tbuckley/cabot-search huggingface dataset:
Molecular Cloning and Characterization of a Moss (Ceratodon purpureus) Nonsymbiotic Hemoglobin Provides Insight into the Early Evolution of Plant Nonsymbiotic Hemoglobins
Authors: V. Garrocho-Villegas, R. Arredondo-Peter
Journal: Molecular Biology and Evolution (2008)

Nonsymbiotic hemoglobins (nsHbs) are widespread in plants including bryophytes. Bryophytes (such as mosses) are among the oldest land plants, thus an analysis of a bryophyte nsHb is of interest from an evolutionary perspective. However, very little is known about bryophyte nsHbs. Here, we report the cloning and characterization of an nshb gene (cerhb) from the moss Ceratodon purpureus. Sequence analysis showed that cerhb is interrupted by 3 introns in identical position as all known plant nshb genes, which suggests that the ancestral nshb gene was interrupted by 3 introns. Expression analysis showed that cerhb expresses in protonemas and gametophytes growing in normal conditions and that it overexpresses in protonemas subjected to osmotic (sucrose), heat-shock, cold-, and nitrate-stress conditions. Also, modeling of the Ceratodon nsHb (CerHb) tertiary structure suggests that CerHb is hexacoordinate and that it binds O(2) with high affinity. Comparative analysis of the predicted CerHb with native rice Hb1 and soybean leghemoglobin a structures revealed that the major evolutionary changes that probably occurred during the evolution of plant Hbs were 1) a hexacoordinate to pentacoordinate transition at the heme prosthetic group, 2) a length decrease at the CD-loop and N- and C-termini regions, and 3) the compaction of the protein into a globular structure.
Reduced functional performance in the lower extremity predicted radiographic knee osteoarthritis five years later
Authors: C A Thorstensson, I F Petersson, L T H Jacobsson, T L Boegård, E M Roos
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Reduced quadriceps strength is an early finding in subjects with knee osteoarthritis, but it is not clear whether it is a cause or a consequence of knee osteoarthritis. <b>Objective:</b> To determine whether reduced functional performance in the lower extremity predicts the incidence or progression of radiographic knee osteoarthritis. <b>Design:</b> Prospective, epidemiological, population based cohort study. <b>Patients:</b> 148 subjects (62 women), aged 35–54 (mean 44.8), with chronic knee pain from a population based cohort. <b>Measurements:</b> Predictors analysed were age, sex, body mass index, baseline knee pain, and three tests of lower extremity functional performance: maximum number of one-leg rises from sitting, time spent walking 300 m, and timed standing on one leg. Weightbearing tibiofemoral knee radiographs were obtained at baseline and after 5 years (median 5.1, range 4.2–6.1), and classified according to Kellgren and Lawrence as no osteoarthritis (Kellgren and Lawrence = 0, n = 94) or prevalent osteoarthritis (Kellgren and Lawrence ⩾1, n = 54). <b>Results:</b> Fewer one-leg rises (median 17 <i>v</i> 25) predicted incident radiographic osteoarthritis five years later (OR 2.6, 95% CI 1.1 to 6.0). The association remained significant after controlling for age, sex, body mass index, and pain. No significant predictor of radiographic progression in the group with prevalent osteoarthritis was found. <b>Conclusion:</b> Reduced functional performance in the lower extremity predicted development of radiographic knee osteoarthritis 5 years later among people aged 35–55 with chronic knee pain and normal radiographs at baseline. These findings suggest that a test of one-leg rises may be useful, and interventions aimed at improving functional performance may be protective against development of knee osteoarthritis.
Mutations in the Phosphatidylinositol-3-Kinase Pathway Predict for Antitumor Activity of the Inhibitor PX-866 whereas Oncogenic Ras Is a Dominant Predictor for Resistance
Authors: Nathan T. Ihle, Robert Lemos, Peter Wipf, Adly Yacoub, Clint Mitchell, Doris Siwak, Gordon B. Mills, Paul Dent, D. Lynn Kirkpatrick, Garth Powis
Journal: Cancer Research (2008)

Abstract The novel phosphatidylinositol-3-kinase (PI3K) inhibitor PX-866 was tested against 13 experimental human tumor xenografts derived from cell lines of various tissue origins. Mutant PI3K (PIK3CA) and loss of PTEN activity were sufficient, but not necessary, as predictors of sensitivity to the antitumor activity of the PI3K inhibitor PX-866 in the presence of wild-type Ras, whereas mutant oncogenic Ras was a dominant determinant of resistance, even in tumors with coexisting mutations in PIK3CA. The level of activation of PI3K signaling measured by tumor phosphorylated Ser473-Akt was insufficient to predict in vivo antitumor response to PX-866. Reverse-phase protein array revealed that the Ras-dependent downstream targets c-Myc and cyclin B were elevated in cell lines resistant to PX-866 in vivo. Studies using an H-Ras construct to constitutively and preferentially activate the three best-defined downstream targets of Ras, i.e., Raf, RalGDS, and PI3K, showed that mutant Ras mediates resistance through its ability to use multiple pathways for tumorigenesis. The identification of Ras and downstream signaling pathways driving resistance to PI3K inhibition might serve as an important guide for patient selection as inhibitors enter clinical trials and for the development of rational combinations with other molecularly targeted agents. [Cancer Res 2009;69(1):143–50]
Radiation and Functional Diversification of Alpha Keratins during Early Vertebrate Evolution
Authors: W. Vandebergh, F. Bossuyt
Journal: Molecular Biology and Evolution (2011)

The conquest of land was arguably one of the most fundamental ecological transitions in vertebrates and entailed significant changes in skin structure and appendages to cope with the new environment. In extant tetrapods, the rigidity of the integument is largely created by type I and type II keratins, which are structural proteins essential in forming a strong cytoplasmic network. It is expected that such proteins have undergone fundamental changes in both stem and crown tetrapods. Here, we integrate genomic, phylogenetic, and expression data in a comprehensive study on the early evolution and functional diversification of tetrapod keratins. Our analyses reveal that all type I and type II tetrapod keratins evolved from only two genes that were present in the ancestor of extant vertebrates. Subsequently, the water-to-land transition in the stem lineage of tetrapods was associated with a major radiation and functional diversification of keratin genes. These duplications acquired functions that serve rigidity in integumental hard structures and were the prime for subsequent independent keratin diversification in tetrapod lineages.
Urban traffic and pollutant exposure related to respiratory outcomes and atopy in a large sample of children
Authors: T. Nicolai, D. Carr, S.K. Weiland, H. Duhme, O. von Ehrenstein, C. Wagner, E. von Mutius
Journal: European Respiratory Journal (2003)

Conflicting results have been reported for the relationship between traffic exposure and inception of atopy. The effect of traffic on the prevalence of asthma and atopy at school age was investigated in a representative population. Random samples of schoolchildren (n=7,509, response rate 83.7%) were studied using the International Study of Asthma and Allergies in Childhood phase­II protocol with skin­prick tests, measurements of specific immunoglobulin E and lung function. Traffic exposure was assessed via traffic counts and by an emission model which predicted soot, benzene and nitrogen dioxide (NO 2 ). Traffic counts were associated with current asthma, wheeze and cough. In children with tobacco­smoke exposure, traffic volume was additionally associated with a positive skin­prick test. Cough was associated with soot, benzene and NO 2 , current asthma with soot and benzene, and current wheeze with benzene and NO 2 . No pollutant was associated with allergic sensitisation. High vehicle traffic was associated with asthma, cough and wheeze, and in children additionally exposed to environmental tobacco smoke, with allergic sensitisation. However, effects of socioeconomic factors associated with living close to busy roads cannot be ruled out.
Radiofrequency ablation therapy in idiopathic left ventricular tachycardia with no obvious structural heart disease.
Authors: M S Wen, S J Yeh, C C Wang, F C Lin, I C Chen, D Wu
Journal: Circulation (1994)

BACKGROUND The feasibility and efficacy of radiofrequency ablation therapy in idiopathic left ventricular tachycardia has not been assessed in a large group of patients. METHODS AND RESULTS Twenty consecutive patients with idiopathic left ventricular tachycardia and without structural heart disease underwent electrophysiological study, pharmacological interventions with administration of verapamil and adenosine, and radiofrequency ablation therapy. There were 17 men and 3 women with a mean age of 28 +/- 8 years. The QRS configuration during tachycardia was of right bundle branch block and superior axis in 13 patients, indeterminate axis in 6 patients, and right axis in 1 patient. The tachycardia was electrically inducible and responsive to verapamil but not to adenosine. Thirteen patients demonstrated entrainment. Activation and pace-mapping studies disclosed that the tachycardia originated from the inferior apical septum in 15 patients, the midseptum in 4 patients, and the anterior lateral wall of the left ventricle in 1 patient. Radiofrequency ablation was successful in 17 of the 20 patients (85%). The successful ablation sites were characterized by an endocardial activation time 30 milliseconds earlier than the onset of QRS during tachycardia and by a pace-mapping QRS similar to or closely resembling the tachycardia. All patients displayed sharp spikes preceding the local ventricular electrogram at the ablation site. However, these sharp spikes also were noted in 15 control patients and were not specific for this tachycardia; they persisted after ablation. There were no complications. A follow-up of 7 +/- 8 months in the 17 successfully ablated patients showed no symptomatic tachyarrhythmias without medications. Six patients underwent repeat electrophysiological study, and no induction of tachycardia was revealed. CONCLUSIONS Radiofrequency ablation therapy is effective and safe in patients with idiopathic left ventricular tachycardia. It should be considered as the primary therapeutic modality in these patients.
Hypertrophy, Fibrosis, and Sudden Cardiac Death in Response to Pathological Stimuli in Mice With Mutations in Cardiac Troponin T
Authors: Alexander H. Maass, Kaori Ikeda, Silke Oberdorf-Maass, Sebastian K.G. Maier, Leslie A. Leinwand
Journal: Circulation (2004)

Background— Transgenic mouse models expressing a missense mutation (R92Q) or a splice donor site mutation (trunc) in the cardiac troponin T (cTnT) model familial hypertrophic cardiomyopathy (FHC) in humans. Although males from these strains share the unusual property of having significantly smaller ventricles and cardiac myocytes, they differ with regard to systolic function, fibrosis, and gene expression. Little is known about how these phenotypes affect the responses to additional pathological stimuli. Methods and Results— We tested the ability of hearts of both sexes of wild-type and mutant mice to respond to defined pathological, pharmacological, hypertrophic stimuli in vivo. Hearts of mutant cTnT models of both sexes were able to undergo hypertrophy in response to at least one stimulus, but the extent differed between the 2 mutants and was sex specific. Interestingly, the trunc-mutant mouse heart was resistant to the development of fibrosis in response to pharmacological stimuli. Stimulation with 2 adrenergic agonists led to sudden cardiac death of all male but not female mutant animals, which suggests altered adrenergic responsiveness in these 2 models of FHC. Conclusions— Hypertrophic signaling is differentially affected by distinct mutations in cTnT and is sex modified. Hearts can respond with either an augmented hypertrophic and fibrotic response or a diminished hypertrophy and resistance to fibrosis. Sudden cardiac death is related to adrenergic stress and is independent of the development of fibrosis but occurred only in male mice. These results suggest that patients with certain TnT mutations may respond to certain pathological situations with a worsened phenotype.
Renal ApoA-1 Amyloidosis with Glu34Lys Mutation and Intra-amyloid Lipid Accumulation
Authors: Nicole K. Andeen, Daniel Y. Lam, Ian H. de Boer, Roberto F. Nicosia
Journal: Journal of the American Society of Nephrology (2014)

Apolipoprotein A-1 (ApoA-1) amyloidosis occurs as a nonhereditary condition in atherosclerotic plaques, but it can also manifest as a hereditary disorder caused by mutations of the APOA1 gene. Hereditary ApoA-1 amyloidosis presents with diverse organ involvement based on the position of the mutation. We describe a case of ApoA-1 amyloidosis with a Glu34Lys mutation; testicular, conjunctival, and renal involvement; and the notable finding of lipid deposition within the amyloid deposits.
Regulation of Low Density Lipoprotein Receptor Function in a Human Hepatoma Cell Line
Authors: Alan M. Leichtner, Monty Krieger, Alan L. Schwartz
Journal: Hepatology (1984)

Low density lipoprotein (LDL) processing was investigated in a human hepatoma-derived cell line, Hep G2. Hep G2 cells bound, internalized and degraded LDL via a saturable, high affinity (Kd — 2 ± 10 −8 M ) pathway similar to that present in other mammalian cells. Although 80% of the uptake and degradation of 125 I-LDL was inhibited by 40-fold excess native LDL, the same concentration of methylated LDL, which cannot bind to LDL receptors, had virtually no effect on processing. When added at low concentrations, the lysosomotropic agent, chloroquine, inhibited degradation (I 50 — 15 μ M ) without affecting the rate of lipoprotein internalization. Receptor activity was decreased 60% by preincubation of the cells in medium containing a source of cholesterol (LDL or unesterified cholesterol) and increased 1.7-fold by preincubation with compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The Hep G2 cell line may prove a useful system both for the further study of hepatic lipoprotein metabolism and for the evaluation of new antihypercholesterolemic agents.
Cognitive Complaints After Breast Cancer Treatments: Examining the Relationship With Neuropsychological Test Performance
Authors: Patricia A. Ganz, Lorna Kwan, Steven A. Castellon, Amy Oppenheim, Julienne E. Bower, Daniel H. S. Silverman, Steve W. Cole, Michael R. Irwin, Sonia Ancoli-Israel, Thomas R. Belin
Journal: JNCI Journal of the National Cancer Institute (2013)

Cognitive complaints are reported frequently after breast cancer treatments. Their association with neuropsychological (NP) test performance is not well-established. Early-stage, posttreatment breast cancer patients were enrolled in a prospective, longitudinal, cohort study prior to starting endocrine therapy. Evaluation included an NP test battery and self-report questionnaires assessing symptoms, including cognitive complaints. Multivariable regression models assessed associations among cognitive complaints, mood, treatment exposures, and NP test performance. One hundred eighty-nine breast cancer patients, aged 21–65 years, completed the evaluation; 23.3% endorsed higher memory complaints and 19.0% reported higher executive function complaints (>1 SD above the mean for healthy control sample). Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments ( P = .01), poorer NP verbal memory performance ( P = .02), and higher depressive symptoms ( P < .001), controlling for age and IQ. For executive functioning complaints, multivariable modeling controlling for age, IQ, and other confounds demonstrated statistically significant associations with better NP visual memory performance ( P = .03) and higher depressive symptoms ( P < .001), whereas combined chemotherapy and radiation treatment ( P = .05) approached statistical significance. About one in five post–adjuvant treatment breast cancer patients had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints. These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance, although their etiology and biology appear to be multifactorial, motivating further transdisciplinary research.
Interleukin-1 receptor antagonist in pleural effusion due to inflammatory and malignant lung disease
Authors: H Yanagawa, S Yano, T Haku, Y Ohmoto, S Sone
Journal: European Respiratory Journal (1996)

Interleukin (IL)-1 is a key cytokine in inflammatory reactions. To clarify the mechanism of inflammation in the pleural cavity, we investigated the contribution of IL-1 and its antagonism to inflammatory processes in the pleural cavity. Interleukin-1 receptor antagonist (IL-1Ra) levels as well as IL-1 beta and interferon-gamma (IFN-gamma) levels were measured by enzyme immunoassay in pleural effusions from 70 patients. Pleural macrophages were also examined as possible sources of these cytokines in 10 patients. IL-1Ra was detectable in 28 patients (40%) out of 70 patients with pleural effusions. Patients with tuberculosis had significantly higher IL-1Ra as well as IFN-gamma levels in pleural effusion than patients with lung cancer. Transudative pleural effusions had low or undetectable IL-IRa levels. On the other hand, IL-1 beta levels were low, except in cases of parapneumonic pleural effusion. Spontaneous production of IL-1Ra pleural macrophages was observed in six patients, and IL-4 significantly augmented its production. Although spontaneous production of IL-1 beta was observed in only two patients, pleural macrophages produced significant amounts of IL-1 beta in response to lipopolysaccharide in all 10 patients examined. These results suggest that interleukin-1 receptor antagonist regulates various reactions by interleukin-1 in pleural effusion, and that pleural macrophages may act in situ as a source of interleukin-1 receptor antagonist.
Cellulose and the human gut.
Authors: J H Cummings
Journal: Gut (1984)

Cellulose and the human gut Cellulose consists of long unbranched chains of glucose, (1-4) a linked D-glucopyranose.In its pure form the straight chains are bound closely together by multiple intermolecular hydrogen bonds producing a water insoluble fibrous substance which is relatively inert.Modified celluloses such as ethyl and carboxymethyl derivatives, (widely used in the food industry), and methyl cellulose (which may.be prescribed as a laxative or as an appetite suppressant), have very different chemical properties from
Neighborhood Characteristics and Components of the Insulin Resistance Syndrome in Young Adults
Authors: Ana V. Diez Roux, David R. Jacobs, Catarina I. Kiefe
Journal: Diabetes Care (2002)

OBJECTIVE—To examine associations of neighborhood characteristics with six components of the insulin resistance syndrome (IRS) in young adults. RESEARCH DESIGN AND METHODS—Cross-sectional data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to examine associations of neighborhood characteristics with the IRS in 3,093 nondiabetic adults aged 28–40 years. Measures of BMI, fasting HDL cholesterol, triglycerides, insulin, glucose, and systolic blood pressure were combined into an IRS score. U.S. Census-derived neighborhood characteristics were summarized into a neighborhood socioeconomic score, with an increasing score signifying increasing socioeconomic advantage. RESULTS—Among white men and women, the IRS score was inversely related to neighborhood socioeconomic score. Neighborhood characteristics remained associated with the IRS score after controlling for personal income and education (adjusted mean differences for 95th vs. 5th percentile of neighborhood score: −0.24 standard deviation units [SE = 0.12] in men and −0.56 standard deviation units [SE = 0.10] in women). Among black participants, neighborhood score was inversely associated with IRS score in persons of high income and education (mean differences 95th vs. 5th percentile −0.54 [SE 0.26] in men and −0.52 [SE 0.26] in women) but positively associated or not associated with IRS score in persons of low income and education (mean differences 0.60 [SE 0.21] in men and 0.00 [SE 0.16] in women). CONCLUSIONS—The IRS score is associated with neighborhood characteristics as early as young adulthood. Features of residential environments may be related to the development of insulin resistance.
The Cell Cycle Factor E2F-1 Activates Bnip3 and the Intrinsic Death Pathway in Ventricular Myocytes
Authors: Natalia Yurkova, James Shaw, Karen Blackie, Danielle Weidman, Ravi Jayas, Bryan Flynn, Lorrie A. Kirshenbaum
Journal: Circulation Research (2007)

The cell cycle factor E2F-1 is known to regulate a variety of cellular processes including apoptosis. Previously we showed that disruption of Rb–E2F-1 complexes provoked apoptosis of postmitotic adult and neonatal ventricular myocytes; however, the underlying mechanism was undetermined. In this report, we show that E2F-1 provokes cell death of ventricular myocytes through a mechanism that directly impinges on the intrinsic death pathway. Furthermore, we show mechanistically that the hypoxia-inducible death factor Bnip3 is a direct transcriptional target of E2F-1 that is necessary and sufficient for E2F-1–induced cell death. Expression of E2F-1 resulted in a 4.9-fold increase ( P &lt;0.001) in nucleosomal DNA fragmentation and cell death by Hoechst 33258 dye and vital staining. E2F-1 provoked mitochondrial perturbations that were consistent with permeability transition pore opening. As determined by quantitative real-time PCR analysis, a 6.2-fold increase ( P &lt;0.001) in endogenous Bnip3 gene transcription was observed in cells expressing wild-type E2F-1 but not in cells expressing a mutation of E2F-1 defective for DNA binding. Rb, the principle regulator of cellular E2F-1 activity, was proteolytically cleaved and inactivated in ventricular myocytes during hypoxia. Consistent with the proteolytic cleavage of Rb, chromatin immunoprecipitation analysis revealed increased binding of E2F-1 to the Bnip3 promoter during hypoxia, a finding concordant with the induction of Bnip3 gene transcription. The Bnip3 homolog Nix/Bnip3L was unaffected in ventricular myocytes by either E2F-1 or hypoxia. Genetic knockdown of E2F-1 or expression of a caspase-resistant form of Rb suppressed basal and hypoxia-inducible Bnip3 gene transcription. Loss-of-function mutations of Bnip3 defective for mitochondrial membrane insertion or small interference RNA directed against Bnip3 suppressed cell death signals elicited by E2F-1. To our knowledge, the data provide the first direct evidence that activation of the intrinsic mitochondrial death pathway by E2F-1 is mutually dependent on and obligatorily linked to the transcriptional activation of Bnip3.