tbuckley/cabot-search huggingface dataset:
Changes in Rubisco Kinetics during the Evolution of C4 Photosynthesis in Flaveria (Asteraceae) Are Associated with Positive Selection on Genes Encoding the Enzyme
Authors: Maxim V. Kapralov, David S. Kubien, Inger Andersson, Dmitry A. Filatov
Journal: Molecular Biology and Evolution (2010)

Rubisco, the primary photosynthetic carboxylase, evolved 3-4 billion years ago in an anaerobic, high CO(2) atmosphere. The combined effect of low CO(2) and high O(2) levels in the modern atmosphere, and the inability of Rubisco to distinguish completely between CO(2) and O(2), leads to the occurrence of an oxygenation reaction that reduces the efficiency of photosynthesis. Among land plants, C(4) photosynthesis largely solves this problem by facilitating a high CO(2)/O(2) ratio at the site of Rubisco that resembles the atmosphere in which the ancestral enzyme evolved. The prediction that such conditions favor Rubiscos with higher kcat(CO2) and lower CO(2)/O(2) specificity (S(C/O)) is well supported, but the structural basis for the differences between C(3) and C(4) Rubiscos is not clear. Flaveria (Asteraceae) includes C(3), C(3)-C(4) intermediate, and C(4) species with kinetically distinct Rubiscos, providing a powerful system in which to study the biochemical transition of Rubisco during the evolution from C(3) to C(4) photosynthesis. We analyzed the molecular evolution of chloroplast rbcL and nuclear rbcS genes encoding the large subunit (LSu) and small subunit (SSu) of Rubisco from 15 Flaveria species. We demonstrate positive selection on both subunits, although selection is much stronger on the LSu. In Flaveria, two positively selected LSu amino acid substitutions, M309I and D149A, distinguish C(4) Rubiscos from the ancestral C(3) species and statistically account for much of the kinetic difference between the two groups. However, although Flaveria lacks a characteristic "C(4)" SSu, our data suggest that specific residue substitutions in the SSu are correlated with the kinetic properties of Rubisco in this genus.
The Decorin High Glucose Response Element and Mechanism of Its Activation in Human Mesangial Cells
Authors: NADIA ABDEL WAHAB, SUSAN PARKER, JEAN-DANIEL SRAER, ROGER M. MASON
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The decorin gene encodes a proteoglycan with putative structural and regulatory functions whose expression is markedly increased in human mesangial cells (HMC) exposed to high concentrations of glucose (15 to 30 mM). The gene has two promoters (P1 and P2) upstream of two alternative first exons. Transcripts driven by both promoters are present in HMC maintained in 4 mM D-glucose medium. After exposure to 30 mM D-glucose for 7 to 21 d, transcripts driven by P1 are markedly increased, whereas those driven by P2 decrease. Culture in 4 mM D-glucose medium containing transforming growth factor-β1 (TGF-β1) (1.25 ng/ml) has the same effect. However, addition of an excess of TGF-β neutralizing antibody to the 30 mM D-glucose cultures only partly suppressed increased decorin transcription from P1. In transformed HMC transfected with a reporter (p-SAEP) driven by P1 or P2, P1 activity increased twofold on treatment with either 30 mM D-glucose or TGF-β1 in 4 mM medium. P2 had little activity under any conditions. 5′ deletion of P1 showed that basal transcriptional activity lies within the proximal 378 bp, while the major high glucose and TGF-β response element is located in the -683 to -583-bp region. A putative cAMP response-like sequence (TGACGTTT) lies within this region. Electrophoretic mobility shift assays revealed the same pattern of multiple complexes between oligonucleotides containing this sequence and nuclear proteins extracted from HMC maintained in either 4 or 30 mM D-glucose conditions, but the latter were more prominent. cAMP response element binding protein (CREB) was identified as one transcription factor forming these complexes but other factors remain unidentified. Increased levels of phospho-(Ser 133) CREB were found in HMC exposed to 30 mM D-glucose. High glucose also activated and led to nuclear translocation of p42/44 mitogen-activated protein kinase and p38 mitogen-activated protein kinase, both of which can activate CREB by phosphorylation of serine 133.
Independent Effects of Residual Renal Function and Dialysis Adequacy on Actual Dietary Protein, Calorie, and Other Nutrient Intake in Patients on Continuous Ambulatory Peritoneal Dialysis
Authors: ANGELA YEE-MOON WANG, MANDY MAN-MEI SEA, RICKY IP, MAN-CHING LAW, KAI-MING CHOW, SIU-FAI LUI, PHILIP KAM-TAO LI, JEAN WOO
Journal: Journal of the American Society of Nephrology (2001)

Previous studies have suggested that the cross-sectional relationship observed between total solute clearance (Kt/V) and dietary protein intake (DPI) in patients undergoing dialysis is possibly mathematical in origin. A cross-sectional study on 242 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was performed to determine the differential effects of dialysis adequacy and residual renal function (RRF) on actual dietary intake. All patients underwent a 7-d food frequency questionnaire to quantify daily dietary protein, calorie (DCI), and other nutrient intake, subjective global assessment (SGA), and collection of 24-h dialysate and urine for total (PD and renal) Kt/V and RRF. Patients were categorized into three groups: I (n = 94), total Kt/V ≥1.7 and GFR >0.5 ml/min per 1.73 m2; II (n = 58), total Kt/V ≥1.7 but GFR <0.5 ml/min per 1.73 m2; and III (n = 90), total Kt/V <1.7. Sixty-nine percent versus 62% versus 42% of group I versus II versus III patients were well nourished according to SGA (P = 0.004). DPI (1.23 [0.47] versus 1.12 [0.49] versus 0.99 [0.40] g/kg per d; P = 0.002) and DCI (27.3 [8.9] versus 23.8 [8.6] versus 23.0 [8.2] kcal/kg per d; P = 0.002) showed significant decline across the three groups. Intake of other nutrients, including carbohydrate, fat, fatty acids, and cholesterol was higher for group I compared with groups II and III. Adjusting for age, gender, weight, and diabetes, every 1 ml/min per 1.73 m2 increase in GFR was associated with a 0.838-fold increase in DCI (95% confidence interval to interval, 0.279 to 1.397; P = 0.003) and a 0.041-fold increase in DPI (95% confidence interval, 0.009 to 0.072; P = 0.012), whereas every 0.25-unit increase in total (PD and renal) Kt/V was associated with a 0.570-fold increase in DCI (95% confidence interval, 0.049 to 1.092; P = 0.032) and a 0.052-fold increase in DPI (95% confidence interval, 0.023 to 0.081; P = 0.001). Greater small-solute clearances are associated with better dietary intake and better nutrition. The study confirmed significant and independent effect of RRF, but not PD solute clearance, on actual DPI, DCI, and other nutrient intake in patients on CAPD.
Assessment of Xenoestrogens Using Three Distinct Estrogen Receptors and the Zebrafish Brain Aromatase Gene in a Highly Responsive Glial Cell System
Authors: Yann Le Page, Martin Scholze, Olivier Kah, Farzad Pakdel
Journal: Environmental Health Perspectives (2005)

The brain cytochrome P450 aromatase (Aro-B) in zebrafish is expressed in radial glial cells and is strongly stimulated by estrogens (E2); thus, it can be used in vivo as a biomarker of xenoestrogen effects on the central nervous system. By quantitative real-time polymerase chain reaction, we first confirmed that the expression of Aro-B gene is robustly stimulated in juvenile zebrafish exposed to several xenoestrogens. To investigate the impact of environmental estrogenic chemicals on distinct estrogen receptor (ER) activity, we developed a glial cell-based assay using Aro-B as the target gene. To this end, the ER-negative glial cell line U251-MG was transfected with the three zebrafish ER subtypes and the Aro-B promoter linked to a luciferase reporter gene. E2 treatment of U251-MG glial cells cotransfected with zebrafish ER-alpha and the Aro-B promoter-luciferase reporter resulted in a 60- to 80-fold stimulation of luciferase activity. The detection limit was <0.05 nM, and the EC50 (median effective concentration) was 1.4 nM. Interestingly, in this glial cell context, maximal induction achieved with the Aro-B reporter was three times greater than that observed with a classical estrogen-response-element reporter gene (ERE-tk-Luc). Dose-response analyses with ethynylestradiol (EE2), estrone (E1), alpha-zeralenol, and genistein showed that estrogenic potency of these agents markedly differed depending on the ER subtype in the assay. Moreover, the combination of these agents showed an additive effect according to the concept of concentration addition. This confirmed that the combined additive effect of the xenoestrogens leads to an enhancement of the estrogenic potency, even when each single agent might be present at low effect concentrations. In conclusion, we demonstrate that our bioassay provides a fast, reliable, sensitive, and efficient test for evaluating estrogenic potency of endocrine disruptors on ER subtypes in a glial context.
Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy
Authors: Fadi G. Akar, David D. Spragg, Richard S. Tunin, David A. Kass, Gordon F. Tomaselli
Journal: Circulation Research (2004)

Heart Failure (HF) is associated with an increased risk of sudden death caused by ventricular tachyarrhythmias. Recent studies have implicated repolarization abnormalities and, in particular, exaggerated heterogeneity of transmural repolarization in the genesis of polymorphic ventricular tachycardia in a canine model of nonischemic dilated cardiomyopathy. The presence and degree to which conduction abnormalities play a role in arrhythmogenesis in this model are uncertain. HF was produced in dogs by rapid RV-pacing for 3 to 4 weeks. High-resolution optical action potentials were recorded from epicardial and endocardial surfaces of arterially perfused canine wedge preparations isolated from LV and RV of normal and failing dogs. Cellular and molecular determinants of conduction were investigated using patch-clamp recordings, Western blot analysis, and immunocytochemistry. HF was associated with marked prolongation (by 33%) of the QRS duration of the volume conducted electrocardiogram and significant (>20%) slowing of epicardial and endocardial conduction velocities (CV) in both LV and RV. Cx43 expression was reduced by >40% in epicardial and endocardial layers of the LV, but was unchanged in the RV of failing hearts. Despite greater epicardial than endocardial Cx43 expression, epicardial CV was consistently slower (P<0.01). Immunocytochemical analysis revealed predominant colocalization of Cx43 with N-cadherin in normal versus failing samples, because Cx43 was redistributed from the intercalated disk to lateral cell borders in failing tissue. Moreover, a significant (P<0.05) increase in hypophosphorylated Cx43 was detected in the LV and RV of failing hearts. Action potential upstroke velocities in isolated ventricular myocytes from normal and failing hearts were not different (P=0.8, not significant), and Masson trichrome staining revealed no significant change in fibrosis content in HF. Nonischemic dilated cardiomyopathy is associated with significant slowing of CV that was not directly related to reduced Cx43 expression. Changes in phosphorylation and localization of Cx43 may contribute to gap-junction dysfunction, CV slowing, and arrhythmias in HF.
EVALUATION OF THE RESULTS OF PSYCHOANALYTIC THERAPY
Authors: ROBERT P. KNIGHT
Journal: American Journal of Psychiatry (1941)

In this study, the writer has attempted to discuss and summarize the difficulties involved in reporting results of psychoanalytic therapy, presenting the valid and invalid reasons usually involved in preventing the publication of therapeutic results, and has made a plea for and suggestions regarding, standard diagnostic criteria and standard criteria for evaluating the outcome of treatment. A total of 952 cases in which analysis was attempted are listed by diagnosis and therapeutic result. These figures demonstrate, the writer believes, that psychoanalysis must be adjudged an effective therapy for the psychoneuroses, sexual disorders and organ neuroses, and a therapy of some promise in the more difficult field of addictions and psychoses.
Doctors are urged to encourage patients to be more active to reduce chronic ill health
Authors: S. Mayor
Journal: BMJ (2015)

Doctors in the United Kingdom have been urged to encourage patients to take small amounts of regular exercise and told that they have a leading role to play in reversing the growing contribution of sedentary lifestyles to chronic ill health.

More than 40% of adults do not reach the minimum recommended level of 30 minutes of moderately intense exercise five times a week, figures reviewed in the Academy of Medical Royal Colleges’ report showed.1

The …
Genomic Analysis Using High-Density Single Nucleotide Polymorphism-Based Oligonucleotide Arrays and Multiplex Ligation-Dependent Probe Amplification Provides a Comprehensive Analysis of <i>INI1/SMARCB1</i> in Malignant Rhabdoid Tumors
Authors: Eric M. Jackson, Angela J. Sievert, Xiaowu Gai, Hakon Hakonarson, Alexander R. Judkins, Laura Tooke, Juan Carlos Perin, Hongbo Xie, Tamim H. Shaikh, Jaclyn A. Biegel
Journal: Clinical Cancer Research (2009)

A high-resolution genomic profiling and comprehensive targeted analysis of INI1/SMARCB1 of a large series of pediatric rhabdoid tumors was done. The aim was to identify regions of copy number change and loss of heterozygosity (LOH) that might pinpoint additional loci involved in the development or progression of rhabdoid tumors and define the spectrum of genomic alterations of INI1 in this malignancy.
New Autophagy Reporter Mice Reveal Dynamics of Proximal Tubular Autophagy
Authors: Ling Li, Zhao V. Wang, Joseph A. Hill, Fangming Lin
Journal: Journal of the American Society of Nephrology (2013)

The accumulation of autophagosomes in postischemic kidneys may be renoprotective, but whether this accumulation results from the induction of autophagy or from obstruction within the autophagic process is unknown. Utilizing the differential pH sensitivities of red fluorescent protein (RFP; pKa 4.5) and enhanced green fluorescent protein (EGFP; pKa 5.9), we generated CAG-RFP-EGFP-LC3 mice to distinguish early autophagic vacuoles from autolysosomes. In vitro and in vivo studies confirmed that in response to nutrient deprivation, renal epithelial cells in CAG-RFP-EGFP-LC3 mice produce autophagic vacuoles expressing RFP and EGFP puncta. EGFP fluorescence diminished substantially in the acidic environment of the autolysosomes, whereas bright RFP signals remained. Under normal conditions, nephrons expressed few EGFP and RFP puncta, but ischemia-reperfusion injury (IRI) led to dynamic changes in the proximal tubules, with increased numbers of RFP and EGFP puncta that peaked at 1 day after IRI. The number of EGFP puncta returned to control levels at 3 days after IRI, whereas the high levels of RFP puncta persisted, indicating autophagy initiation at day 1 and autophagosome clearance during renal recovery at day 3. Notably, proliferation decreased in cells containing RFP puncta, suggesting that autophagic cells are less likely to divide for tubular repair. Furthermore, 87% of proximal tubular cells with activated mechanistic target of rapamycin (mTOR), which prevents autophagy, contained no RFP puncta. Conversely, inhibition of mTOR complex 1 induced RFP and EGFP expression and decreased cell proliferation. In summary, our results highlight the dynamic regulation of autophagy in postischemic kidneys and suggest a role of mTOR in autophagy resolution during renal repair.
A pilot study for markers which can reflect asthmatic activity before and after reduction of inhaled corticosteroids
Authors: Koichiro Takahashi, Go Kato, Shinichiro Hayashi
Journal: European Respiratory Journal (2013)

Background; Evaluation of airway inflammation is important in achieving adequate dosing of ICS in the treatment of bronchial asthma. However, evaluation tools which can be used in actual clinical setting still remain to be established.  Methods; This is a 12-weeks, single arm, open label clinical study performed at a single university hospital. Twenty five patients, 6 male and 19 female, with stable asthma were included in this study. The primary endpoint was to investigate whether higher levels of nitrite and nitrate in exhaled breath condensate (EBC) will be associated with unstable control after ICS reduction. Blood eosinophils, serum IgE, hs-CRP, IL-13, IL-17 and periostin were also examined. We judged following status as unstable; unscheduled visit due to asthmatic symptom, declined week average PEF more than 10%.  Results; Unstable status was detected in 5 of 25 patients. Age, sex, asthma duration, the score of ACT and AQLQ were not different between both groups. The concentration of nitrite (7.87 mmol/l vs 1.84 mmol/l) and nitrate (2.59 mmol/l vs 1.27 mmol/l) in EBC at the first visit were higher in unstable group than those in stable group, while the difference did not reach significant level. The peripheral blood eosinophil count (536.8/ml vs 362.3/ml, p  Conclusion; An attention should be paid when we reduce ICS of stable asthmatic patients who have wide diurnal of PEF, higher peripheral blood eosinophil and higher periostin.
Activation of Notch-Mediated Protective Signaling in the Myocardium
Authors: Natalie A. Gude, Gregory Emmanuel, Weitao Wu, Christopher T. Cottage, Kimberlee Fischer, Pearl Quijada, John A. Muraski, Roberto Alvarez, Marta Rubio, Eric Schaefer, Mark A. Sussman
Journal: Circulation Research (2008)

The Notch network regulates multiple cellular processes, including cell fate determination, development, differentiation, proliferation, apoptosis, and regeneration. These processes are regulated via Notch-mediated activity that involves hepatocyte growth factor (HGF)/c-Met receptor and phosphatidylinositol 3-kinase/Akt signaling cascades. The impact of HGF on Notch signaling was assessed following myocardial infarction as well as in cultured cardiomyocytes. Notch1 is activated in border zone cardiomyocytes coincident with nuclear c-Met following infarction. Intramyocardial injection of HGF enhances Notch1 and Akt activation in adult mouse myocardium. Corroborating evidence in cultured cardiomyocytes shows treatment with HGF or insulin increases levels of Notch effector Hes1 in immunoblots, whereas overexpression of activated Notch intracellular domain prompts a 3-fold increase in phosphorylated Akt. Infarcted hearts injected with adenoviral vector expressing Notch intracellular domain treatment exhibit improved hemodynamic function in comparison with control mice after 4 weeks, implicating Notch signaling in a cardioprotective role following cardiac injury. These results indicate Notch activation in cardiomyocytes is mediated through c-Met and Akt survival signaling pathways, and Notch1 signaling in turn enhances Akt activity. This mutually supportive crosstalk suggests a positive survival feedback mechanism between Notch and Akt signaling in adult myocardium following injury.
Renal Function, Digoxin Therapy, and Heart Failure Outcomes
Authors: Michael G. Shlipak, Grace L. Smith, Saif S. Rathore, Barry M. Massie, Harlan M. Krumholz
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Renal dysfunction is a common complication for patients with heart failure, but its association with clinical outcomes has not been fully characterized. We evaluated the association of glomerular filtration rate (GFR) with heart failure survival and the effect of digoxin on heart failure outcomes across GFR strata. A secondary analysis from the Digitalis Intervention Group trial was conducted of 6800 outpatients with systolic heart failure. Renal function was categorized as estimated GFR (expressed in ml/min per 1.73 m2). All-cause mortality (mean, 3 yr) was inversely proportional to GFR (GFR >60, 31% mortality; GFR 30 to 60, 46% mortality; GFR <30, 62% mortality; P < 0.001). Among patients with a GFR <50, lower GFR were associated with greater adjusted mortality risk (GFR <30: hazard ratio [HR], 2.06, 95% confidence interval [CI], 1.69 to 2.51; GFR 30 to 40: HR, 1.42, 95% CI, 1.22 to 1.67; GFR 40 to 50: HR, 1.22, 95% CI, 1.07 to 1.39; GFR 50 to 60: HR, 1.00, referent). In contrast, participants with GFR 60 to 70 had similar risk (HR, 1.00; 95% CI, 0.88 to 1.14) compared with GFR 50 to 60, and those with GFR >70 had a slightly lower mortality hazard (0.89; 95% CI, 0.78 to 1.00). Linear spline analyses confirmed that GFR = 50 was the appropriate risk threshold; above 50, GFR had no association with mortality, whereas below 50, mortality risk increased sharply with declining GFR (spline coefficient, P < 0.0001). Digoxin efficacy did not differ by level of GFR (P = 0.19 for interaction). Renal dysfunction is strongly associated with mortality in stable outpatients with heart failure, notably in patients with estimated GFR <50 ml/min per 1.73 m2. The effect of digoxin did not differ by level of renal function.
Effect of training on patient outcomes following lobectomy
Authors: N Chaudhuri
Journal: Thorax (2006)

<b>Background:</b> Little is known about the effect of surgical training on outcomes in thoracic surgery. The impact of surgeon training on outcomes following lung resection was examined, focusing on lobectomy as a marker operation. <b>Methods:</b> 328 consecutive patients who underwent lobectomy at our institution between 1 October 2001 and 30 June 2003 were studied. Data were collected prospectively during the patient’s admission as part of routine clinical practice and validated by a designated audit officer. Patient characteristics and postoperative outcomes were compared between trainee led and consultant led operations. <b>Results:</b> In 115 cases (35.1%) the operation was performed by a trainee thoracic surgeon as the first operator. There were no significant differences in patient characteristics between the two groups. In-hospital mortality was similar for operations led by trainees and consultants (3.5% and 2.8%, respectively; p&gt;0.99). Outcomes in the two groups did not differ significantly with respect to respiratory, cardiovascular, renal, neurological, chest infection, bleeding, and gastrointestinal complications. Survival rates at 1 year were 82.6% for procedures led by trainees compared with 81.7% for procedures led by consultants (p = 0.83). <b>Conclusions:</b> With appropriate supervision, trainee thoracic surgeons can perform lobectomies safely without compromising short or intermediate term patient outcome.
Normal First Heart Sounds with Nonfunctional Tricuspid Valve or Right Ventricle
Authors: ALDO A. LUISADA, HARRY KURZ, SHELDON J. SLODKI, DONALD M. MACCANON, BERNARDO KROL, I. Harvey
Journal: Circulation (1967)

A case of Ebstein's malformation of the tricuspid valve with persistent foramen secundum and right bundle-branch block is presented. Preoperative tracings revealed three distinct components of the first sound with normal intervals between them. After resection of a single floating tricuspid leaflet, closure of the septal defect, and insertion of a Starr-Edwards valve, the phonocardiogram again showed three normal components of the first heart sound, followed by a loud closing snap of the prosthetic tricuspid valve. This case demonstrates the occurrence of the three normal components of the first heart sound independently of right ventricular contraction and of tricuspid closure or tensing. In five dogs left ventricular phonocardiograms, made after right heart bypass and destruction of the free ventricular wall, revealed three normal components of the first heart sounds in three animals, and of the first two components, separated by normal intervals in two others. These experiments exclude any participation of the right ventricle or tricuspid valve in the mechanism of origin of the first heart sound. The authors conclude that the three normal components of the first heart sound are of left-sided origin and that the designation "tricuspid" for the second component should be abandoned.