tbuckley/cabot-search huggingface dataset:
The Complete Mitochondrial DNA Sequence of the Green Alga Pseudendoclonium akinetum (Ulvophyceae) Highlights Distinctive Evolutionary Trends in the Chlorophyta and Suggests a Sister-Group Relationship Between the Ulvophyceae and Chlorophyceae
Authors: J.-F. Pombert
Journal: Molecular Biology and Evolution (2004)

The mitochondrial genome has undergone radical changes in both the Chlorophyta and Streptophyta, yet little is known about the dynamics of mtDNA evolution in either of these lineages. In the Chlorophyta, which comprises four of the five recognized classes of green algae (Prasinophyceae, Trebouxiophyceae, Ulvophyceae, and Chlorophyceae), the mitochondrial genome varies from 16 to 55 kb. This genome has retained a compact gene organization and a relatively complex gene repertoire ("ancestral" pattern) in the basal lineages represented by the Trebouxiophyceae and Prasinophyceae, whereas it has been reduced in size and gene complement and tends to evolve much more rapidly at the sequence level ("reduced-derived" pattern of evolution) in the Chlorophyceae and the lineage leading to the enigmatic chlorophyte Pedinomonas. To gain information about the evolutionary trends of mtDNA in the Ulvophyceae and also to gain insights into the phylogenetic relationships between ulvophytes and other chlorophytes, we have determined the mtDNA sequence of Pseudendoclonium akinetum. At 95,880 bp, Pseudendoclonium mtDNA is the largest green-algal mitochondrial genome sequenced to date and has the lowest gene density. These derived features are reminiscent of the "expanded" pattern exhibited by embryophyte mtDNAs, indicating that convergent evolution towards genome expansion has occurred independently in the Chlorophyta and Streptophyta. With 57 conserved genes, the gene repertoire of Pseudendoclonium mtDNA is slightly smaller than those of the prasinophyte Nephroselmis olivacea and the trebouxiophyte Prototheca wickerhamii. This ulvophyte mtDNA contains seven group I introns, four of which have homologs in green-algal mtDNAs displaying an "ancestral" or a "reduced-derived" pattern of evolution. Like its counterpart in the chlorophycean green alga Scenedesmus obliquus, it features numerous small, dispersed repeats in intergenic regions and introns. Its overall rate of sequence evolution appears to be accelerated to an intermediary level as compared with the rates observed in "ancestral" and "reduced-derived" mtDNAs. In agreement with the finding that Pseudendoclonium mtDNA exhibits features typical of both the "ancestral" and "reduced-derived" patterns of evolution, phylogenetic analyses of seven mtDNA-encoded proteins revealed a sister-group relationship between this ulvophyte and chlorophytes displaying "reduced-derived" mtDNAs.
Effect of ON 01910.Na, an Anticancer Mitotic Inhibitor, on Cell-Cycle Progression Correlates with RanGAP1 Hyperphosphorylation
Authors: Irina A. Oussenko, James F. Holland, E. Premkumar Reddy, Takao Ohnuma
Journal: Cancer Research (2011)

The benzyl styryl sulfone, ON 01910.Na, is a novel anticancer agent that inhibits mitotic progression and induces apoptosis in most cancer cell lines. We examined the effect of ON 01910.Na on DNA damage-signaling molecules upstream of Cdc25C (Chk1, Chk2, and H2AX), as well as on Ran GTPase-activating protein 1 conjugated to small ubiquitin-related modifier 1 (RanGAP1·SUMO1), a mitosis coordinator. Prostate cancer, lymphoma, and leukemic cells were incubated with the drug for 4, 16, or 24 hours. Cell lysates were resolved on SDS-PAGE and analyzed by Western blot. Camptothecin and doxorubicin treatment caused activation/phosphorylation of DNA damage-responsive molecules by 4 hours, whereas ON 01910.Na did not do so. ON 01910.Na caused hyperphosphorylation of RanGAP1·SUMO1 within 4 hours that was sustained for more than 24 hours. Mild phosphorylation of Chk2 was observed only after 24-hour exposure, indicating that DNA damage response was not an initial effect of ON 01910.Na. MOLT-3 cells, synchronized by double-thymidine block, when released into a medium containing ON 01910.Na, accumulated mitotic cell number with a peak from 10 to 14 hours and remained near plateau for 20 hours, which corresponded with the time of RanGAP phosphorylation. ON 01910.Na had minimal effects on tubulin polymerization. These findings imply that ON 01910.Na neither induces DNA damage directly nor acts as a tubulin toxin. Its biological activity appears to rely on prolonged phosphorylation/hyperphosphorylation of RanGAP1·SUMO1. M-phase arrest and the consequent induction of apoptosis that follows could possibly be attributed to it. ON 01910.Na may act as an inhibitor of a RanGAP1·SUMO1 phosphatase or a stimulant of a new kinase. RanGAP1·SUMO1 appears to be a new target pathway for cancer chemotherapy.
Visfatin Response to Glucose Is Reduced in Women With Gestational Diabetes Mellitus
Authors: Dominik G. Haider, Ammon Handisurya, Angela Storka, Elena Vojtassakova, Anton Luger, Giovanni Pacini, Andrea Tura, Michael Wolzt, Alexandra Kautzky-Willer
Journal: Diabetes Care (2007)

Abstract The insulin-mimetic adipocytokine visfatin has been associated with insulin resistance in some studies and is regulated by glucose. We hypothesized that glucose-induced changes in plasma visfatin are different in women with gestational diabetes mellitus (GDM). Plasma visfatin concentrations were studied in 10 women with GDM and 10 age-matched healthy women in pregnancy week 24-28 during a standard oral glucose tolerance test (OGTT). Women with GDM had lower systemic visfatin concentrations than controls (1.9±0.8 ng/ml vs 5.2±4.4 ng/ml, respectively, p<0.05), which were associated with fasting glucose (p<0.05). The glucose-induced increase in visfatin over baseline was smaller in GDM, with an area under the curve of 409±106 ng/ml*min versus 780±345 ng/ml*min in controls (p<0.05). Reduced glucose-induced increases in circulating visfatin may be associated with impaired glucose tolerance in women with GDM.
Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy
Authors: Hyun Hor, Zoltán Kutalik, Yves Dauvilliers, Armand Valsesia, Gert J Lammers, Claire E H M Donjacour, Alex Iranzo, Joan Santamaria, Rosa Peraita Adrados, José L Vicario, Sebastiaan Overeem, Isabelle Arnulf, Ioannis Theodorou, Poul Jennum, Stine Knudsen, Claudio Bassetti, Johannes Mathis, Michel Lecendreux, Geert Mayer, Peter Geisler, Antonio Benetó, Brice Petit, Corinne Pfister, Julie Vienne Bürki, Gérard Didelot, Michel Billiard, Guadalupe Ercilla, Willem Verduijn, Frans H J Claas, Peter Vollenweider, Gerard Waeber, Dawn M Waterworth, Vincent Mooser, Raphaël Heinzer, Jacques S Beckmann, Sven Bergmann, Mehdi Tafti
Journal: Nature Genetics (2010)
Phenotypic predictors for hospital admission in adults with asthma: A case-controlled study
Authors: Josef Micallef, Eleanor Gerada, Richard Pullicino, Mariana Gauci, Steven Montefort
Journal: European Respiratory Journal (2012)

Background:  RTIs are a known risk factor for admission with asthma exacerbation. Few studies give further insight to other possible risk factors.   Aim:  To correlate asthma phenotypes with hospitalisation, in acute exacerbations of asthma.   Methods:  We included 100 asthmatics admitted with an acute exacerbation over 14 months; matched for age and sex with a 100 well-controlled asthmatics from asthma clinic. Information on sociodemographic variables, clinical and laboratory data was collected. Acute and convalescent (at 6 weeks) titres of serum immunoglobulin E (Se Ig E) and serum eosinophil count were taken. SPSS was used for statistical analysis.   Results:  We detected a positive correlation between age of asthma onset and a history of atopy (p 0.05). There was no significant difference in the number of hospitalisations over the previous year between smokers and non-smokers (p=0.308). The difference between convalescent Se IgE levels in males (mean 324) and females (mean 159) was statistically significant (p=0.029). Acute Se Ig E levels and eosinophils were found to be positively correlated (p=0.027), however, no correlation was established between acute or convalescent Se IgE and duration of asthma, personal or family history of atopy (p>0.05). There is no significant difference between Se IgE levels in different BMI classes or in different age groups (p>0.05).   Conclusions:  Asthma exacerbation is more likely in those who are atopic and have a longer duration of asthma. This was not evident for smoking asthmatics and BMI. Convalescent Ig E levels are higher in males post exacerbation.
Deletion of interleukin (IL)-12p35 induces liver fibrosis in dominant-negative TGFβ receptor type II mice
Authors: Masanobu Tsuda, Weici Zhang, Guo-Xiang Yang, Koichi Tsuneyama, Yugo Ando, Kazuhito Kawata, Ogyi Park, Patrick S.C. Leung, Ross L. Coppel, Aftab A. Ansari, William M. Ridgway, Bin Gao, Zhe-Xiong Lian, Richard Flavell, Xiao-Song He, Eric M. Gershwin
Journal: Hepatology (2012)

Mice with a dominant-negative transforming growth factor β receptor restricted to T cells (dnTGFβRII mice) develop an inflammatory biliary ductular disease that strongly resembles human primary biliary cirrhosis (PBC). Furthermore, deletion of the gene encoding interleukin (IL)-12p40 resulted in a strain (IL-12p40−/−dnTGFβRII) with dramatically reduced autoimmune cholangitis. To further investigate the role of the IL-12 cytokine family in dnTGFβRII autoimmune biliary disease, we deleted the gene encoding the IL-12p35 subunit from dnTGFβRII mice, resulting in an IL-12p35−/− dnTGFβRII strain which is deficient in two members of the IL-12 family, IL-12 and IL-35. In contrast to IL-12p40−/− mice, the IL-12p35−/−mice developed liver inflammation and bile duct damage with similar severity but delayed onset as the parental dnTGFβRII mice. The p35−/− mice also demonstrated a distinct cytokine profile characterized by a shift from a T-helper 1 (Th1) to a Th17 response. Strikingly, liver fibrosis was frequently observed in IL-12p35−/− mice. In conclusion, IL-12p35−/− dnTGFβRII mice, histologically and immunologically, reflect key features of PBC, providing a useful generic model to understand the immunopathology of human PBC.
Wnt Inhibitor Screen Reveals Iron Dependence of β-Catenin Signaling in Cancers
Authors: Siyuan Song, Tania Christova, Stephen Perusini, Solmaz Alizadeh, Ren-Yue Bao, Bryan W. Miller, Rose Hurren, Yulia Jitkova, Marcela Gronda, Methvin Isaac, Babu Joseph, Ratheesh Subramaniam, Ahmed Aman, Anh Chau, Donna E. Hogge, Scott J. Weir, James Kasper, Aaron D. Schimmer, Rima Al-awar, Jeff L. Wrana, Liliana Attisano
Journal: Cancer Research (2011)

Excessive signaling from the Wnt pathway is associated with numerous human cancers. Using a high throughput screen designed to detect inhibitors of Wnt/β-catenin signaling, we identified a series of acyl hydrazones that act downstream of the β-catenin destruction complex to inhibit both Wnt-induced and cancer-associated constitutive Wnt signaling via destabilization of β-catenin. We found that these acyl hydrazones bind iron in vitro and in intact cells and that chelating activity is required to abrogate Wnt signaling and block the growth of colorectal cancer cell lines with constitutive Wnt signaling. In addition, we found that multiple iron chelators, desferrioxamine, deferasirox, and ciclopirox olamine similarly blocked Wnt signaling and cell growth. Moreover, in patients with AML administered ciclopirox olamine, we observed decreased expression of the Wnt target gene AXIN2 in leukemic cells. The novel class of acyl hydrazones would thus be prime candidates for further development as chemotherapeutic agents. Taken together, our results reveal a critical requirement for iron in Wnt signaling and they show that iron chelation serves as an effective mechanism to inhibit Wnt signaling in humans.
Collagen–phosphorylcholine interpenetrating network hydrogels as corneal substitutes
Authors: Wenguang Liu, Chao Deng, Christopher R. McLaughlin, Per Fagerholm, Neil S. Lagali, Belinda Heyne, Juan C. Scaiano, Mitchell A. Watsky, Yasuhiro Kato, Rejean Munger, Naoshi Shinozaki, Fengfu Li, May Griffith
Journal: Biomaterials (2008)
Comparison of bran, ispaghula, and lactulose on colon function in diverticular disease.
Authors: M A Eastwood, A N Smith, W G Brydon, J Pritchard
Journal: Gut (1978)

<h3>Abstract</h3> Learning invariance across a set of transformations is an important step in mapping high-dimensional inputs to a limited number of classes. After understanding the set of\ invariances, can a new class be learned from one element? We propose a representation which can facilitate such learning: if the variability in representing individual elements across trials aligns with the variability among different elements in a class, then class boundaries learned from the variable representations of one element should be representative of the entire class. In this study, we test whether such a representation occurs in mouse visual systems. We use Neuropixels probes recording single unit activity in mice observing 200 repeats of natural movies taken from a set of 9 continuous clips. We observe that the trial-by-trial variability in the representation of individual frames is well aligned to the variability in representation of multiple frames from the same clip, but not well aligned to the variability among frames from different clips. Thus, the variable representations of images in the mouse cortex can be efficiently used to classify images into their clips. We compare these representations to those in artificial neural networks. We find that, when introducing noise in networks trained for classification (both feed-forward and recurrent networks), the variability in the representation of elements aligns with the in-class variance. The networks which best reproduce the in-vivo observed directions of variability were those trained on a hierarchical classification task. Taken together, these results point to a solution which the cortex can use for one-shot learning of a class: by using noise as a mechanism for generalization. This is a potential computational explanation for the high level of noise observed in the cortex.
Omeprazole induces altered bile acid metabolism
Authors: K Shindo, M Machida, M Fukumura, K Koide, R Yamazaki
Journal: Gut (1998)

It has been reported that the acidity of gastric contents could be an important factor in regulating jejunal flora.To investigate the effects of omeprazole induced changes in gastric pH on jejunal flora and bile acid metabolism.Twenty one patients with gastric ulcer and 19 healthy volunteers were studied. Deconjugation of bile acids was detected using a bile acid breath test. Jejunal fluid was aspirated using a double lumen tube with a rubber cover on the tip and deconjugation was examined using thin layer chromatography. Fat malabsorption was detected by a triolein breath test.In the bile acid breath test, expired breath samples from all patients and healthy volunteers showed significantly greater 14CO2 specific activity after omeprazole treatment (20 mg/day) than before treatment. Bacterial overgrowth was found in the jejunal fluid and gastric juice of both ulcer patients and healthy volunteers after omeprazole treatment. The following species were identified: Escherichia coli, Candida albicans, enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uniformis, Eubacterium lentum, Eu parvum, and Corynebacterium granulosum. All of these species, except E coli and C albicans, deconjugate bile acids. There was a significant correlation between 14CO2 activity and gastric pH, both before and after omeprazole treatment in both groups. The triolein breath test revealed impaired fat absorption in both groups after omeprazole treatment.Both patients with gastric ulcer and healthy volunteers exhibited increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum and fat malabsorption after omeprazole treatment. The bacterial over-growth consisted of both anaerobes and aerobes with deconjugation ability and was probably associated with an omeprazole induced shift to neutral pH in the gastric juice.
Neuronal Nitric Oxide Synthase Protects Against Myocardial Infarction-Induced Ventricular Arrhythmia and Mortality in Mice
Authors: Dylan E. Burger, Xiangru Lu, Ming Lei, Fu-Li Xiang, Lamis Hammoud, Mao Jiang, Hao Wang, Douglas L. Jones, Stephen M. Sims, Qingping Feng
Journal: Circulation (2009)

Background— Neuronal nitric oxide synthase (nNOS) is expressed in cardiomyocytes and plays a role in regulating cardiac function and Ca 2+ homeostasis. However, the role of nNOS in cardiac electrophysiology after myocardial infarction (MI) is unclear. We hypothesized that nNOS deficiency increases ventricular arrhythmia and mortality after MI. Methods and Results— MI was induced in wild-type (WT) or nNOS −/− mice by ligation of the left coronary artery. Thirty-day mortality was significantly higher in nNOS −/− compared with WT mice. Additionally, nNOS −/− mice had impaired cardiac function 2 days after MI. Telemetric ECG monitoring showed that compared with WT, nNOS −/− mice had significantly more ventricular arrhythmias and were more likely to develop ventricular fibrillation after MI. Treatment with the L-type Ca 2+ channel blocker verapamil reduced the incidence of arrhythmia and ventricular fibrillation in nNOS −/− mice after MI. To assess the role of nNOS in Ca 2+ handling, patch-clamp and Ca 2+ fluorescence techniques were used. Ca 2+ transients and L-type Ca 2+ currents were higher in nNOS −/− compared with WT cardiomyocytes. Additionally, nNOS −/− cardiomyocytes exhibited significantly higher systolic and diastolic Ca 2+ over a range of pacing frequencies. Treatment with the NO donor S -nitroso N -acetyl-penicillamine decreased Ca 2+ transients and L-type Ca 2+ current in both nNOS −/− and WT cardiomyocytes. Furthermore, S -nitrosylation of Ca 2+ handling proteins was significantly decreased in nNOS −/− myocardium after MI. Conclusions— Deficiency in nNOS increases ventricular arrhythmia and mortality after MI in mice. The antiarrhythmic effect of nNOS involves inhibition of L-type Ca 2+ channel activity and regulation of Ca 2+ handling proteins via S -nitrosylation.
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis
Authors: Edor Kabashi, Paul N Valdmanis, Patrick Dion, Dan Spiegelman, Brendan J McConkey, Christine Vande Velde, Jean-Pierre Bouchard, Lucette Lacomblez, Ksenia Pochigaeva, Francois Salachas, Pierre-Francois Pradat, William Camu, Vincent Meininger, Nicolas Dupre, Guy A Rouleau
Journal: Nature Genetics (2008)
Renal Glucose Handling
Authors: Ele Ferrannini, Stephan A. Veltkamp, Ronald A. Smulders, Takeshi Kadokura
Journal: Diabetes Care (2013)

OBJECTIVE Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function. RESEARCH DESIGN AND METHODS Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 ± 9 years, fasting glucose 133 ± 39 mg/dL, mean ± SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 ≥90 mL · min–1 · 1.73 m−2), mild (eGFR2 ≥60 to &amp;lt;90), moderate (eGFR3 ≥30 to &amp;lt;60), or severe reduction in eGFR (eGFR4 ≤15 to &amp;lt;30). RESULTS Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P &amp;lt; 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR1 to 8 mg/min [7] in eGFR4, P &amp;lt; 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P &amp;lt; 0.0001 for both, r2 = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL/min decline in eGFR and an increase of 7 g for each 10 mg/dL increase in glucose above fasting normoglycemia. CONCLUSIONS In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment.
Precordial and epicardial surface potentials during Myocardial ischemia in the pig. A theoretical and experimental analysis of the TQ and ST segments.
Authors: R P Holland, H Brooks
Journal: Circulation Research (1975)

The solid angle theorem was used to analyze the relationships between TQ and ST segment deflections recorded from precordial and epicardial locations and the time course, size, shape, and transmural location of the ischemic process in the ventricular myocardium. Mathematical predictions were compared with experimental data from the intact heart. Precordial electrograms obtained in anesthetized close-chest pigs were compared with epicardial electrograms recorded directly from the heart's surface. Various areas of ischemia were produced by occluding large and small coronary artery branches, and the resultant changes in ischemic shape were delineated with Thioflavin S injections and postmortem ultraviolet photography. Formally derived equations and cumulative experimental data were in close agreement, suggesting that in the ischemic ventricle (1) TQ depression always accompanies ST elevation, (2) TQ and ST segment changes in magnitude and polarity are complex functions of ischemic size, shape, and transmural location; (3) precordial electrocardiogram (ECG) ST segment elevation is directly related to ischemic size; and (4) epicardial ECG ST segment elevation is inversely related to ischemic size. It is thus concluded that precordial and epicardial ECG TQ and ST segment deflections are complex functions of ischemic geometry and that their accurate interpretation with respect to ischemic size and shape and in the presence of pharmacological interventions is often difficult and may be misleading.
Expression of an exogenous interleukin 6 gene in human Epstein Barr virus B cells confers growth advantage and in vivo tumorigenicity.
Authors: G Scala, I Quinto, M R Ruocco, A Arcucci, M Mallardo, P Caretto, G Forni, S Venuta
Journal: The Journal of Experimental Medicine (1990)

The biological role of interleukin 6 (IL-6) molecules in human B cell tumorigenesis was studied by using an episomal expression vector, pHEBoSV-IL6, to introduce stably the human IL-6 gene into human Epstein Barr virus (EBV)-transformed B lymphoblasts. The gene was present in the IL-6-transfected cells in a high copy number and was efficiently expressed, resulting in the secretion of consistent levels of IL-6 molecules. The constitutive expression of the IL-6 gene led to an altered pattern of growth and to a malignant phenotype, as shown by clonogenicity in to an altered pattern of growth and to a malignant phenotype, as shown by clonogenicity in soft agar cultures and tumorigenicity in nude mice. These data suggest that the combined action of EBV, which exerts an immortalizing function, and of the growth-promoting activity of IL-6 molecules, can give rise to fully transformed B cell tumors in immunodeficient subjects.