tbuckley/cabot-search huggingface dataset:
The role of emotions on pacing strategies and performance in middle and long duration sport events
Authors: B Baron, F Moullan, F Deruelle, T D Noakes
Journal: British Journal of Sports Medicine (2009)

Thepacing strategy may be defined as the process in which the total energy expenditure during exercise is regulated on a moment-to-moment basis in order to ensure that the exercise bout can be completed in a minimum time and without a catastrophic biological failure. Experienced athletes develop a stable template of the power outputs they are able to sustain for different durations of exercise, but it is not known how they originally develop this template or how that template changes with training and experience. While it is understood that the athlete9s physiological state makes an important contribution to this process, there has been much less interest in the contribution that the athlete9s emotional status makes. The aim of this review is to evaluate the literature of physiological, neurophysiological and perceptual responses during exercise in order to propose a complex model interpretation of this process which may be a critical factor determining success in middle- and long-duration sporting competitions. We describe unconscious/physiological and conscious/emotional mechanisms of control, the focus of which are to ensure that exercise terminates before catastrophic failure occurs in any bodily system. We suggest that training sessions teach the athlete to select optimal pacing strategies by associating a level of emotion with the ability to maintain that pace for exercise of different durations. That pacing strategy is then adopted in future events. Finally, we propose novel perspectives to maximise performance and to avoid overtraining by paying attention also to the emotional state in training process.
Clinical Significance of Gastric Dysplasia: A Multicenter Follow-Up Study
Authors: A. M. Fertitta, U. Comin, V. Terruzzi, G. Minoli, A. Zambelli, G. Cannatelli, P. Bodini, G. Bertoli, R. Negri, S. Brunati, R. Fiocca, F. Turpini, A. Prada, E. Ceretti, R. Gullotta, M. Cornaggia
Journal: Endoscopy (1993)

The evolution of gastric moderate and severe dysplasia was examined in a prospective multicenter study. One-hundred-and-nine of 141 patients with the endoscopic-bioptic diagnosis of moderate or severe dysplasia had an adequate follow-up and were included into the study. After revision of the initial slides by a gastrointestinal pathologist, 57 patients whose lesions did not meet the histological criteria for dysplasia were excluded, being reclassified as hyperplastic or metaplastic lesions (group 2). The 52 patients with confirmed moderate or severe dysplasia (group 1) were followed up for at least six months or underwent surgery for confirmed dysplasia or cancer. Thirty-two cancers were found in group 1 (33 % in patients with moderate and 81 % in patients with severe dysplasia). Among them, about half (n = 17) were early gastric cancers. Neither severe dysplasia nor cancer were found during the follow-up in group 2. Mean follow-up time was 13 months in group 1 and 16 months in group 2. Our results indicate that: 1) Confirmed moderate dysplasia shows a high risk of cancer development and requires strict bioptic follow-up; 2) Surgery is indicated in confirmed severe gastric dysplasia seen in the early detection of gastric cancer.
Targets for Body Fat, Blood Pressure, Lipids, and Glucose-Lowering Interventions in Healthy Older People
Authors: Constantine Tsigos, Rafael Bitzur, Yosef Kleinman, Hofit Cohen, Avivit Cahn, Gianmaria Brambilla, Giuseppe Mancia, Guido Grassi
Journal: Diabetes Care (2013)

Improving cardiovascular (CV) risk profile, by lowering elevated body weight, blood pressure (BP), plasma cholesterol, and blood glucose (BG) levels, is of relevance for decreasing fatal and nonfatal CV events in young and middle-aged patients (1–4). Evidence also exists that the above-mentioned interventions are also highly effective in older patients, i.e., in subjects >65 years of age (3–6). However, it is unclear whether the same therapeutic approaches should be always used to treat old patients, taking into account on one hand the heterogeneity of the aged population and on the other the fact that frequently there is a discrepancy between chronological and biological age values. In addition, it is still undefined whether the threshold values used for initiating treatment of patients of younger ages should also apply to the older patients. Finally, it is debated whether the targets for treatment used for younger patients should be used for the older ones.

Here, we aim to provide a general review on the above-mentioned issues, giving, whenever possible, indications useful for current clinical practice and having as a specific target the general population of healthy older patients. The review will be focused on aged individuals without major disabilities, such as multiple comorbidities, severe cognitive impairment, and in general, systemic diseases that will require continuous medical and nursing assistance. With this aim, the information available for the various variables, such as BMI, BP, blood cholesterol (BC), and BG, will be analyzed separately in the following sections.

### BMI in healthy older subjects

Obesity is becoming a global epidemic, causing a sharp rise in many chronic diseases including diabetes, hyperlipidemia, and hypertension (7). Among older adults, the rate of obesity has also risen dramatically over the last few decades, independent of sex, race, and educational level (8). Obesity has significant implications on the health status of …
In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors.
Authors: P Lemarchand, M Jones, I Yamada, R G Crystal
Journal: Circulation Research (1993)

Replication-deficient recombinant adenovirus vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in the endothelium. To evaluate the feasibility of adenovirus-mediated gene transfer in vivo in normal intact blood vessels, adenovirus vectors containing the Escherichia coli lacZ gene or a human alpha 1-antitrypsin (alpha 1AT) cDNA were injected in vivo into the lumen of an occluded vessel segment of sheep jugular vein and/or carotid artery. After 15 minutes of incubation, circulation was restored; the vessels were harvested 1-28 days later and evaluated for gene transfer and expression. Three days after in vivo exposure to the lacZ adenovirus vector, the endothelium of jugular veins and carotid arteries expressed beta-galactosidase. Exposure of jugular veins and carotid arteries in vivo to the alpha 1AT adenovirus vector resulted in the expression of alpha 1AT mRNA transcripts detected by Northern analysis and in the synthesis and secretion of alpha 1AT detected by ex vivo [35S]methionine labeling. Expression with the adenovirus vectors was efficient and easily detectable 1-14 days after injection, with maximum expression at 7 days. Expression was no longer evident at 28 days. Thus, adenovirus vectors are capable of transferring exogenous genes to the endothelium of normal arteries and veins with expression for at least 2 weeks, suggesting that these vectors have the potential for a variety of cardiovascular experimental and clinical applications.
Protective role of IL-33/ST2 axis in Con A-induced hepatitis
Authors: Vladislav Volarevic, Marina Mitrovic, Marija Milovanovic, Ivanka Zelen, Ivana Nikolic, Slobodanka Mitrovic, Nada Pejnovic, Nebojsa Arsenijevic, Miodrag L. Lukic
Journal: Journal of Hepatology (2011)
Spectrum of Mutations in Gitelman Syndrome
Authors: Rosa Vargas-Poussou, Karin Dahan, Diana Kahila, Annabelle Venisse, Eva Riveira-Munoz, Huguette Debaix, Bernard Grisart, Franck Bridoux, Robert Unwin, Bruno Moulin, Jean-Philippe Haymann, Marie-Christine Vantyghem, Claire Rigothier, Bertrand Dussol, Michel Godin, Hubert Nivet, Laurence Dubourg, Ivan Tack, Anne-Paule Gimenez-Roqueplo, Pascal Houillier, Anne Blanchard, Olivier Devuyst, Xavier Jeunemaitre
Journal: Journal of the American Society of Nephrology (2011)

Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.
Human Vascular Smooth Muscle Cells Express Interleukin-1β–converting Enzyme (ICE), but Inhibit Processing of the Interleukin-1β Precursor by ICE
Authors: Uwe Schönbeck, Mona Herzberg, Arnd Petersen, Claudia Wohlenberg, Johannes Gerdes, Hans-Dieter Flad, Harald Loppnow
Journal: The Journal of Experimental Medicine (1997)

Local immunoregulatory processes during normal vascular biology or pathogenesis are mediated in part by the production of and response to cytokines by vessel wall cells. Among these cytokines interleukin (IL)-1 is considered to be of major importance. Although vascular smooth muscle (SMC) and endothelial cells (EC) expressed both IL-1α and IL-1β as cell-associated, 33-kilodalton (kD) precursors, SMC neither contained detectable mature IL-1β, nor processed recombinant IL-1β precursor into its mature 17-kD form. Thus, we investigated the expression and function of IL-1β–converting enzyme (ICE) in vascular cells. We demonstrate in processing experiments with recombinant IL-1 precursor molecules that EC processed IL-1β, in contrast to SMC. Despite the failure of SMC to process IL-1β, these cells expressed ICE mRNA, immunoreactive ICE protein, and the expected IL-1β nucleotide sequence. The lack of processing was explained by our finding that extracts of SMC specifically and concentration dependently blocked processing of IL-1β precursor by recombinant or native ICE. The initial biochemical characterization of the inhibitory activity showed that it is heat-labile, has a molecular size of 50–100 kD, and is associated to the cell membrane compartment. Inhibition of processing, i.e., activation of IL-1β precursor by SMC may constitute a novel regulatory mechanism during normal vascular biology or pathogenesis of vascular diseases.
Expression of sarcoplasmic reticulum Ca(2+)-ATPase and calsequestrin genes in rat heart during ontogenic development and aging.
Authors: A M Lompré, F Lambert, E G Lakatta, K Schwartz
Journal: Circulation Research (1991)

Little is known concerning the molecular mechanisms responsible for changes in sarcoplasmic reticulum (SR) function during ontogenic development and aging except that the amount of SR Ca(2+)-ATPase mRNA varies in these conditions. The aim of the present work was to determine whether SR maturation requires expression of specific isoforms and synchronous accumulation of mRNAs encoding proteins located in SR. Thus, we have studied expression of SR Ca(2+)-ATPase and calsequestrin genes in the rat at different developmental stages from 14 fetal days to 24 months of age. Analysis of alternative splicing of the major Ca(2+)-ATPase gene expressed in heart by nuclease S1 mapping led us to conclude that the Ca(2+)-ATPase gene expressed in heart was not differentially spliced during ontogenic development and senescence. A single calsequestrin mRNA isoform was also detected in rat heart whatever the developmental stage. The amount of specific mRNA was then measured by dot blot and normalized to 18S ribosomal RNA or to myosin heavy chain mRNA. The amount of Ca(2+)-ATPase mRNA relative to 18S RNA increases substantially at the end of fetal life and in the early postnatal period (9.5 +/- 0.5% in the 14-15 day fetus versus 99 +/- 7% in the 4-day-old rat). A stable high level is observed during adulthood. In aged rats (24 months), Ca(2+)-ATPase mRNA represents only 44.6% the amount observed in young adults (1-2 months).(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of ventilatory thresholds during graded and maximal exercise test using time varying analysis of respiratory sinus arrhythmia * Commentary
Authors: G Blain, O Meste, T Bouchard, S Bermon
Journal: British Journal of Sports Medicine (2005)

To test whether ventilatory thresholds, measured during an exercise test, could be assessed using time varying analysis of respiratory sinus arrhythmia frequency (f(RSA)).Fourteen sedentary subjects and 12 endurance athletes performed a graded and maximal exercise test on a cycle ergometer: initial load 75 W (sedentary subjects) and 150 W (athletes), increments 37.5 W/2 min. f(RSA) was extracted from heart period series using an evolutive model. First (T(V1)) and second (T(V2)) ventilatory thresholds were determined from the time course curves of ventilation and ventilatory equivalents for O(2) and CO(2).f(RSA) was accurately extracted from all recordings and positively correlated to respiratory frequency (r = 0.96 (0.03), p<0.01). In 21 of the 26 subjects, two successive non-linear increases were determined in f(RSA), defining the first (T(RSA1)) and second (T(RSA2)) f(RSA) thresholds. When expressed as a function of power, T(RSA1) and T(RSA2) were not significantly different from and closely linked to T(V1) (r = 0.99, p<0.001) and T(V2) (r = 0.99, p<0.001), respectively. In the five remaining subjects, only one non-linear increase was observed close to T(V2). Significant differences (p<0.04) were found between athlete and sedentary groups when T(RSA1) and T(RSA2) were expressed in terms of absolute and relative power and percentage of maximal aerobic power. In the sedentary group, T(RSA1) and T(RSA2) were 150.3 (18.7) W and 198.3 (28.8) W, respectively, whereas in the athlete group T(RSA1) and T(RSA2) were 247.3 (32.8) W and 316.0 (28.8) W, respectively.Dynamic analysis of f(RSA) provides a useful tool for identifying ventilatory thresholds during graded and maximal exercise test in sedentary subjects and athletes.
Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes
Authors: Carl de Luca, Timothy J. Kowalski, Yiying Zhang, Joel K. Elmquist, Charlotte Lee, Manfred W. Kilimann, Thomas Ludwig, Shun-Mei Liu, Streamson C. Chua
Journal: Journal of Clinical Investigation (2005)

We have generated mice that carry a neuron-specific leptin receptor (LEPR) transgene whose expression is driven by the rat synapsin I promoter synapsin-LEPR B (SYN-LEPR-B). We have also generated mice that are compound hemizygotes for the transgenes SYN-LEPR-B and neuron-specific enolase-LEPR B (NSE-LEPR-B). We observed a degree of correction in db/db mice that are hemizygous (Syn db/db) and homozygous (Syn/Syn db/db) for the SYN-LEPR-B transgene similar to that previously reported for the NSE-LEPR-B transgene. We also show complete correction of the obesity and related phenotypes of db/db mice that are hemizygous for both NSE-LEPR-B and SYN-LEPR-B transgenes (Nse+Syn db/db). Body composition, insulin sensitivity, and cold tolerance were completely normalized in Nse+Syn db/db mice at 12 weeks of age compared with lean controls. In situ hybridization for LEPR B isoform expression in Nse+Syn db/db mice showed robust expression in the energy homeostasis-relevant regions of the hypothalamus. Expression of 3 neuropeptide genes, agouti-related peptide (Agrp), neuropeptide Y (Npy), and proopiomelanocortin (Pomc), was fully normalized in dual transgenic db/db mice. The 2 transgenes in concert conferred normal fertility to male and female db/db mice. Male mice with partial peripheral deletion of Lepr, induced in the periweaning phase, did not show alterations in body composition or mass. In summary, we show that brain-specific leptin signaling is sufficient to reverse the obesity, diabetes, and infertility of db/db mice.
YKL-40 Expression is Associated with Poorer Response to Radiation and Shorter Overall Survival in Glioblastoma
Authors: Christopher E. Pelloski, Anita Mahajan, Moshe Maor, Eric L. Chang, Shiao Woo, Mark Gilbert, Howard Colman, Helen Yang, Alicia Ledoux, Hilary Blair, Sandra Passe, Robert B. Jenkins, Kenneth D. Aldape
Journal: Clinical Cancer Research (2005)

YKL-40 is a secreted protein that has been reported to be overexpressed in epithelial cancers and gliomas, although its function is unknown. Previous data in a smaller sample set suggested that YKL-40 was a marker associated with a poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here we test these findings in a larger series of patients with glioblastoma, and in particular, determine if tumor YKL-40 expression is associated with radiation response.Patients (n=147) with subtotal resections were studied for imaging-assessed changes in tumor size in serial studies following radiation therapy. An additional set (n=140) of glioblastoma patients who underwent a gross-total resection was tested to validate the survival association and extend them to patients with minimal residual disease.In the subtotal resection group, higher YKL-40 expression was significantly associated with poorer radiation response, shorter time to progression and shorter overall survival. The association of higher YKL-40 expression with poorer survival was validated in the gross-total resection group. In multivariate analysis with both groups combined (n = 287), YKL-40 was an independent predictor of survival after adjusting for patient age, performance status, and extent of resection. YKL-40 expression was also compared with genetically defined subsets of glioblastoma by assessing epidermal growth factor receptor amplification and loss at chromosome 10q, two of the common recurring aberrations in these tumors, using fluorescent in situ hybridization. YKL-40 was significantly associated with 10q loss.The findings implicate YKL-40 as an important marker of therapeutic response and genetic subtype in glioblastomas and suggest that it may play an oncogenic role in these tumors.
The Primate Premotor Cortex: Past, Present, and Preparatory
Authors: S P Wise
Journal: Annual Review of Neuroscience (1985)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns
Authors: Kenneth J. Oestreich, Albert C. Huang, Amy S. Weinmann
Journal: The Journal of Experimental Medicine (2011)

The T-box transcription factor T-bet is important for the differentiation of naive CD4+ T helper cells (Th cells) into the Th1 phenotype. Much is known about T-bet’s role as a transcriptional activator, but less is known about the mechanisms by which T-bet functionally represses alternative Th cell genetic programs. In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet. Significantly, T-bet’s role in the repression of these genes is through a direct interaction with their promoters. Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells. Importantly, T-bet’s novel role in transcriptional repression is because of its ability to physically associate with, and functionally recruit, the transcriptional repressor Bcl-6 to a subset of promoters. Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity. Collectively, these data establish a novel mechanism for T-bet–mediated gene repression in which two lineage-defining transcription factors, one a classical activator and one a repressor, collaborate to promote and properly regulate Th1 development.
Intratumoral Delivery and Suppression of Prostate Tumor Growth by Attenuated<i>Salmonella enterica</i>serovar<i>typhimurium</i>Carrying Plasmid-Based Small Interfering RNAs
Authors: Ling Zhang, Lifang Gao, Lijuan Zhao, Baofeng Guo, Kun Ji, Yong Tian, Jinguo Wang, Hao Yu, Jiadi Hu, Dhananjaya V. Kalvakolanu, Dennis J. Kopecko, Xuejian Zhao, De-Qi Xu
Journal: Cancer Research (2007)

Abstract The facultative anaerobic, invasive Salmonella enterica serovar typhimurium (S. typhimurium) has been shown to retard the growth of established tumors. We wondered if a more effective antitumor response could be achieved in vivo if these bacteria were used as tools for delivering specific molecular antitumor therapeutics. Constitutively activated transcription factor signal transducer and activator of transcription 3 (STAT3) promotes the survival of a number of human tumors. In this study, we investigated the relative efficacies of attenuated S. typhimurium alone or combined with Stat3-specific small interfering RNA (siRNA) in terms of tumor growth and metastasis. The bacteria preferentially homed into tumors over normal liver and spleen tissues in vivo. S. typhimurium expressing plasmid-based Stat3-specific siRNAs significantly inhibited tumor growth, reduced the number of metastastic organs, and extended the life time for C57BL6 mice bearing an implanted prostate tumor, versus bacterial treatment alone. These results suggest that attenuated S. typhimurium combined with an RNA interference approach might be more effective for the treatment of primary as well as metastatic cancer. [Cancer Res 2007;67(12):5859–64]
Electroanatomic Characterization of Post-Infarct Scars
Authors: Andrei Codreanu, Freddy Odille, Etienne Aliot, Pierre-Yves Marie, Isabelle Magnin-Poull, Marius Andronache, Damien Mandry, Wassila Djaballah, Denis Régent, Jacques Felblinger, Christian de Chillou
Journal: Journal of the American College of Cardiology (2008)
ABCC9 mutations identified in human dilated cardiomyopathy disrupt catalytic KATP channel gating
Authors: Martin Bienengraeber, Timothy M Olson, Vitaliy A Selivanov, Eva C Kathmann, Fearghas O'Cochlain, Fan Gao, Amy B Karger, Jeffrey D Ballew, Denice M Hodgson, Leonid V Zingman, Yuan-Ping Pang, Alexey E Alekseev, Andre Terzic
Journal: Nature Genetics (2004)