tbuckley/cabot-search huggingface dataset:
Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera)
Authors: Robert Parker, M Marta Guarna, Andony P Melathopoulos, Kyung-Mee Moon, Rick White, Elizabeth Huxter, Stephen F Pernal, Leonard J Foster
Journal: Genome biology (2012)

Abstract Background Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor . The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. Results We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor . We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Conclusions Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation.
The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis
Authors: R. Amin, P. Subbarao, W. Lou, A. Jabar, S. Balkovec, R. Jensen, S. Kerrigan, P. Gustafsson, F. Ratjen
Journal: European Respiratory Journal (2010)

Outcome measures to assess therapeutic interventions in cystic fibrosis (CF) patients with mild lung disease are lacking. Our aim was to determine if the lung clearance index (LCI) can detect a treatment response to dornase alfa in paediatric CF patients with normal spirometry. CF patients between 6–18 yrs of age with FEV 1 ≥80% pred were eligible. In a crossover design, 17 patients received 4 weeks of dornase alfa and placebo in a randomised sequence separated by a 4-week washout period. The primary end-point was the change in LCI from dornase alfa versus placebo. A mixed model approach incorporating period-dependent baselines was used. The mean± sd age was 10.32±3.35 yrs. Dornase alfa improved LCI versus placebo (0.90±1.44; p = 0.022). Forced expiratory flow at 25–75% expired volume measured by % pred and z-scores also improved in subjects on dornase alfa (6.1%±10.34%; p = 0.03 and 0.28±0.46 z-score; p = 0.03). Dornase alfa significantly improved LCI. Therefore the LCI may be a suitable tool to assess early intervention strategies in this patient population.
Differential effect of sunitinib on the distribution of temozolomide in an orthotopic glioma model
Authors: Qingyu Zhou, James M. Gallo
Journal: Neuro-Oncology (2008)

Normalization of tumor vasculature by antiangiogenic agents may improve the delivery of cytotoxic drugs to the tumor, leading to more effective therapy. In this study, we used pharmacokinetic and pharmacodynamic approaches to investigate how sunitinib at different dose levels affects brain distribution of temozolomide (TMZ), and to ascertain the relationship between intratumoral TMZ concentrations and tumor vascularity in an orthotopic human glioma model. Three groups of intracerebral U87MG tumor-bearing mice were given either vehicle or sunitinib at 20 mg/kg or 60 mg/kg per day for 7 days before receiving a steady-state regimen of TMZ that consisted of an intravenous bolus and a 3-h intraarterial infusion. TMZ concentrations in plasma, normal brain, and brain tumor were determined, and several biomarkers related to the antiangiogenic activity of sunitinib were examined. TMZ distribution in the normal brain as indicated by the brain-to-plasma steady-state TMZ concentration ratios was analogous across the three treatment groups. The brain tumor-to-plasma steady-state TMZ concentration (ss Ct/Cp) ratio was significantly increased in the 20 mg/kg sunitinib group (0.98 ± 0.17) compared with the control (0.76 ± 0.17) and 60 mg/kg sunitinib (0.68 ± 0.09) groups. The ss Ct/Cp ratios were significantly correlated with the vascular normalization index (VNI), derived from the expression of CD31, collagen IV, and α-smooth muscle actin, which represents the fraction of functioning vessels out of the total tumor vessels. In conclusion, the effect of sunitinib on the brain tumor distribution of TMZ was dose dependent and indicated that optimal tumor exposure was achieved at a lower dose and was associated with the VNI.
Serum C-Peptide, Insulin-Like Growth Factor (IGF)-I, IGF-Binding Proteins, and Colorectal Cancer Risk in Women
Authors: R. Kaaks
Journal: JNCI Journal of the National Cancer Institute (2000)

Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York.We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided.Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]).Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I.
Consolidate the donor register with unambiguous affirmation from next of kin
Authors: M. D. D. Bell
Journal: BMJ (2012)

Shaw argues that we should not let families stop organ donation from their dead relatives.1 He seems never to have considered the practicalities of taking a brainstem dead ventilated patient to the operating theatre without the cooperation of the next of kin, or the practicalities of expecting the family to agree with an arbitrary time frame for removal …
Environmental Sequence Data from the Sargasso Sea Reveal That the Characteristics of Genome Reduction in Prochlorococcus Are Not a Harbinger for an Escalation in Genetic Drift
Authors: J. Hu, J. L. Blanchard
Journal: Molecular Biology and Evolution (2008)

The marine cyanobacterium Prochlorococcus MED4 has the smallest sequenced genome of any photosynthetic organism. Prochlorococcus MED4 shares many genomic characteristics with chloroplasts and bacterial endosymbionts, including a reduced coding capacity, missing DNA repair genes, a minimal transcriptional regulatory network, a marked AT% bias, and an accelerated rate of amino acid changes. In chloroplasts and endosymbionts, these molecular phenotypes appear to be symptomatic of a relative increase in genetic drift due to restrictions on effective population size in the host environment. As a free-living bacterium, Prochlorococcus MED4 is not known to be subject to similar ecological constraints. To test whether the high-light-adapted Prochlorococcus MED4 is experiencing a reduction in selection efficiency resulting from genetic drift, we examine two data sets, namely, the environmental genome shotgun sequencing data from the Sargasso Sea and a set of cyanobacterial genome sequences. After integrating these data sets, we compare the evolutionary profile of a high-light Prochlorococcus group to that of a group of Synechococcus (a closely related group of marine cyanobacteria) that does not exhibit a similar small-genome syndrome. The average pairwise dN/dS ratios in the high-light-adapted Prochlorococcus group are significantly lower than those in the Synechococcus group, leading us to reject the hypothesis that the Prochlorococcus group is currently experiencing higher levels of genetic drift.
The Expanding Role of Air Pollution in Cardiovascular Disease
Authors: C. Arden Pope
Journal: Circulation (2009)

S cientific efforts to understand the health effects of air pollution and public policy efforts to control air pollution have a fascinating history.The early "killer smog" episodes in Meuse Valley, Belgium (1930), Donora, Pa (1948), and London, UK (1952) provided stark evidence of deleterious respiratory and cardiovascular health effects of severe air pollution exposure.This evidence motivated early public policy efforts to improve air quality.In the United States, Britain, and elsewhere, legislative, regulatory, and related efforts to control air pollution were initiated.Ambient air quality standards and guidelines were established.Severe air pollution episodes were largely mitigated, and concern about adverse air pollution-related health effects abated.Nearly all air pollution researchers agreed that air pollution at very high concentrations posed serious health hazards.By the late 1970s and through the 1980s, however, it was argued by many that air pollution, at levels then common to the United States and Britain, was no longer a significant threat and that the potential health effects of air pollution could not be disentangled from effects from other factors.
Consumption of fresh fruit rich in vitamin C and wheezing symptoms in children
Authors: F. Forastiere
Journal: Thorax (2000)

A beneficial effect of fresh fruit consumption on lung function has been observed in several studies. The epidemiological evidence of the effect on respiratory symptoms and asthma is limited. The consumption of fruit rich in vitamin C was examined in relation to wheezing and other respiratory symptoms in cross sectional and follow up studies of Italian children.Standardised respiratory questionnaires were filled in by parents of 18 737 children aged 6-7 years living in eight areas of Northern and Central Italy. The winter intake of citrus fruit and kiwi fruit by the children was categorised as less than once per week, 1-2 per week, 3-4 per week, and 5-7 per week. A subset of 4104 children from two areas was reinvestigated after one year using a second parental questionnaire to record the occurrence of wheezing symptoms over the intervening period.In the cross sectional analysis, after controlling for several confounders (sex, study area, paternal education, household density, maternal smoking, paternal smoking, dampness or mould in the child's bedroom, parental asthma), intake of citrus fruit or kiwi fruit was a highly significant protective factor for wheeze in the last 12 months (odds ratio (OR) = 0.66, 95% confidence intervals (CI) 0.55 to 0.78, for those eating fruit 5-7 times per week compared with less than once per week), shortness of breath with wheeze (OR = 0.68, 95% CI 0.56 to 0.84), severe wheeze (OR = 0.59, 95% CI 0.40 to 0.85), nocturnal cough (OR = 0.73, 95% CI 0.65 to 0.83), chronic cough (OR = 0.75, 95% CI 0.65 to 0.88), and non-coryzal rhinitis (OR = 0.72, 95% CI 0.63 to 0.83). In the follow up study fruit intake recorded at baseline was a strong and independent predictor of all symptoms investigated except non-coryzal rhinitis. In most cases the protective effect was evident even among children whose intake of fruit was only 1-2 times per week and no clear dose-response relationship was found. The effect was stronger (although not significantly so (p = 0.13)) in subjects with a history of asthma; those eating fresh fruit at least once a week experienced a lower one year occurrence of wheeze (29. 3%) than those eating fruit less than once per week (47.1%) (OR = 0. 46, 95% CI 0.27 to 0.81).Although the effect of other dietary components cannot be excluded, it is concluded that the consumption of fruit rich in vitamin C, even at a low level of intake, may reduce wheezing symptoms in childhood, especially among already susceptible individuals.
Correlation of Antiarrhythmic Effects of Diphenylhydantoin with Digoxin-Induced Changes in Myocardial Contractility, Sodium-Potassium Adenosine Triphosphatase Activity, and Potassium Efflux
Authors: ROBERT E. GOLDSTEIN, STANLEY C. PENZOTTI, KAREN S. KUEHL, KIRK H. PRINDLE, CLIFFORD A. HALL, ELWOOD O. TITUS, STEPHEN E. EPSTEIN
Journal: Circulation Research (1973)

To clarify the suppressant action of diphenylhydantoin (DPH) on digitalis-induced arrhythmias we studied effects of DPH and digoxin, alone and in combination, on contractile force, sodium-potassium adenosinetriphosphatase (Na + -K + ATPase) activity, and potassium (K + ) balance in dog hearts perfused with Krebs-Ringer's solution. Neither control perfusion nor DPH alone (3 x 10 -5 M) altered Na + -K + ATPase activity or produced K + loss; DPH alone depressed contractile force. Digoxin alone (10 -6 M) caused a 59% rise in contractile force at the onset of arrhythmia along with a net rate of K + loss (K + efflux) of 50 ± 12, µmoles/min and a decrease in Na + -K + ATPase activity from 13.8 to 5.2 µmoles phosphorus/mg protein hour -1 ( P &lt; 0.001). Perfusion with combined DPH and digoxin delayed toxicity by 13 minutes (or 82%), at which time contractile force was higher (92% above base line, P&lt;0.05), K + efflux was greater (87 ± 20 µmoles/min), and Na + -K + ATPase activity was lower (2.6 µmoles/mg hour -1 , P &lt;0.05) than they were with digoxin alone. Combined DPH and digoxin perfusion lasting only until the time toxicity appeared with digoxin alone, however, yielded higher Na + -K + ATPase activity (7.7 µmoles/mg hour -1 , P &lt;0.02) and less rise in contractile force (25% above base line, P &lt;0.05). Thus, DPH appeared to retard digoxin-induced inhibition of Na + -K + ATPase activity. Nevertheless, digoxin in the presence of DPH ultimately produced greater inhibition of Na + -K + ATPase activity, greater increase in contractile force, and greater K + efflux prior to toxicity than did digoxin without DPH. These findings suggest that the antiarrhythmic effects of DPH cannot be attributed solely to prevention of inhibition of Na + -K + ATPase activity or to diminution of K + efflux, two changes characteristically accompanying digoxin administration.
Akt Activation Synergizes with <i>Trp53</i> Loss in Oral Epithelium to Produce a Novel Mouse Model for Head and Neck Squamous Cell Carcinoma
Authors: Marta Moral, Carmen Segrelles, M. Fernanda Lara, Ana Belén Martínez-Cruz, Corina Lorz, Mirentxu Santos, Ramón García-Escudero, Jerry Lu, Kaoru Kiguchi, Agueda Buitrago, Clotilde Costa, Cristina Saiz, Jose L. Rodriguez-Peralto, Francisco J. Martinez-Tello, Maria Rodriguez-Pinilla, Montserrat Sanchez-Cespedes, Marina Garín, Teresa Grande, Ana Bravo, John DiGiovanni, Jesús M. Paramio
Journal: Cancer Research (2009)

Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia with poor prognosis and survival that frequently displays Akt overactivation. Here we show that mice displaying constitutive Akt activity (myrAkt) in combination with Trp53 loss in stratified epithelia develop oral cavity tumors that phenocopy human HNSCC. The myrAkt mice develop oral lesions, making it a possible model of human oral dysplasia. The malignant conversion of these lesions, which is hampered due to the induction of premature senescence, is achieved by the subsequent ablation of Trp53 gene in the same cells in vivo. Importantly, mouse oral tumors can be followed by in vivo imaging, show metastatic spreading to regional lymph nodes, and display activation of nuclear factor-kappaB and signal transducer and activator of transcription-3 pathways and decreased transforming growth factor-beta type II receptor expression, thus resembling human counterparts. In addition, malignant conversion is associated with increased number of putative tumor stem cells. These data identify activation of Akt and p53 loss as a major mechanism of oral tumorigenesis in vivo and suggest that blocking these signaling pathways could have therapeutic implications for the management of HNSCC.
p73 Regulates Neurodegeneration and Phospho-Tau Accumulation during Aging and Alzheimer's Disease
Authors: Monica K. Wetzel, Sibel Naska, Christine L. Laliberté, Vladimir V. Rymar, Masashi Fujitani, Jeffrey A. Biernaskie, Christy J. Cole, Jason P. Lerch, Shoshana Spring, S.-H. Wang, Paul W. Frankland, R. Mark Henkelman, Sheena A. Josselyn, Abbas F. Sadikot, Freda D. Miller, David R. Kaplan
Journal: Neuron (2008)
Haemopoietic stem cell transplantation in the treatment of severe autoimmune diseases 2000
Authors: A Tyndall
Journal: Annals of the Rheumatic Diseases (2001)

An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries, with the aim of assessing the existing data on autologous haemopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease, and to decide on future trial planning. Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others. The major disease categories and number of patients receiving transplant were: multiple sclerosis (MS) 127, systemic sclerosis (SSc) 72, rheumatoid arthritis (RA) 70, juvenile idiopathic arthritis (JIA) 36, systemic lupus erythematosus (SLE) 34, dermatomyositis/polymyositis (DM/PM) 5, idiopathic thrombocytopenic purpura (ITP) 7. Single or several cases of other autoimmune diseases were reported. Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA. Treatment was associated with a significant morbidity and mortality. In the EULAR/EBMT database (71 centres in 22 countries), a mobilisation associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases. The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA. After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomised phase III trials are now appropriate in SSc, MS, and RA. A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and vasculitis. The need for continuing collection of all cases after mobilisation by the standardised EBMT and IBMTR data forms was emphasised.
Optimizing the Frequency of Follow-Up Visits for Patients Treated for Localized Primary Cutaneous Melanoma
Authors: Robin M. Turner, Katy J.L. Bell, Rachael L. Morton, Andrew Hayen, Anne Brecht Francken, Kirsten Howard, Bruce Armstrong, John F. Thompson, Les Irwig
Journal: Journal of Clinical Oncology (2011)

To develop more evidence-based guidelines for the frequency of patient follow-up after treatment of localized (American Joint Committee on Cancer [AJCC] stage I or II) melanoma.We used data from Melanoma Institute Australia on an inception cohort of 3,081 consecutive patients first diagnosed with stage I or II melanoma between January 1985 and December 2009. Kaplan-Meier curves and Cox models were used to characterize the time course and predictors for recurrence and new primaries. We modeled the delay in diagnosis of recurrence or new primary as well as the number of monitoring visits required using two monitoring schedules: first, according to 2008 Australian and New Zealand guidelines and, second, with fewer visits, especially for those at lowest risk of recurrence.For every 1,000 patients beginning follow-up, 229 developed recurrence and 61 developed new primary within 10 years. There was only a small difference in modeled delay in diagnosis (extra 44.9 and 9.6 patients per 1,000 for recurrence and new primary, respectively, with delay greater than 2 months) using a schedule that requires far fewer visits (3,000 fewer visits per 1,000 patients) than recommended by current guidelines. AJCC substage was the most important predictor of recurrence, whereas age and date of primary diagnosis were important predictors of developing new primary.By providing less intensive monitoring, more efficient follow-up strategies are possible. Fewer visits with a more focused approach may address the needs of patients and clinicians to detect recurrent or new melanoma.