bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct measurement of the round window niche dimensions using a 3‐dimensional moulding technique – a human cadaveric temporal bone study
Authors: Shakeel M. , Spielmann P.M. , Jones S.E. , Hussain S.S.M. 
Published: April 2015

ObjectivesTo directly measure the various dimensions of the RWN focusing on the bony overhang and the vertical height between the free margin of the bony overhang and floor of the niche.DesignLaboratory‐based anatomical study using formalin‐preserved human cadaveric temporal bones.SettingTemporal Bone laboratory, Department of Otolaryngology University of Dundee Medical School & Ninewells Hospital, Dundee, UK.ParticipantsNA.Main outcome measuresThree measurements were carried out (i) the depth of the round window niche extending from the free margin of the bony overhang to the fundus; (ii) vertical height from the free margin of the overhang to the floor of the niche (entrance) and (iii) the antero‐posterior (AP) dimension of the niche.ResultsBased on mould technique, the three dimensions were calculated as follows: mean bony overhang = 2.1 mm (range 1.9–2.4 mm), height of RWN = 2.0 mm (1.8–2.15 mm) and AP length = 4.0 mm (3.3–4.95 mm).ConclusionsOur data demonstrate that the mean dimension of the bony overhang superior to the RWM is 2.1 mm.
Two dose‐ranging studies with PF‐04937319, a systemic partial activator of glucokinase, as add‐on therapy to metformin in adults with type 2 diabetes
Authors: Amin N. B. , Aggarwal N. , Pall D. , Paragh G. , Denney W. S. , Le V. , Riggs M. , Calle R. A. 
Published: April 2015

AimTo assess the efficacy and safety of a range of doses of a systemic, partial, glucokinase activator, PF‐04937319, as add‐on therapy to metformin, in patients with type 2 diabetes mellitus (T2DM).MethodsPatients were randomized to once‐daily PF‐04937319 doses of 10, 50, 100 mg, or matching placebo (Study B1621002); or PF‐04937319 doses of 3, 20, 50, 100 mg, or matching placebo (Study B1621007). Titrated glimepiride (Study B1621002) or sitagliptin (Study B1621007) were included in a double‐dummy manner. The primary measure was change from baseline in glycated haemoglobin (HbA1c) at week 12. Key secondary measures included other glycaemic variables and safety and tolerability.ResultsIn the 639 patients randomized, the minimally efficacious PF‐04937319 dose was identified as 50 mg once daily. At the highest PF‐04937319 dose tested (100 mg), on average, a clinically significant reduction in HbA1c [−4.94 or −5.11 mmol/mol (−0.45 or −0.47%), placebo‐adjusted], which was similar to that achieved with sitagliptin [−4.69 mmol/mol (−0.43%)] but lower than that achieved with titrated glimepiride [−9.07 mmol/mol (−0.83%)], was observed. At this dose, the effect on fasting plasma glucose was not consistent between the two studies (Study B1621002 vs Study B1621007: placebo‐adjusted mean change of −0.83 vs +0.50 mmol/l). PF‐04937319 was well tolerated at doses up to 100 mg. Hypoglycaemia was reported in 2.5% of patients (on placebo), 5.1% of patients (on PF‐04937319 100 mg), 1.8% of patients (on sitagliptin) and 34.4% of patients (on titrated glimepiride).ConclusionsIn patients on metformin monotherapy, the addition of a 100‐mg dose of PF‐04937319 improved glycaemic control and was well tolerated.
An Unexpected Guest in the Proximal Ascending Aorta
Authors: Toffetti Laura , Pugno Alice , Massironi Laura , Tresoldi Silvia , Mantero Antonio G. 
Published: April 2015

Mini‐AbstractA 72‐year‐old asymptomatic woman with history of ischemic heart disease and repeat coronary percutaneous interventions underwent a routine transthoracic echocardiogram (TTE). A 9‐mm long, fixed, echo dense mass was visualized in the proximal ascending aorta. We performed a two and three‐dimensional transesophageal echocardiogram and a cardiac multidetector‐row contrast‐enhanced computed tomography with ECG gating, which revealed the unexplained mass to be an ostial right coronary artery stent protruding 9 mm into the ascending aorta. Coronary stent protrusion is a very unusual finding observed during routine 2DTTE, but it has many potential clinical consequences. This case suggests that 2DTTE is feasible and useful for the identification and follow‐up of protruding ostial coronary stents.
The effects of starvation and repeated disturbance on mass loss, pit construction, and spatial pattern in a trap‐building predator
Authors: SCHARF INON , DOR ROI 
Published: April 2015

1. Starvation tolerance is an important trait for animals, as most will encounter starvation within their lifetime. Sit‐and‐wait predators are better adapted to starvation owing to their naturally low encounter rate with prey.2. Starvation tolerance was studied under three levels of disturbance of wormlion larvae, a strict sit‐and‐wait predator that constructs pits.3. Frequently disturbed wormlions constructed pits less often, and larger individuals continued to construct pits more frequently than smaller ones. It was expected that a high disturbance level would lead to a high rate of mass loss, however, surprisingly, the rate of mass loss was not higher for the frequently disturbed group. This suggests that the energetic cost of pit construction and maintenance is not as high as previously suggested for other pit‐building predators.4. Larger individuals tolerated starvation better, in losing a lower proportion of their initial body mass and having higher chances of survival throughout the experiment.5. The effect of starvation on the distance to neighbours was also investigated, and starved individuals were expected to maximise this distance in order to avoid interference competition. However, wormlions were usually clumped, and starvation or feeding had no effect on the pits' spatial pattern, suggesting that interference competition plays a minor role in this species.6. Generally, wormlion larvae demonstrated a high starvation tolerance and low mortality rates even after 9 weeks of starvation.
Artificial night lighting disrupts sex pheromone in a noctuid moth
Authors: VAN GEFFEN KOERT G. , GROOT ASTRID T. , VAN GRUNSVEN ROY H. A. , DONNERS MAURICE , BERENDSE FRANK , VEENENDAAL ELMAR M. 
Published: April 2015

1. One major, yet poorly studied, change in the environment is the increase in nocturnal light pollution. Although this strongly alters the habitat of nocturnal species, the ecological consequences are poorly known. Moths are well known to be attracted to artificial light sources, but artificial light may affect them in other ways as well.2. In this study, female Mamestra brassicae moths were subjected to various types of low‐intensity artificial night lighting with contrasting spectral compositions (green‐rich, red‐rich, warm white) or to a dark control treatment and the effects on their sex pheromone production and composition were tested.3. Artificial night lighting reduced sex pheromone production and altered the chemical composition of the pheromone blend, irrespective of spectral composition. Specifically, amounts of the main pheromone component Z11‐16:Ac were reduced, while the deterring compounds Z9‐14:Ac, Z9‐16:Ac, and Z11‐16:OH were increased relative to Z11‐16:Ac when females were kept under artificial light. These changes may reduce the effectiveness of the sex pheromones, becoming less attractive for males.4. These results show for the first time that artificial light at night affects processes that are involved in moth reproduction. The potential for mitigation through manipulation of the spectral composition of artificial light appears limited.
Spectroscopic characterization of radicals and radical pairs in fruit fly cryptochrome – protonated and nonprotonated flavin radical‐states
Authors: Paulus Bernd , Bajzath Csaba , Melin Frédéric , Heidinger Lorenz , Kromm Viktoria , Herkersdorf Christoph , Benz Ulrike , Mann Lisa , Stehle Patricia , Hellwig Petra , Weber Stefan , Schleicher Erik 
Published: April 2015

Drosophila melanogaster cryptochrome is one of the model proteins for animal blue‐light photoreceptors. Using time‐resolved and steady‐state optical spectroscopy, we studied the mechanism of light‐induced radical‐pair formation and decay, and the photoreduction of the FAD cofactor. Exact kinetics on a microsecond to minutes timescale could be extracted for the wild‐type protein using global analysis. The wild‐type exhibits a fast photoreduction reaction from the oxidized FAD to the FAD•− state with a very positive midpoint potential of ~ +125 mV, although no further reduction could be observed. We could also demonstrate that the terminal tryptophan of the conserved triad, W342, is directly involved in electron transfer; however, photoreduction could not be completely inhibited in a W342F mutant. The investigation of another mutation close to the FAD cofactor, C416N, rather unexpectedly reveals accumulation of a protonated flavin radical on a timescale of several seconds. The obtained data are critically discussed with the ones obtained from another protein, Escherichia coli photolyase, and we conclude that the amino acid opposite N(5) of the isoalloxazine moiety of FAD is able to (de)stabilize the protonated FAD radical but not to significantly modulate the kinetics of any light‐inducted reactions.
Simulations of chlorophyll fluorescence incorporated into the Community Land Model version 4
Authors: Lee Jung‐Eun , Berry Joseph A. , van der Tol Christiaan , Yang Xi , Guanter Luis , Damm Alexander , Baker Ian , Frankenberg Christian 
Published: April 2015

AbstractSeveral studies have shown that satellite retrievals of solar‐induced chlorophyll fluorescence (SIF) provide useful information on terrestrial photosynthesis or gross primary production (GPP). Here, we have incorporated equations coupling SIF to photosynthesis in a land surface model, the National Center for Atmospheric Research Community Land Model version 4 (NCAR CLM4), and have demonstrated its use as a diagnostic tool for evaluating the calculation of photosynthesis, a key process in a land surface model that strongly influences the carbon, water, and energy cycles. By comparing forward simulations of SIF, essentially as a byproduct of photosynthesis, in CLM4 with observations of actual SIF, it is possible to check whether the model is accurately representing photosynthesis and the processes coupled to it. We provide some background on how SIF is coupled to photosynthesis, describe how SIF was incorporated into CLM4, and demonstrate that our simulated relationship between SIF and GPP values are reasonable when compared with satellite (Greenhouse gases Observing SATellite; GOSAT) and in situ flux‐tower measurements. CLM4 overestimates SIF in tropical forests, and we show that this error can be corrected by adjusting the maximum carboxylation rate (Vmax) specified for tropical forests in CLM4. Our study confirms that SIF has the potential to improve photosynthesis simulation and thereby can play a critical role in improving land surface and carbon cycle models.
CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma
Authors: Shibuya Ryo , Matsuyama Atsuji , Shiba Eisuke , Harada Hiroshi , Yabuki Kei , Hisaoka Masanori 
Published: April 2015

AimsThe diagnosis of epithelioid haemangioendothelioma (EHE) is usually straightforward, based on characteristic histological features. However, it is sometimes difficult to differentiate EHE from a variety of other tumours with epithelioid morphology. The WW domain‐containing transcription regulator 1–calmodulin‐binding transcription activator 1 (WWTR1–CAMTA1) fusion gene, resulting in the overexpression of CAMTA1, is demonstrated in approximately 90% of EHEs, and the yes‐associated protein 1–transcription factor E3 (YAP1–TFE3) fusion gene, associated with the strong and diffuse nuclear expression of TFE3, is present in another small subset of EHEs. The aim of our study was to examine CAMTA1 expression in EHEs and a variety of other tumours to evaluate its diagnostic utility, and to analyse TFE3 expression status in EHEs.Methods and resultsImmunohistochemistry was performed on 16 EHEs, including five cases with CAMTA1 rearrangement and 276 non‐EHE tumours. Fourteen of 16 EHEs and only one case of ductal carcinoma of the breast were positive for CAMTA1 and its expression was focal and weak in the latter (sensitivity 87.5%, specificity 99.6%). TFE3 expression was expressed focally and weakly in three (19%) EHEs (two with the CAMTA1 rearrangement).ConclusionsNuclear CAMTA1 expression is sensitive and highly specific for EHE and can be applied to diagnostic immunohistochemistry in epithelioid tumours.
Hepatitis regulation by the inflammasome signaling pathway
Authors: Negash Amina A. , Gale Michael 
Published: April 2015

SummaryHepatitis is damage and inflammation of the liver. It is triggered by both environmental and endogenous insults and is a platform for developing liver cirrhosis and cancer. Both innate and adaptive immune activation contribute to hepatic inflammation and disease. Viral hepatitis is the most common form of hepatitis and is typically associated with chronic viral infection. Alcohol‐induced and non‐alcoholic steatohepatitis are two rising hepatic problems. The innate immune inflammasome signaling cascade mediates the production of essential proinflammatory cytokines interleukin‐1β (IL‐1β) and IL‐18. These cytokines regulate hepatic cell interaction and crosstalk of the various inflammatory pathways and influence disease outcome.
Pyroptotic cell death defends against intracellular pathogens
Authors: Jorgensen Ine , Miao Edward A. 
Published: April 2015

SummaryInflammatory caspases play a central role in innate immunity by responding to cytosolic signals and initiating a twofold response. First, caspase‐1 induces the activation and secretion of the two prominent pro‐inflammatory cytokines, interleukin‐1β (IL‐1β) and IL‐18. Second, either caspase‐1 or caspase‐11 can trigger a form of lytic, programmed cell death called pyroptosis. Pyroptosis operates to remove the replication niche of intracellular pathogens, making them susceptible to phagocytosis and killing by a secondary phagocyte. However, aberrant, systemic activation of pyroptosis in vivo may contribute to sepsis. Emphasizing the efficiency of inflammasome detection of microbial infections, many pathogens have evolved to avoid or subvert pyroptosis. This review focuses on molecular and morphological characteristics of pyroptosis and the individual inflammasomes and their contribution to defense against infection in mice and humans.
The cooperation between the autophagy machinery and the inflammasome to implement an appropriate innate immune response: do they regulate each other?
Authors: Abdelaziz Dalia H. A. , Khalil Hany , Cormet‐Boyaka Estelle , Amer Amal O. 
Published: April 2015

SummaryAutophagy is originally described as the main catabolic pathway responsible for maintaining intracellular nutritional homeostasis that involves the formation of a unique vacuole, the autophagosome, and the interaction with the endosome‐lysosome pathways. This conserved machinery plays a key role in immune‐protection against different invaders, including pathogenic bacteria, intracellular parasites, and some viruses like herpes simplex and hepatitis C virus. Importantly, autophagy is linked to a number of human diseases and disorders including neurodegenerative disease, Crohn's disease, type II diabetes, tumorigenesis, cardiomyopathy, and fatty liver disease. On the other hand, inflammasomes are multiprotein platforms stimulated upon several environmental conditions and microbial infection. Once assembled, the inflammasomes mediate the maturation of pro‐inflammatory cytokines and promote phagosome‐lysosome fusion to sustain an innate immune response. The intersections between autophagy and inflammasome have been observed in various diseases and microbial infections. This review highlights the molecular aspects involved in autophagy and inflammasome interactions during different medical conditions and microbial infections.
Inhibiting the inflammasome: one domain at a time
Authors: Dorfleutner Andrea , Chu Lan , Stehlik Christian 
Published: April 2015

SummaryInflammasomes are protein complexes that promote the maturation and release of pro‐inflammatory cytokines and danger signals as well as pyroptosis in response to infections and cellular stress. Inflammasomes consist of a sensor, an adapter, and the effector caspase‐1, which interact through homotypic interactions of caspase recruitment domains (CARDs) or PYRIN domains (PYDs). Hence, decoy proteins encoding only a CARD or PYD, COPs and POPs, respectively, are assumed to inhibit inflammasome assembly. Sensors encoding a PYD belong to the families of NOD‐like receptors containing a PYD (NLRPs) or AIM2‐like receptors (ALRs), which interact with the PYD‐ and CARD‐containing adapter ASC through homotypic PYD interactions. Subsequently, ASC undergoes PYD‐dependent oligomerization, which promotes CARD‐mediated interactions between ASC and caspase‐1, resulting in caspase‐1 activation. POPs are suggested to interfere with the interaction between NLRPs/ALRs and ASC to prevent nucleation of ASC and therefore prevent an oligomeric platform for caspase‐1 activation. Similarly, COPs are suggested to bind to the CARD of caspase‐1 to prevent its recruitment to the oligomeric ASC platform and its activation. Alternatively, the adapter ASC may regulate inflammasome activity by expressing different isoforms, which are either capable or incapable of assembling an oligomeric ASC platform. The molecular mechanism of inflammasome assembly has only recently been elucidated, but the effects of most COPs and POPs on inflammasome assembly have not been investigated. Here, we discuss our model of COP‐ and POP‐mediated inflammasome regulation.
Inflammasomes in host response to protozoan parasites
Authors: Zamboni Dario S. , Lima‐Junior Djalma S. 
Published: April 2015

SummaryInflammasomes are multimeric complexes of proteins that are assembled in the host cell cytoplasm in response to specific stress signals or contamination of the cytoplasm by microbial molecules. The canonical inflammasomes are composed of at least three main components: an inflammatory caspase (caspase‐1, caspase‐11), an adapter molecule (such as ASC), and a sensor protein (such as NLRP1, NLRP3, NLRP12, NAIP1, NAIP2, NAIP5, or AIM2). The sensor molecule determines the inflammasome specificity by detecting specific microbial products or cell stress signals. Upon activation, these molecular platforms facilitate restriction of microbial replication and trigger an inflammatory form of cell death called pyroptosis, thus accounting for the genesis of inflammatory processes. Inflammasome activation has been widely reported in response to pathogenic bacteria. However, recent reports have highlighted the important role of the inflammasomes in the host response to the pathogenesis of infections caused by intracellular protozoan parasites. Herein, we review the activation and specific roles of inflammasomes in recognition and host responses to intracellular protozoan parasites such as Trypanosoma cruzi, Toxoplasma gondii, Plasmodium spp., and Leishmania spp.
Negative regulation of the inflammasome: keeping inflammation under control
Authors: Pedraza‐Alva Gustavo , Pérez‐Martínez Leonor , Valdez‐Hernández Laura , Meza‐Sosa Karla F. , Ando‐Kuri Masami 
Published: April 2015

SummaryIn addition to its roles in controlling infection and tissue repair, inflammation plays a critical role in diverse and distinct chronic diseases, such as cancer, metabolic syndrome, and neurodegenerative disorders, underscoring the harmful effect of an uncontrolled inflammatory response. Regardless of the nature of the stimulus, initiation of the inflammatory response is mediated by assembly of a multimolecular protein complex called the inflammasome, which is responsible for the production of inflammatory cytokines, such as interleukin‐1β (IL‐1β) and IL‐18. The different stimuli and mechanisms that control inflammasome activation are fairly well understood, but the mechanisms underlying the control of undesired inflammasome activation and its inactivation remain largely unknown. Here, we review recent advances in our understanding of the molecular mechanisms that negatively regulate inflammasome activation to prevent unwanted activation in the resting state, as well as those involved in terminating the inflammatory response after a specific insult to maintain homeostasis.
L'avenir des relations professionnelles dans l'Union européenne: idées, paradoxes et sources du changement
Authors: KEUNE Maarten 
Published: April 2015

RésuméL'avenir des relations professionnelles en Europe dépendra de la résolution de trois paradoxes. Premièrement, l'individualisation des relations d'emploi, fondée sur l'autonomie (fictive) des individus, mais qui entretient leur dépendance au marché et leur vulnérabilité. Deuxièmement, la détérioration de la qualité des emplois et la montée de la précarité du travail avec un besoin croissant de protection, mais qui se heurte à la faiblesse des syndicats et à leur échec à élargir leur base. Troisièmement, l'orientation actuelle de l'Union européenne qui privilégie le marché, mais favorise ainsi des conditions d'emploi qui finiront par susciter un rejet politique de l'Union elle‐même.
Single cell migration in oral squamous cell carcinoma – possible evidence of epithelial–mesenchymal transition in vivo
Authors: Jensen David H. , Reibel Jesper , Mackenzie Ian C. , Dabelsteen Erik 
Published: April 2015

BackgroundThe invasion of cancer cells into the surrounding normal tissue is one of the defining features of cancer. While the phenomena of tumour budding, epithelial–mesenchymal transition and the presence of myofibroblasts have independently been shown to be related to a poor prognosis of oral carcinomas, their relationship has not been examined in detail.MethodsParaffin‐embedded tissues from 28 patients with oral squamous cell carcinomas were stained with antibodies to cytokeratin, α‐SMA, vimentin, E‐cadherin, N‐cadherin and Twist and evaluated for their expression in relation to invasive cancer cells and the surrounding tumour stroma.Results and conclusionsA direct, histological relationship between invading, budding tumour cells and myofibroblasts was occasionally seen but was not a general feature. Most of the budding tumour cells at the invasive front had a decreased expression of E‐cadherin, but we did not find that this was associated with a consistent or clear increase in either N‐cadherin or vimentin. We therefore suggest that the budding of tumour cells is not dependent upon either myofibroblasts or a complete epithelial–mesenchymal transition and that these phenomena most likely represent separate processes in tumour progression.