Exposure to acetylcholinesterase inhibitors alters the physiology and motor function of honeybees

Cholinergic signalling is fundamental to neuro-muscular function in most organisms. Sub-lethal doses of neurotoxic pesticides that target cholinergic signalling can alter the behaviour of insects in subtle ways; their influence on non-target organisms may not be readily apparent in simple mortality studies. Beneficial arthropods such as honeybees perform sophisticated behavioural sequences during foraging that, if influenced by pesticides, could impair foraging success and reduce colony health. Here, we investigate the behavioural effects on honeybees of exposure to a selection of pesticides that target cholinergic signalling by inhibiting acetylcholinesterase (AChE). To examine how continued exposure to AChE inhibitors affected motor function, we fed adult foraging worker honeybees sub-lethal concentrations of these compounds in sucrose solution for 24 h. Using an assay for locomotion in bees, we scored walking, stopped, grooming, and upside down behaviour continuously for 15 min. At a 10nM concentration, all the AChE inhibitors caused similar effects on behaviour, notably increased grooming activity and changes in the frequency of bouts of behaviour such as head grooming. Coumaphos caused dose-dependent effects on locomotion as well as grooming behaviour, and a 1µM concentration of coumaphos induced symptoms of malaise such as abdomen grooming and defecation. Biochemical assays confirmed that the 4 compounds we assayed (coumaphos, aldicarb, chlorpyrifos, and donepezil) or their metabolites acted as AChE inhibitors in bees. Furthermore, we show that transcript expression levels of two honeybee acetylcholinesterase inhibitors were selectively upregulated in the brain and in gut tissues in response to AChE inhibitor exposure. The results of our study imply that the effects of pesticides that rely on this mode of action have subtle yet profound effects on physiological effects on behaviour that could lead to reduced survival

Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprin

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malignancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macrocytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response. © 2010 Soman et al., publisher and licensee Adis Data Information BV

Process, Mechanism, and Modeling in Macroecology

Macroecology has traditionally relied on descriptive characterization of large-scale ecological patterns to offer narrative explanations for the origin and maintenance of those patterns. Only recently have macroecologists begun to employ models termed ‘process-based’ and ‘mechanistic’, in contrast to other areas of ecology, where such models have a longer history. Here, we define and differentiate between process-based and mechanistic features of models, and we identify and discuss important advantages of working with models possessing such features. We describe some of the risks associated with process-based and mechanistic model-centered research programs, and we propose ways to mitigate these risks. Giving process-based and mechanistic models a more central role in research programs can reinvigorate macroecology by strengthening the link between theory and data

Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprine

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malig-nancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macro¬cytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response

The Lantern Vol. 52, No. 2, Spring 1986

• The Cartoonist • Balance • Haiku • Moment of Truth • There Was a Man • Mad Song / Cassandra\u27s Song • Part I - The Descent • Political Thought • Beast • Questions Yet Unanswered • Aphrodite: A Lover\u27s Lament • The Most Limber Boy • Style And • Thoughts From My Confusion • Andy • Momma Wake Up • In The Suburbs • Tommy • When the Phone Rings • There\u27s Something Soothing • Starting Over • A Day in the Life of a Flower • Pretension • It Seems Like So Long Ago • I Walk Along • Insignificant Man • Variations on a Latin Theme • The Riddle • Roll the Dice - Its Your Turn • This Is Your Day • One Night Stand • Make My Day • You Really Can\u27t Expect • Medusa • Don\u27t Think • Broken Chain • Life...A Hammock? • To My Friend • Ode On a Grecian Keghttps://digitalcommons.ursinus.edu/lantern/1128/thumbnail.jp

The Lantern Vol. 51, No. 2, Spring 1985

• Electric Pink • Derby Day • Conversation • Seasons of Sonnets • Long After Killing Us • Haunting Memory • Sacrifice • Is This Positive Enough? • My Teddy Bear • A Gentleman of Ten • Hartman Center • Yesterday\u27s Child • Mors Pueris • Momentary Reflections • Children Sleeping • There\u27s No Place Like Home • I Set My Pleasures Adrift • The Beer Can • Fragments of an Epic • Actaeon • She Sleeps • Chicago • Death Light • Tea With Louise • Balance • The Rivers • Chapel • The Hour of Prayer • Une Fille / Une Femme • A One-Way Mirror • Nonconformity • Cada Noche, Lloro • Reflections on an Empty House Down the Street • Evening Melancholy • Abandoned Road • Big Boy • Baby Brothers • Metro Oscuro • Chuchoterhttps://digitalcommons.ursinus.edu/lantern/1126/thumbnail.jp

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12.

Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants.To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation.3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array. An analysis of risk of COPD was carried out using ever smoking controls (n=4784). Associations with %predicted FEV1 were tested in cases. We followed-up signals of interest (p<10(-5)) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays.Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10(-6)). In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10(-6)). We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5. No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10(-7)).This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study

Degradation of Internalized αvβ5 Integrin Is Controlled by uPAR Bound uPA: Effect on β1 Integrin Activity and α-SMA Stress Fiber Assembly

Myofibroblasts (Mfs) that persist in a healing wound promote extracellular matrix (ECM) accumulation and excessive tissue contraction. Increased levels of integrin αvβ5 promote the Mf phenotype and other fibrotic markers. Previously we reported that maintaining uPA (urokinase plasminogen activator) bound to its cell-surface receptor, uPAR prevented TGFβ-induced Mf differentiation. We now demonstrate that uPA/uPAR controls integrin β5 protein levels and in turn, the Mf phenotype. When cell-surface uPA was increased, integrin β5 levels were reduced (61%). In contrast, when uPA/uPAR was silenced, integrin β5 total and cell-surface levels were increased (2–4 fold). Integrin β5 accumulation resulted from a significant decrease in β5 ubiquitination leading to a decrease in the degradation rate of internalized β5. uPA-silencing also induced α-SMA stress fiber organization in cells that were seeded on collagen, increased cell area (1.7 fold), and increased integrin β1 binding to the collagen matrix, with reduced activation of β1. Elevated cell-surface integrin β5 was necessary for these changes after uPA-silencing since blocking αvβ5 function reversed these effects. Our data support a novel mechanism by which downregulation of uPA/uPAR results in increased integrin αvβ5 cell-surface protein levels that regulate the activity of β1 integrins, promoting characteristics of the persistent Mf