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Hannes Schuler, Peter Kern, Wolfgang Arthofer, Heidrun Vogt, Maximilian Fischer, Christian Stauffer, Markus Riegler
The eastern cherry fruit fly, Rhagoletis cingulata Loew (Diptera: Tephritidae), is an economically important pest of cherries in North America. In 1983 it was first reported in Europe where it shares its ecological niche with the native European cherry fruit fly, Rhagoletis cerasi L. (Diptera: Tephritidae). Their coexistence in Europe led to the recent horizontal transmission of the Wolbachia strain wCer1 from R. cerasi to R. cingulata Horizontal Wolbachia transmission is mediated by either sharing of ecological niches or by interacting species such as parasitoids...
October 15, 2016: Environmental Entomology
Maarten Danial, Angela Stauffer, Frederik R Wurm, Michael J Root, Harm-Anton Klok
A popular strategy to overcome the limited plasma half-life of peptide heptad repeat 2 (HR2) fusion inhibitors against HIV-1 is through conjugation with biocompatible polymers such as poly(ethylene glycol) (PEG). However, despite improved resistance to proteolysis and reduced renal elimination, covalent attachment of polymers often causes a loss in therapeutic potency. In this study, we investigated the molecular origins of the loss in potency upon conjugation of linear, mid-functional and hyperbranched PEG-like polymers to peptides that inhibit HIV-1 - host cell membrane fusion...
October 13, 2016: Bioconjugate Chemistry
Hazem M Zakaria, John A Stauffer, Massimo Raimondo, Timothy A Woodward, Michael B Wallace, Horacio J Asbun
AIM: To identify the current indications and outcomes of total pancreatectomy at a high-volume center. METHODS: A single institutional retrospective study of patients undergoing total pancreatectomy from 1995 to 2014 was performed. RESULTS: One hundred and three patients underwent total pancreatectomy for indications including: Pancreatic ductal adenocarcinoma (n = 42, 40.8%), intraductal papillary mucinous neoplasms (n = 40, 38.8%), chronic pancreatitis (n = 8, 7...
September 27, 2016: World Journal of Gastrointestinal Surgery
Shan Li, Adrianus F Konings, Jay R Jr Stauffer
Lake Malaŵi is known for its endemic haplochromine species flock, most notably the rock-dwelling cichlids known as mbuna. The group of mbuna referred to as the Pseudotropheus elongatus species group is currently comprised of Metriaclima spp., Tropheops spp., Cynotilapia spp., and Pseudotropheus spp. In this study, Chindongo, a new genus with the type species C. bellicosus, is described for additional species in this group. Chindongo is distinguished from other mbuna genera by 1) the presence of bicuspid teeth in the anterior portion of the outer row of both upper and lower jaw; 2) a moderately to steeply sloped vomer with a narrow rostral tip which makes an angle of between 53° and 68° with the parasphenoid; 3) a small mouth with the lower jaw slightly shorter than the upper; 4) a broad anterior dentigerous area on both premaxilla and dentary with three or more rows of teeth (usually 5-6 rows); 5) a flank melanin pattern consisting of vertical bars without horizontal elements at any stage of development...
September 15, 2016: Zootaxa
Julia M Selfridge, Tetsuya Gotoh, Samuel Schiffhauer, JingJing Liu, Philip E Stauffer, Andrew Li, Daniel G S Capelluto, Carla V Finkielstein
Circadian rhythms are a collection of endogenously driven biochemical, physiological, and behavioral processes that oscillate in a 24-h cycle and can be entrained by external cues. Circadian clock molecules are responsible for the expression of regulatory components that modulate, among others, the cell's metabolism and energy consumption. In clinical practice, the regulation of clock mechanisms is relevant to biotransformation of therapeutics. Accordingly, xenobiotic metabolism and detoxification, the two processes that directly influence drug effectiveness and toxicity, are direct manifestations of the daily oscillations of the cellular and biochemical processes taking place within the gastrointestinal, hepatic/biliary, and renal/urologic systems...
October 3, 2016: Drugs
Janina Stauffer, Bineet Panda, Tapio Eeva, Miia Rainio, Petteri Ilmonen
Telomere length may reflect the expected life span and possibly individual quality. Environmental stressors are known to increase oxidative stress and accelerate telomere attrition: however the interactions between redox status and telomere dynamics are not fully understood. We investigated whether exposure to heavy metal pollution is associated with oxidative stress and telomere damage in two insectivorous passerines, the Great tit (Parus major) and the Pied flycatcher (Ficedula hypoleuca). We were also interested to know whether within-brood competition could influence the nestling redox status or telomere length...
September 29, 2016: Science of the Total Environment
Virginia L Stauffer, Peng Liu, Celine Goldberger, Lauren B Marangell, Craig Nelson, Philip Gorwood, Maurizio Fava
OBJECTIVE: To identify symptoms potentially representative of a noradrenergic symptom cluster as possible predictors of response to the selective norepinephrine reuptake inhibitor (NRI) edivoxetine when used as monotherapy or adjunctive treatment in patients with DSM-IV-TR major depressive disorder (MDD). METHODS: Pooled data from 4 adjunctive treatment trials (selective serotonin reuptake inhibitor [SSRI] + edivoxetine 6-18 mg/d vs SSRI + placebo; N = 2,066) and data from 1 monotherapy trial (edivoxetine 6-18 mg/d versus placebo; N = 495) were used to identify predictors of response related to noradrenergic symptoms using a resampling-based ensemble tree method...
September 27, 2016: Journal of Clinical Psychiatry
Caitlin A Dow, Grace M Lincenberg, Jared J Greiner, Brian L Stauffer, Christopher A DeSouza
Metabolic syndrome (MetS) typically presents with obesity; however, obesity is not a requisite characteristic for MetS classification and related vascular risk. We tested the hypothesis that MetS, independent of excess adiposity, is associated with impaired endothelial vasodilator dysfunction. Thirty-two sedentary, middle-aged adults were studied: 11 normal weight (9 male and 2 female; body mass index (BMI), 24.0 ± 0.3 kg/m(2)); 11 normal weight with MetS (9 male and 2 female; BMI, 24.7 ± 0.3 kg/m(2)); and 10 obese without MetS (8 male and 2 female; BMI, 31...
October 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Katie Jo Stauffer, Alisa Arunamata, Shreyas S Vasanawala, Sarina K Behera, Alaina K Kipps, Norman H Silverman
The levoatrial cardinal vein (LACV), first described in 1926, acts as a decompressing vessel for pulmonary venous return in cases of severe left-sided obstruction with an intact or significantly restrictive atrial septum. The LACV and the persistent left superior vena cava (LSVC) are thought to share similar embryologic origins. To challenge this notion, we present a unique case of a neonate with hypoplastic left heart syndrome, cor triatriatum, and a decompressing LACV in the presence of bilateral superior venae cavae...
September 2016: Echocardiography
J R Jr Stauffer, A F Konings, T M Ryan
Pseudotropheus livingstonii and P. elegans are two sand-dwelling cichlid species that belong to the so-called mbuna, a group of predominantly rock-dwelling haplochromines of Lake Malaŵi. The identity of these two species has confused taxonomists for almost a century until a recent rediscovery of representatives of P. elegans close to its type locality. New diagnoses for both species are provided.
2016: Zootaxa
William R Stauffer, Armin Lak, Aimei Yang, Melodie Borel, Ole Paulsen, Edward S Boyden, Wolfram Schultz
Optogenetic studies in mice have revealed new relationships between well-defined neurons and brain functions. However, there are currently no means to achieve the same cell-type specificity in monkeys, which possess an expanded behavioral repertoire and closer anatomical homology to humans. Here, we present a resource for cell-type-specific channelrhodopsin expression in Rhesus monkeys and apply this technique to modulate dopamine activity and monkey choice behavior. These data show that two viral vectors label dopamine neurons with greater than 95% specificity...
September 8, 2016: Cell
Vijay Mohan K Namboodiri, Garret D Stuber
The recent advent of technologies enabling cell-type-specific recording and manipulation of neuronal activity spurred tremendous progress in neuroscience. However, they have been largely limited to mice, which lack the richness in behavior of primates. Stauffer et al. now present a generalizable method for achieving cell-type specificity in monkeys.
September 8, 2016: Cell
Matthew Goers, Maurice O Ope, Aaron Samuels, Natalia Gitu, Saul Akandwanaho, Gladys Nabwami, Raymond Nyoka, Martin S Cetron, Warren Dalal, Andrea L Conroy, Paul Cantey, Chandy John, Marwan Naoum, Michelle Weinberg, Nina Marano, William Stauffer
Approximately 70,000-90,000 refugees are resettled to the United States each year, and during the next 5 years, 50,000 Congolese refugees are expected to arrive in the United States. The International Organization for Migration (IOM) performs refugee medical examinations overseas for the U.S. Refugee Resettlement Program. In 2014, IOM reported that a large number of U.S.-bound Congolese refugees from Uganda had spleens that were enlarged on examination. During two evaluations of refugee populations in western Uganda in March and July 2015, refugees with splenomegaly on physical examination were offered additional assessment and treatment, including abdominal ultrasonography and laboratory testing...
2016: MMWR. Morbidity and Mortality Weekly Report
John A Stauffer, Alessandro Coppola, Diego Villacreses, Kabir Mody, Elizabeth Johnson, Zhuo Li, Horacio J Asbun
BACKGROUND: Pancreaticoduodenectomy remains as the only treatment that offers a chance for cure in patients with pancreatic ductal adenocarcinoma (PDAC) of the head of the pancreas. In recent years, laparoscopic pancreaticoduodenectomy (LPD) has been introduced as a feasible alternative to open pancreaticoduodenectomy (OPD) when performed by experienced surgeons. This study reviews and compares perioperative results and long-term survival of patients undergoing LPD versus OPD at a single institution over a 20-year time period...
September 7, 2016: Surgical Endoscopy
Philippe Sonnet, Louise Stauffer, Marie Gille, David Bléger, Stefan Hecht, Cesare Cejas, Gérald Dujardin, Andrew Mayne
In the framework of Density Functional Theory (DFT), we investigate the adsorption of the halogenated polycyclic aromatic hydrocarbon 2,11-diiodohexabenzocoronene (HBC-I2) on the SiC(0001)-3x3 surface. Non-dissociative and dissociative molecular adsorption is considered, and the simulated STM images are compared with the corresponding experimental observations. Our calculations show that dissociative adsorption is favourable. The calculations reveal the crucial importance of the extended flat carbon core on the molecule-surface interaction in dissociative adsorption, while the iodine atom-surface interaction is of minor importance...
September 6, 2016: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Vibe Skov, Mark Burton, Mads Thomassen, Thomas Stauffer Larsen, Caroline H Riley, Ann Brinch Madelung, Lasse Kjær, Henrik Bondo, Inger Stamp, Mats Ehinger, Rasmus Dahl-Sørensen, Nana Brochmann, Karsten Nielsen, Jürgen Thiele, Morten K Jensen, Ole Weis Bjerrum, Torben A Kruse, Hans Carl Hasselbalch
Recent studies have shown that a large proportion of patients classified as essential thrombocythemia (ET) actually have early primary prefibrotic myelofibrosis (prePMF), which implies an inferior prognosis as compared to patients being diagnosed with so-called genuine or true ET. According to the World Health Organization (WHO) 2008 classification, bone marrow histology is a major component in the distinction between these disease entities. However, the differential diagnosis between them may be challenging and several studies have not been able to distinguish between them...
2016: PloS One
Klemens Hoegenauer, Nicolas Soldermann, Frédéric Stauffer, Pascal Furet, Nadege Graveleau, Alexander B Smith, Christina Hebach, Gregory J Hollingworth, Ian Lewis, Sascha Gutmann, Gabriele Rummel, Mark Knapp, Romain M Wolf, Joachim Blanz, Roland Feifel, Christoph Burkhart, Frédéric Zécri
Inhibition of the lipid kinase PI3Kδ is a promising principle to treat B and T cell driven inflammatory diseases. Using a scaffold deconstruction-reconstruction strategy, we identified 4-aryl quinazolines that were optimized into potent PI3Kδ isoform selective analogues with good pharmacokinetic properties. With compound 11, we illustrate that biochemical PI3Kδ inhibition translates into modulation of isoform-dependent immune cell function (human, rat, and mouse). After oral administration of compound 11 to rats, proximal PD markers are inhibited, and dose-dependent efficacy in a mechanistic plaque forming cell assay could be demonstrated...
August 11, 2016: ACS Medicinal Chemistry Letters
Chao Chen, Hugh Zhu, Frédéric Stauffer, Giorgio Caravatti, Susanne Vollmer, Rainer Machauer, Philipp Holzer, Henrik Möbitz, Clemens Scheufler, Martin Klumpp, Ralph Tiedt, Kim S Beyer, Keith Calkins, Daniel Guthy, Michael Kiffe, Jeff Zhang, Christoph Gaul
Oncogenic MLL fusion proteins aberrantly recruit Dot1L, a histone methyltransferase, to ectopic loci, leading to local hypermethylation of H3K79 and misexpression of HoxA genes driving MLL-rearranged leukemias. Inhibition of the methyltransferase activity of Dot1L in this setting is predicted to reverse aberrant H3K79 methylation, leading to repression of leukemogenic genes and tumor growth inhibition. In the context of our Dot1L drug discovery program, high-throughput screening led to the identification of 2, a weak Dot1L inhibitor with an unprecedented, induced pocket binding mode...
August 11, 2016: ACS Medicinal Chemistry Letters
Clemens Scheufler, Henrik Möbitz, Christoph Gaul, Christian Ragot, Céline Be, César Fernández, Kim S Beyer, Ralph Tiedt, Frédéric Stauffer
Mixed lineage leukemia (MLL) gene rearrangement induces leukemic transformation by ectopic recruitment of disruptor of telomeric silencing 1-like protein (DOT1L), a lysine histone methyltransferase, leading to local hypermethylation of H3K79 and misexpression of genes (including HoxA), which drive the leukemic phenotype. A weak fragment-based screening hit identified by SPR was cocrystallized with DOT1L and optimized using structure-based ligand optimization to yield compound 8 (IC50 = 14 nM). This series of inhibitors is structurally not related to cofactor SAM and is not interacting within the SAM binding pocket but induces a pocket adjacent to the SAM binding site...
August 11, 2016: ACS Medicinal Chemistry Letters
Nathan M Shaw, Craig Stauffer, Michael L Eisenberg
OBJECTIVE: To report the finding and management of a case of Leydig cell tumor discovered during the infertility evaluation of a patient with mosaic Klinefelter syndrome. DESIGN: Single case report. SETTING: Academic hospital. PATIENT(S): Patient seeking assistance with fertility after a diagnosis of mosaic Klinefelter syndrome. INTERVENTION(S): The patient underwent microscopic testicular sperm extraction (mTESE) for sperm identification after the diagnosis of mosaic Klinefelter syndrome...
August 11, 2016: Fertility and Sterility
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