tbuckley/cabot-search huggingface dataset:
Opsin Clines in Butterflies Suggest Novel Roles for Insect Photopigments
Authors: Francesca D. Frentiu, Furong Yuan, Wesley K. Savage, Gary D. Bernard, Sean P. Mullen, Adriana D. Briscoe
Journal: Molecular Biology and Evolution (2014)

Opsins are ancient molecules that enable animal vision by coupling to a vitamin-derived chromophore to form light-sensitive photopigments. The primary drivers of evolutionary diversification in opsins are thought to be visual tasks related to spectral sensitivity and color vision. Typically, only a few opsin amino acid sites affect photopigment spectral sensitivity. We show that opsin genes of the North American butterfly Limenitis arthemis have diversified along a latitudinal cline, consistent with natural selection due to environmental factors. We sequenced single nucleotide (SNP) polymorphisms in the coding regions of the ultraviolet (UVRh), blue (BRh), and long-wavelength (LWRh) opsin genes from ten butterfly populations along the eastern United States and found that a majority of opsin SNPs showed significant clinal variation. Outlier detection and analysis of molecular variance indicated that many SNPs are under balancing selection and show significant population structure. This contrasts with what we found by analysing SNPs in the wingless and EF-1 alpha loci, and from neutral amplified fragment length polymorphisms, which show no evidence of significant locus-specific or genome-wide structure among populations. Using a combination of functional genetic and physiological approaches, including expression in cell culture, transgenic Drosophila, UV-visible spectroscopy, and optophysiology, we show that key BRh opsin SNPs that vary clinally have almost no effect on spectral sensitivity. Our results suggest that opsin diversification in this butterfly is more consistent with natural selection unrelated to spectral tuning. Some of the clinally varying SNPs may instead play a role in regulating opsin gene expression levels or the thermostability of the opsin protein. Lastly, we discuss the possibility that insect opsins might have important, yet-to-be elucidated, adaptive functions in mediating animal responses to abiotic factors, such as temperature or photoperiod.
Case-control study of the effect of mechanical trauma on the risk of herpes zoster
Authors: S L Thomas, J G Wheeler, Andrew J Hall
Journal: BMJ (2004)

Herpes zoster results from reactivation of latent varicella zoster virus infection.2][3] Case reports and case series have indicated that mechanical trauma may be a risk factor. 4But these studies had no control group, and physical mishaps and surgical trauma are common in older people.We investigated whether trauma is associated with increased risk of zoster using a case-control design.Table A on bmj.com gives details of 14 people who had recent trauma at the site of subsequent rash in the case
Chromosome <i>8p</i> Deletions and <i>8q</i> Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer
Authors: Alexander T. El Gammal, Michael Brüchmann, Jozef Zustin, Hendrik Isbarn, Olaf J.C. Hellwinkel, Jens Köllermann, Guido Sauter, Ronald Simon, Waldemar Wilczak, Jörg Schwarz, Carsten Bokemeyer, Tim H. Brümmendorf, Jakob R. Izbicki, Emre Yekebas, Margit Fisch, Hartwig Huland, Markus Graefen, Thorsten Schlomm
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Deletions of 8p and gains of 8q belong to the most frequent cytogenetic alterations in prostate cancer. The target genes of these alterations and their biological significance are unknown. Experimental Design: To determine the relationship between chromosome 8 changes, and prostate cancer phenotype and prognosis, a set of 1.954 fully annotated prostate cancers were analyzed in a tissue microarray format by fluorescence in situ hybridization. Results: Both 8p deletions and 8q gains increased in number during different stages of prostate cancer progression. 8p deletions/8q gains were found in 26.1%/4.8% of 1,239 pT2 cancers, 38.5%/9.8% of 379 pT3a cancers, 43.5%/8.9% of 237 pT3b cancers, 40.7%/14.8% of 27 pT4 cancers, 39.1%/34.8% of 23 nodal metastases, 51.9%/33.3% of 27 bone metastases, and 45.5%/59.9% of 22 hormone refractory cancers (P &amp;lt; 0.0001 each). Both 8p deletions and 8q gains were also significantly associated with high Gleason grade and with each other (P &amp;lt; 0.0001 each). In primary tumors, 8p deletions were seen in only 27.3% of 1,882 cancers without 8q gain but in 57.4% of 122 tumors with 8q gain (P &amp;lt; 0.0001). Among cancers treated with radical prostatectomy, 8p deletions (P = 0.003) and 8q gains (P = 0.02) were associated with biochemical tumor recurrence. However, multivariate analysis (including prostate-specific antigen, pT/pN stage, Gleason score, and surgical margin status) did not reveal any statistically independent effect of 8p or 8q alterations on biochemical tumor recurrence. Conclusions: 8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application. Clin Cancer Res; 16(1); 56–64
Cholangitis and subsequent gastrointestinal cancer risk: a Danish population-based cohort study
Authors: Kirstine Kobberøe Søgaard, Rune Erichsen, Jennifer Leigh Lund, Dóra Körmendiné Farkas, Henrik Toft Sørensen
Journal: Gut (2013)

<h3>Objective</h3> While patients with gastrointestinal cancer are at increased risk of cholangitis, it is less clear whether cholangitis is also a marker for occult gastrointestinal cancer. If an undiagnosed cancer obstructs the bile duct system and causes cholangitis, the short-term risk of cancer will appear increased. However, an increased long-term risk of cancer may originate from chronic inflammatory processes. We assessed the risk of a gastrointestinal cancer diagnosis subsequent to a cholangitis diagnosis during a 17-year period in Denmark. <h3>Design</h3> We conducted a nationwide population-based cohort study by linking Danish medical registries during 1994–2010. We quantified the excess risk of cancer in cholangitis patients using relative (standardised incidence ratio; SIR) and absolute (excess absolute risk per 1000 person-years at risk; EAR) risk calculations. <h3>Results</h3> 4333 patients with cholangitis (including 178 with primary sclerosing cholangitis) were followed for 17 222 person-years. During the follow-up period, 477 gastrointestinal cancers occurred versus 59 expected, corresponding to a SIR of 8.12 (95% CI 7.41 to 8.88). Risk was increased mainly for cancer in the small intestine (SIR 18.2; 95% CI 8.69 to 33.4), liver (SIR 16.3; 95% CI 11.6 to 22.2), gallbladder and biliary tract (SIR 70.9; 95% CI 59.0 to 84.4) and pancreas (SIR 31.7; 95% CI 27.8 to 36.0). During the first 6 months of follow-up, 314 patients were diagnosed with gastrointestinal cancer, corresponding to a SIR of 49.8 (95% CI 44.4 to 55.6) and an EAR of 175. <h3>Conclusions</h3> Cholangitis is a marker of occult gastrointestinal cancer.
Adenine nucleotide degradation in the human myocardium during cardioplegia
Authors: A SOLLEVI, W SCHMIDT, E JANSSON, V BOMFIM, L KAIJSER
Journal: Cardiovascular Research (1987)

Journal Article Adenine nucleotide degradation in the human myocardium during cardioplegia Get access A SOLLEVI, A SOLLEVI † From the Department of Anaesthesiology, Karolinska Hospital, Stockholm, Sweden§ Department of Pharmacology, Karolinska Institute, Stockholm, Sweden Address for correspondence and reprints: Dr Alf Sollevi, Department of Pharmacology, Karolinska Institute, Box 60 400, S-104 01 Stockholm. Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar W SCHMIDT, W SCHMIDT ** From the Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar E JANSSON, E JANSSON ** From the Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar V BOMFIM, V BOMFIM ‡ From the Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar L KAIJSER L KAIJSER ** From the Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 21, Issue 5, May 1987, Pages 358–361, https://doi.org/10.1093/cvr/21.5.358 Published: 01 May 1987 Article history Accepted: 27 March 1986 Received: 26 September 1986 Published: 01 May 1987
Arthroplasty implant biomaterial particle associated macrophages differentiate into lacunar bone resorbing cells.
Authors: R Pandey, J Quinn, C Joyner, D W Murray, J T Triffitt, N A Athanasou
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To study the pathogenesis of aseptic loosening: in particular, to determine whether macrophages responding to particles of biomaterials commonly used in arthroplasty surgery for arthritis are capable of differentiating into osteoclastic bone resorbing cells, and the cellular and hormonal conditions required for this to occur. METHODS: Biomaterial particles (polymethylmethacrylate, high density polyethylene, titanium, chromium-cobalt, stainless steel) were implanted subcutaneously into mice. Macrophages were isolated from the foreign body granulomas that resulted, cultured on bone slices and coverslips, and assessed for both cytochemical and functional evidence of osteoclast differentiation. RESULTS: Tartrate resistant acid phosphatase (TRAP) negative macrophages isolated from granulomas containing particles of all types of biomaterial composition were capable of differentiating into TRAP positive cells capable of extensive lacunar bone resorption (assessed by scanning electron microscopy). The presence of both UMR106 rat osteoblast-like cells and 1,25-dihydroxy vitamin D3 was necessary for this to occur. CONCLUSION: All implant materials produce wear particles that are the focus of a heavy foreign body macrophage response in the fibrous membrane between a loose implant component and the host bone undergoing resorption. These findings underline the importance of biomaterial wear particle generation and the macrophage response to different types of biomaterial wear particles in the pathogenesis of aseptic loosening.
Blood stained nappy
Authors: A. R. Gatrad, A. Sheikh
Journal: BMJ (2012)

A young mother attends the surgery concerned about blood in her 7 month old daughter’s nappy.

### Was it blood?

Urinary urate crystals can stain the nappy red, but this is not clinically significant. Medications such as rifampicin products that are excreted in the urine can make the stools appear red.1

### Bleeding and blood

Ask if there is a family history of a bleeding disorder and/or whether the baby has bled from other sites, such as the nose, or has any bruising.

Ask about the colour of the blood, whether it was mixed with the stools, and if there was any associated pain. Bright red blood on a wipe or on a nappy (but not mixed with the stools) suggests bleeding from the anal region. Although constipation and an anal fissure usually coexist in cases of blood in the nappy, constipation is the commonest cause of a rectal bleed beyond the neonatal period, irrespective of whether an anal fissure is visible.2 A fissure associated with constipation usually results in a baby …
Requirement for Focal Adhesion Kinase in the Early Phase of Mammary Adenocarcinoma Lung Metastasis Formation
Authors: Maroesja J. van Nimwegen, Saertje Verkoeijen, Liesbeth van Buren, Danny Burg, Bob van de Water
Journal: Cancer Research (2005)

Abstract An increased expression of focal adhesion kinase (FAK) in a variety of cancers is associated with a poor disease prognosis. To study the role of FAK in breast tumor growth and metastasis formation, we used conditional doxycycline-regulated expression of a dominant-negative acting splice variant of FAK, FAK-related non-kinase (FRNK), in MTLn3 mammary adenocarcinoma cells in a syngeneic Fischer 344 rat tumor and metastasis model. In cell culture, doxycycline-mediated expression of FRNK inhibited MTLn3 cell spreading and migration in association with reduced formation of focal adhesions and phosphorylation of FAK on Tyr397, but FRNK did not cause apoptosis. Continuous expression of FRNK decreased the primary tumor growth in the mammary fat pad by 60%, which was not due to induction of apoptosis. Lung metastasis formation was almost completely prevented when FRNK was already expressed 1 day before tumor cell injection, whereas expression of FRNK 11 days after injection did not affect lung metastasis formation. FRNK expression during the first 5 days was sufficient to block metastasis formation, excluding the possibility of FRNK-induced dormancy of tumor cells. Together, these data fit with a model wherein FAK is required for breast tumor cell invasion/migration processes that take place in the early phase of metastasis formation. Our findings suggest that FAK is a good candidate for therapeutic intervention of metastasis formation.
Nicotinamide Phosphoribosyltransferase Regulates Cell Survival Through NAD <sup>+</sup> Synthesis in Cardiac Myocytes
Authors: Chiao-Po Hsu, Shinichi Oka, Dan Shao, Nirmala Hariharan, Junichi Sadoshima
Journal: Circulation Research (2009)

NAD+ acts not only as a cofactor for cellular respiration but also as a substrate for NAD(+)-dependent enzymes, such as Sirt1. The cellular NAD+ synthesis is regulated by both the de novo and the salvage pathways. Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the salvage pathway.Here we investigated the role of Nampt in mediating NAD+ synthesis in cardiac myocytes and the function of Nampt in the heart in vivo.Expression of Nampt in the heart was significantly decreased by ischemia, ischemia/reperfusion and pressure overload. Upregulation of Nampt significantly increased NAD+ and ATP concentrations, whereas downregulation of Nampt significantly decreased them. Downregulation of Nampt increased caspase 3 cleavage, cytochrome c release, and TUNEL-positive cells, which were inhibited in the presence of Bcl-xL, but did not increase hairpin 2-positive cells, suggesting that endogenous Nampt negatively regulates apoptosis but not necrosis. Downregulation of Nampt also impaired autophagic flux, suggesting that endogenous Nampt positively regulates autophagy. Cardiac-specific overexpression of Nampt in transgenic mice increased NAD+ content in the heart, prevented downregulation of Nampt, and reduced the size of myocardial infarction and apoptosis in response to prolonged ischemia and ischemia/reperfusion.Nampt critically regulates NAD+ and ATP contents, thereby playing an essential role in mediating cell survival by inhibiting apoptosis and stimulating autophagic flux in cardiac myocytes. Preventing downregulation of Nampt inhibits myocardial injury in response to myocardial ischemia and reperfusion. These results suggest that Nampt is an essential gatekeeper of energy status and survival in cardiac myocytes.
G-CSF rescues the memory impairment of animal models of Alzheimer's disease
Authors: Kuen-Jer Tsai, Yueh-Chiao Tsai, Che-Kun James Shen
Journal: The Journal of Experimental Medicine (2007)

Most of the current clinical treatments for Alzheimer's disease (AD) are largely symptomatic and can have serious side effects. We have tested the feasibility of using the granulocyte colony-stimulating factor (G-CSF), which is known to mobilize hematopoietic stem cells (HSCs) from the bone marrow into the peripheral blood, as a therapeutic agent for AD. Subcutaneous administration of G-CSF into two different β-amyloid (Aβ)–induced AD mouse models substantially rescued their cognitive/memory functions. The rescue was accompanied by the accumulation of 5-bromo-2′deoxyuridine–positive HSCs, as well as local neurogenesis surrounding the Aβ aggregates. Furthermore, the level of acetylcholine in the brains of Tg2576 mice was considerably enhanced upon G-CSF treatment. We suggest that G-CSF, a drug already extensively used for treating chemotherapy-induced neutropenia, should be pursued as a novel, noninvasive therapeutic agent for the treatment of AD.
Characterization of mutant myosins of Dictyostelium discoideum equivalent to human familial hypertrophic cardiomyopathy mutants. Molecular force level of mutant myosins may have a prognostic implication.
Authors: H Fujita, S Sugiura, S Momomura, M Omata, H Sugi, K Sutoh
Journal: Journal of Clinical Investigation (1997)

Recent studies have revealed that familial hypertrophic cardiomyopathy (FHC) is caused by missence mutations in myosin heavy chain or other sarcomeric proteins. To investigate the functional impact of FHC mutations in myosin heavy chain, mutants of Dictyostelium discoideum myosin II equivalent to human FHC mutations were generated by site-directed mutagenesis, and their motor function was characterized at the molecular level. These mutants, i.e., R397Q, F506C, G575R, A699R, K703Q, and K703W are respectively equivalent to R403Q, F513C, G584R, G716R, R719Q, and R719W FHC mutants. We measured the force generated by these myosin mutants as well as the sliding velocity and the actin-activated ATPase activity. These measurements showed that the A699R, K703Q, and K703W myosins exhibited unexpectedly weak affinity with actin and the lowest level of force, though their ATPase activity remained rather high. F506C mutant which has been reported to have benign prognosis exhibited the least impairment of the motile and enzymatic activities. The motor functions of R397Q and G575R myosins were classified as intermediate. These results suggest that the force level of mutant myosin molecule may be one of the key factors for pathogenesis which affect the prognosis of human FHC.
A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate
Authors: P Mease, V Strand, L Shalamberidze, A Dimic, T Raskina, Li-An Xu, Y Liu, J Smith
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Interleukin 6 (IL-6) plays a key role in the inflammatory cascade in rheumatoid arthritis. BMS945429 is a humanised, monoclonal antibody that potently binds IL-6. <h3>Objective</h3> To conduct aphase II study to determine the efficacy and safety of BMS945429 in patients with active rheumatoid arthritis and an inadequate response to methotrexate. <h3>Methods</h3> Patients were randomised 1:1:1:1 to BMS945429 (80, 160 or 320 mg; administered intravenously) or placebo plus methotrexate during this 16-week, double-blind trial. The primary efficacy end point was the proportion of patients with a 20% improvement in American College of Rheumatology responses (ACR20) at week 12. Additional end points included ACR50 and ACR70 responses and 28-joint Disease Activity Scores (DAS28). <h3>Results</h3> Of 127 randomised and treated patients, 116 completed the trial. ACR20 responders at week 12 were 81% (80 mg; p&lt;0.0001 vs placebo), 71% (160 mg; p=0.0005 vs placebo), 82% (320 mg; p&lt;0.0001 vs placebo) and 27% (placebo), respectively. By week 16, 14% (80 mg), 28% (160 mg) and 44% (320 mg) of BMS945429 patients were in DAS28 remission (DAS28 score &lt;2.6). Statistically significant and clinically meaningful improvements in health-related quality of life (HRQoL) were reported in all active treatment groups. Administration of BMS945429 was associated with increases in liver enzymes and in serum cholesterol. There were no serious infections, infusion reactions or apparent immunogenicity. <h3>Conclusions</h3> In this phase II study, BMS945429 was associated with rapid and significant improvements in disease activity and HRQoL in patients with active rheumatoid arthritis and an inadequate response to methotrexate.
Accurate Estimation of Gene Evolutionary Rates Using XRATE, with an Application to Transmembrane Proteins
Authors: A. Heger, C. P. Ponting, I. Holmes
Journal: Molecular Biology and Evolution (2009)

XRATE implements algorithms for comparative annotation, ancestral reconstruction, evolutionary rate estimation, and simulation. Its modeling repertoire includes phylogenetic stochastic context-free grammars and phylo-hidden Markov models. Following earlier tests of XRATE as a machine-learning tool suitable for alignment annotation, we now report the first tests of XRATE as a precise quantitative instrument for estimating evolutionary rates. We implement a codon model similar to that of Goldman and Yang (1994) (A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11: 725-736) and show that XRATE's parameter estimates are consistent with those of PAML. To demonstrate its utility, we apply the model to measure the difference in selective strength (omega) between intracellular and secreted regions of type I transmembrane proteins. In 215 of 303 instances, a complex model with individual omega for each region provides a better fit to the data than the simpler single omega value model. Secreted portions of type I transmembrane proteins show an elevation in omega similar to that seen for secreted protein genes. Less stringent purifying selection is thus a general property of the extracellular milieu, rather than being specific to only soluble and secreted proteins.
Residential Proximity to Major Roadway and 10-Year All-Cause Mortality After Myocardial Infarction
Authors: Joshua I. Rosenbloom, Elissa H. Wilker, Kenneth J. Mukamal, Joel Schwartz, Murray A. Mittleman
Journal: Circulation (2012)

Background— The relationship between residential proximity to roadway and long-term survival after acute myocardial infarction (AMI) is unknown. We investigated the association between distance from residence and major roadway and 10-year all-cause mortality after AMI in the Determinants of Myocardial Infarction Onset Study (Onset Study), hypothesizing that living closer to a major roadway at the time of AMI would be associated with increased risk of mortality. Methods and Results— The Onset Study enrolled 3886 individuals hospitalized for AMI in 64 centers across the United States from 1989 to 1996. Institutionalized patients, those providing only post office boxes, and those whose addresses could not be geocoded were excluded, leaving 3547 patients eligible for analysis. Addresses were geocoded, and distance to the nearest major roadway was assigned. Cox regression was used to calculate hazard ratios, with adjustment for personal characteristics (age, sex, race, education, marital status, distance to nearest acute care hospital), clinical characteristics (smoking, body mass index, comorbidities, medications), and neighborhood-level characteristics derived from US Census block group data (household income, education, urbanicity). There were 1071 deaths after 10 years of follow-up. In the fully adjusted model, compared with living &gt;1000 m, hazard ratios (95% confidence interval) for living ≤100 m were 1.27 (1.01–1.60), for 100 to ≤200 m were 1.19 (0.93–1.60), and for 200 to ≤1000 m were 1.13 (0.99–1.30) ( P trend =0.016). Conclusions— In this multicenter study, living close to a major roadway at the time of AMI was associated with increased risk of all-cause 10-year mortality; this relationship persisted after adjustment for individual and neighborhood-level covariates.