Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort. We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships. Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51). The single-nucleotide polymorphisms rs10273639 at the PRSS1-PRSS2 locus and rs7057398 and rs12688220 at the CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Hansen, Hans Nørgaard; Arlø, Uffe Rolf
topography is transcribed onto the plastic part through complex mechanisms. This replication however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... moulding of surface microstructures. Emphasis is put on the ability to replicate surface microstructures under normal injection moulding conditions, notably with low cost materials at low mould temperatures. The replication of surface microstructures in injection moulding has been explored...... for Polypropylene at low mould temperatures. The process conditions were varied over the recommended process window for the material. The geometry of the obtained structures was analyzed. Evidence suggests that step height replication quality depends linearly on structure width in a certain range. Further...
Fragkos, Michalis; Naim, Valeria
Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.
Maksim I. Sorokin
Full Text Available The yeast Saccharomyces cerevisiae is successfully used as a model organism to find genes responsible for lifespan control of higher organisms. As functional decline of higher eukaryotes can start as early as one quarter of the average lifespan, we asked whether S. cerevisiae can be used to model this manifestation of aging. While the average replicative lifespan of S. cerevisiae mother cells ranges between 15 and 30 division cycles, we found that resistances to certain stresses start to decrease much earlier. Looking into the mechanism, we found that knockouts of genes responsible for mitochondriato-nucleus (retrograde signaling, RTG1 or RTG3, significantly decrease the resistance of cells that generated more than four daughters, but not of the younger ones. We also found that even young mother cells frequently contain mitochondria with heterogeneous transmembrane potential and that the percentage of such cells correlates with replicative age. Together, these facts suggest that retrograde signaling starts to malfunction in relatively young cells, leading to accumulation of heterogeneous mitochondria within one cell. The latter may further contribute to a decline in stress resistances.
Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio
Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.
Bhattacharya, Souparno; Srinivasan, Kalayarasan; Abdisalaam, Salim; Su, Fengtao; Raj, Prithvi; Dozmorov, Igor; Mishra, Ritu; Wakeland, Edward K; Ghose, Subroto; Mukherjee, Shibani; Asaithamby, Aroumougame
RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Diaz, Jason; Wang, Xin; Tsang, Sabrina H.; Jiao, Jing; You, Jianxin
Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells
Diaz, Jason; Wang, Xin; Tsang, Sabrina H. [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Jiao, Jing [Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); You, Jianxin, E-mail: firstname.lastname@example.org [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)
Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells.
Full Text Available Abstract Background Research conducted with forensic psychiatric patients found moderate correlations between violence in institutions and psychopathy. It is unclear though, whether the PCL-R is an accurate instrument for predicting aggressive behavior in prisons. Results seem to indicate that the instrument is better suited for predicting verbal rather than physical aggression of prison inmates. Methods PCL-R scores were assessed for a sample of 113 imprisoned sex and violent offenders in Switzerland. Logistic regression analyses were used to estimate physical and verbal aggression as a function of the PCL-R sum score. Additionally, stratified analyses were conducted for Factor 1 and 2. Infractions were analyzed as to their motives and consequences. Results The mean score of the PCL-R was 12 points. Neither the relationship between physical aggression and the sum score of the PCL-R, nor the relationship between physical aggression and either of the two factors of the PCL-R were significant. Both the sum score and Factor 1 predicted the occurrence of verbal aggression (AUC = 0.70 and 0.69, while Factor 2 did not. Conclusion Possible explanations are discussed for the weak relationship between PCL-R scores and physically aggressive behavior during imprisonment. Some authors have discussed whether the low base rate of violent infractions can be considered an explanation for the non-significant relation between PCL-R-score and violence. The base rate in this study, however, with 27%, was not low. It is proposed that the distinction between reactive and instrumental motives of institutional violence must be considered when examining the usefulness of the PCL-R in predicting in-prison physical aggressive behavior.
Wolf, Christian; Schütz, Alexander C
Saccades bring objects of interest onto the fovea for high-acuity processing. Saccades to rewarded targets show shorter latencies that correlate negatively with expected motivational value. Shorter latencies are also observed when the saccade target is relevant for a perceptual discrimination task. Here we tested whether saccade preparation is equally influenced by informational value as it is by motivational value. We defined informational value as the probability that information is task-relevant times the ratio between postsaccadic foveal and presaccadic peripheral discriminability. Using a gaze-contingent display, we independently manipulated peripheral and foveal discriminability of the saccade target. Latencies of saccades with perceptual task were reduced by 36 ms in general, but they were not modulated by the information saccades provide (Experiments 1 and 2). However, latencies showed a clear negative linear correlation with the probability that the target is task-relevant (Experiment 3). We replicated that the facilitation by a perceptual task is spatially specific and not due to generally heightened arousal (Experiment 4). Finally, the facilitation only emerged when the perceptual task is in the visual but not in the auditory modality (Experiment 5). Taken together, these results suggest that saccade latencies are not equally modulated by informational value as by motivational value. The facilitation by a perceptual task only arises when task-relevant visual information is foveated, irrespective of whether the foveation is useful or not.
Yuan, Yao; Jiaxin, Qiao; Jing, Li; Hui, Li; Morigen, Morigen
The two-component systems, which could sense and respond to environmental changes, widely exist in bacteria as a signal transduction pathway. The bacterial CckA/CtrA, ArcA/ArcB and PhoP/PhoQ two-component systems are associated with initiation of DNA replication and cell division, however, the effects of the TorS/TorR system on cell cycle and DNA replication remains unknown. The TorS/TorR system in Escherichia coli can sense changes in trimethylamine oxide (TMAO) concentration around the cells. However, it is unknown if it also affects initiation of DNA replication. We detected DNA replication patterns in ΔtorS and ΔtorR mutant strains by flow cytometry. We found that the average number of replication origins (oriCs) per cell and doubling time in ΔtorS mutants were the same while the average number of oriCs in ΔtorR mutants was increased compared with that in wild-type cells. These results indicated that absence of TorR led to an earlier initiation of DNA replication than that in wild-type cells. Strangely, neither overexpression of TorR nor co-expression of TorR and TorS could restore ΔtorR mutant phenotype to the wild type. However, overexpression of SufD in both wild type and ΔtorR mutants promoted initiation of DNA replication, while mutation of SufD delayed it in ΔtorR mutants. Thus, TorR may affect initiation of DNA replication indirectly through regulating gene expression of sufD.