tbuckley/cabot-search huggingface dataset:
Substitution bias, weighted parsimony, and amniote phylogeny as inferred from 18S rRNA sequences.
Authors: C R Marshall
Journal: Molecular Biology and Evolution (1992)

Recently published rRNA sequences (Hedges et al. 1990) provide important new information on tetrapod relationships.Specifically Hedges et al's ( 1990) data support a monophyletic Lissamphibia, Amniota, Squamata, Mammalia, and Aves.It is surprising that the 18s rRNA sequences also support a close relationship between the two birds and the four mammals sequenced.Paleontological data provide considerable evidence for a close bird-crocodile relationship (e.g., see Gauthier et al. 1988; Donoghue et al. 1989), and the strength of these data suggested the possibility that the support for a bird-mammal relationship shown by the 1% rRNA sequences may be an artifact created by substitution biases.Table 1 shows that there are indeed pronounced substitution biases in the amniote 18s rRNA sequences.In particular, there is both a significant overrepresentation of T-to-C substitutions and a significant underrepresentation of A-to-T and T-to-A substitutions.It is interesting that a disproportionately large number of sites that support a bird-mammal relationship are T-to-C substitutions (table 1).The only site that involves T-to-A and/or A-to-T substitutions is site 13 17 in Hedges et al. % ( 1990) figure A 1 (note that there are 140 nucleotides/line in their fig.A 1, not 150 as indicated), and on the most parsimonious tree this site is homoplasious, requiring both a T-to-A substitution in the branch leading to the four mammals and either a T-to-A substitution in the Coelacanth or an A-to-T substitution at the base of the amniotes.However, when viewed in isolation, site 13 17 supports a clade including birds and crocodiles, to the exclusion of mammals.Note that the substitution biases are quite complex.The T/C transitions are vastly overrepresented, yet A/G transitions are not.Similarly, A/T transversions are underrepresented, but C/G transversions are not (table I). Dynamically Weighted Parsimony'
Repaglinide Versus Metformin in Combination With Bedtime NPH Insulin in Patients With Type 2 Diabetes Established on Insulin/Metformin Combination Therapy
Authors: Niall J. Furlong, Shirley A. Hulme, Sarah V. O’Brien, Kevin J. Hardy
Journal: Diabetes Care (2002)

OBJECTIVE—To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician’s discretion, aiming for a fasting blood glucose (FBG) ≤6.0 mmol/l. RESULTS—Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA1c (Diabetes Control and Complications Trial–aligned assay, normal range 4.6–6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 ± 0.4 kg (means ± SE) (P = 0.01) versus 2.7 ± 0.4 kg (P &amp;lt; 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 ± 0.8 to 34.1 ± 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 ± 0.9 to 29.1 ± 1.3 (P &amp;lt; 0.002) with insulin/repaglinide. CONCLUSIONS—Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.
Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity
Authors: Johannes Vogel, Isabel Kiessling, Katja Heinicke, Thomas Stallmach, Pete Ossent, Olga Vogel, Michael Aulmann, Thomas Frietsch, Holger Schmid-Schönbein, Wolfgang Kuschinsky, Max Gassmann
Journal: Blood (2003)
The construction and characterization of Neisseria gonorrhoeae lacking protein III in its outer membrane.
Authors: L M Wetzler, E C Gotschlich, M S Blake, J M Koomey
Journal: The Journal of Experimental Medicine (1989)

Protein III (PIII) is a highly conserved, antigenically stable gonococcal outer membrane protein that is closely associated with the major outer membrane protein, protein I (PI). We have previously reported the cloning of the PIII gene. This gene was inserted into the Eco RI site of the runaway plasmid pMOB45. The beta-lactamase (beta la) Bam HI restriction fragment from the gonococcal plasmid pFA3 was inserted at the Xba I site in the PIII gene. The plasmid construct was Hae III methylated and the PIII/beta la insert was excised with Eco RI and used to transform gonococcal strain F62. One beta la+, ampicillin-resistant transformant was isolated and designated 2D. A Western blot of 2D whole cell lysate was probed with affinity-purified polyclonal PIII antisera. No PIII reactivity was detected. Southern blot analysis was performed on F62 and 2D chromosomal DNA that were cut with Eco RI or Cla I. A PIII DNA probe hybridized with fragments 2.2 kb larger in strain 2D than strain F62. This corresponds to the size of the beta la insert. A beta la-specific probe hybridized with the same 2D restriction fragments as above, but did not react with any F62 fragments, confirming that homologous recombination had occurred. There were minimal phenotypic changes between 2D and its parent strain, F62. Chromosomal DNA from 2D was able to transform gonococcal strains F62, UU1, and Pgh 3-2, rendering these PIII-. 2D and other PIII- transformants can now be used to study the role of PIII in gonococcal physiology, metabolism, membrane structure, and pathogenesis. Moreover, we now have organisms from which we can purify gonococcal proteins without PIII contamination.
CD8β Endows CD8 with Efficient Coreceptor Function by Coupling T Cell Receptor/CD3 to Raft-associated CD8/p56lck Complexes
Authors: Alexandre Arcaro, Claude Grégoire, Talitha R. Bakker, Lucia Baldi, Martin Jordan, Laurence Goffin, Nicole Boucheron, Florian Wurm, P. Anton van der Merwe, Bernard Malissen, Immanuel F. Luescher
Journal: The Journal of Experimental Medicine (2001)

The extraordinary sensitivity of CD8+ T cells to recognize antigen impinges to a large extent on the coreceptor CD8. While several studies have shown that the CD8beta chain endows CD8 with efficient coreceptor function, the molecular basis for this is enigmatic. Here we report that cell-associated CD8alphabeta, but not CD8alphaalpha or soluble CD8alphabeta, substantially increases the avidity of T cell receptor (TCR)-ligand binding. To elucidate how the cytoplasmic and transmembrane portions of CD8beta endow CD8 with efficient coreceptor function, we examined T1.4 T cell hybridomas transfected with various CD8beta constructs. T1.4 hybridomas recognize a photoreactive Plasmodium berghei circumsporozoite (PbCS) peptide derivative (PbCS (4-azidobezoic acid [ABA])) in the context of H-2K(d), and permit assessment of TCR-ligand binding by TCR photoaffinity labeling. We find that the cytoplasmic portion of CD8beta, mainly due to its palmitoylation, mediates partitioning of CD8 in lipid rafts, where it efficiently associates with p56(lck). In addition, the cytoplasmic portion of CD8beta mediates constitutive association of CD8 with TCR/CD3. The resulting TCR-CD8 adducts exhibit high affinity for major histocompatibility complex (MHC)-peptide. Importantly, because CD8alphabeta partitions in rafts, its interaction with TCR/CD3 promotes raft association of TCR/CD3. Engagement of these TCR/CD3-CD8/lck adducts by multimeric MHC-peptide induces activation of p56(lck) in rafts, which in turn phosphorylates CD3 and initiates T cell activation.
Molecular Biology and Immunology in Hepatology. Advances in the Treatment of Intractable Liver Diseases: Edited by T Tsuji, T Higashi, M Zeniya, et al. Amsterdam: Elsevier Science BV, 2002, b/w, pp 342. ISBN 0-444-50653-5
Authors: J A Eksteen
Journal: Gut (2003)

scintigraphy; CBD, common bile duct; LFT, liver function test; PPV, positive predictive value; NPV, negative predictive value.
Reproducibility of Graft Preparations in Descemet's Membrane Endothelial Keratoplasty
Authors: Ursula Schlötzer-Schrehardt, Bjoern O. Bachmann, Theofilos Tourtas, Claus Cursiefen, Matthias Zenkel, Kathrin Rössler, Friedrich E. Kruse
Journal: Ophthalmology (2013)
Neurotransmitter mechanisms of dreaming: Implication of modulatory systems based on dream intensity
Authors: E. K. Perry, M. A. Piggott
Journal: Behavioral and Brain Sciences (2000)

Based on increasing dream intensity and alterations in neurophysiological activity from waking, through NREM to REM sleep, dreaming appears to correlate with sustained midbrain dopaminergic and basal forebrain cholinergic, in conjunction with decreasing brainstem 5-HT and noradrenergic neuronal activities. This, model, with features in common with the modulatory transmitter models of Hobson et al. and Solms, is consistent with some clinical observations on drug induced alterations in dreaming and transmitter correlates of delusions. [Hobson et al.; Solms]
Antigen-reactive T cell clones. II. Unique homozygous and (high responder x low responder)F1 hybrid antigen-presenting determinants detected using poly(Tyr, Glu)-poly D, L-Ala--poly Lys-reactive T cell clones.
Authors: M Kimoto, C G Fathman
Journal: The Journal of Experimental Medicine (1981)

Using murine (T,G)-A--L-reactive T cell clones, we have demonstrated the existence of unique homozygous antigen-presenting determinants expressed on C57bl/6 mice, controlled by the I-A subregion of the murine major histocompatibility complex (MHC), which are not expressed on semisyngeneic (C57Bl/6 x A/J)F1 [(B6A)F1] cells. Additionally, we were able to demonstrate that there exist (T,G)-A--L-reactive clones in F1 mice derived between low responder and high responder parents [(B6A)F1] that recognize antigen in association with transcomplementing hybrid I-A subregion determinants expressed uniquely on (B6A)F1 cells not expressed on cells of either of the parental strains. These data suggest that phenotypic high responsiveness exhibited by (higher responder x low responder)F1 mice was not simply controlled by the high responder parental genome, but was controlled at the phenotypic level of expression of antigen-presenting determinants. Such antigen-presenting determinants can be created by complementation using products of the low responder as well as high responder genome. The significance of the existence of such F1 specific hybrid antigen-presenting determinants for T cell specificity and recognition of self was discussed.
Lack of a late asthmatic response after hypertonic saline challenge in children
Authors: W Eder, M Schreuer, J Riedler
Journal: European Respiratory Journal (1999)

Hypertonic saline challenge has become a standardized method for measuring airway responsiveness. However, there is still uncertainty about the occurrence of a late asthmatic response. Therefore, the present study was designed to assess a possible late asthmatic response after hypertonic saline challenge in children. Twenty-one children with mild to moderate bronchial hyperresponsiveness were studied. On days 1 and 2, forced expiratory volume in one second (FEV1) was measured hourly from 10:00 h to 22:00 h to assess diurnal variation of lung function. On the third study day, a hypertonic saline challenge was performed and FEV1 was measured as on control days. The possibility of a late asthmatic response was tested by comparing FEV1 levels up to 12 h after the challenge on the intervention day to FEV1 levels on control days. In no subjects were the FEV1 values following the challenge found to be considerably below the individual mean of the control days. Furthermore, a nonparametric approach was applied for each child and the population looked into as a whole. Again, no late asthmatic response was detectable. The results of this study suggest that in children with mild to moderate bronchial hyperresponsiveness a late asthmatic response does not occur 4-12 h after a 4.5% saline challenge.
The impact of physical activity on health-related fitness and quality of life for patients with head and neck cancer: a systematic review
Authors: Lauren C Capozzi, Kathryn C Nishimura, Margaret L McNeely, Harold Lau, S Nicole Culos-Reed
Journal: British Journal of Sports Medicine (2015)

Background Patients with head and neck cancer often face a plethora of cancer and treatment-related side effects, negatively impacting their lean body mass, physical functioning, quality of life and fatigue management. Physical activity is a potential mediator of many of these side effects. This is the first systematic review reporting on head and neck cancer and physical activity literature. Methods A literature search was conducted up to January 2015. Two reviewers independently identified articles using the outlined inclusion criteria, assessing the study methodology, risk of bias and extracting the necessary data from studies evaluating the impact of full-body physical activity on patients with head and neck cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement was used to guide this review. Results We identified 16 articles published from 2003 to 2014, the majority of which were published within the past 5 years. Physical activity interventions were feasible, safe and beneficial in mediating cancer and treatment-related side effects. Specifically, patients experienced improvements in lean body mass, muscular strength, physical functioning, quality of life and fatigue management. Owing to significant study heterogeneity, data were not pooled. Reflecting the early state of the literature, included studies were found to vary greatly in design, quality and reporting characteristics. Conclusions There is early evidence that supports the benefit of physical activity interventions for patients with head and neck cancer, both during and following treatment. Future research is necessary to determine the benefits of different physical activity interventions, and their impact on patients with different head and neck cancers.
Body Surface Mapping During Pacing at Multiple Sites in the Human Atrium
Authors: Arne SippensGroenewegen, Heidi A. P. Peeters, Emile R. Jessurun, Andre C. Linnenbank, Etienne O. Robles de Medina, Michael D. Lesh, Norbert M. van Hemel
Journal: Circulation (1998)

Background —The morphology and polarity of the P wave on 12-lead ECG are of limited clinical value in localizing ectopic atrial rhythms. It was the aim of this study to assess the spatial resolution of body surface P-wave integral mapping in identifying the site of origin of ectopic right atrial (RA) impulse formation in patients without structural atrial disease. Methods and Results —Sixty-two–lead ECG recordings were obtained during RA pacing at 86 distinct endocardial sites in nine patients with normal biatrial anatomy. After P-wave integral maps were generated for each paced activation sequence, 17 groups with nearly identical map features were visually selected, and a mean P-wave integral map was computed for each group. Supportive statistical analysis to corroborate qualitative group selection was performed by assessment of (1) intragroup pattern uniformity by use of jackknife correlation coefficient analysis of the integral maps contained in each group and (2) intergroup pattern variability by use of the calculation of cross correlations between the 17 mean integral maps. The spatial resolution of paced P-wave body surface mapping in the right atrium was obtained by estimating the area size of endocardial segments with nearly identical P-wave integral maps by use of a biplane fluoroscopic method to compute the three-dimensional position of each pacing site. The latter approach yielded a mean endocardial segment size of 3.5±2.9 cm 2 (range, 0.79 to 10.75 cm 2 ). Conclusions —Use of the P-wave morphology on the 62-lead surface ECG in patients with normal biatrial anatomy allows separation of the origin of ectopic RA impulse formation into one of 17 different endocardial segments with an approximated area size of 3.5 cm 2 . This database of paced P-wave integral maps provides a versatile clinical tool to perform detailed noninvasive localization of right-sided atrial tachycardia before radiofrequency catheter ablation.
Large-scale gene expression in bone marrow mesenchymal stem cells: a putative role for COL10A1 in osteoarthritis
Authors: J. R. Lamas, L. Rodriguez-Rodriguez, A. G. Vigo, R. Alvarez-Lafuente, P. Lopez-Romero, F. Marco, E. Camafeita, A. Dopazo, S. Callejas, E. Villafuertes, J. A. Hoyas, M. P. Tornero-Esteban, E. Urcelay, B. FernAndez-Gutierrez
Journal: Annals of the Rheumatic Diseases (2010)

To elucidate disease-specific molecular changes occurring in osteoarthritis (OA) by analysing the differential gene expression profiles of bone marrow mesenchymal stem cells (BM-MSCs) from patients with OA compared with those without OA.Expression profiles of BM-MSCs from eight paired patients with OA and patients with hip fracture without signs of OA were compared by DNA microarray expression analysis and significant differences were evaluated by computational Gene Set Enrichment Analysis. To validate the involvement of COL10A1 as part of the most downregulated gene set in OA, three tagging single nucleotide polymorphisms were genotyped in 191 patients with OA and 283 controls. COL10A1 expression was also assessed by quantitative RT-PCR in additional subjects.Expression levels in 9% (1967) of the overall transcripts were significantly different (p<0.05) between MSCs from patients with OA and controls (532 genes reached twofold differences: 240 were upregulated and 292 were downregulated). Cell development and differentiation were the functional categories accounting for most genes with altered expression. Interestingly, several genes related to the Wnt/-catenin pathway and collagen genes were downregulated in MSCs from patients with OA. The collagen gene set was clearly downregulated in OA. Furthermore, the expression of COL10A1 was significantly reduced in patients with OA. A genetic association between the COL10A1 rs11965969 polymorphism and OA was also found.COL10A1 downregulation seems to have a role in the establishment of a defective and/or unstable subchondral cartilage matrix in OA disease. It is proposed that OA may be linked to the intrinsic defective regenerative potential of BM-MSCs resulting from its reduced expression of fate commitment-related genes.
mTORC1 and mTORC2 Regulate EMT, Motility, and Metastasis of Colorectal Cancer via RhoA and Rac1 Signaling Pathways
Authors: Pat Gulhati, Kanika A. Bowen, Jianyu Liu, Payton D. Stevens, Piotr G. Rychahou, Min Chen, Eun Y. Lee, Heidi L. Weiss, Kathleen L. O'Connor, Tianyan Gao, B. Mark Evers
Journal: Cancer Research (2011)

Abstract Activation of phosphoinositide 3-kinase (PI3K)/Akt signaling is associated with growth and progression of colorectal cancer (CRC). We have previously shown that the mTOR kinase, a downstream effector of PI3K/Akt signaling, regulates tumorigenesis of CRC. However, the contribution of mTOR and its interaction partners toward regulating CRC progression and metastasis remains poorly understood. We found that increased expression of mTOR, Raptor, and Rictor mRNA was noted with advanced stages of CRC, suggesting that mTOR signaling may be associated with CRC progression and metastasis. mTOR, Raptor, and Rictor protein levels were also significantly elevated in primary CRCs (stage IV) and their matched distant metastases compared with normal colon. Inhibition of mTOR signaling, using rapamycin or stable inhibition of mTORC1 (Raptor) and mTORC2 (Rictor), attenuated migration and invasion of CRCs. Furthermore, knockdown of mTORC1 and mTORC2 induced a mesenchymal–epithelial transition (MET) and enhanced chemosensitivity of CRCs to oxaliplatin. We observed increased cell–cell contact and decreased actin cytoskeletal remodeling concomitant with decreased activation of the small GTPases, RhoA and Rac1, upon inhibition of both mTORC1 and mTORC2. Finally, establishment of CRC metastasis in vivo was completely abolished with targeted inhibition of mTORC1 and mTORC2 irrespective of the site of colonization. Our findings support a role for elevated mTORC1 and mTORC2 activity in regulating epithelial–mesenchymal transition (EMT), motility, and metastasis of CRCs via RhoA and Rac1 signaling. These findings provide the rationale for including mTOR kinase inhibitors, which inhibit both mTORC1 and mTORC2, as part of the therapeutic regimen for CRC patients. Cancer Res; 71(9); 3246–56. ©2011 AACR.
Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hämatologie und Onkologie OSHO-53 phase II study
Authors: T. Kiefer, C. Hirt, C. Späth, F. Schüler, H.K. Al-Ali, H.-H. Wolf, R. Herbst, G. Maschmeyer, K. Helke, C. Kessler, D. Niederwieser, C. Busemann, H. Schroeder, S. Vogelgesang, M. Kirsch, M. Montemurro, W.H. Krüger, G. Dölken
Journal: Annals of Oncology (2011)
A Parallel Dose-Escalation Study of Weekly and Twice-Weekly Bortezomib in Combination with Gemcitabine and Cisplatin in the First-Line Treatment of Patients with Advanced Solid Tumors
Authors: Jens Voortman, Egbert F. Smit, Richard Honeywell, Bart C. Kuenen, Godefridus J. Peters, Helgi van de Velde, Giuseppe Giaccone
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To establish maximum tolerated dose (MTD) and tolerability of two schedules of bortezomib in combination with cisplatin and gemcitabine as first-line treatment of patients with advanced solid tumors. Experimental Design: Patients were assigned to increasing doses of bortezomib days 1 and 8 (weekly schedule) or days 1, 4, 8, and 11 (twice-weekly schedule), in addition to gemcitabine 1,000 mg/m2 days 1 and 8 and cisplatin 70 mg/m2 day 1, every 21 days. Maximum of six cycles. Plasma pharmacokinetics of cisplatin and gemcitabine were determined at MTD. Results: Thirty-four patients were enrolled of whom 27 had non–small cell lung cancer (NSCLC). Diarrhea, neutropenia, and thrombocytopenia were dose-limiting toxicities leading to an MTD of bortezomib 1.0 mg/m2 in the weekly schedule. Febrile neutropenia and thrombocytopenia with bleeding were dose-limiting toxicities in the twice-weekly schedule, leading to an MTD of bortezomib 1.0 mg/m2 as well. Most common ≥grade 3 treatment-related toxicities were thrombocytopenia and neutropenia. No grade ≥3 treatment-related sensory neuropathy was reported. Of 34 evaluable patients, 13 achieved partial responses, 17 stable disease, and 4 progressive disease. Response and survival of NSCLC patients treated with twice weekly or weekly bortezomib were similar. However, increased dose intensity of bortezomib led to increased gastrointestinal toxicity as well as myelosuppression. Pharmacokinetic profiles of cisplatin and gemcitabine were not significantly different in patients receiving either schedule. Conclusions: Weekly bortezomib 1.0 mg/m2 plus gemcitabine 1,000 mg/m2 and cisplatin 70 mg/m2 is the recommended phase 2 schedule, constituting a safe combination, with activity in NSCLC.