bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Transcription Factor Mlc Promotes Vibrio cholerae Biofilm Formation through Repression of Phosphotransferase System Components
Authors: Pickering Bradley S. , Lopilato Jane E. , Smith Daniel R. , Watnick Paula I. 
Published: April 2014

ABSTRACT

The phosphoenol phosphotransferase system (PTS) is a multicomponent signal transduction cascade that regulates diverse aspects of bacterial cellular physiology in response to the availability of high-energy sugars in the environment. Many PTS components are repressed at the transcriptional level when the substrates they transport are not available. In
Escherichia
coli, the transcription factor Mlc (for
m
akes
l
arge
c
olonies) represses transcription of the genes encoding enzyme I (EI), histidine protein (HPr), and the glucose-specific enzyme IIBC (EIIBC
Glc
) in defined media that lack PTS substrates. When glucose is present, the unphosphorylated form of EIIBC
Glc
sequesters Mlc to the cell membrane, preventing its interaction with DNA. Very little is known about
Vibrio cholerae
Mlc. We found that
V. cholerae
Mlc activates biofilm formation in LB broth but not in defined medium supplemented with either pyruvate or glucose. Therefore, we questioned whether
V. cholerae
Mlc functions differently than
E. coli
Mlc. Here we have shown that, like
E. coli
Mlc,
V. cholerae
Mlc represses transcription of PTS components in both defined medium and LB broth and that
E. coli
Mlc is able to rescue the biofilm defect of a
V. cholerae
Δ
mlc
mutant. Furthermore, we provide evidence that Mlc indirectly activates transcription of the
vps
genes by repressing expression of EI. Because activation of the
vps
genes by Mlc occurs under only a subset of the conditions in which repression of PTS components is observed, we conclude that additional inputs present in LB broth are required for activation of
vps
gene transcription by Mlc.
Monitoring of Commitment, Blocking, and Continuation of Nutrient Germination of Individual Bacillus subtilis Spores
Authors: Zhang Pengfei , Liang Jintao , Yi Xuan , Setlow Peter , Li Yong-qing 
Published: April 2014

ABSTRACT

Short exposures of
Bacillus
spores to nutrient germinants can commit spores to germinate when germinants are removed or their binding to the spores' nutrient germinant receptors (GRs) is inhibited.
Bacillus subtilis
spores were exposed to germinants for various periods, followed by germinant removal to prevent further commitment. Release of spore dipicolinic acid (DPA) was then measured by differential interference contrast microscopy to monitor germination of multiple individual spores, and spores did not release DPA after 1 to 2 min of germinant exposure until ∼7 min after germinant removal. With longer germinant exposures, percentages of committed spores with times for completion of DPA release (
T
release
) greater than the time of germinant removal (
T
b
) increased, while the time
T
lag
−
T
b
, where
T
lag
represents the time when rapid DPA release began, was decreased but rapid DPA release times (Δ
T
release
=
T
release
−
T
lag
) were increased; Factors affecting average
T
release
values and the percentages of committed spores were germinant exposure time, germinant concentration, sporulation conditions, and spore heat activation, as previously shown for commitment of spore populations. Surprisingly, germination of spores given a 2nd short germinant exposure 30 to 45 min after a 1st exposure of the same duration was significantly higher than after the 1st exposure, but the number of spores that germinated in the 2nd germinant exposure decreased as the interval between germinant exposures increased up to 12 h. The latter results indicate that spores have some memory, albeit transient, of their previous exposure to nutrient germinants.
Mechanistic Study of Classical Translocation-Dead SpoIIIE36 Reveals the Functional Importance of the Hinge within the SpoIIIE Motor
Authors: Besprozvannaya Marina , Pivorunas Valerie L. , Burton Briana M. 
Published: April 2014

ABSTRACT

SpoIIIE/FtsK ATPases are central players in bacterial chromosome segregation. It remains unclear how these DNA translocases harness chemical energy (ATP turnover) to perform mechanical work (DNA movement).
Bacillus subtilis
sporulation provides a dramatic example of intercompartmental DNA transport, in which SpoIIIE moves 70% of the chromosome across the division plane. To understand the mechanistic requirements for DNA translocation, we investigated the DNA translocation defect of a classical nontranslocating allele,
spoIIIE36
. We found that the translocation phenotype is caused by a single substitution, a change of valine to methionine at position 429 (V429M), within the motor of SpoIIIE. This substitution is located at the base of a hinge between the RecA-like β domain and the α domain, which is a domain unique to the SpoIIIE/FtsK family and currently has no known function. V429M interferes with both protein-DNA interactions and oligomer assembly. These mechanistic defects disrupt coordination between ATP turnover and DNA interaction, effectively uncoupling ATP hydrolysis from DNA movement. Our data provide the first functional evidence for the importance of the hinge in DNA translocation.
The art of being healthy: a qualitative study to develop a thematic framework for understanding the relationship between health and the arts
Authors: Davies Christina R , Knuiman Matthew , Wright Peter , Rosenberg Michael 
Published: April 2014

ObjectiveIn recent years the health–arts nexus has received increasing attention; however, the relationship is not well understood and the extent of possible positive, negative and unintended outcomes is unknown. Guided by the biopsychosocial model of health and theories of social epidemiology, the aim of this study was to develop a framework pertaining to the relationship between arts engagement and population health that included outcomes, confounders and effect modifiers. A health–arts framework is of value to researchers seeking to build the evidence base; health professionals interested in understanding the health–arts relationship, especially those who use social prescribing for health promotion or to complement treatments; in teaching medical, nursing and health-science students about arts outcomes, as well as artists and health professionals in the development of policy and programmes.DesignA qualitative study was conducted. Semistructured interviews were analysed thematically.SettingWestern Australia.Participants33 Western Australian adults (18+ years). Participants were randomly selected from a pool of general population nominees who engaged in the arts for enjoyment, entertainment or as a hobby (response rate=100%).ResultsA thematic analysis was conducted using QSR-NVivo10. The resulting framework contained seven outcome themes and 63 subthemes. Three themes specifically related to health, that is, mental, social and physical health, while economic, knowledge, art and identity outcomes were classified as health determinants. Within each theme, positive, negative and unintended outcomes (subthemes) were identified and categorised as relating to the individual and/or to the community. A list of confounding and/or effect modifying factors, related to both the arts and health, was identified.ConclusionsGiven the increasing pressure on health resources, the arts have the potential to assist in the promotion of health and healing. This framework expands on current knowledge, further defines the health–arts relationship and is a step towards the conceptualisation of a causal health–arts model.
Weight a minute - iatrogenic paracetamol toxicity is preventable by utilisation of well-designed drug charts
Authors: Khan Amad , Flavin Kathryn , Tsang Jason 
Published: April 2014

AbstractIatrogenic Paracetamol toxicity is a potentially life-threatening yet avoidable cause of acute liver failure. Unfortunately, several cases have recently been reported nationally (1,2). The impetus behind our project was a recent case of iatrogenic Paracetamol induced hepatotoxicity within our trust, a London-based District General Hospital. According to the British National Formulary, for adults weighing 10-50kg the intravenous (IV) dose is 15mg/kg every 4-6hours (max. 60mg/kg daily), not the usual 1 gram QDS oral dose which is applied irrespective of weight (3). We audited 100 adult patients in April 2013 and re-audited in July 2013. Both of the randomly selected samples consisted of an equal number of surgical and medical patients, with an equal gender ratio. Data of interest included whether patients were on IV Paracetamol, appropriately dosed; if and when patients had been weighed during admission; and whether the WHO pain ladder of analgesia was followed. Identified shortcomings included patient weight on admission not being recorded, and IV Paracetamol dose adjustment not being made in patients <50kg. 3 months were spent raising awareness of the importance to record patient weights and to dose-adjust IV Paracetamol when indicated. Patients weighed on admission improved from 37% to 68% (p<0.0001) and those on the inappropriate dose of Paracetamol fell from 18 (25% of the patients on Paracetamol) to 5 (5.75% of the patients on Paracetamol) p=0.0013. There was a marked improvement in the number of patients with the weight written on their drug chart from 27% to 53% post-intervention. (p=0.0003) In conclusion, every patient should be weighed on admission. In order to prevent potential hepatotoxicity, staff should document patient weights on the drug charts and be aware of the fact that patients who weigh <50 kg should be on a 15 mg/kg/dose of IV Paracetamol, not 1 gram QDS.
Building collaborative technology learning environments
Authors: Janz Kenneth , Graetz Ken , Kjorlien Chad 
Published: April 2014

The rapid advance of technology has enabled students to use powerful technology both inside and outside of the classroom. A major issue facing higher education is whether students truly know how to use this technology, can our learning spaces support it, and can it be integrated with other technologies to extend students' capabilities?
This paper focuses on the how Winona State University went about improving learning spaces on campus. It includes six major sections. First, the development of the e-Warrior: Digital Life and Learning Program and Technology Master Plan provided the foundation. Second, quantifying the quality of classroom spaces on campus through the development of an online database and a campus report card provided a common point of reference. Third, faculty members engaged in the design of new learning spaces on campus to align design with pedagogy. Fourth, new technologies supported the online delivery of what used to be classroom lecture, paving the way for classroom flipping. Fifth, the intersection between formal and informal learning spaces played a role in instruction. Sixth, WSU developed two new flipped classrooms; the Math Achievement Center and Visual Media Studio. The Math Achievement Center and Visual Media Studio are collaborative classrooms designed by faculty that demonstrate the potential of mobile computing integration. Finally, recommendations for improving learning spaces found on any campus are offered. This paper provides a replicable roadmap for developing collaborative technology learning environments and highlights the many successes and challenges you may experience along the way.
Crafting great user experiences
Authors: Bertino Nic , Corrales Andrew , Chen Allan 
Published: April 2014

As a user of products and technology, one often experiences a wide range of emotions: happiness, frustration, gratitude, irritation, excitement, and apathy amongst others. Yet, as designers and deliverers of these tools and services, the human factor is often neglected with dire consequences. Deadlines and budgets become more important than analyzing the needs and behaviors of the user, unlinking the resource from its consumer. This degrades the perception of the offering and can be irreversible (and potentially fatal) to the reputation of software companies, IT departments, and hardware manufacturers. Despite the failings of many companies that have neglected the human element - companies that lacked empathy for their users - products continue to be delivered that are unintuitive, over designed, or inefficient.
A great product or offering considers the user's experience (UX) when interacting with the service. The product is efficient and intuitive, while being transparent in presentation. UX is generally associated with software, but experiences are designed outside of computing as well. An often-polarizing example is customer service; customers remember great customer service experiences as much as they remember poor experiences. Technology often enhances the user experience, but the experience itself is not confined to interactions with specific tools. Training IT help desk staff on how to interact with customers may not be something traditionally thought of as a UX initiative, but this is one small part of the experience that is designed for individuals having issues with their devices.
At Santa Clara Law, the Law Technology and Academic Computing (LTAC) group has improved efficiency, customer satisfaction, and saved time by considering UX principles early and often. Decisions once made with dangerous assumptions on the user's behalf are now considered with comprehensive data collected from a variety of different sources. Listening to what users are saying also helps LTAC adapt to the users' changing needs and continually enhance offerings.
Connecting digital cancer model repositories with markup
Authors: Johnson David , McKeever Steve , Deisboeck Thomas S. , Wang Zhihui 
Published: April 2014

The cancer research community requires a standardized way of describing mathematical and computational models to enable interoperation between systems, repositories, and between the models themselves. In this paper we describe a new markup language, TumorML, for describing computational models that fall within the domain of cancer. TumorML is an XML-based markup language that wraps existing cancer model implementations with metadata for model curation, parametric interface description, implementation description, and compound model linking.
In this paper we first introduce the rationale for a new markup language for computational cancer model description based on our experiences and requirements from the European Commission's 'Transatlantic Tumor Model Repositories' project. The aim of the project is to develop a European-based digital cancer model repository to link and interoperate with a similar established repository based in the United States. TumorML was developed to enable this interoperation between repositories. We introduce the language and describe the main features of the specification and go on to describe a real application of TumorML where a molecular pathway model has been packaged using the new markup language.
NCOA1 Directly Targets M-CSF1 Expression to Promote Breast Cancer Metastasis
Authors: Qin Li , Wu Ye-Lin , Toneff Michael J. , Li Dabing , Liao Lan , Gao Xiuhua , Bane Fiona T. , Tien Jean C.-Y. , Xu Yixiang , Feng Zhen , Yang Zhihui , Xu Yan , Theissen Sarah M. , Li Yi , Young Leonie , Xu Jianming 
Published: April 2014

Abstract
In breast cancer, overexpression of the nuclear coactivator NCOA1 (SRC-1) is associated with disease recurrence and resistance to endocrine therapy. To examine the impact of NCOA1 overexpression on morphogenesis and carcinogenesis in the mammary gland (MG), we generated MMTV-hNCOA1 transgenic [Tg(NCOA1)] mice. In the context of two distinct transgenic models of breast cancer, NCOA1 overexpression did not affect the morphology or tumor-forming capability of MG epithelial cells. However, NCOA1 overexpression increased the number of circulating breast cancer cells and the efficiency of lung metastasis. Mechanistic investigations showed that NCOA1 and c-Fos were recruited to a functional AP-1 site in the macrophage attractant CSF1 promoter, directly upregulating colony-simulating factor 1 (CSF1) expression to enhance macrophage recruitment and metastasis. Conversely, silencing NCOA1 reduced CSF1 expression and decreased macrophage recruitment and breast cancer cell metastasis. In a cohort of 453 human breast tumors, NCOA1 and CSF1 levels correlated positively with disease recurrence, higher tumor grade, and poor prognosis. Together, our results define an NCOA1/AP-1/CSF1 regulatory axis that promotes breast cancer metastasis, offering a novel therapeutic target for impeding this process. Cancer Res; 74(13); 3477–88. ©2014 AACR.
Immunotherapy for Brain Cancer: Recent Progress and Future Promise
Authors: Jackson Christopher M. , Lim Michael , Drake Charles G. 
Published: April 2014

Abstract
Immunotherapy is emerging as the newest pillar of cancer treatment, with the potential to assume a place alongside surgical debulking, radiotherapy, and chemotherapy. Early experiences with antitumor vaccines demonstrated the feasibility and potential efficacy of this approach, and newer agents, such as immune checkpoint blocking antibodies and modern vaccine platforms, have ushered in a new era. These efforts are headlined by work in melanoma, prostate cancer, and renal cell carcinoma; however, substantial progress has been achieved in a variety of other cancers, including high-grade gliomas. A recurrent theme of this work is that immunotherapy is not a one-size-fits-all solution. Rather, dynamic, tumor-specific interactions within the tumor microenvironment continually shape the immunologic balance between tumor elimination and escape. High-grade gliomas are a particularly fascinating example. These aggressive, universally fatal tumors are highly resistant to radiotherapy and chemotherapy and inevitably recur after surgical resection. Located in the immune-privileged central nervous system, high-grade gliomas also use an array of defenses that serve as direct impediments to immune attack. Despite these challenges, vaccines have shown activity against high-grade gliomas, and anecdotal, preclinical, and early clinical data bolster the notion that durable remission is possible with immunotherapy. Realizing this potential, however, will require an approach tailored to the unique aspects of glioma biology. Clin Cancer Res; 20(14); 3651–9. ©2014 AACR.
Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy
Authors: Manceau Gilles , Imbeaud Sandrine , Thiébaut Raphaële , Liébaert François , Fontaine Karine , Rousseau Francis , Génin Bérengère , Corre Delphine Le , Didelot Audrey , Vincent Marc , Bachet Jean-Baptiste , Chibaudel Benoist , Bouché Olivier , Landi Bruno , Bibeau Frédéric , Leroy Karen , Penault-Llorca Frédérique , Van Laethem Jean-Luc , Demetter Pieter , Tejpar Sabine , Rossi Simona , Mosakhani Neda , Österlund Pia , Ristamäki Raija , Sarhadi Virinder , Knuutila Sakari , Boige Valérie , André Thierry , Laurent-Puig Pierre 
Published: April 2014

Abstract
Purpose: To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).
Experimental Design: miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.
Results: After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1–15.3; P &lt; 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1–5.4; P = 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r2 = 0.49; P = 0.0035) and risk status determined by hsa-miR-31-3p expression level (P = 0.02, Kruskal–Wallis rank test). Nomograms were built and validated to predict PFS-depending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p.
Conclusion: Hsa-miR-31-3p seems to be a new mCRC biomarker whose expression level allows for the identification of patients with wild-type KRAS mCRC who are more likely to respond to anti-EGFR therapy. Clin Cancer Res; 20(12); 3338–47. ©2014 AACR.
RNAi Screen Identifies a Synthetic Lethal Interaction between PIM1 Overexpression and PLK1 Inhibition
Authors: van der Meer Riet , Yong Song Ha , Park Seong-Hoon , Abdulkadir Sarki A. , Roh Meejeon 
Published: April 2014

Abstract
Purpose: To identify genes whose depletion is detrimental to Pim1-overexpressing prostate cancer cells and to validate this finding in vitro and in vivo.
Experimental Design: RNAi screening was used to identify genes whose depletion is detrimental to Pim1-overexpressing cells. Our finding was validated using shRNA or PLK1-specific inhibitor BI 2536. Xenograft studies were performed using both PLK1-knockdown cells and BI 2536 to investigate the effects of PLK1 inhibition on tumorigenesis in Pim1-overexpressing cells. Finally, PLK1 and PIM1 expression patterns in human prostate tumors were examined by immunohistochemistry using tissue microarrays.
Results: We identified the mitotic regulator polo-like kinase (PLK1) as a gene whose depletion is particularly detrimental to the viability of Pim1-overexpressing prostate cancer. Inhibition of PLK1 by shRNA or BI 2536 in Pim1-overexpressing prostate cancer xenograft models resulted in a dramatic inhibition of tumor progression. Notably, Pim1-overexpressing cells were more prone to mitotic arrest followed by apoptosis due to PLK1 inhibition than control cells. Furthermore, inhibition of PLK1 led to the reduction of MYC protein levels both in vitro and in vivo. Our data also suggest that PIM1 and PLK1 physically interact and PIM1 might phosphorylate PLK1. Finally, PLK1 and PIM1 are frequently co-expressed in human prostate tumors, and co-expression of PLK1 and PIM1 was significantly correlated to higher Gleason grades.
Conclusions: Our findings demonstrate that PIM1-overexpressing cancer cells are particularly sensitive to PLK1 inhibition, suggesting that PIM1 might be used as a marker for identifying patients who will benefit from PLK1 inhibitor treatment. Clin Cancer Res; 20(12); 3211–21. ©2014 AACR.