bluuebunny/crossref_metadata_2025 huggingface dataset:
IscR Regulates Synthesis of Colonization Factor Antigen I Fimbriae in Response to Iron Starvation in Enterotoxigenic Escherichia coli
Authors: Haines Sara , Arnaud-Barbe Nadège , Poncet David , Reverchon Sylvie , Wawrzyniak Julien , Nasser William , Renauld-Mongénie Geneviève
Published: June 2015

Iron availability functions as an environmental cue for enteropathogenic bacteria, signaling arrival within the human host. As enterotoxigenic
Escherichia coli
(ETEC) is a major cause of human diarrhea, the effect of iron on ETEC virulence factors was evaluated here. ETEC pathogenicity is directly linked to production of fimbrial colonization factors and secretion of heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST). Efficient colonization of the small intestine further requires at least the flagellin binding adhesin EtpA. Under iron starvation, production of the CFA/I fimbriae was increased in the ETEC H10407 prototype strain. In contrast, LT secretion was inhibited. Furthermore, under iron starvation, gene expression of the
cfa
(CFA/I) and
etp
(EtpBAC) operons was induced, whereas transcription of toxin genes was either unchanged or repressed. Transcriptional reporter fusion experiments focusing on the
cfa
operon further showed that iron starvation stimulated
cfaA
promoter activity in ETEC, indicating that the impact of iron on CFA/I production was mediated by transcriptional regulation. Evaluation of
cfaA
promoter activity in heterologous
E. coli
single mutant knockout strains identified IscR as the regulator responsible for inducing
cfa
fimbrial gene expression in response to iron starvation, and this was confirmed in an ETEC Δ
iscR
strain. The global iron response regulator, Fur, was not implicated. IscR binding sites were identified
in silico
within the
cfaA
promoter and fixation confirmed by DNase I footprinting, indicating that IscR directly binds the promoter region to induce CFA/I.

IMPORTANCE
Pathogenic enterobacteria modulate expression of virulence genes in response to iron availability. Although the Fur transcription factor represents the global regulator of iron homeostasis in
Escherichia coli
, we show that several ETEC virulence factors are modulated by iron, with expression of the major fimbriae under the control of the iron-sulfur cluster regulator, IscR. Furthermore, we demonstrate that the apo form of IscR, lacking an Fe-S cluster, is able to directly fix the corresponding promoter region. These results provide further evidence implicating IscR in bacterial virulence and suggest that IscR may represent a more general regulator mediating the iron response in enteropathogens.
Cyclic Di-GMP Regulates Type IV Pilus-Dependent Motility in Myxococcus xanthus
Authors: Skotnicka Dorota , Petters Tobias , Heering Jan , Hoppert Michael , Kaever Volkhard , Søgaard-Andersen Lotte
Published: June 2015

The nucleotide-based second messenger bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes.
Myxococcus xanthus
undergoes major lifestyle changes in response to nutrient availability, with the formation of spreading colonies in the presence of nutrients and spore-filled fruiting bodies in the absence of nutrients. Here, we investigated the function of c-di-GMP in
M. xanthus
and show that this bacterium synthesizes c-di-GMP during growth. Manipulation of the c-di-GMP level by expression of either an active, heterologous diguanylate cyclase or an active, heterologous phosphodiesterase correlated with defects in type IV pilus (T4P)-dependent motility, whereas gliding motility was unaffected. An increased level of c-di-GMP correlated with reduced transcription of the
pilA
gene (which encodes the major pilin of T4P), reduced the assembly of T4P, and altered cell agglutination, whereas a decreased c-di-GMP level correlated with altered cell agglutination. The systematic inactivation of the 24 genes in
M. xanthus
encoding proteins containing GGDEF, EAL, or HD-GYP domains, which are associated with c-di-GMP synthesis, degradation, or binding, identified three genes encoding proteins important for T4P-dependent motility, whereas all mutants had normal gliding motility. Purified DmxA had diguanylate cyclase activity, whereas the hybrid histidine protein kinases TmoK and SgmT, each of which contains a GGDEF domain, did not have diguanylate cyclase activity. These results demonstrate that c-di-GMP is important for T4P-dependent motility in
M. xanthus
.

IMPORTANCE
We provide the first direct evidence that
M. xanthus
synthesizes c-di-GMP and demonstrate that c-di-GMP is important for T4P-dependent motility, whereas we did not obtain evidence that c-di-GMP regulates gliding motility. The data presented uncovered a novel mechanism for regulation of T4P-dependent motility, in which increased levels of c-di-GMP inhibit transcription of the
pilA
gene (which encodes the major pilin of T4P), ultimately resulting in the reduced assembly of T4P. Moreover, we identified an enzymatically active diguanylate cyclase that is important for T4P-dependent motility.
Deletion of
nfnAB
in Thermoanaerobacterium saccharolyticum and Its Effect on Metabolism
Authors: Lo Jonathan , Zheng Tianyong , Olson Daniel G. , Ruppertsberger Natalie , Tripathi Shital A. , Guss Adam M. , Lynd Lee R.
Published: June 2015

NfnAB catalyzes the reversible transfer of electrons from reduced ferredoxin and NADH to 2 NADP
+
. The NfnAB complex has been hypothesized to be the main enzyme for ferredoxin oxidization in strains of
Thermoanaerobacterium saccharolyticum
engineered for increased ethanol production. NfnAB complex activity was detectable in crude cell extracts of
T. saccharolyticum
. Activity was also detected using activity staining of native PAGE gels. The
nfnAB
gene was deleted in different strains of
T. saccharolyticum
to determine its effect on end product formation. In wild-type
T. saccharolyticum
, deletion of
nfnAB
resulted in a 46% increase in H
2
formation but otherwise little change in other fermentation products. In two engineered strains with 80% theoretical ethanol yield, loss of
nfnAB
caused two different responses: in one strain, ethanol yield decreased to about 30% of the theoretical value, while another strain had no change in ethanol yield. Biochemical analysis of cell extracts showed that the Δ
nfnAB
strain with decreased ethanol yield had NADPH-linked alcohol dehydrogenase (ADH) activity, while the Δ
nfnAB
strain with unchanged ethanol yield had NADH-linked ADH activity. Deletion of
nfnAB
caused loss of NADPH-linked ferredoxin oxidoreductase activity in all cell extracts. Significant NADH-linked ferredoxin oxidoreductase activity was seen in all cell extracts, including those that had lost
nfnAB
. This suggests that there is an unidentified NADH:ferredoxin oxidoreductase (distinct from
nfnAB
) playing a role in ethanol formation. The NfnAB complex plays a key role in generating NADPH in a strain that had become reliant on NADPH-ADH activity.

IMPORTANCE
Thermophilic anaerobes that can convert biomass-derived sugars into ethanol have been investigated as candidates for biofuel formation. Many anaerobes have been genetically engineered to increase biofuel formation; however, key aspects of metabolism remain unknown and poorly understood. One example is the mechanism for ferredoxin oxidation and transfer of electrons to NAD(P)
+
. The electron-bifurcating enzyme complex NfnAB is known to catalyze the reversible transfer of electrons from reduced ferredoxin and NADH to 2 NADP
+
and is thought to play key roles linking NAD(P)(H) metabolism with ferredoxin metabolism. We report the first deletion of
nfnAB
and demonstrate a role for NfnAB in metabolism and ethanol formation in
Thermoanaerobacterium saccharolyticum
and show that this may be an important feature among other thermophilic ethanologenic anaerobes.
Slipping with the waste (a wheelie bin hand injury)
Authors: Parkes Rebekah , Weerasuriya Thisara , Gibson Suzy
Published: June 2015

A right hand dominant man in his 60s was moving his wheelie bin when he tripped and landed still holding on to the handle. His hand was trapped between the handle and the ground. He sustained lacerations at the level of the proximal interphalangeal joints of all the fingers of his right hand. The index and middle fingers had damage to the proximal phalangeal articular cartilage and central slip. The central slip loss in the middle finger required reconstruction. The wounds healed without complication by 4 weeks, at which point the patient's fingers were mobilised; he regained almost full range of movement by 3 months.
Gun ownership and social gun culture
Authors: Kalesan Bindu , Villarreal Marcos D , Keyes Katherine M , Galea Sandro
Published: June 2015

We assessed gun ownership rates in 2013 across the USA and the association between exposure to a social gun culture and gun ownership. We used data from a nationally representative sample of 4000 US adults, from 50 states and District of Columbia, aged >18 years to assess gun ownership and social gun culture performed in October 2013. State-level firearm policy information was obtained from the Brady Law Center and Injury Prevention and Control Center. One-third of Americans reported owning a gun, ranging from 5.2% in Delaware to 61.7% in Alaska. Gun ownership was 2.25-times greater among those reporting social gun culture (PR=2.25, 95% CI 2.02 to 2.52) than those who did not. In conclusion, we found strong association between social gun culture and gun ownership. Gun cultures may need to be considered for public health strategies that aim to change gun ownership in the USA.
Effects of brief intervention on subgroups of injured patients who drink at risk levels
Authors: Cochran Gerald , Field Craig , Foreman Michael , Ylioja Thomas , Brown Carlos V R
Published: June 2015

Alcohol-related injuries are a major source of admission for trauma care. Screening and brief intervention (SBI) for injured patients can result in decreased drinking and risk behaviors. It is not clear SBI is equally beneficial for all injured patients. A secondary data analysis of 553 patients admitted to two Level-1 trauma centers was conducted. Latent class analysis was used to identify patient subgroups based on injury-related risks and consequences of alcohol use. Intervention effects on drinking were examined among subgroups. Five subgroups were identified. Drinking improved in patients reporting multiple risks and injuries/accidents and drinking and driving. Patients that reported drinking and driving and taking foolish risks or fighting while drinking and taking foolish risks did not show improvements. Trauma centers may benefit from targeting interventions based on injury-related risks and consequences of alcohol use. Further research is needed to test bedside approaches for tailored interventions.
Procalcitonin
Authors: Davies Julie
Published: June 2015

Procalcitonin (PCT) is the 116 amino acid precursor of the hormone calcitonin, produced by the C cells of the thyroid. Its synthesis is upregulated in bacterial infection and downregulated by viral infection. Consequently, with the increasing development of antibiotic resistance, interest has focused on the ability of this marker to not only diagnose infection but to tailor antibiotic treatment and help reduce the development of antibiotic resistance. The value of PCT depends on the specific clinical situation and pretest probability of disease. This article discusses the role of PCT in these different situations, namely primary care, the emergency department and the intensive care unit. The true cost effectiveness of this test remains difficult to prove as evidence for the potential impact of using PCT on slowing the development of bacterial resistance remains largely circumstantial.
CD10-positive mantle cell lymphoma: biologically distinct entity or an aberrant immunophenotype? Insight, through gene expression profile in a unique case series
Authors: Akhter Ariz , Mahe Etienne , Street Lesley , Pournazari Payam , Perizzolo Marco , Shabani-Rad Meer-Taher , Stewart Douglas A , Mansoor Adnan
Published: June 2015

Background

Mantle cell lymphoma (MCL) is an aggressive disease with genetic heterogeneity and discrete clinical subtypes. MCL is rarelyCD10positive. These cases raise the question whether a subset of MCL may be germinal centre (GC) derived, and have distinct clinicopathological characteristics.

Aims and methods

A series of nineCD10-positive MCL cases is described herein. The clinicopathological and immunophenotypic features, immunoglobulin somatic hypermutation (SHM) status and gene expression profile (GEP) data are detailed. These features were compared with two independent sets (n=20, each) ofCD10-negative MCL cases (controls), which were randomly selected from our institutional registry.

Results

GEP showed distinct expression of a GC signature inCD10-positive MCL cases with minimal impact on downstream signalling pathways. There were no significant differences in the clinicopathological features or clinical outcome between ourCD10-positive andCD10-negative MCL cases. The frequency of SHM was comparable with established data.

Conclusions

This study provides convincing evidence thatCD10expression is related to a distinct GC signature in MCL cases, but without clinical or biological implications.
Pancreatic cancer: current understanding of molecular and genetic aetiologies
Authors: Gall Tamara M H , Wasan Harpreet , Jiao Long R
Published: June 2015

Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancers where prognosis has not improved over the past few decades. However, there have been several advances in our understanding of the disease leading to earlier detection and targeted therapeutic treatment. It is now understood that specific somatic and germline mutations lead to the development of the disease, and the risk factors associated with this are clearer. Further, several precursor lesions have been identified which, with early detection and surveillance, allows treatment before the development of carcinoma. PDAC can now be diagnosed with a high sensitivity and specificity following advances in radiology, and treatment can be commenced at an earlier stage of the disease. With continued research we are hopeful that the next decade will see an improved survival rate for all patients with pancreatic cancer.
Metastasising hepatic neuroendocrine carcinoma in a pygmy goat (Caprahircus hircus)
Authors: Völker Iris , Kummrow Maya , von Dörnberg Katja , Wohlsein Peter , Hewicker‐Trautwein Marion
Published: June 2015

An adult, female pygmy goat showed clinical injury and later lameness caused by marked swelling and ulceration of the left lateral hind claw. Conservative treatments failed and due to the development of excessive granulation tissue the lateral claw was amputated. Histologically, a malignant tumour invading the dermis was diagnosed. Fourteen weeks after surgery the goat became recumbent, showed increased values of liver enzymes. Euthanasia followed for humane reasons. At postmortem examination, the liver tissue was almost completely replaced by a solid tumour mass. Additional neoplastic nodules were found in several organs and lymph nodes. Histological and immunohistochemical examination revealed a primary metastasising hepatic neuroendocrine carcinoma (PHNEC) expressing chromogranin A and neuron‐specific enolase. Neuroendocrine carcinomas have not been described in goats yet. A metastasis in the claw was the first clinical sign observed in this case. Pedal tumour metastasis should be considered as a differential diagnosis for lameness in goats.
The interplay between resource supply and demand determines the influence of predation on prey body size
Authors: DeLong John P. , Walsh Matthew
Published: June 2015

Predation has been shown to either increase or decrease the body mass of fish, as well as cause variable changes in growth rate. The mechanisms underlying these contrasting responses are not well understood. Here we compared intraspecific body size and growth responses to predation against a backdrop of 2006 estimates of asymptotic mass and growth constants (i.e., von Bertalanffy parameters) across species. We show that intraspecific responses can be quite large relative to interspecific variation and confirm that the magnitude and direction of body size responses is variable. We then employed the supply–demand (SD) model of body mass evolution to explore how predator-induced changes in resource demand or supply could alter body mass. The SD model predicts that any combination of increasing or decreasing body mass and increasing or decreasing growth rate is possible when predation risk is increased, which is consistent with the literature. Finally, we use three case studies to illustrate how the interplay of resource supply and resource demand determines the actual body mass and growth rate response to predation.
Network growth with preferential attachment and without “rich get richer” mechanism
Authors: Lachgar A. , Achahbar A.
Published: June 2015

We propose a simple preferential attachment model of growing network using the complementary probability of Barabási–Albert (BA) model, i.e. [Formula: see text]. In this network, new nodes are preferentially attached to not well connected nodes. Numerical simulations, in perfect agreement with the master equation solution, give an exponential degree distribution. This suggests that the power law degree distribution is a consequence of preferential attachment probability together with “rich get richer” phenomena. We also calculate the average degree of a target node at time t[Formula: see text] and its fluctuations, to have a better view of the microscopic evolution of the network, and we also compare the results with BA model.
INFLUENCE OF DEPOSITION TEMPERATURE ON OPTICAL AND LASER-INDUCED DAMAGE PROPERTIES OF LaTiO3 FILMS
Authors: SU JUNHONG , XU JUNQI , YANG CHEN , CHENG YAOJIN
Published: June 2015

LaTiO 3 films were prepared at room temperature, 60, 140 and 220°C using a thermal vapor deposition technique with an electronic beam gun to investigate the relationship between deposition temperatures and the optical properties of the samples. In the ellipsometric analysis, the corresponding refractive indexes were 1.8993, 1.9123, 1.9197 and 1.9283 at a wavelength of 1064 nm. At the same time, extremely low absorption characteristics of all the samples presented in the visible and IR regions. With the same high-energy testing laser of 200 mJ (about 40 J/cm2) at a wavelength of 1064 nm and a pulse width of 10 ns, the laser-induced damage threshold (LIDT) of the LaTiO 3 samples prepared at different temperatures were 15.5, 16.7, 18.5 and 18.2 J/cm2, respectively. This shows that a higher LIDT may be obtained at higher deposition temperatures.
Efficient Processing of Skyline-Join Queries over Multiple Data Sources
Authors: Nagendra Mithila , Candan K. Selçuk
Published: June 2015

Efficient processing of skyline queries has been an area of growing interest. Many of the earlier skyline techniques assumed that the skyline query is applied to a single data table. Naturally, these algorithms were not suitable for many applications in which the skyline query may involve attributes belonging to multiple data sources. In other words, if the data used in the skyline query are stored in multiple tables, then
join
operations would be required before the skyline can be searched. The task of computing skylines on multiple data sources has been coined as the
skyline-join
problem and various
skyline-join
algorithms have been proposed. However, the current proposals suffer several drawbacks: they often need to scan the input tables exhaustively in order to obtain the set of skyline-join results; moreover, the pruning techniques employed to eliminate the tuples are largely based on expensive pairwise tuple-to-tuple comparisons. In this article, we aim to address these shortcomings by proposing two novel skyline-join algorithms, namely
skyline-sensitive join
(S
2
J) and
symmetric skyline-sensitive join
(S
3
J), to process skyline queries over two data sources. Our approaches compute the results using a novel
layer/region pruning
technique (
LR-pruning
) that prunes the join space in blocks as opposed to individual data points, thereby avoiding excessive pairwise point-to-point dominance checks. Furthermore, the S
3
J algorithm utilizes an early stopping condition in order to successfully compute the skyline results by accessing only a subset of the input tables. In addition to S
2
J and S
3
J, we also propose the S
2
J-M and S
3
J-M algorithms. These algorithms extend S
2
J's and S
3
J's two-way skyline-join ability to efficiently process skyline-join queries over more than two data sources. S
2
J-M and S
3
J-M leverage the extended concept of
LR-pruning
, called
M
-way
LR-pruning
, to compute multi-way skyline-joins in which more than two data sources are integrated during skyline processing. We report extensive experimental results that confirm the advantages of the proposed algorithms over state-of-the-art skyline-join techniques.
A General-Purpose Sensing Floor Architecture for Human-Environment Interaction
Authors: Vezzani Roberto , Lombardi Martino , Pieracci Augusto , Santinelli Paolo , Cucchiara Rita
Published: June 2015

Smart environments are now designed as natural interfaces to capture and understand human behavior without a need for explicit human-computer interaction. In this article, we present a general-purpose architecture that acquires and understands human behaviors through a sensing floor. The pressure field generated by moving people is captured and analyzed. Specific actions and events are then detected by a low-level processing engine and sent to high-level interfaces providing different functions. The proposed architecture and sensors are modular, general-purpose, cheap, and suitable for both small- and large-area coverage. Some sample entertainment and virtual reality applications that we developed to test the platform are presented.
Closing the Gap
Authors: Beedkar Kaustubh , Berberich Klaus , Gemulla Rainer , Miliaraki Iris
Published: June 2015

Frequent sequence mining is one of the fundamental building blocks in data mining. While the problem has been extensively studied, few of the available techniques are sufficiently scalable to handle datasets with billions of sequences; such large-scale datasets arise, for instance, in text mining and session analysis. In this article, we propose MG-FSM, a scalable algorithm for frequent sequence mining on MapReduce. MG-FSM can handle so-called “gap constraints”, which can be used to limit the output to a controlled set of frequent sequences. Both positional and temporal gap constraints, as well as appropriate maximality and closedness constraints, are supported. At its heart, MG-FSM partitions the input database in a way that allows us to mine each partition independently using any existing frequent sequence mining algorithm. We introduce the notion of ω-equivalency, which is a generalization of the notion of a “projected database” used by many frequent pattern mining algorithms. We also present a number of optimization techniques that minimize partition size, and therefore computational and communication costs, while still maintaining correctness. Our experimental study in the contexts of text mining and session analysis suggests that MG-FSM is significantly more efficient and scalable than alternative approaches.
Context-Aware Automated Analysis and Annotation of Social Human--Agent Interactions
Authors: Baur Tobias , Mehlmann Gregor , Damian Ionut , Lingenfelser Florian , Wagner Johannes , Lugrin Birgit , André Elisabeth , Gebhard Patrick
Published: June 2015

The outcome of interpersonal interactions depends not only on the contents that we communicate verbally, but also on nonverbal social signals. Because a lack of social skills is a common problem for a significant number of people, serious games and other training environments have recently become the focus of research. In this work, we present NovA (
No
n
v
erbal behavior
A
nalyzer), a system that analyzes and facilitates the interpretation of social signals automatically in a bidirectional interaction with a conversational agent. It records data of interactions, detects relevant social cues, and creates descriptive statistics for the recorded data with respect to the agent's behavior and the context of the situation. This enhances the possibilities for researchers to automatically label corpora of human--agent interactions and to give users feedback on strengths and weaknesses of their social behavior.
Efficient Processing of Spatial Group Keyword Queries
Authors: Cao Xin , Cong Gao , Guo Tao , Jensen Christian S. , Ooi Beng Chin
Published: June 2015

With the proliferation of geo-positioning and geo-tagging techniques, spatio-textual objects that possess both a geographical location and a textual description are gaining in prevalence, and spatial keyword queries that exploit both location and textual description are gaining in prominence. However, the queries studied so far generally focus on finding individual objects that each satisfy a query rather than finding groups of objects where the objects in a group together satisfy a query.

We define the problem of retrieving a group of spatio-textual objects such that the group's keywords cover the query's keywords and such that the objects are nearest to the query location and have the smallest inter-object distances. Specifically, we study three instantiations of this problem, all of which are NP-hard. We devise exact solutions as well as approximate solutions with provable approximation bounds to the problems. In addition, we solve the problems of retrieving top-
k
groups of three instantiations, and study a weighted version of the problem that incorporates object weights. We present empirical studies that offer insight into the efficiency of the solutions, as well as the accuracy of the approximate solutions.
CRMP5 Controls Glioblastoma Cell Proliferation and Survival through Notch-Dependent Signaling
Authors: Moutal Aubin , Honnorat Jérôme , Massoma Patrick , Désormeaux Pauline , Bertrand Caroline , Malleval Céline , Watrin Chantal , Chounlamountri Naura , Mayeur Marie-Eve , Besançon Roger , Naudet Nicolas , Magadoux Léa , Khanna Rajesh , Ducray François , Meyronet David , Thomasset Nicole
Published: June 2015

Collapsin response mediator protein 5 (CRMP5) belongs to a family of five cytosolic proteins that play a major role in nervous system development. This protein was first described in cancer-induced autoimmune processes, causing neurodegenerative disorders (paraneoplastic neurologic syndromes). CRMP5 expression has been reported to serve as a biomarker for high-grade lung neuroendocrine carcinomas; however, its functional roles have not been examined in any setting of cancer pathophysiology. In this study, we report two different CRMP5 expression patterns observed in human glioblastoma (GBM) biopsies that establish connections between CRMP5 expression, Notch receptor signaling, and GBM cell proliferation. We demonstrated that elevated CRMP5 promotes Notch receptor expression and Akt activation in human tumor cell lines, GBM stem cells, and primary tumor biopsies. We have shown that the high CRMP5 and Notch expression in GBM xenograft is related to stem cells. This suggests that high CRMP5 expression pattern in GBM biopsies encompasses a subset of stem cells. Mechanistically, CRMP5 functioned by hijacking Notch receptors from Itch-dependent lysosomal degradation. Our findings suggest that CRMP5 serves as a major mediator of Notch signaling and Akt activation by controlling the degradation of the Notch receptor, with implications for defining a biomarker signature in GBM that correlates with and may predict patient survival. Cancer Res; 75(17); 3519–28. ©2015 AACR.
Identification of Prognostic Groups in High-Grade Serous Ovarian Cancer Treated with Platinum–Taxane Chemotherapy
Authors: Chen Ping , Huhtinen Kaisa , Kaipio Katja , Mikkonen Piia , Aittomäki Viljami , Lindell Rony , Hynninen Johanna , Auranen Annika , Grénman Seija , Lehtonen Rainer , Carpén Olli , Hautaniemi Sampsa
Published: June 2015

Disseminated high-grade serous ovarian cancer (HGS-OvCa) is an aggressive disease treated with platinum and taxane combination therapy. While initial response can be favorable, the disease typically relapses and becomes resistant to treatment. As genomic alterations in HGS-OvCa are heterogeneous, identification of clinically meaningful molecular markers for outcome prediction is challenging. We developed a novel computational approach (PSFinder) that fuses transcriptomics and clinical data to identify HGS-OvCa prognostic subgroups for targeted treatment. Application of PSFinder to transcriptomics data from 180 HGS-OvCa patients treated with platinum–taxane therapy revealed 61 transcript isoforms that characterize two poor and one good survival-associated groups (P = 0.007). These groups were validated in eight independent data sets, including a prospectively collected ovarian cancer cohort. Two poor prognostic groups have distinct expression profiles and are characteristic by increased hypermethylation and stroma-related genes. Integration of the PSFinder signature and BRCA1/2 mutation status allowed even better stratification of HGS-OvCa patients' prognosis. The herein introduced novel and generally applicable computational approach can identify outcome-related subgroups and facilitate the development of precision medicine to overcome drug resistance. A limited set of biomarkers divides HGS-OvCa into three prognostic groups and predicts patients in need of targeted therapies. Cancer Res; 75(15); 2987–98. ©2015 AACR.
Diverse Targets of β-Catenin during the Epithelial–Mesenchymal Transition Define Cancer Stem Cells and Predict Disease Relapse
Authors: Chang Yi-Wen , Su Ying-Jhen , Hsiao Michael , Wei Kuo-Chen , Lin Wei-Hsin , Liang Chi-Jung , Chen Shin-Cheh , Lee Jia-Lin
Published: June 2015

Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that are activated by epithelial–mesenchymal transition (EMT). However, the mechanistic relationship between EMT and the Wnt pathway in CSC is not entirely clear. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) indicated that EMT induces a switch from the β-catenin/E-cadherin/Sox15 complex to the β-catenin/Twist1/TCF4 complex, the latter of which then binds to CSC-related gene promoters. Tandem coimmunoprecipitation and re-ChIP experiments with epithelial-type cells further revealed that Sox15 associates with the β-catenin/E-cadherin complex, which then binds to the proximal promoter region of CASP3. Through this mechanism, Twist1 cleavage is triggered to regulate a β-catenin–elicited promotion of the CSC phenotype. During EMT, we documented that Twist1 binding to β-catenin enhanced the transcriptional activity of the β-catenin/TCF4 complex, including by binding to the proximal promoter region of ABCG2, a CSC marker. In terms of clinical application, our definition of a five-gene CSC signature (nuclear β-cateninHigh/nuclear Twist1High/E-cadherinLow/Sox15Low/CD133High) may provide a useful prognostic marker for human lung cancer. Cancer Res; 75(16); 3398–410. ©2015 AACR.
Endothelial Thermotolerance Impairs Nanoparticle Transport in Tumors
Authors: Bagley Alexander F. , Scherz-Shouval Ruth , Galie Peter A. , Zhang Angela Q. , Wyckoff Jeffrey , Whitesell Luke , Chen Christopher S. , Lindquist Susan , Bhatia Sangeeta N.
Published: June 2015

The delivery of diagnostic and therapeutic agents to solid tumors is limited by physical transport barriers within tumors, and such restrictions directly contribute to decreased therapeutic efficacy and the emergence of drug resistance. Nanomaterials designed to perturb the local tumor environment with precise spatiotemporal control have demonstrated potential to enhance drug delivery in preclinical models. Here, we investigated the ability of one class of heat-generating nanomaterials called plasmonic nanoantennae to enhance tumor transport in a xenograft model of ovarian cancer. We observed a temperature-dependent increase in the transport of diagnostic nanoparticles into tumors. However, a transient, reversible reduction in this enhanced transport was seen upon reexposure to heating, consistent with the development of vascular thermotolerance. Harnessing these observations, we designed an improved treatment protocol combining plasmonic nanoantennae with diffusion-limited chemotherapies. Using a microfluidic endothelial model and genetic tools to inhibit the heat-shock response, we found that the ability of thermal preconditioning to limit heat-induced cytoskeletal disruption is an important component of vascular thermotolerance. This work, therefore, highlights the clinical relevance of cellular adaptations to nanomaterials and identifies molecular pathways whose modulation could improve the exposure of tumors to therapeutic agents. Cancer Res; 75(16); 3255–67. ©2015 AACR.
Defects in the Fanconi Anemia Pathway and Chromatid Cohesion in Head and Neck Cancer
Authors: Stoepker Chantal , Ameziane Najim , van der Lelij Petra , Kooi Irsan E. , Oostra Anneke B. , Rooimans Martin A. , van Mil Saskia E. , Brink Arjen , Dietrich Ralf , Balk Jesper A. , Ylstra Bauke , Joenje Hans , Feller Stephan M. , Brakenhoff Ruud H.
Published: June 2015

Failure to repair DNA damage or defective sister chromatid cohesion, a process essential for correct chromosome segregation, can be causative of chromosomal instability (CIN), which is a hallmark of many types of cancers. We investigated how frequent this occurs in head and neck squamous cell carcinoma (HNSCC) and whether specific mechanisms or genes could be linked to these phenotypes. The genomic instability syndrome Fanconi anemia is caused by mutations in any of at least 16 genes regulating DNA interstrand crosslink (ICL) repair. Since patients with Fanconi anemia have a high risk to develop HNSCC, we investigated whether and to which extent Fanconi anemia pathway inactivation underlies CIN in HNSCC of non–Fanconi anemia individuals. We observed ICL-induced chromosomal breakage in 9 of 17 (53%) HNSCC cell lines derived from patients without Fanconi anemia. In addition, defective sister chromatid cohesion was observed in five HNSCC cell lines. Inactivation of FANCM was responsible for chromosomal breakage in one cell line, whereas in two other cell lines, somatic mutations in PDS5A or STAG2 resulted in inadequate sister chromatid cohesion. In addition, FANCF methylation was found in one cell line by screening an additional panel of 39 HNSCC cell lines. Our data demonstrate that CIN in terms of ICL-induced chromosomal breakage and defective chromatid cohesion is frequently observed in HNSCC. Inactivation of known Fanconi anemia and chromatid cohesion genes does explain CIN in the minority of cases. These findings point to phenotypes that may be highly relevant in treatment response of HNSCC. Cancer Res; 75(17); 3543–53. ©2015 AACR.
Assessment of Serum Copper State after Gastrectomy with Roux-en-Y Reconstruction for Gastric Cancer
Authors: Nakagawa Masatoshi , Kojima Kazuyuki , Inokuchi Mikito , Kato Keiji , Sugita Hirofumi , Otsuki Sho , Higuchi Kyoko , Kobayashi Kenta , Sugihara Kenichi
Published: June 2015

Background: Some recent reports have noted that copper deficiency can occur in obese patients who have undergone bariatric surgery, such as Roux-en-Y (RY) gastric bypass or biliopancreatic diversion, or in patients who receive enteral nutrition through a jejunostomy. No reports appear to have assessed the serum copper state of patients following gastrectomy with RY reconstruction for gastric cancer. Methods: A cross-sectional study was conducted from June 2013 to December 2014. Serum copper levels (SCLs) in 242 out-clinic patients who underwent curative gastrectomy were obtained. Patients were classified into an RY group (n = 208) and a non-RY group (n = 34). Results: Hypocupremia was identified in 3 patients in the RY group (1.4%), and 2 patients in the non-RY group (5.9%; p = 0.146), but none experienced any symptoms caused by hypocupremia. No significant difference in the mean SCL was seen between the RY group (105.8 ± 21.2 µg/dl) and non-RY group (107.9 ± 22.7 µg/dl; p = 0.499). In the RY group, the mean SCL was significantly lower in younger patients, patients with follow-up period <3 years, and male patients. Conclusion: Some patients developed hypocupremia after gastrectomy with RY reconstruction, but the number is acceptably low, and physical symptoms were unusual.
The Phytotherapeutic Fenugreek as Trigger of Toxic Epidermal Necrolysis
Authors: Bentele-Jaberg Nicoletta , Guenova Emmanuella , Mehra Tarun , Nägeli Mirjam , Chang Yung-Tsan , Cozzio Antonio , French Lars E. , Hoetzenecker Wolfram
Published: June 2015

We describe the case of a 32-year-old woman who presented to the hospital with generalized painful exanthema, blisters and erosions 1 month after giving birth to a healthy girl. The patient's medical history was inconspicuous for comorbidities; however, it included the incidental intake of pain killers and a herbal preparation (fenugreek), which she took regularly over the last 4 weeks to improve lactation. Based on the clinical characteristics, we suspected toxic epidermal necrolysis (TEN), a severe cutaneous adverse drug reaction, which was confirmed by skin biopsy. The patient was treated with high-dose intravenous human immunoglobulins and was discharged 2 weeks after hospital admission in good condition. The allergological workup identified fenugreek as the most likely causative agent. Given the increased self-medication of freely available phytotherapeutics by patients in industrialized countries, herbal mixtures should be taken into consideration in the diagnostic workup of TEN.
Prediction of Locally Advanced Urothelial Carcinoma of the Bladder Using Clinical Parameters before Radical Cystectomy - A Prospective Multicenter Study
Authors: Martini Thomas , Aziz Atiqullah , Roghmann Florian , Rink Michael , Chun Felix K. , Fisch Margit , Trojan Lutz , Hakenberg Oliver W. , Zastrow Stefan , Wirth Manfred P. , Moersdorf Johannes , Brookman-May Sabine , Stief Christian G. , Haferkamp Axel , Wagenlehner Florian , Hohenfellner Markus , Herrmann Edwin , Lusuardi Lukas , Grimm Marc-Oliver , Müller Stephan C. , Roigas Jan , Bastian Patrick J. , Gierth Michael , Burger Maximilian , Pycha Armin , Seitz Christian , May Matthias , Bolenz Christian
Published: June 2015

Introduction: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. Materials and Methods: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. Results: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. Conclusion: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters.
Hypercortisolemic Depressed Women: Lean but Viscerally Obese?
Authors: Deuschle Michael , Gilles Maria
Published: June 2015

Background: Activation of the hypothalamic-pituitary-adrenal (HPA) system in depressed patients has been related to visceral adiposity. In contrast, low HPA system activity is associated with increased body fat in the general population. Our study intended to clarify whether HPA system activity is related to body weight and composition in depressed inpatients. Methods: In a cohort of 51 female and 20 male depressed inpatients, we measured saliva cortisol (HPA system activity), body mass index (BMI), waist circumference as well as body composition as reflected by bioimpedance. Results: In female patients, cortisol in saliva was negatively associated with fat-to-muscle ratio and BMI. Conclusion: In depressed inpatients, especially women, there is evidence that activation of the HPA system is related to relatively low body weight and low body fat content.
Oscar Masotta y Roland Barthes. Homologías estructurales de una crítica de vanguardia
Authors: Nácher Max Hidalgo
Published: June 2015

El artículo propone una lectura comparada de la obra de Oscar Masotta y de Roland Barthes hasta los años setenta. Beatriz Sarlo y Pierre Bourdieu han visto en estos autores, respectivamente, un síntoma de la época. Así, más que fijarnos en sus contenidos, proponemos una lectura en movimiento a partir del descubrimiento de una homología estructural: Masotta y Barthes comparten una misma posición de enunciación. Como podrá verse en el artículo, ésta va ligada, a su vez, a la precariedad de su posición institucional y a una apuesta decidida por la vanguardia intelectual.
Roland Barthes na revista Língua e Literatura (USP)
Authors: Brandini Laura Taddei
Published: June 2015

Este artigo visa a descrever e analisar a recepção às obras de Roland Barthes na crítica universitária paulista tendo como corpus a revista uspiana Língua e Literatura, criada em 1972 e ainda em circulação. A seleção dos conceitos barthesianos presentes nos artigos da revista evidencia a dinâmica que rege a percepção da imagem de Barthes a cada momento histórico brasileiro: de líder do estruturalismo, nos anos 70, a libertário pós-moderno, nos anos 2000, apontando não só para uma diferença de valorização de seus escritos, como também para a mudança de perfil dos críticos acadêmicos.
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Authors: Pino Claudia Amigo , Fontanari Rodrigo , Bergonzoni Gisela Anauate , Bellocchio Carolina Molinar , Oliveira Priscila Pesce Lopes de
Published: June 2015

Sem resumo
Ensino da leitura em tecnologia virtual na escola
Authors: Pereira Vera Wannmacher
Published: June 2015

A pesquisa aqui relatada teve como objetivos específicos: produzir materiais de leitura virtuais para alunos de 7ª série do EF; desenvolver oficinas com esses materiais para esse público; verificar os benefícios das oficinas para o desenvolvimento da compreensão leitora dos alunos e a aprendizagem de conhecimentos linguísticos textuais; gerar um e-book para uso por professores; disponibilizar esse e-book no site da Editora da PUCRS – EDIPUCRS. A metodologia envolveu: realização de trabalho cooperativo em torno de ações de ensino (oficinas de aplicação dos materiais virtuais gerados), pesquisa (elaboração e aplicação de instrumentos de pesquisa) e extensão (produção e disponibilização de e-book). Constituíram-se em resultados: uma rede produtiva entre a Universidade e as escolas; um acervo de materiais de desenvolvimento da compreensão leitora de alunos de 7ª série do Ensino Fundamental; o desenvolvimento da compreensão leitora dos alunos e a aprendizagem de conhecimentos linguísticos na relação pré/pós-teste; o e-book gerado e implantado no site da EDIPUCRS.
A abordagem singular de Zélia Monteiro
Authors: Spirópulos Flávia Scheye
Published: June 2015

O artigo pretende apresentar o modo como a artista Zélia Monteiro vem desenvolvendo seu trabalho com dança, apontando que sua abordagem se configura a partir de um pensamento estético que se desdobra nos ambientes de criação, cena e pedagogia de forma codependente e coimplicada.
Prática artística como espaço político
Authors: Purper Raquel
Published: June 2015

O processo contemporâneo de prática artística suscita questões que dizem respeito ao artista, ao seu contexto político-social e a todos os outros fatores que, combinados, compõem sua maneira de posicionar-se no mundo. O político norteia as escolhas estéticas e, consequentemente, as posturas éticas, e por isso é necessário que se reflita sobre como a relação entre artistas envolvidos no desenvolvimento de uma prática artística pode transformar esse espaço de trabalho em um espaço político. Para isso, apresenta-se o conceito de política, as conexões entre subjetividade, singularidade, intersubjetividade e afeto e as discussões entre consenso e dissenso, as quais atravessam essas relações, no intuito de compreender o que potencializa esse espaço como político.
Resenha do livro 'Regimes de historicidade: presentismo e experiências do tempo'
Authors: Pimenta João Paulo Garrido
Published: June 2015

HARTOG, François. Regimes de historicidade: presentismo e experiências do tempo. Tradução de Andréa S. de Menezes, Bruna Breffart, Camila R. Moraes, Maria Cristina de A. Silva e Maria Helena Martins. Belo Horizonte: Autêntica, 2014
A SITUAÇÃO DAS EMPREGADAS DOMÉSTICAS NA PRIMEIRA DÉCADA DO SÉCULO XXI, NO OESTE E NO SUDOESTE DA REGIÃO METROPOLITANA DE SÃO PAULO
Authors: Luchiari Ailton
Published: June 2015

Este artigo tem o objetivo de elaborar a caracterização das mulheres dedicadas aos serviços domésticos no mercado de trabalho. A análise de dados coletados e distribuídos pelos órgãos oficiais de recenseamento permitiu observar as transformações ocorridas no primeiro decênio deste século. As principais alterações foram observadas nos rendimentos, nos níveis de instrução, na formalização no emprego e na participação das mulheres no mercado de trabalho.