bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diel behaviour and time budget of the adult pine weevil Hylobius abietis
Authors: Fedderwitz Frauke , Björklund Niklas , Ninkovic Velemir , Nordlander Göran 
Published: April 2014

AbstractThe pine weevil [Hylobius abietis (L.); Coleoptera: Curculionidae] has a high economic impact on forest regeneration in Europe. The general biology of the pine weevil has received considerable attention, although there is insufficient knowledge about its diel behaviour and time budget. Therefore, in the present study, the feeding and locomotion behaviour of individual adult weevils on Norway spruce seedlings [Picea abies (L.) Karst.] is observed for 24‐h periods in the laboratory. Both girdled and nongirdled seedlings are used to assess how the behaviour of weevils is influenced by the physiological response of plants to the girdling. The locomotion pattern shows a distinct maximum during the beginning of the dark phase, whereas most feeding occurs during the second half of the dark phase and the first hours of the subsequent light phase. The girdling treatment increases the time that weevils spend on the seedlings during the first part of an observation session, although it has no effect on their feeding pattern. The time budgets of weevils on girdled and nongirdled seedlings are similar. On average, weevils spend 34% of their time in locomotion and 6% on feeding. Females spend more time feeding than males (7.1% versus 4.2%), possibly because they have higher food requirements (e.g. for egg production). Females also spend more time in total on the seedlings than males (26.3% versus 7.0%). The present study reveals, in high temporal resolution, the diel feeding and locomotion behaviour and time budget of male and female pine weevils.
Ubiquitin–proteasome‐mediated degradation of S‐RNase in a solanaceous cross‐compatibility reaction
Authors: Entani Tetsuyuki , Kubo Ken‐ichi , Isogai Shin , Fukao Yoichiro , Shirakawa Masahiro , Isogai Akira , Takayama Seiji 
Published: April 2014

SummaryMany plants have a self‐incompatibility (SI) system in which the rejection of self‐pollen is determined by multiple haplotypes at a single locus, termed S. In the Solanaceae, each haplotype encodes a single ribonuclease (S‐RNase) and multiple S‐locus F‐box proteins (SLFs), which function as the pistil and pollen SI determinants, respectively. S‐RNase is cytotoxic to self‐pollen, whereas SLFs are thought to collaboratively recognize non‐self S‐RNases in cross‐pollen and detoxify them via the ubiquitination pathway. However, the actual mechanism of detoxification remains unknown. Here we isolate the components of a SCFSLF (SCF = SKP1‐CUL1‐F‐box‐RBX1) from Petunia pollen. The SCFSLF polyubiquitinates a subset of non‐self S‐RNases in vitro. The polyubiquitinated S‐RNases are degraded in the pollen extract, which is attenuated by a proteasome inhibitor. Our findings suggest that multiple SCFSLF complexes in cross‐pollen polyubiquitinate non‐self S‐RNases, resulting in their degradation by the proteasome.
Pathogen reduction treatment using riboflavin and ultraviolet light impairs platelet reactivity toward specific agonists in vitro
Authors: Zeddies Sabrina , De Cuyper Iris M. , van der Meer Pieter F. , Daal Brunette B. , de Korte Dirk , Gutiérrez Laura , Thijssen‐Timmer Daphne C. 
Published: April 2014

BackgroundRecent studies showed that Mirasol pathogen reduction treatment (PRT) leads to increased P‐selectin expression and increased oxygen and glucose consumption in resting platelets (PLTs). This study investigates the effect of PRT on PLT activation.Study Design and MethodsUntreated or Mirasol‐treated PLTs were analyzed at different time points during storage. Microaggregation upon stimulation with phorbol myristate acetate (PMA), convulxin, and ristocetin was measured. Alpha granule contents and release upon thrombin stimulation were assessed by flow cytometry and Western blotting. PLT spreading was determined on collagen‐coated glass slides.ResultsMirasol PRT led to spontaneous aggregation (hyperreactivity), as measured by flow cytometry in the absence of agonist throughout storage time. PMA‐induced aggregation was significantly higher in Mirasol PRT PLTs compared to controls. Aggregation in response to convulxin and ristocetin was significantly lower and directly influenced by storage time after Mirasol PRT, compared to untreated stored PLT concentrates. Despite the reported hyperreactivity of resting PLTs, PLT activation with thrombin on Day 8 after Mirasol PRT resulted in less P‐selectin–positive PLTs. Furthermore, platelet factor 4 (PF4) secretion was reduced upon thrombin stimulation on Day 8 after PRT compared to controls. Significantly decreased spreading of Mirasol PRT PLTs over collagen‐coated slides was observed directly after PRT and persisted throughout storage.ConclusionMirasol PRT leads to hyperreactive PLTs, probably caused by continuous basal degranulation through storage time. This results in a reduction in the degranulation capacity upon acute stimulation, which influences PLT spreading, but not overtly microaggregation. The clinical relevance needs to be investigated.
High Proportion of Heteroresistance in
gyrA
and
gyrB
in Fluoroquinolone-Resistant Mycobacterium tuberculosis Clinical Isolates
Authors: Eilertson Brandon , Maruri Fernanda , Blackman Amondrea , Herrera Miguel , Samuels David C. , Sterling Timothy R. 
Published: April 2014

ABSTRACT

Heteroresistance is the coexistence of populations with differing nucleotides at a drug resistance locus within a sample of organisms. Although Sanger sequencing is the gold standard for sequencing, it may be less sensitive than deep sequencing for detecting fluoroquinolone heteroresistance in
Mycobacterium tuberculosis
. Twenty-seven fluoroquinolone monoresistant and 11 fluoroquinolone-susceptible
M. tuberculosis
isolates were analyzed by Sanger and Illumina deep sequencing. Individual sequencing reads were analyzed to detect heteroresistance in the
gyrA
and
gyrB
genes. Heteroresistance to fluoroquinolones was identified in 10/26 (38%) phenotypically fluoroquinolone-resistant samples and 0/11 (
P
= 0.02) fluoroquinolone-susceptible controls. One resistant sample was excluded because of contamination with the laboratory strain
M. tuberculosis
H37Rv. Sanger sequencing revealed resistance-conferring mutations in 15 isolates, while deep sequencing revealed mutations in 20 isolates. Isolates with fluoroquinolone resistance-conferring mutations by Sanger sequencing all had at least those same mutations identified by deep sequencing. By deep sequencing, 10 isolates had a single fixed (defined as >95% frequency) mutation, while 10 were heteroresistant, 5 of which had a single unfixed (defined as <95% frequency) mutation and 5 had multiple unfixed mutations. Illumina deep sequencing identified a higher proportion of fluoroquinolone-resistant
M. tuberculosis
isolates with heteroresistance than did Sanger sequencing. The heteroresistant isolates frequently demonstrated multiple mutations, but resistant isolates with fixed mutations each had only a single mutation.
Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication
Authors: Liu Kai Y. , Du Fang C. , Fu Qiang , Zhang Wei J. , Sun Hong W. , Zhang Yi , Gan Le L. , Yue Zhi Y. , Zou Quan M. , Guo Gang 
Published: April 2014

ABSTRACT

This study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of
Helicobacter pylori
. Mongolian gerbils infected with
H. pylori
received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of
H. pylori
. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (
P
= 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in
H. pylori
eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on
H. pylori
collectively. Thus, pronase may enhance the level of antibiotics for eradication of
H. pylori
in the clinic.
The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection
Authors: Chen Gang , Wang Xiaowei , Severo Maiara S. , Sakhon Olivia S. , Sohail Mohammad , Brown Lindsey J. , Sircar Mayukh , Snyder Greg A. , Sundberg Eric J. , Ulland Tyler K. , Olivier Alicia K. , Andersen John F. , Zhou Yi , Shi Guo-Ping , Sutterwala Fayyaz S. , Kotsyfakis Michail , Pedra Joao H. F. 
Published: April 2014

ABSTRACT

Saliva from arthropod vectors facilitates blood feeding by altering host inflammation. Whether arthropod saliva counters inflammasome signaling, a protein scaffold that regulates the activity of caspase-1 and cleavage of interleukin-1β (IL-1β) and IL-18 into mature molecules, remains elusive. In this study, we provide evidence that a tick salivary protein, sialostatin L2, inhibits inflammasome formation during pathogen infection. We show that sialostatin L2 targets caspase-1 activity during host stimulation with the rickettsial agent
Anaplasma phagocytophilum
.
A. phagocytophilum
causes macrophage activation and hemophagocytic syndrome features. The effect of sialostatin L2 in macrophages was not due to direct caspase-1 enzymatic inhibition, and it did not rely on nuclear factor κB or cathepsin L signaling. Reactive oxygen species from NADPH oxidase and the Loop2 domain of sialostatin L2 were important for the regulatory process. Altogether, our data expand the knowledge of immunoregulatory pathways of tick salivary proteins and unveil an important finding in inflammasome biology.
Comparison of Becton Dickinson Vacutainer rapid serum tube with the serum separator tube for routine chemistry and immunoassay tests
Authors: Yan Ronald , Lou Amy , Watts Gail , Tarr Heather , Smith Hilary , Kinney Lois , Chen Yu 
Published: April 2014

AimsTo shorten the clotting time and resolve the delayed clotting or no clotting on specimens from patients on anticoagulant therapy, Becton Dickinson (BD) recently developed the Vacutainer rapid serum tube (RST). The aim of this study was to systematically compare the new RST tube with the widely used serum separator tube (SST) for routine chemistry and immunoassay tests on 3 common analyser platforms.MethodsBlood from 45 people (24 women and 21 men, age 21–77 years) was collected using the SST and RST tubes in sequence. Sera from both tubes were separated and analysed simultaneously for 54, 50, and 10 chemistry and/or immunoassay tests on the Roche Modular, Abbott Architect, and Siemens Centaur analysers, respectively.ResultsThe results from the RST tube were comparable with those from the SST tube on most analytes. Although the results for a few analytes showed statistically significant differences between the two tubes (p<0.05), the differences had no clinical significance for most assays. Only for parathyroid hormone on the Abbott Architect, the RST tube demonstrated clinical significant bias versus the SST tube (−15.3%, p<0.01).ConclusionsThe RST tube provides acceptable performance for routine chemistry and immunoassay tests.
Interview with Bebo White
Authors: Atzenbeck Claus 
Published: April 2014

Bebo White is a Departmental Associate (Emeritus) at the SLAC National Accelerator Laboratory, the U.S. national laboratory for high-energy physics and basic energy science at Stanford University. Working as a computational physicist, he first became involved with the emerging Web technology while on sabbatical at CERN in 1989.
Upon his return he was part of the team that established the first American Web site at SLAC (the fifth site in the world). Ever since, his academic research interests have evolved in parallel with Web technology. He is often considered to be the "first American Webmaster" and one of the founders of the discipline of Web Engineering.
In addition to his work at SLAC, he also holds faculty appointments at several other institutions, is involved with a number of major conferences series, and is a frequent conference speaker. He is the author (or co-author) of nine books, and over 100 papers and journal articles. His current research interests are Web Science, Social Media in Education, and Cloud Computing. However, given the opportunity, he will talk mercilessly about high-energy physics, jug band music and wine.
Additional information can be found at www.bebowhite.com
Endogenous Two-Photon Fluorescence Imaging Elucidates Metabolic Changes Related to Enhanced Glycolysis and Glutamine Consumption in Precancerous Epithelial Tissues
Authors: Varone Antonio , Xylas Joanna , Quinn Kyle P. , Pouli Dimitra , Sridharan Gautham , McLaughlin-Drubin Margaret E. , Alonzo Carlo , Lee Kyongbum , Münger Karl , Georgakoudi Irene 
Published: April 2014

Abstract
Alterations in the balance between different metabolic pathways used to meet cellular bioenergetic and biosynthetic demands are considered hallmarks of cancer. Optical imaging relying on endogenous fluorescence has been used as a noninvasive approach to assess tissue metabolic changes during cancer development. However, quantitative correlations of optical assessments with variations in the concentration of relevant metabolites or in the specific metabolic pathways that are involved have been lacking. In this study, we use high-resolution, depth-resolved imaging, relying entirely on endogenous two-photon excited fluorescence in combination with invasive biochemical assays and mass spectrometry to demonstrate the sensitivity and quantitative nature of optical redox ratio tissue assessments. We identify significant differences in the optical redox ratio of live, engineered normal and precancerous squamous epithelial tissues. We establish that while decreases in the optical redox ratio are associated with enhanced levels of glycolysis relative to oxidative phosphorylation, increases in glutamine consumption to support energy production are associated with increased optical redox ratio values. Such mechanistic insights in the origins of optical metabolic assessments are critical for exploiting fully the potential of such noninvasive approaches to monitor and understand important metabolic changes that occur in live tissues at the onset of cancer or in response to treatment. Cancer Res; 74(11); 3067–75. ©2014 AACR.
Sphingosine Kinase 2 Promotes Acute Lymphoblastic Leukemia by Enhancing MYC Expression
Authors: Wallington-Beddoe Craig T. , Powell Jason A. , Tong Daochen , Pitson Stuart M. , Bradstock Kenneth F. , Bendall Linda J. 
Published: April 2014

Abstract
Sphingosine kinase 2 (SK2) may have utility as a prognostic marker in inflammatory diseases such as cancer in which it has been rationalized as a candidate therapeutic target. Here, we show that SK2 has an oncogenic role in acute lymphoblastic leukemia (ALL) by influencing expression of MYC. Genetic ablation of SK2 impaired leukemia development in a mouse model of ALL and pharmacologic inhibition extended survival in mouse xenograft models of human disease. SK2 attenuation in both the settings reduced MYC expression in leukemic cells, with reduced levels of acetylated histone H3 within the MYC gene associated with reduced levels of MYC protein and expression of MYC-regulated genes. Our results demonstrated that SK2 regulates MYC, which has a pivotal role in hematologic malignancies, providing a preclinical proof of concept for this pathway as a broad-based therapeutic target in this setting. Cancer Res; 74(10); 2803–15. ©2014 AACR.
MCL-1 Degradation Mediated by JNK Activation via MEKK1/TAK1-MKK4 Contributes to Anticancer Activity of New Tubulin Inhibitor MT189
Authors: Wang Wei , Wang Ying-Qing , Meng Tao , Yi Jun-Mei , Huan Xia-Juan , Ma Lan-Ping , Tong Lin-Jiang , Chen Yi , Ding Jian , Shen Jing-Kang , Miao Ze-Hong 
Published: April 2014

Abstract
Colchicine site–targeted tubulin inhibitors are a promising type of anticancer drugs. MT189 is a new derivative of MT119, a previously reported colchicine site–binding antitubulin agent. In this study, MT189 was demonstrated to retain the property of MT119 in disrupting microtubulin via binding to the colchicine site, causing mitotic arrest and inducing apoptosis, and to display 8.7-fold enhanced proliferative inhibition in a panel of cancer cells. MT189 was shown to elicit in vivo anticancer effects on MDA-MB-231 xenografts in nude mice, and the tumor growth was suppressed by 35.9% over 14 days. MT189 led to degradation of MCL-1, a member of the antiapoptotic BCL-2 protein family. Its overexpression reduced but its silenced expression increased the apoptotic induction followed by the treatment with MT189. Moreover, the treatment with MT189 caused activation of the MEKK1/TAK1–MKK4–JNK signaling pathway. The activated JNK resulted in phosphorylation of MCL-1, which facilitated its ubiquitination-mediated degradation. Our results show that MT189 inhibits microtubulin polymerization by binding to the colchicine site. Relief of apoptotic suppression by MCL-1 degradation together with mitotic arrest contributes to the anticancer activity of MT189. Mol Cancer Ther; 13(6); 1480–91. ©2014 AACR.
Differential Antitumor Activity of Aflibercept and Bevacizumab in Patient-Derived Xenograft Models of Colorectal Cancer
Authors: Chiron Marielle , Bagley Rebecca G. , Pollard Jack , Mankoo Parminder K. , Henry Christophe , Vincent Loïc , Geslin Catherine , Baltes Nina , Bergstrom Donald A. 
Published: April 2014

AbstractThe recombinant fusion protein aflibercept (ziv-aflibercept in the United States) binds VEGF-A, VEGF-B, and placental growth factor (PlGF). The monoclonal antibody bevacizumab binds VEGF-A. Recent studies hypothesized that dual targeting of VEGF/PlGF is more beneficial than targeting either ligand. We compared activity of aflibercept versus bevacizumab in 48 patient-derived xenograft (PDX) colorectal cancer models. Nude mice engrafted subcutaneously with PDX colorectal cancer tumors received biweekly aflibercept, bevacizumab, or vehicle injections. Differential activity between aflibercept and bevacizumab, determined by mouse (m), human (h), VEGF-A, and PlGF levels in untreated tumors, was measured. Aflibercept induced complete tumor stasis in 31 of 48 models and bevacizumab in 2 of 48. Based on statistical analysis, aflibercept was more active than bevacizumab in 39 of 48 models; in 9 of 39 of these models, bevacizumab was considered inactive. In 9 of 48 remaining models, aflibercept and bevacizumab had similar activity. Tumor levels of hVEGF-A (range 776–56,039 pg/mg total protein) were ∼16- to 1,777-fold greater than mVEGF-A (range 8–159 pg/mg total protein). Tumor levels of mPlGF (range 104–1,837 pg/mg total protein) were higher than hPlGF (range 0–543 pg/mg total protein) in 47 of 48 models. Tumor cells were the major source of VEGF; PlGF was primarily produced by tumor stroma. Because tumor levels of hVEGF-A were far greater than mVEGF-A, bevacizumab's inability to bind mVEGF-A is unlikely to explain higher and more consistent aflibercept activity. Neutralizing PlGF and VEGFR-1 activation may be a factor and should be investigated in future studies. In these colorectal cancer PDX models, aflibercept demonstrated greater antitumor activity than bevacizumab. Mol Cancer Ther; 13(6); 1636–44. ©2014 AACR.
Targeting Multiple Key Signaling Pathways in Melanoma Using Leelamine
Authors: Gowda Raghavendra , Madhunapantula SubbaRao V. , Kuzu Omer F. , Sharma Arati , Robertson Gavin P. 
Published: April 2014

Abstract
Melanoma is a highly drug-resistant cancer with resistance developing to agents targeting single proteins. To circumvent this problem, a new class of agent inhibiting multiple key pathways important in this disease is being developed to reduce the likelihood of developing resistant disease. The phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and STAT3 pathways are constitutively activated in 50% to 70% of melanomas, promoting disease development. To identify a drug simultaneously targeting the PI3K, MAPK, and STAT3 cascades, a natural product library was screened to identify leelamine as a potential inhibitor. Leelamine was 4.5-fold more effective at inhibiting cultured melanoma cell survival than normal cells, with average IC50 values of 2 and 9.3 μmol/L, respectively. It inhibited cellular proliferation at a concentration of 2.5 μmol/L by 40% to 80% and longer exposure increased apoptosis 600%. Leelamine inhibited the growth of preexisting xenografted melanoma tumors by an average of 60% by targeting the PI3K, MAPK, and STAT3 pathways without affecting animal body weight or blood markers of major organ function. The mechanism of action of leelamine is mediated by disruption of cholesterol transport, causing decreased cellular proliferation and consequently leading to increased tumor cell apoptosis as well as decreased tumor vascularization. Thus, a unique agent and novel mechanism of action has been identified for the treatment of melanoma that acts by inhibiting the activity of three major signaling pathways regulating the development of this disease. Mol Cancer Ther; 13(7); 1679–89. ©2014 AACR.