bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osmolality-Dependent Relocation of Penicillin-Binding Protein PBP2 to the Division Site in Caulobacter crescentus
Authors: Hocking Jason , Priyadarshini Richa , Takacs Constantin N. , Costa Teresa , Dye Natalie A. , Shapiro Lucy , Vollmer Waldemar , Jacobs-Wagner Christine 
Published: April 2012

ABSTRACT

The synthesis of the peptidoglycan cell wall is carefully regulated in time and space. In nature, this essential process occurs in cells that live in fluctuating environments. Here we show that the spatial distributions of specific cell wall proteins in
Caulobacter crescentus
are sensitive to small external osmotic upshifts. The penicillin-binding protein PBP2, which is commonly branded as an essential cell elongation-specific transpeptidase, switches its localization from a dispersed, patchy pattern to an accumulation at the FtsZ ring location in response to osmotic upshifts as low as 40 mosmol/kg. This osmolality-dependent relocation to the division apparatus is initiated within less than a minute, while restoration to the patchy localization pattern is dependent on cell growth and takes 1 to 2 generations. Cell wall morphogenetic protein RodA and penicillin-binding protein PBP1a also change their spatial distribution by accumulating at the division site in response to external osmotic upshifts. Consistent with its ecological distribution,
C. crescentus
displays a narrow range of osmotolerance, with an upper limit of 225 mosmol/kg in minimal medium. Collectively, our findings reveal an unsuspected level of environmental regulation of cell wall protein behavior that is likely linked to an ecological adaptation.
Molecular Basis of Yersinia enterocolitica Temperature-Dependent Resistance to Antimicrobial Peptides
Authors: Reinés Mar , Llobet Enrique , Llompart Catalina M. , Moranta David , Pérez-Gutiérrez Camino , Bengoechea José A. 
Published: April 2012

ABSTRACT

Antimicrobial peptides (APs) belong to the arsenal of weapons of the innate immune system against infections. In the case of Gram-negative bacteria, APs interact with the anionic lipid A moiety of the lipopolysaccharide (LPS). In yersiniae most virulence factors are temperature regulated. Studies from our laboratory demonstrated that
Yersinia enterocolitica
is more susceptible to polymyxin B, a model AP, when grown at 37°C than at 22°C (J. A. Bengoechea, R. Díaz, and I. Moriyón, Infect. Immun. 64:4891–4899, 1996), and here we have extended this observation to other APs, not structurally related to polymyxin B. Mechanistically, we demonstrate that the lipid A modifications with aminoarabinose and palmitate are downregulated at 37°C and that they contribute to AP resistance together with the LPS O-polysaccharide. Bacterial loads of lipid A mutants in Peyer's patches, liver, and spleen of orogastrically infected mice were lower than those of the wild-type strain at 3 and 7 days postinfection. PhoPQ and PmrAB two-component systems govern the expression of the loci required to modify lipid A with aminoarabinose and palmitate, and their expressions are also temperature regulated. Our findings support the notion that the temperature-dependent regulation of loci controlling lipid A modifications could be explained by H-NS-dependent negative regulation alleviated by RovA. In turn, our data also demonstrate that PhoPQ and PmrAB regulate positively the expression of
rovA
, the effect of PhoPQ being more important. However,
rovA
expression reached wild-type levels in the
phoPQ pmrAB
mutant background, hence indicating the existence of an unknown regulatory network controlling
rovA
expression in this background.
The Pseudomonas aeruginosa Global Regulator VqsR Directly Inhibits QscR To Control Quorum-Sensing and Virulence Gene Expression
Authors: Liang Haihua , Deng Xin , Ji Quanjiang , Sun Fei , Shen Tuo , He Chuan 
Published: April 2012

ABSTRACT

The opportunistic pathogen
Pseudomonas aeruginosa
has at least three quorum-sensing (QS) systems, including the acyl-homoserine lactone (acyl-HSL)-mediated
las
and
rhl
systems, as well as the 2-alkyl-4(1H)-quinolone (AHQ) signal-based system. A group of key regulators of these QS systems have been identified, such as
qteE
,
vqsM
,
vqsR
, and
vfr
. However, the underlying regulatory mechanisms of these QS systems are not yet fully understood. Here, using electrophoretic mobility shift assays, we demonstrated that VqsR indirectly regulates acyl-HSL systems but specifically binds to the
qscR
promoter region, which indicates that VqsR influences QS-controlled pathways through QscR. Through a dye-based DNase I footprint assay, we showed that VqsR interacts with an inverted repeat (IR) motif (TCGCCN
8
GGCGA, where N is any nucleotide) in the promoter region of
qscR
. A genome-wide search identified 50 other promoter regions carrying the same putative IR motif. The recombinant VqsR protein exists as a homodimer in solution. In addition, using a
qscR
-
lux
reporter assay and Northern blot hybridization, we found that the transcription level of
qscR
increased 4-fold in the
vqsR
deletion strain compared to the wild-type PAO1 strain, indicating
vqsR
as a negative regulator of
qscR
. Taken together, these findings provide new insights into the complex regulation network of QS systems in
P. aeruginosa
.
Cost and clinical effectiveness of MRI in occult scaphoid fractures: a randomised controlled trial
Authors: Patel Nirav K , Davies Nigel , Mirza Zulfiquar , Watson Martin 
Published: April 2012

BackgroundClinical and radiographic diagnoses of scaphoid fractures are often challenging at the time of injury. Patients are therefore usually reassessed which has cost implications. Various investigations exist but MRI has been suggested as effective in diagnosing these injuries early.AimTo determine whether early MRI in suspected occult scaphoid fractures is more clinically and cost effective than conventional management with immobilisation and reassessment.MethodsAll patients presenting to the Emergency Department at a district general hospital with a suspected occult scaphoid fracture were randomised into two groups, MRI (early scan of the wrist, discharged if no injury) and control (reassessment in clinic).Results84 patients were randomised into MRI (45) and control (39) groups. There were no baseline differences apart from greater dominant hand injuries in the MRI group (62% (26) vs 36% (14), p=0.02). There were three (6.7%) scaphoid fractures in the MRI group and four (10.3%) in the control group (p=0.7). More fractures (15.6% (7) vs 5.1% (2), p=0.9) and other injuries were detected in the MRI group who had fewer mean clinic appointments (1.1±0.5 vs 2.3±0.8, p=0.001) and radiographs (1.2±0.8 vs 1.7±1.1, p=0.03). Mean management costs were £504.13 (MRI) and £532.87 (control) (p=0.9). The MRI group had better pain and satisfaction scores (not significant) with comparable time off work and sporting activities.ConclusionEarly MRI in occult scaphoid fractures is marginally cost saving compared with conventional management and may reduce potentially large societal costs of unnecessary immobilisation. It enables early detection and appropriate treatment of scaphoid and other injuries.
Burnout among advanced life support paramedics in Johannesburg, South Africa
Authors: Stassen Willem , Van Nugteren Benjamin , Stein Christopher 
Published: April 2012

ObjectivesTo establish the prevalence of burnout among advanced life support (ALS) paramedics in Johannesburg, South Africa and assess the relationship between burnout and a number of demographic characteristics of the sampled ALS paramedics.DesignCross-sectional internet-based survey.MethodSurvey invitations were sent via email to 98 registered ALS paramedics in the Johannesburg area. The survey questionnaire was created by combining the Copenhagen Burnout Inventory (CBI) with numerous distractor questions. Burnout was defined as a CBI score >50. Descriptive analysis was performed and results subjected to Chi-square testing in order to establish dependencies between burnout scores and demographic factors.ResultsA 46% (n=45) response rate was obtained. Forty responses were eligible for analysis. 30% of these respondents had total burnout according to their CBI score, while 63% exhibited some degree of burnout in one of the CBI subcategories. The results of the subcategory analyses showed that 23% of respondents experienced burnout in the patient care-related category, 38% experienced burnout in the work-related category and 53% experienced burnout in the personal burnout category. There were no statistical differences in the burnout scores according to gender (p=0.292), position held (p=0.193), employment sector (p=0.414), years of experience (p=0.228) or qualification (p=0.846). Distractor questions showed that paramedics feel overworked, undervalued, poorly remunerated and unsupported by their superiors.ConclusionThis sample of Johannesburg-based paramedics had a greater prevalence of burnout compared with their international counterparts. Further research is needed to identify the true extent of this problem.
Mathematical and drug calculation abilities of paramedic students
Authors: Eastwood Kathryn , Boyle Malcolm J , Williams Brett 
Published: April 2012

AimThe objective of this study was to determine if undergraduate paramedics could accurately perform common drug calculations and basic mathematical computations normally required in the workplace.MethodA descriptive paper-based questionnaire collecting demographical data, student attitudes regarding their drug calculation performance, and answers to a series of basic mathematical and drug calculation questions was administered to undergraduate paramedic students.ResultsThe mean score was 39.5% with only 3.3% of students (n=3) scoring greater than 90%, and 63%(n=58) scoring 50% or less. Conceptual errors made up 48.5%, arithmetical 31.1% and computational 17.4%.ConclusionThis study suggests undergraduate paramedics have deficiencies in performing accurate calculations with conceptual errors indicating a fundamental lack of mathematical understanding.
Should an alternative to the Glasgow Coma Scale be taught to paramedic students?
Authors: Winship Christian , Williams Brett , Boyle Malcolm J 
Published: April 2012

BackgroundThe accurate assessment of a patient's conscious state using the Glasgow Coma Scale (GCS) is an important skill for paramedics as it may determine the patient's initial and ongoing management. The objective of this study was to determine if undergraduate paramedic students from a large Australian University were able to accurately interpret a variety of conscious states.MethodsA prospective double-blinded observational pilot study requiring students to interpret the conscious state of four adult patients using the GCS by viewing a simulation DVD package.ResultsThere were 137 students who participated in the study, of whom 65% (n=87) were female students. The results demonstrated that undergraduate paramedic students were unable to accurately interpret a number of patient conscious states with only 20% and 37% of students able to accurately identify the GCS of patients 2 (GCS=12) and 3 (GCS=7). The motor component of the GCS appeared to be the component where the least accurate interpretation occurred, with only 47% of students being able to accurately identify the criteria that patient 3 displayed. Participants were however able to accurately interpret the GCS of both patient 1 (GCS=14) (86%) and patient 4 (GCS=15) (92%).ConclusionThis pilot study demonstrates that undergraduate paramedic students from an Australian university were unable to accurately interpret a patient's conscious state if their GCS score was <14. These findings have provided academic staff with important information for considering alternative teaching and learning strategies and approaches in conscious state assessment in current paramedic curricula.
Validity of smoke alarm self-report measures and reasons for over-reporting
Authors: Stepnitz Rebecca , Shields Wendy , McDonald Eileen , Gielen Andrea 
Published: April 2012

ObjectivesMany residential fire deaths occur in homes with no or non-functioning smoke alarms (SAs). Self-reported SA coverage is high, but studies have found varying validity for self-report measures. The authors aim to: (1) determine over-reporting of coverage, (2) describe socio-demographic correlates of over-reporting and (3) report reasons for over-reporting.MethodsThe authors surveyed 603 households in a large, urban area about fire safety behaviours and then tested all SAs in the home. 23 participants who over-reported their SA coverage were telephoned and asked about why they had misreported.ResultsFull coverage was reported in 70% of households but observed in only 41%, with a low positive predictive value (54.2%) for the self-report measure. Most over-reporters assumed alarms were working because they were mounted or did not think a working alarm in a basement or attic was needed to be fully protected.ConclusionsIf alarms cannot be tested, researchers or those counselling residents on fire safety should carefully probe self-reported coverage. Our findings support efforts to equip more homes with hard-wired or 10 year lithium battery alarms to reduce the need for user maintenance.
Imaging in children presenting with acute neurological deficit: stroke
Authors: Rasalkar Darshana D , Chu Winnie C W 
Published: April 2012

Abstract
Neurological deficits in the paediatric age group are much rarer than in adults; however, it is an urgent condition that relies heavily on imaging for a prompt accurate diagnosis. Neurological deficits caused by cerebrovascular diseases are defined as stroke, whereas conditions manifesting with neurological deficits without underlying cerebrovascular diseases are referred to as stroke mimics. To the best of the authors' knowledge, there is a lack of systematic pictorial review that collectively describes the imaging of neurological deficit in children. The purpose of the present series is to discuss the causes and imaging appearance of neurological deficits in childhood, based on the experience of a tertiary paediatric referral centre These are broadly categorised into stroke, infection, inflammation, metabolic disorder, cerebral neoplasms and drug poisoning. Different entities of stroke and their respective imaging findings are discussed. Paediatric stroke can further be divided into arterial ischaemic stroke, sino-venous stroke, haemorrhagic stroke and hypoxic–ischaemic encephalopathy.
Expression of P2X7 Receptor IncreasesIn VivoTumor Growth
Authors: Adinolfi Elena , Raffaghello Lizzia , Giuliani Anna Lisa , Cavazzini Luigi , Capece Marina , Chiozzi Paola , Bianchi Giovanna , Kroemer Guido , Pistoia Vito , Di Virgilio Francesco 
Published: April 2012

AbstractThe P2X7 receptor is an ATP-gated ion channel known for its cytotoxic activity. However, recent evidence suggests a role for P2X7 in cell proliferation. Here, we found that P2X7 exhibits significant growth-promoting effects in vivo. Human embryonic kidney cells expressing P2X7 exhibited a more tumorigenic and anaplastic phenotype than control cells in vivo, and the growth rate and size of these tumors were significantly reduced by intratumoral injection of the P2X7 inhibitor–oxidized ATP. The accelerated growth of P2X7-expressing tumors was characterized by increased proliferation, reduced apoptosis, and a high level of activated transcription factor NFATc1. These tumors also showed a more developed vascular network than control tumors and secreted elevated amounts of VEGF. The growth and neoangiogenesis of P2X7-expressing tumors was blocked by intratumoral injection of the VEGF-blocking antibody Avastin (bevacizumab), pharmacologic P2X7 blockade, or P2X7 silencing in vivo. Immunohistochemistry revealed strong P2X7 positivity in several human cancers. Together, our findings provide direct evidence that P2X7 promotes tumor growth in vivo. Cancer Res; 72(12); 2957–69. ©2012 AACR.
Gene Immunotherapy of Chronic Lymphocytic Leukemia: A Phase I Study of Intranodally Injected Adenovirus Expressing a Chimeric CD154 Molecule
Authors: Castro Januario E. , Melo-Cardenas Johanna , Urquiza Mauricio , Barajas-Gamboa Juan S. , Pakbaz Ramin S. , Kipps Thomas J. 
Published: April 2012

Abstract
New therapies for chronic lymphocytic leukemia (CLL) are needed, particularly those that can eradicate residual disease and elicit anti-CLL immune responses. CD40 ligation on CLL cells, which can be achieved using adenovirus encoding chimeric CD154 (Ad-ISF35), enhances their ability to function as antigen-presenting cells and increases their sensitivity to clearance by immune-effector mechanisms. In this study, we report the results of a first-in-man phase I trial of intranodal direct injection (IDI) of Ad-ISF35 in patients with CLL to evaluate toxicity, safety, and tolerability. Fifteen patients received a single IDI of 1 × 1010 to 33 × 1010 Ad-ISF35 viral particles (vp), with a defined maximum tolerated dose as 1 × 1011 vp. Although the most common adverse events were transient grade 1 to 2 pain at the injection site and flu-like symptoms following IDI, some patients receiving the highest dose had transient, asymptomatic grade 3 to 4 hypophosphatemia, neutropenia, or transaminitis. Increased expression of death receptor, immune costimulatory molecules, and Ad-ISF35 vector DNA was detected in circulating CLL cells. Notably, we also observed preliminary clinical responses, including reductions in leukemia cell counts, lymphadenopathy, and splenomegaly. Six patients did not require additional therapy for more than 6 months, and three achieved a partial remission. In conclusion, Ad-ISF35 IDI was safely delivered in patients with CLLs and induced systemic biologic and clinical responses. These results provide the rationale for phase II studies in CLLs, lymphomas, and CD40-expressing solid tumors. Cancer Res; 72(12); 2937–48. ©2012 AACR.
Polycomb Protein EZH2 Regulates Tumor Invasion via the Transcriptional Repression of the Metastasis Suppressor RKIP in Breast and Prostate Cancer
Authors: Ren Gang , Baritaki Stavroula , Marathe Himangi , Feng Jingwei , Park Sungdae , Beach Sandy , Bazeley Peter S. , Beshir Anwar B. , Fenteany Gabriel , Mehra Rohit , Daignault Stephanie , Al-Mulla Fahd , Keller Evan , Bonavida Ben , de la Serna Ivana , Yeung Kam C. 
Published: April 2012

Abstract
Epigenetic modifications such as histone methylation play an important role in human cancer metastasis. Enhancer of zeste homolog 2 (EZH2), which encodes the histone methyltransferase component of the polycomb repressive complex 2 (PRC2), is overexpressed widely in breast and prostate cancers and epigenetically silences tumor suppressor genes. Expression levels of the novel tumor and metastasis suppressor Raf-1 kinase inhibitor protein (RKIP) have been shown to correlate negatively with those of EZH2 in breast and prostate cell lines as well as in clinical cancer tissues. Here, we show that the RKIP/EZH2 ratio significantly decreases with the severity of disease and is negatively associated with relapse-free survival in breast cancer. Using a combination of loss- and gain-of-function approaches, we found that EZH2 negatively regulated RKIP transcription through repression-associated histone modifications. Direct recruitment of EZH2 and suppressor of zeste 12 (Suz12) to the proximal E-boxes of the RKIP promoter was accompanied by H3-K27-me3 and H3-K9-me3 modifications. The repressing activity of EZH2 on RKIP expression was dependent on histone deacetylase promoter recruitment and was negatively regulated upstream by miR-101. Together, our findings indicate that EZH2 accelerates cancer cell invasion, in part, via RKIP inhibition. These data also implicate EZH2 in the regulation of RKIP transcription, suggesting a potential mechanism by which EZH2 promotes tumor progression and metastasis. Cancer Res; 72(12); 3091–104. ©2012 AACR.
High Expression of IL-13 Receptor α2 in Colorectal Cancer Is Associated with Invasion, Liver Metastasis, and Poor Prognosis
Authors: Barderas Rodrigo , Bartolomé Rubén A. , Fernandez-Aceñero María Jesús , Torres Sofia , Casal J. Ignacio 
Published: April 2012

AbstractAutocrine secretion of cytokines by metastatic colorectal cancer cells and their role during invasion and liver homing has been poorly characterized. In this study, we used cytokine arrays to analyze the secretomes of poorly and highly metastatic colorectal cancer cells. Compared with poorly metastatic cancer cells, highly metastatic cells expressed increased levels of the immunosuppressive cytokines interleukin (IL)-4 and IL-13 in addition to increased surface expression of the high affinity IL-13 receptor IL-13Rα2, suggesting that IL-13Rα2 mediates IL-13 effects in colorectal cancer cells. Silencing of IL-13Rα2 in highly metastatic cells led to a decrease in adhesion capacity in vitro and a reduction in liver homing and increased survival in vivo, revealing a role for this receptor in cell adhesion, migration, invasion, and metastatic colonization. In support of this, IL-13 signaling activated the oncogenic signaling molecules phosphoinositide 3-kinase, AKT, and SRC in highly metastatic cells. Clinically, high expression of IL-13Rα2 was associated with later stages of disease progression and poor outcome in patients with colorectal cancer. Our findings therefore support a critical role for IL-13Rα2 expression in colon cancer invasion and metastasis. Cancer Res; 72(11); 2780–90. ©2012 AACR.
In Vivo Imaging of Drug-Induced Mitochondrial Outer Membrane Permeabilization at Single-Cell Resolution
Authors: Earley Sarah , Vinegoni Claudio , Dunham Joshua , Gorbatov Rostic , Feruglio Paolo Fumene , Weissleder Ralph 
Published: April 2012

Abstract
Observing drug responses in the tumor microenvironment in vivo can be technically challenging. As a result, cellular responses to molecularly targeted cancer drugs are often studied in cell culture, which does not accurately represent the behavior of cancer cells growing in vivo. Using high-resolution microscopy and fluorescently labeled genetic reporters for apoptosis, we developed an approach to visualize drug-induced cell death at single-cell resolution in vivo. Stable expression of the mitochondrial intermembrane protein IMS-RP was established in human breast and pancreatic cancer cells. Image analysis was then used to quantify release of IMS-RP into the cytoplasm upon apoptosis and irreversible mitochondrial permeabilization. Both breast and pancreatic cancer cells showed higher basal apoptotic rates in vivo than in culture. To study drug-induced apoptosis, we exposed tumor cells to navitoclax (ABT-263), an inhibitor of Bcl-2, Bcl-xL, and Bcl-w, both in vitro and in vivo. Although the tumors responded to Bcl-2 inhibition in vivo, inducing apoptosis in around 20% of cancer cells, the observed response was much higher in cell culture. Together, our findings show an imaging technique that can be used to directly visualize cell death within the tumor microenvironment in response to drug treatment. Cancer Res; 72(12); 2949–56. ©2012 AACR.