bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY11-03: Sirt1 transgenic and cancer models
Authors: Serrano Manuel 
Published: July 2012

Abstract
Sir2 is an evolutionary conserved protein deacetylase that in lower organisms has been shown to extend the lifespan when overexpressed and to mediate the effects of calorie restriction. In mammals, the situation is more complex due to the existence of seven Sir2 family members, Sirt1 being the closest mammalian homologue of Sir2. We have generated transgenic mice moderately overexpressing (2-3 fold) Sirt1 under its own regulatory elements (Sirt1-tg mice) to study its effect on mammalian metabolism, cancer and aging. We have found that Sirt1-tg mice are protected from the metabolic damage associated to high dietary fat intake due to a decreased inflammatory response[1]. Moreover, and contrary to what may have been expected, Sirt1-tg mice do not live longer, but they preserve a better health at old ages according to a variety of physiological indicators[2]. Regarding cancer, Sirt1 role is controversial, yet all the in vivo studies published so far support a tumor suppressor role for Sirt1. In our Sirt1-tg mice we have found that Sirt1 is able to protect from aging-associated spontaneous cancer development, as well as, from metabolic syndrome-associated liver cancer [2], and our results indicate that this beneficial effect of Sirt1 is due to its impact both on metabolism [1,2] and genomic integrity [2]. On the other hand, different genetic crosses of Sirt1-tg mice are helping us to further refine Sirt1 roles in cancer. Thus, we have found scenarios in which Sirt1 overexpression is able to accelerate tumorigenesis in certain tissues, which also show higher Sirt1 expression in human tumors, and this constitutes the first in vivo demonstration of an oncogenic role for Sirt1. I will present the latest data on Sirt1 and cancer, which suggest that Sirt1 plays a highly complex and tissue-specific role.
References:
1. Pfluger, P.T., Herranz, D., et al., (2008). Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci U S A 105, 9793-9798.
2. Herranz, D. et al., (2010). Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun 1:3, doi: 10.1038/ncomms1001
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY11-03. doi:10.1158/1538-7445.AM2011-SY11-03
Progesterone and AdipoQ Receptor 11 Links Ras Signaling to Cardiac Development in Zebrafish
Authors: Huang Heng , Jin Ting , He Jing , Ding Qiurong , Xu Daqian , Wang Lingdi , Zhang Yixuan , Pan Yi , Wang Zhenzhen , Chen Yan 
Published: July 2012

Objective—
Progesterone and adipoQ receptor (PAQR) 10 and PAQR11 are 2 highly homologous genes involved in compartmentalized Ras signaling in the Golgi apparatus. The aim of this study was to investigate the physiological functions of PAQR10 and PAQR11.

Methods and Results—
We used zebrafish as a model system to analyze the potential function of PAQR10/PAQR11. The expression profiles of PAQR10 and PAQR11 in zebrafish embryos are overlapping in many areas, but only PAQR11 is expressed in the developing heart. Knockdown of PAQR11 but not PAQR10 in zebrafish embryos causes cardiac developmental defects, including dilation of cardiac chambers, abnormal heart looping, disruption of atrioventricular cushion formation, heart edema, and blood regurgitation. PAQR11 knockdown markedly reduces the number and proliferation rate of cardiomyocytes and alters the morphology of myocardial cells during early heart development. The cardiac defects caused by PAQR11 knockdown can be phenocopied by MEK inhibitors and a dominant negative Ras. Furthermore, constitutively active Ras and especially a Golgi-localized but not a plasma membrane–localized Ras are able to rescue the cardiac defects caused by PAQR11 knockdown.

Conclusion—
This study not only provides in vivo evidence that PAQR11 plays a critical role in heart morphogenesis but also pinpoints the importance of compartmentalized Ras signaling during development.
Nonalcoholic Fatty Liver Disease Is Associated With Atherosclerosis in Middle-Aged and Elderly Chinese
Authors: Huang Yun , Bi Yufang , Xu Min , Ma Zhimin , Xu Yu , Wang Tiange , Li Mian , Liu Yu , Lu Jieli , Chen Yuhong , Huang Fei , Xu Baihui , Zhang Jie , Wang Weiqing , Li Xiaoying , Ning Guang 
Published: July 2012

Objective—
To evaluate the associations between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis.

Methods and Results—

A total of 8632 participants aged ≥40 years from Jiading district, Shanghai, were included in the present study. The presence of NAFLD was evaluated by ultrasonography. Carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) were measured in each participant. The prevalence of NAFLD was 30.0% in the total population, with 30.3% in men and 29.9% in women, respectively. Subjects with NAFLD had remarkably higher CIMT and ba-PWV compared with those without NAFLD (0.594±0.105 mm versus 0.578±0.109 mm,
P
<0.0001; 1665±424 cm/s versus 1558±430 cm/s,
P
<0.0001). Subjects with both NAFLD and metabolic syndrome had significantly higher CIMT and ba-PWV compared with those with neither or either of these 2 diseases after adjustment for age and sex (all
P
<0.05). Logistic regressions also revealed that NAFLD conferred 35% and 30% increased odds ratios of elevated CIMT and ba-PWV, independent of conventional risk factors and the presence of metabolic syndrome.

Conclusion—
NAFLD was associated with elevated CIMT and ba-PWV, independent of conventional cardiovascular disease risk factors and metabolic syndrome. The effects of NAFLD and metabolic syndrome on atherosclerosis might not fully overlap.
ADP-Stimulated Activation of Akt During Integrin Outside-In Signaling Promotes Platelet Spreading by Inhibiting Glycogen Synthase Kinase-3β
Authors: O’Brien Kelly A. , Gartner T. Kent , Hay Nissim , Du Xiaoping 
Published: July 2012

Objective—
Integrins mediate platelet adhesion and transmit outside-in signals leading to platelet spreading. Phosphoinositide 3-kinases (PI3Ks) play a critical role in outside-in signaling and platelet spreading; however, the mechanisms of PI3K activation and function in outside-in signaling are unclear. We sought to determine the role of the Akt family of serine/threonine kinases and activation mechanisms of the PI3K/Akt pathway in outside-in signaling.

Methods and Results—
Akt inhibitors and Akt3 knockout inhibited platelet spreading on fibrinogen, indicating that Akt is important in integrin outside-in signaling. Akt inhibitors and Akt3 knockout also diminished integrin-dependent phosphorylation of glycogen synthase kinase-3β. Inhibition of glycogen synthase kinase-3β reversed the inhibitory effects of Akt3 knockout and inhibitors of Akt or PI3K on platelet spreading, indicating that glycogen synthase kinase-3β is a downstream target of Akt in outside-in signaling. Integrin-dependent activation of the PI3K-Akt pathway requires Src family kinase. Akt phosphorylation is also significantly inhibited in ADP receptor P2Y12 knockout platelets and further inhibited in P2Y12 knockout platelets treated with a P2Y1 antagonist. Consistently, P2Y12 knockout and P2Y1 inhibition together reduced platelet spreading.

Conclusion—
These results demonstrate that integrin outside-in signaling and platelet spreading requires Src family kinase–dependent and ADP receptor–amplified activation of the PI3K-Akt-GSK-3β pathway.
Determining Stroke's Rank as a Cause of Death Using Multicause Mortality Data
Authors: Burke James F. , Lisabeth Lynda D. , Brown Devin L. , Reeves Matthew J. , Morgenstern Lewis B. 
Published: July 2012

Background and Purpose—
Stroke has fallen from the second to the fourth leading cause of death in the United States without large declines in stroke incidence or case fatality. We explored whether this decline may be attributable to changes in mortality attribution methodology.

Methods—
Multicause mortality files from 2000 to 2008 were used to compare changes in reporting of stroke as underlying cause of death (UCOD) with changes in death certificates reporting any mention (AMCOD) of stroke. In addition, the UCOD/AMCOD ratio was calculated for the 6 leading organ and disease-specific causes of death. If stroke mortality is underestimated by the system of mortality attribution, we hypothesized that we would find: (1) a greater decline in stroke as UCOD than as AMCOD; and (2) a decline in the UCOD/AMCOD ratio compared with other causes of death.

Results—
Age-adjusted death rates for stroke as UCOD (61 per 100 000 in 2000 versus 41 in 2008) and AMCOD (102 per 100 000 versus 68) both declined by 33%. The ratio of UCOD to AMCOD for stroke did not change over time (0.595 in 2000 versus 0.598 in 2008). Changes in UCOD/AMCOD ratio for the diagnoses that surpassed stroke as UCOD were too small (no change for lung cancer and a slight increase from 0.49 to 0.52 for chronic lower respiratory diseases) to explain stroke's decline as UCOD.

Conclusion—
Changes in mortality attribution methodology are not likely responsible for stroke's decline as a leading cause of death. The discordant trends in incidence, case fatality, and mortality require further study.
Evaluating Performance of the Spetzler-Martin Supplemented Model in Selecting Patients With Brain Arteriovenous Malformation for Surgery
Authors: Kim Helen , Pourmohamad Tony , Westbroek Erick M. , McCulloch Charles E. , Lawton Michael T. , Young William L. 
Published: July 2012

Background and Purpose—
Our recently proposed point scoring model includes the widely-used Spetzler-Martin (SM)-5 variables, along with age, unruptured presentation, and diffuse border (SM-Supp). Here we evaluate the SM-Supp model performance compared with SM-5, SM-3, and Toronto prediction models using net reclassification index, which quantifies the correct movement in risk reclassification, and validate the model in an independent data set.

Methods—
Bad outcome was defined as worsening between preoperative and final postoperative modified Rankin Scale score. Point scores for each model were used as predictors in logistic regression and predictions evaluated using net reclassification index at varying thresholds (10%–30%) and any threshold (continuous net reclassification index >0). Performance was validated in an independent data set (n=117).

Results—

Net gain in risk reclassification was better using the SM-Supp model over a range of threshold values (net reclassification index=9%–25%) and significantly improved overall predictions for outcomes in the development data set, yielding a continuous net reclassification index of 64% versus SM-5, 67% versus SM-3, and 61% versus Toronto (all
P
<0.001). In the validation data set, the SM-Supp model again correctly reclassified a greater proportion of patients versus SM-5 (82%), SM-3 (85%), and Toronto models (69%).

Conclusions—
The SM-Supp model demonstrated better discrimination and risk reclassification than several existing models and should be considered for clinical practice to estimate surgical risk in patients with brain arteriovenous malformation.
Diagnostic Accuracy of Nocturnal Oximetry for Detection of Sleep Apnea Syndrome in Stroke Rehabilitation
Authors: Aaronson Justine A. , van Bezeij Tijs , van den Aardweg Joost G. , van Bennekom Coen A.M. , Hofman Winni F. 
Published: July 2012

Background and Purpose—
Sleep apnea syndrome (SAS) is a common sleep disorder in stroke patients and is associated with decreased recovery and increased risk of recurrent stroke and mortality. The standard diagnostic test for SAS is poly(somno)graphy, but this is often not feasible in stroke rehabilitation settings. This study investigated the diagnostic value of nocturnal oximetry for screening SAS in stroke rehabilitation.

Methods—
Fifty-six stroke patients underwent nocturnal polygraphy and oximetry. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index were calculated. Patient and sleep characteristics were used to develop a predictive model of apnea–hypopnea index.

Results—
Forty-six percent of the stroke patients had SAS. The majority of SAS patients was male, older, and had a higher body mass index than patients without SAS. Sensitivity, specificity, and positive and negative predictive values for the oxygen desaturation index ≥15 were, respectively, 77%, 100%, 100%, and 83%. Oxygen desaturation index predicted 87% of the variance in the apnea–hypopnea index. Patient characteristics did not add significantly to the prediction model.

Conclusion—
Nocturnal oximetry is an accurate diagnostic screening instrument for the detection of SAS in stroke patients.
Compensation through Increased Functional Connectivity: Neural Correlates of Inhibition in Old and Young
Authors: Geerligs Linda , Saliasi Emi , Maurits Natasha M. , Lorist Monicque M. 
Published: July 2012

AbstractWith increasing age, people experience more difficulties with suppressing irrelevant information, which may have a major impact on cognitive functioning. The extent of decline of inhibitory functions with age is highly variable between individuals. In this study, we used ERPs and phase locking analyses to investigate neural correlates of this variability in inhibition between individuals. Older and younger participants performed a selective attention task in which relevant and irrelevant information was presented simultaneously. The participants were split into high and low performers based on their level of inhibition inefficiency, that is, the slowing of RTs induced by information that participants were instructed to ignore. P1 peak amplitudes were larger in low performers than in high performers, indicating that low performers were less able to suppress the processing of irrelevant stimuli. Phase locking analyses were used as a measure of functional connectivity. Efficient inhibition in both age groups was related to the increased functional connectivity in the alpha band between frontal and occipito-parietal ROIs in the prestimulus interval. In addition, increased power in the alpha band in occipito-parietal ROIs was related to better inhibition both before and after stimulus onset. Phase locking in the upper beta band before and during stimulus presentation between frontal and occipito-parietal ROIs was related to a better performance in older participants only, suggesting that this is an active compensation mechanism employed to maintain adequate performance. In addition, increased top–down modulation and increased power in the alpha band appears to be a general mechanism facilitating inhibition in both age groups.
Does This Ring a Bell? Music-cued Retrieval of Semantic Knowledge and Metamemory Judgments
Authors: Zuckerman Maya , Levy Daniel A. , Tibon Roni , Reggev Niv , Maril Anat 
Published: July 2012

AbstractFailed knowledge recall attempts are sometimes accompanied by a strong feeling of imminent success, giving rise to a “tip-of-the-tongue” (TOT) experience. Similar to successful retrieval (i.e., the Know state, K), a TOT commences with strong cue familiarity but involves only partial retrieval of related information. We sought to characterize the cognitive processes and temporal dynamics of these retrieval states and to extend the applicability of previous findings about TOT to the auditory modality. Participants heard 3-sec initial segments of popular songs and were asked to recall their names. EEG was recorded while participants indicated their retrieval state via button press. Stimulus-locked analyses revealed a significant early left fronto-central difference between TOT and K, at 300–550 msec postcue onset. Post hoc analysis revealed that, in this time window, TOT also differed from DK (Don't Know) responses, which themselves were similar to the K responses. This finding indicates that neural processes, which may reflect strategy selection, ease of semantic processing, familiarity-related processes, or conflict monitoring, are indicative of the fate of our knowledge judgments long before we actually execute them.
The Circulation Response to Idealized Changes in Stratospheric Water Vapor
Authors: Maycock Amanda C. , Joshi Manoj M. , Shine Keith P. , Scaife Adam A. 
Published: July 2012

Abstract
Observations show that stratospheric water vapor (SWV) concentrations increased by ~30% between 1980 and 2000. SWV has also been projected to increase by up to a factor of 2 over the twenty-first century. Trends in SWV impact stratospheric temperatures, which may lead to changes in the stratospheric circulation. Perturbations in temperature and wind in the stratosphere have been shown to influence the extratropical tropospheric circulation. This study investigates the response to a uniform doubling in SWV from 3 to 6 ppmv in a comprehensive stratosphere-resolving atmospheric GCM. The increase in SWV causes stratospheric cooling with a maximum amplitude of 5–6 K in the polar lower stratosphere and 2–3 K in the tropical lower stratosphere. The zonal wind on the upper flanks of the subtropical jets is more westerly by up to ~5 m s−1. Changes in resolved wave drag in the stratosphere result in an increase in the strength of tropical upwelling associated with the Brewer–Dobson circulation of ~10% throughout the year. In the troposphere, the increase in SWV causes significant meridional dipole changes in the midlatitude zonal-mean zonal wind of up to 2.8 m s−1 at 850 hPa, which are largest in boreal winter in both hemispheres. This suggests a more poleward storm track under uniformly increased stratospheric water vapor. The circulation changes in both the stratosphere and troposphere are almost entirely due to the increase in SWV at pressures greater than 50 hPa. The results show that long-term trends in SWV may impact stratospheric temperatures and wind, the strength of the Brewer–Dobson circulation, and extratropical surface climate.
The Late Quaternary Flow through the Bering Strait Has Been Forced by the Southern Ocean Winds
Authors: Ortiz Joseph D. , Nof Doron , Polyak Leonid , St-Onge Guillaume , Lisé-Pronovost Agathe , Naidu Sathy , Darby Dennis , Brachfeld Stefanie 
Published: July 2012

Abstract
Because North and South America are surrounded by water, they constitute together a gigantic island whose peripheral sea level is controlled by the winds east of the island, winds along the western boundary of the island, the freshwater flux, and the meridional overturning cell. This idea has been expressed in several articles where a series of analytical models show that the Bering Strait (BS) flow is controlled by the interplay of the Southern Winds (sometimes referred to as the “Subantarctic Westerlies”), and the North Hemisphere freshwater flux. Here, the authors report a paleoceanographic analysis of proxies in the BS as well as the Southern Ocean, which clearly support the above through employment of a slowly varying time-dependent version of the coupled Sandal–Nof model.
This study shows a very strong correlation between the Southern Ocean winds and the BS flow. A mid-Holocene weakening of the Southern Winds followed by the cession of freshwater fluxes from the melting Laurentide ice sheet strengthened the BS flow for several thousand years. Increasing the Southern Winds enhances the near surface, cross-equatorial flow from the Southern Ocean to the Northern Hemisphere. This cross-equatorial flow decreases the Arctic outflow into the Atlantic demonstrating a dynamic linkage between the Southern Ocean Winds and the mean flow through the BS.
Effectiveness of Part-Task Training and Increasing-Difficulty Training Strategies
Authors: Wickens Christopher D. , Hutchins Shaun , Carolan Thomas , Cumming John 
Published: July 2012

Objective: The objective was to conduct meta-analyses that investigated the effects of two training strategies, increasing difficulty (ID) and part-task training (PTT), on transfer of skills and the variables that moderate effectiveness of the strategies. Background: Cognitive load theory (CLT) provides a basis for predicting that training strategies reducing the intrinsic load of a task during training avail more resources to be devoted to learning. Two strategies that accomplish this goal, by dividing tasks in parts or by simplifying tasks in early training trials, have offered only mixed success. Method: A pair of complementary effect size measures were used in the meta-analyses conducted on 37 transfer studies employing the two training strategies: (a) a transfer ratio analysis on the ratio of treatment transfer performance to control transfer performance and (b) a Hedges’ g analysis on the standardized difference between treatment and control group means. Results: PTT generally produced negative transfer when the parts were performed concurrently in the whole transfer task but not when the parts were performed in sequence. Variable-priority training of the whole task was a successful technique. ID training was successful when the increases were implemented adaptively but not when increased in fixed steps. Both strategies provided evidence that experienced learners benefited less, or suffered more, from the strategy, consistent with CLT. Conclusion: PTT can be successful if the integrated parts are varied in the priority they are given to the learner. ID training is successful if the increases are adaptive. The fundamental elements of CLT are confirmed.
Response Time, Pistol Fire Position Variability, and Pistol Draw Success Rates for Hip and Thigh Holsters
Authors: Campbell Amity , Roelofs Andrea , Davey Paul , Straker Leon 
Published: July 2012

Objective: The aim of this study was to investigate the effect of pistol holster position on pistol draw time and performance of police officers. Background: Proficient use of the lethal force option is critical to an officer’s ability to survive. Traditionally, pistols were worn in hip holsters; however, recently, thigh holsters have also become popular. The effect of holster position on pistol draw performance has not been investigated. Method: For this study, 27 police officers, representing a range of holster familiarity, years of service, and gender, were assessed drawing a training pistol from both the thigh and hip holster positions via a 3-D motion analysis system. Participants were required to draw and fire toward a target as quickly and accurately as possible following a visual stimulus, three times successfully. Temporal characteristics, accuracy variability, and draw success rate were compared between the thigh and hip holster with repeated-measures ANOVA both unadjusted and adjusted for familiarity, years of service, and gender ( p < .05). Results: No differences in the temporal variables, accuracy variability, or success rate were detected between the hip and thigh holster positions, either adjusted or unadjusted. Holster familiarity was found to significantly affect draw success rate, with participants more successful when drawing from their familiar holster. Conclusion: Hip and thigh holster positions are both viable options in terms of draw time and accuracy. However, draw success rate will be negatively affected during initial use of an unfamiliar holster position. Further research should address the effect of familiarization on draw performance.