bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production during Stationary Phase
Authors: Purcell Erin B. , McKee Robert W. , Courson David S. , Garrett Elizabeth M. , McBride Shonna M. , Cheney Richard E. , Tamayo Rita 
Published: June 2017

ABSTRACT

The signaling molecule cyclic diguanylate (c-di-GMP) mediates physiological adaptation to extracellular stimuli in a wide range of bacteria. The complex metabolic pathways governing c-di-GMP synthesis and degradation are highly regulated, but the specific cues that impact c-di-GMP signaling are largely unknown. In the intestinal pathogen
Clostridium difficile
, c-di-GMP inhibits flagellar motility and toxin production and promotes pilus-dependent biofilm formation, but no specific biological functions have been ascribed to any of the individual c-di-GMP synthases or phosphodiesterases (PDEs). Here, we report the functional and biochemical characterization of a c-di-GMP PDE, PdcA, 1 of 37 confirmed or putative c-di-GMP metabolism proteins in
C. difficile
630. Our studies reveal that
pdcA
transcription is controlled by the nutrient-regulated transcriptional regulator CodY and accordingly increases during stationary phase. In addition, PdcA PDE activity is allosterically regulated by GTP, further linking c-di-GMP levels to nutrient availability. Mutation of
pdcA
increased biofilm formation and reduced toxin biosynthesis without affecting swimming motility or global intracellular c-di-GMP. Analysis of the transcriptional response to
pdcA
mutation indicates that PdcA-dependent phenotypes manifest during stationary phase, consistent with regulation by CodY. These results demonstrate that inactivation of this single PDE gene is sufficient to impact multiple c-di-GMP-dependent phenotypes, including the production of major virulence factors, and suggest a link between c-di-GMP signaling and nutrient availability.
Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome
Authors: Reckziegel Diane , Bailey Helen , Cottam William J , Tench Christopher R , Mahajan Ravi P , Walsh David A , Knaggs Roger D , Auer Dorothee P 
Published: June 2017

IntroductionOsteoarthritis (OA) pain is a major cause of long-term disability and chronic pain in the adult population. One in five patients does not receive satisfactory pain relief, which reflects the complexity of chronic pain and the current lack of understanding of mechanisms of chronic pain. Recently, duloxetine has demonstrated clinically relevant pain relief, but only in half of treated patients with OA. Here, the aim is to investigate the neural mechanisms of pain relief and neural signatures that may predict treatment response to duloxetine in chronic knee OA pain.Methods and analysisThis is an ongoing single-centre randomised placebo-controlled mechanistic study (2:1 (placebo) allocation), using a multimodal neuroimaging approach, together with psychophysiological (quantitative sensory testing), genetics and questionnaire assessments. Eighty-one subjects with chronic knee OA pain are planned to power for between-group comparisons (placebo, duloxetine responder and duloxetine non-responder). Participants have a baseline assessment and, following 6 weeks of duloxetine (30 mg for 2 weeks, then 60 mg for 4 weeks), a follow-up evaluation. Brain imaging is performed at 3T with blood-oxygen-level dependent functional MRI at rest and during pin-prick nociceptive stimulation for main outcome assessment; arterial spin labelling and structural imaging (T1-weighted) for secondary outcome assessment. Questionnaires evaluate pain, negative affect, quality of sleep and cognition.Ethics and disseminationThe study has been approved by the East Midlands, Nottingham and is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. Results will be disseminated in peer-reviewed journals and at scientific conferences.Trial registration numberThis trial is registered at ClinicalTrials.gov (NCT02208778).This work was supported by Arthritis Research UK (Grant 18769).
Timing of complications during and after elective endovascular intracranial aneurysm coiling
Authors: Kameda-Smith Michelle Masayo , Klurfan Paula , van Adel Brian Anthony , Larrazabal Ramiro , Farrokhyar Forough , Bennardo Michael , Gunnarsson Thorsteinn 
Published: June 2017

ObjectiveTo determine the time to complications during and after elective endovascular intracranial aneurysm coiling.MethodsA retrospective chart review of patients undergoing elective endovascular aneurysm coiling between March 2006 and October 2013 in one large Eastern Canadian Neurointerventional Service was performed. Data regarding the incidence, time and type of complication related to the endovascular coiling procedure and clinical outcome at last follow-up were collected. Patient, aneurysm and operation factors were analyzed to determine any factors associated with complication occurrence.ResultsOf the 150 patient procedures analyzed, 16% experienced a coiling-related complication, although none resulted in death. 6.7% of patients experienced an intraoperative complication, of which thromboembolism was the most common type. The majority of the complications were detected in the first 6 hours after reversal of anesthesia, and a small proportion the next morning prior to discharge. Only 3.3% of patients had persistent neurological deficit after the procedure on last follow-up. Duration of the operation demonstrated a strong association with the occurrence of procedure-related complications.ConclusionThis study demonstrates that coiling-related complications of elective endovascular coiling tend to occur either intraoperatively or are detected shortly after reversal of anesthesia. Further investigation with a larger cohort may help to guide important preoperative communication with patients and identify a select group of patients who may not necessarily require prolonged admission to hospital for observation.
Structure and Function Relationship of Activated Retinal Glia in Primary Open-Angle Glaucoma Patients
Authors: Nützi Christoph , Schötzau Andreas , Grieshaber Matthias C. 
Published: June 2017

Purpose. To evaluate clinically activated retinal astrocytes and Müller cells (ARAM) regarding retinal sensitivity and retinal nerve fiber layer (RNFL) thickness in primary open-angle glaucoma (POAG). Methods. Central visual field (VF; i.e., retinal sensitivity) was measured with a custom-made macular pattern by microperimetry and correlated with the presence (ARAM+) or absence (ARAM−) of ARAM on red-free fundus photography and with the corresponding RNFL by optical coherence tomography (OCT). Results. In the eyes of POAG patients, ARAM+ had overall a significantly lower retinal sensitivity (ARAM+: 7.34 dB, ARAM−: 11.9 dB; p<0.001) and lower RNFL thickness in the inferior peripapillary quadrants compared to ARAM− (RNFL superior: ARAM+ 74.2 μm, ARAM− 77.5 μm; RNFL temporal: ARAM+ 46.8 μm, ARAM− 53.0 μm, p<0.001; and RNFL inferior: ARAM+ 63.2 μm, ARAM− 73.1 μm, p<0.001). Within the same eye, ARAM+ showed a lower retinal sensitivity compared to ARAM− ([ARAM− (11.13 dB)] − [ARAM+ (9.56 dB) = 1.57 dB; p=0.25). The proportion of ARAM+ per eye correlated strongly with reduced retinal light sensitivity (p=0.02), corresponding lower peripapillary RNFL thickness (p=0.02), and lower RNFL temporal quadrant thickness (p<0.01), but not with greater age (p=0.45). Conclusion. ARAM was more frequently identified in the eyes with a lower retinal sensitivity and peripapillary RNFL thickness and may be a clinical sign in the macula for an advanced stage of POAG.
Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma
Authors: Marchan Rosemarie , Büttner Bettina , Lambert Jörg , Edlund Karolina , Glaeser Iris , Blaszkewicz Meinolf , Leonhardt Gregor , Marienhoff Lisa , Kaszta Darius , Anft Moritz , Watzl Carsten , Madjar Katrin , Grinberg Marianna , Rempel Eugen , Hergenröder Roland , Selinski Silvia , Rahnenführer Jörg , Lesjak Michaela S. , Stewart Joanna D. , Cadenas Cristina , Hengstler Jan G. 
Published: June 2017

Abstract
Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth. Cancer Res; 77(17); 4589–601. ©2017 AACR.
Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells
Authors: Zarei Mahsa , Lal Shruti , Parker Seth J. , Nevler Avinoam , Vaziri-Gohar Ali , Dukleska Katerina , Mambelli-Lisboa Nicole C. , Moffat Cynthia , Blanco Fernando F. , Chand Saswati N. , Jimbo Masaya , Cozzitorto Joseph A. , Jiang Wei , Yeo Charles J. , Londin Eric R. , Seifert Erin L. , Metallo Christian M. , Brody Jonathan R. , Winter Jordan M. 
Published: June 2017

Abstract
Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C &gt; 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal or gemcitabine treatment, but depriving PDAC cells of nutrients before gemcitabine treatment attenuated this effect. Mechanistic investigations based on RNAi or CRISPR approaches implicated the RNA binding protein HuR in preserving survival under nutrient withdrawal, with or without gemcitabine. Notably, RNA deep sequencing and functional analyses in HuR-deficient PDAC cell lines identified isocitrate dehydrogenase 1 (IDH1) as the sole antioxidant enzyme under HuR regulation. HuR-deficient PDAC cells lacked the ability to engraft successfully in immunocompromised mice, but IDH1 overexpression in these cells was sufficient to fully restore chemoresistance under low nutrient conditions. Overall, our findings highlight the HuR–IDH1 regulatory axis as a critical, actionable therapeutic target in pancreatic cancer. Cancer Res; 77(16); 4460–71. ©2017 AACR.
MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of CD73 during Immunotherapy
Authors: Reinhardt Julia , Landsberg Jennifer , Schmid-Burgk Jonathan L. , Ramis Bartomeu Bibiloni , Bald Tobias , Glodde Nicole , Lopez-Ramos Dorys , Young Arabella , Ngiow Shin Foong , Nettersheim Daniel , Schorle Hubert , Quast Thomas , Kolanus Waldemar , Schadendorf Dirk , Long Georgina V. , Madore Jason , Scolyer Richard A. , Ribas Antoni , Smyth Mark J. , Tumeh Paul C. , Tüting Thomas , Hölzel Michael 
Published: June 2017

Abstract
Evolution of tumor cell phenotypes promotes heterogeneity and therapy resistance. Here we found that induction of CD73, the enzyme that generates immunosuppressive adenosine, is linked to melanoma phenotype switching. Activating MAPK mutations and growth factors drove CD73 expression, which marked both nascent and full activation of a mesenchymal-like melanoma cell state program. Proinflammatory cytokines like TNFα cooperated with MAPK signaling through the c-Jun/AP-1 transcription factor complex to activate CD73 transcription by binding to an intronic enhancer. In a mouse model of T-cell immunotherapy, CD73 was induced in relapse melanomas, which acquired a mesenchymal-like phenotype. We also detected CD73 upregulation in melanoma patients progressing under adoptive T-cell transfer or immune checkpoint blockade, arguing for an adaptive resistance mechanism. Our work substantiates CD73 as a target to combine with current immunotherapies, but its dynamic regulation suggests limited value of CD73 pretreatment expression as a biomarker to stratify melanoma patients. Cancer Res; 77(17); 4697–709. ©2017 AACR.
Clinical Pathways: Recommendations for Putting Patients at the Center of Value-Based Care
Authors: Abrahams Edward , Balch Alan , Goldsmith Patricia , Kean Marcia , Miller Amy M. , Omenn Gilbert , Sonet Ellen , Sprandio John , Tyne Courtney , Westrich Kimberly 
Published: June 2017

Abstract
Two major trends that have been affecting the provision of oncology care in the United States are a shift from volume-based to value-based care and a push toward patient-centered healthcare. However, these two trends are not always completely aligned with each other. Value-based payment models, including clinical pathways, are one strategy being implemented by oncology stakeholders to help encourage the uptake of value-based oncology care. If structured with the patient in mind, they can improve quality of care for patients with cancer, decrease inappropriate care while enabling appropriate personalization of care, and constrain rising prices by demanding a stronger link between cost and value. If not structured appropriately, they can limit patient choice, impede access to innovative treatments, and encourage one-size-fits-all oncology care. Clin Cancer Res; 23(16); 4545–9. ©2017 AACR.
Interhemispheric Binding of Ambiguous Visual Motion Is Associated with Changes in Beta Oscillatory Activity but Not with Gamma Range Synchrony
Authors: Costa Gabriel Nascimento , Duarte João Valente , Martins Ricardo , Wibral Michael , Castelo-Branco Miguel 
Published: June 2017

Abstract
In vision, perceptual features are processed in several regions distributed across the brain. Yet, the brain achieves a coherent perception of visual scenes and objects through integration of these features, which are encoded in spatially segregated brain areas. How the brain seamlessly achieves this accurate integration is currently unknown and is referred to as the “binding problem.” Among the proposed mechanisms meant to resolve the binding problem, the binding-by-synchrony hypothesis proposes that binding is carried out by the synchronization of distant neuronal assemblies. This study aimed at providing a critical test to the binding-by-synchrony hypothesis by evaluating long-range connectivity using EEG during a motion integration visual task that entails binding across hemispheres. Our results show that large-scale perceptual binding is not associated with long-range interhemispheric gamma synchrony. However, distinct perceptual interpretations were found to correlate with changes in beta power. Increased beta activity was observed during binding under ambiguous conditions and originates mainly from parietal regions. These findings reveal that the visual experience of binding can be identified by distinct signatures of oscillatory activity, regardless of long-range gamma synchrony, suggesting that such type of synchrony does not underlie perceptual binding.
Sageretia liuzhouensis (Rhamnaceae), a new species from Guangxi, China
Authors: YANG YI , ZHANG JIAN-WEN , SUN LU , SUN HANG 
Published: June 2017

Sageretia liuzhouensis, a new species discovered in Guangxi Zhuang Autonomous Region, China, is described and illustrated. This species was found growing in sparse forests or thickets on the top of towering limestone hills with sunny, dry habitats. It is very similar to S. camelliifolia in morphology but differs with pubescent inflorescence rachises and charcoal-gray branches, as well as smaller leaves and shorter petioles. The delimitation of this new species is also supported by phylogenetic analyses based on five DNA loci (ITS, ETS, trnL-trnF, psbA-trnH and petA-psbJ). S. camelliifolia is within a clade separated from the new species and S. thea is more closely related to S. subcaudata and S. rugosa than the new species.
Two new species of Elaphoidella (Copepoda, Harpacticoida) from caves in southern Thailand and a key to the species of Southeast Asia
Authors: WATIROYRAM SANTI , SANOAMUANG LA-ORSRI , BRANCELJ ANTON 
Published: June 2017

Elaphoidella paraaffinis sp. nov. and E. ligorae sp. nov. are described from Phra Kayang and Khao Plu caves respectively in southern Thailand. They both belong to Group I sensu Lang (1948). Elaphoidella paraaffinis and E. ligorae are similar to E. affinis Chappuis, 1933 and E. cabezasi Petkovski, 1982 respectively. Elaphoidella paraaffinis differs from E. affinis by (1) its larger sized setae on Exp P5, (2) the absence of an inner seta on Endp P1–P4, (3) fewer setae on P3 Endp-2, and (4) a larger number of ventral spinules on its anal segment. Elaphoidella ligorae differs from E. cabezasi by (1) its serrated posterior margins of urosomites, (2) the presence of strong inner spinules on its caudal ramus, (3) larger sized and a lower number of ventral spinules on its anal segment in male and female respectively, (4) larger sized setae on P5 in female, (5) the presence of an inner seta on Endp-1 P2, and (6) a larger number of setae on Endp-2 P2 in male. An identification key to the Southeast Asian species of the genus Elaphoidella Chappuis, 1929 is provided.
Reclaiming Adolescent Sexuality: Images of Girlhood in Petra Collins’s Babe
Authors: Kamińska Aleksandra 
Published: June 2017

Reclaiming Adolescent Sexuality: Images of Girlhood in Petra Collins’s BabeThis paper examines photographs, drawings, collages and other art forms collected in the book Babe, edited by photographer Petra Collins and published by Prestel in 2015. I read the collected artwork as an attempt to present the image of the girl (including her sexuality) from a young woman’s perspective. Babe, which includes works such as photographs of teenagers with visible period blood on the underwear or a to-do list with the goal of never faking another orgasm, asks who a contemporary girl is and how young artists can challenge traditional images of femininity. In my analysis I focus on the excessive use of the color pink in Babe, characterizing the way artists blend innocence with eroticism. I argue that by playing with artifacts of “girlishness,” artists can both expose the absurdity of the image of the girl in popular culture and reclaim symbols of girlhood. I suggest that Collins – despite her ambitions to create an inclusive platform for female artists – does not present a diverse image of girls, who in Babe is still predominantly white and able-bodied. I introduce the potential reading of Babe as a feminist visual manifesto, in reference to the Riot Grrrl movement and the cultural phenomenon of “girl power.” I suggest that the book offers a possibility of exploring the figure of the girl from the perspective of young female artists. Odzyskując młodzieńczą seksualność: wizerunki dziewczyńskości w „Babe” Petry CollinsArtykuł jest analizą fotografii, rysunków, kolaży i innych prac zebranych przez fotografkę Petrę Collins w albumie „Babe", wydanym w 2015 roku przez Prestel. W artykule odczytuję zebrane prace jako szansę zaprezentowania wizerunku dziewczyny (w tym jej seksualności) z perspektywy młodej kobiety. Babe – w której znajdują się zarówno fotografie nastolatek z widoczną krwią menstruacyjną na bieliźnie, jak i zdjęcie listy zadań, na której artystka umieszcza postanowienie, by nigdy więcej nie udawać orgazmu – zadaje pytanie kim dzisiaj jest dziewczyna i w jaki sposób młode artystki mogą kwestionować utarte obrazy kobiecości. Podczas analizy skupiam się na przewadze różu w warstwie wizualnej albumu, ukazując sposób, w jaki artystki łączą pozorną niewinność z erotyzmem. Twierdzę, że poprzez grę z konwencjami „dziewczyńskości” autorki prac mogą zarówno eksponować sztuczność wizerunku młodej kobiety w kulturze popularnej, jak i odzyskiwać symbole dziewczęcości. Sugeruję, że Collins – mimo próby stworzenia inkluzywnej platformy dla artystek – nie oferuje zróżnicowanego obrazu dziewczyny, która w Babe wciąż jest przeważnie biała i pełnosprawna. W odczytaniu Babe jako feministycznego wizualnego manifestu odwołuję się do ruchu Riot Grrrl i fenomenu kulturowego reprezentowanego przez hasło „girl power”. Sugeruję, że album oferuje zgłębienie postaci dziewczyny z punktu widzenia młodych artystek.
The Effect of Cloud Cover on the Meridional Heat Transport: Lessons from Variable Rotation Experiments
Authors: Liu Xiaojuan , Battisti David S. , Roe Gerard H. 
Published: June 2017

Abstract
The question “What determines the meridional heat transport (MHT)?” is explored by performing a series of rotation-rate experiments with an aquaplanet GCM coupled to a slab ocean. The change of meridional heat transport with rotation rate falls into two regimes: in a “slow rotating” regime (rotation rate &lt; 1/2 modern rotation) MHT decreases with increasing rotation rate, whereas in a “fast rotating” regime (rotation rate ≥ 1/2 modern rotation) MHT is nearly invariant. The two-regime feature of MHT is primarily related to the reduction in tropical clouds and increase in tropical temperature that are associated with the narrowing and weakening of the Hadley cell with increasing rotation rate. In the slow-rotating regime, the Hadley cell contracts and weakens as rotation rate is increased; the resulting warming causes a local increase in outgoing longwave radiation (OLR), which consequently decreases MHT. In the fast-rotating regime, the Hadley cell continues to contract as rotation rate is increased, resulting in a decrease in tropical and subtropical clouds that increases the local absorbed shortwave radiation (ASR) by an amount that almost exactly compensates the local increases in OLR. In the fast-rotating regime, the model heat transport is approximately diffusive, with an effective eddy diffusivity that is consistent with eddy mixing-length theory. The effective eddy diffusivity decreases with increasing rotation rate. However, this decrease is nearly offset by a strong increase in the meridional gradient of moist static energy and hence results in a near-constancy of MHT. The results herein extend previous work on the MHT by highlighting that the spatial patterns of clouds and the factors that influence them are leading controls on MHT.