bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclic Rhamnosylated Elongation Factor P Establishes Antibiotic Resistance in Pseudomonas aeruginosa
Authors: Rajkovic Andrei , Erickson Sarah , Witzky Anne , Branson Owen E. , Seo Jin , Gafken Philip R. , Frietas Michael A. , Whitelegge Julian P. , Faull Kym F. , Navarre William , Darwin Andrew J. , Ibba Michael
Published: June 2015

Elongation factor P (EF-P) is a ubiquitous bacterial protein that is required for the synthesis of poly-proline motifs during translation. In
Escherichia coli
and
Salmonella enterica
, the posttranslational β-lysylation of Lys34 by the PoxA protein is critical for EF-P activity. PoxA is absent from many bacterial species such as
Pseudomonas aeruginosa
, prompting a search for alternative EF-P posttranslation modification pathways. Structural analyses of
P. aeruginosa
EF-P revealed the attachment of a single cyclic rhamnose moiety to an Arg residue at a position equivalent to that at which β-Lys is attached to
E. coli
EF-P. Analysis of the genomes of organisms that both lack
poxA
and encode an Arg32-containing EF-P revealed a highly conserved glycosyltransferase (EarP) encoded at a position adjacent to
efp
. EF-P proteins isolated from
P. aeruginosa
Δ
earP
, or from a Δ
rmlC
::
acc1
strain deficient in dTDP-
l
-rhamnose biosynthesis, were unmodified.
In vitro
assays confirmed the ability of EarP to use dTDP-
l
-rhamnose as a substrate for the posttranslational glycosylation of EF-P. The role of rhamnosylated EF-P in translational control was investigated in
P. aeruginosa
using a Pro
4
-green fluorescent protein (Pro
4
GFP)
in vivo
reporter assay, and the fluorescence was significantly reduced in Δ
efp
, Δ
earP
, and Δ
rmlC
::
acc1
strains. Δ
rmlC
::
acc1
, Δ
earP
, and Δ
efp
strains also displayed significant increases in their sensitivities to a range of antibiotics, including ertapenem, polymyxin B, cefotaxim, and piperacillin. Taken together, our findings indicate that posttranslational rhamnosylation of EF-P plays a key role in
P. aeruginosa
gene expression and survival.

IMPORTANCE
Infections with pathogenic
Salmonella
,
E. coli
, and
Pseudomonas
isolates can all lead to infectious disease with potentially fatal sequelae. EF-P proteins contribute to the pathogenicity of the causative agents of these and other diseases by controlling the translation of proteins critical for modulating antibiotic resistance, motility, and other traits that play key roles in establishing virulence. In
Salmonella
spp. and
E. coli
, the attachment of β-Lys is required for EF-P activity, but the proteins required for this posttranslational modification pathway are absent from many organisms. Instead, bacteria such as
P. aeruginosa
activate EF-P by posttranslational modification with rhamnose, revealing a new role for protein glycosylation that may also prove useful as a target for the development of novel antibiotics.
Just another abdominal pain? Psoas abscess-likemetastasis in large cell lung cancer with adrenal insufficiency
Authors: Bernardino Vera , Val-Flores Luis Silva , Lopes Dias João , Bento Luís
Published: June 2015

The authors report the case of a 69-year-old man with chronic obstructive pulmonary disease and previous pulmonary tuberculosis, who presented to the emergency department with abdominal and low back pain, anorexia and weight loss, rapidly evolving into shock. An initial CT scan revealed pulmonary condensation with associated cavitation and an iliopsoas mass suggestive of a psoas abscess. He was admitted in an intensive care unit unit; after a careful examination and laboratory assessment, the aetiology was yet undisclosed. MRI showed multiple retroperitoneal lymphadenopathies, bulky nodular adrenal lesions and bilateral iliac lytic lesions. Hypocortisolism was detected and treated with steroids. A CT-guided biopsy to the psoas mass and lytic lesions identified infiltration of non-small lung carcinoma. The patient died within days. Psoas metastases and adrenal insufficiency as initial manifestations of malignancy are rare and can be misdiagnosed, particularly in the absence of a known primary tumour.
Parapelvic solitary neurofibroma of the kidney
Authors: Singh Bhupendra Pal , Krishnaswamy Srinivas Arakalagud , Singhai Atin , Sankhwar Satyanarayan
Published: June 2015

A middle-aged man presented with intermittent gross haematuria and dull aching left flank pain for 1 month. He was a chronic smoker for 15 years. Contrast-enhanced CT scan of the abdomen detected a 4.5×3.0×2.5 cm, heterogeneous and poorly contrast-enhancing mass in the left renal sinus and upper ureteric region causing narrowing of the pelviureteric junction and upper ureter. Considering it to be a transitional cell carcinoma of upper urinary tract, the patient underwent laparoscopic radical nephroureterectomy. Histopathology revealed the mass to be a neurofibroma in the renal sinus extending around the upper ureter.
Comparative test of radiological exposure between femoral and radial techniques, development of a protective device and clinical trial design
Authors: Bienert Igor R C , Andrade Pedro B , Rinaldi Fabio S , Vilela Fernanda D T , Silva Paulo A , Braga Joao C S , Waib Paulo H , Rodrigues Alexandre , Filho Fábio V G , Okoshi Katashi
Published: June 2015

Background

Interventional procedures via radial technique have progressively increased due to improved patient comfort, lower complication rates and reduced mortality in some scenarios. One area of interest is radiation exposure and ways of minimising it. Most studies focus on patient radiation risk with conflicting results, but there is reasonable consensus for increased operator exposure from the radial technique. The aim of this study was to evaluate radiological exposure under controlled radial and femoral access simulation tests, mapping radiation paths and developing a radiological protection device for the transradial technique.

Methods and results

Radiation exposure was simulated under controlled conditions for femoral and radial techniques using a pressurised ionisation chamber and water phantom. Different measurement points were defined according to standard positions to simulate radiation received by the operator in the gonads, thyroid and eyes at different angles during real procedures. The radial technique increased total exposure by 33% over the femoral technique. A protective device was developed and tested after radiation mapping. The protective device reduced cumulative radiation by 52% against the radial and 36% against the femoral technique.

Conclusions

In our study, operator exposure to cumulative ionising radiation was higher from the radial technique and the protective device reduced radiation exposure levels in the radial and femoral techniques. These results provided the basis for a clinical trial design to better define the impact of the protection device and radiation exposure during real world practice using different interventional techniques.

Trial registration number

http://www.clinicaltrials.gov. Unique identifier:NCT02200783.
Benzodiazepine prescribing in children under 15 years of age receiving free medical care on the General Medical Services scheme in Ireland
Authors: O'Sullivan K , Reulbach U , Boland F , Motterlini N , Kelly D , Bennett K , Fahey T
Published: June 2015

Objective

To examine the prevalence and secular trends in benzodiazepine (BZD) prescribing in the Irish paediatric population. In addition, we examine coprescribing of antiepileptic, antipsychotic, antidepressant and psychostimulants in children receiving BZD drugs and compare BZD prescribing in Ireland to that in other European countries.

Setting

Data were obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive (HSE)—Primary Care Reimbursement Services (PCRS).

Participants

Children aged 0–15 years, on the HSE-PCRS database between January 2002 and December 2011, were included.

Primary and secondary outcome measures

Prescribing rates were reported over time (2002–2011) and duration (≤ or >90 days). Age (0–4, 5–11, 12–15) and gender trends were established. Rates of concomitant prescriptions for antiepileptic, antipsychotics, antidepressants and psychostimulants were reported. European prescribing data were retrieved from the literature.

Results

Rates decreased from 2002 (8.56/1000 GMS population: 95% CI 8.20 to 8.92) to 2011 (5.33/1000 GMS population: 95% CI 5.10 to 5.55). Of those children currently receiving a BZD prescription, 6% were prescribed BZD for >90 days. Rates were higher for boys in the 0–4 and 5–11 age ranges, whereas for girls they were higher in the 12–15 age groups. A substantial proportion of children receiving BZD drugs are also prescribed antiepileptic (27%), antidepressant (11%), antipsychotic (5%) and psychostimulant (2%) medicines. Prescribing rates follow a similar pattern to that in other European countries.

Conclusions

While BZD prescribing trends have decreased in recent years, this study shows that a significant proportion of the GMS children population are being prescribed BZD in the long term. This study highlights the need for guidelines for BZD prescribing in children in terms of clinical indication and responsibility, coprescribing, dosage and duration of treatment.
Cost-effectiveness of nurse practitioners in primary and specialised ambulatory care: systematic review
Authors: Martin-Misener Ruth , Harbman Patricia , Donald Faith , Reid Kim , Kilpatrick Kelley , Carter Nancy , Bryant-Lukosius Denise , Kaasalainen Sharon , Marshall Deborah A , Charbonneau-Smith Renee , DiCenso Alba
Published: June 2015

Objective

To determine the cost-effectiveness of nurse practitioners delivering primary and specialised ambulatory care.

Design

A systematic review of randomised controlled trials reported since 1980.

Data sources

10 electronic bibliographic databases, handsearches, contact with authors, bibliographies and websites.

Included studies

Randomised controlled trials that evaluated nurse practitioners in alternative and complementary ambulatory care roles and reported health system outcomes.

Results

11 trials were included. In four trials ofalternative provider ambulatory primary care roles, nurse practitioners were equivalent to physicians in all but seven patient outcomes favouring nurse practitioner care and in all but four health system outcomes, one favouring nurse practitioner care and three favouring physician care. In a meta-analysis of two studies (2689 patients) with minimal heterogeneity and high-quality evidence, nurse practitioner care resulted in lower mean health services costs per consultation (mean difference: −€6.41; 95% CI −€9.28 to −€3.55; p<0.0001) (2006 euros). In two trials ofalternative provider specialised ambulatory care roles, nurse practitioners were equivalent to physicians in all but three patient outcomes and one health system outcome favouring nurse practitioner care. In five trials ofcomplementary provider specialised ambulatory care roles, 16 patient/provider outcomes favouring nurse practitioner plus usual care, and 16 were equivalent. Two health system outcomes favoured nurse practitioner plus usual care, four favoured usual care and 14 were equivalent. Four studies of complementary specialised ambulatory care compared costs, but only one assessed costs and outcomes jointly.

Conclusions

Nurse practitioners in alternative provider ambulatory primary care roles have equivalent or better patient outcomes than comparators and are potentially cost-saving. Evidence for their cost-effectiveness in alternative provider specialised ambulatory care roles is promising, but limited by the few studies. While some evidence indicates nurse practitioners in complementary specialised ambulatory care roles improve patient outcomes, their cost-effectiveness requires further study.
Are family, neighbourhood and school social capital associated with higher self-rated health among Croatian high school students? A population-based study
Authors: Novak Dario , Suzuki Etsuji , Kawachi Ichiro
Published: June 2015

Objectives

We investigated the associations between self-rated health and social capital among Croatian high school students.

Design

A cross-sectional survey among high school students was carried out in the 2013–2014 school year.

Setting

High schools in Croatia.

Participants

Subjects were 3427 high school students (1688 males and 1739 females), aged 17–18 years.

Main outcome measure

Self-rated health was assessed by the single item: “How do you perceive your health?”. Possible responses were arranged along a five-item Likert-type scale: 1 very poor, 2 poor, 3 fair, 4 good, 5 excellent. The outcome was binarised as ‘good health’ (excellent, good or fair) versus ‘poor health’ (poor or very poor).

Methods

We calculated ORs and 95% CIs for good self-rated health associated with family, neighbourhood and school social capital, while adjusting for gender, self-perceived socioeconomic status, psychological distress, physical activity and body mass index. We used generalised estimating equations using an exchangeable correlation matrix with robust SEs.

Results

Good self-rated health was significantly associated with higher family social capital (OR 2.43; 95% CI 1.55 to 3.80), higher neighbourhood trust (OR 2.02; 95% CI 1.48 to 2.76) and higher norms of reciprocity at school (OR 1.79; 95% CI 1.13 to 2.84). When all of the social capital variables were entered simultaneously, good self-rated health remained significantly associated with higher family social capital (OR 1.98; 95% CI 1.19 to 3.30), neighbourhood trust (OR 1.77; 95% CI 1.25 to 2.51) and reciprocity at school (OR 1.71; 95% CI 1.08 to 2.73).

Conclusions

Higher levels of social capital were independently associated with higher self-rated health among youth. Intervention and policies that leverage community social capital might serve as an avenue for health promotion in youth.
Pain sensitisation and the risk of poor outcome following physiotherapy for patients with moderate to severe knee osteoarthritis: protocol for a prospective cohort study
Authors: O'Leary Helen , Smart Keith M , Moloney Niamh A , Blake Catherine , Doody Catherine M
Published: June 2015

Introduction

Pain is the dominant symptom of knee osteoarthritis (OA), and recent evidence suggests factors outside of local joint pathology, such as pain sensitisation, can contribute significantly to the pain experience. It is unknown how pain sensitisation influences outcomes from commonly employed interventions such as physiotherapy. The aims of this study are, first, to provide a comprehensive description of the somatosensory characteristics of people with pain associated with knee OA. Second, we will investigate if indicators of pain sensitisation in patients with knee osteoarthritis are predictive of non-response to physiotherapy.

Methods and analysis

This is a multicentre prospective cohort study with 140 participants. Eligible patients with moderate to severe symptomatic knee osteoarthritis will be identified at outpatient orthopaedic and rheumatology clinics. A baseline assessment will provide a comprehensive description of the somatosensory characteristics of each participant by means of clinical examination, quantitative sensory testing, and validated questionnaires measuring pain and functional capacity. Participants will then undergo physiotherapy treatment. The primary outcome will be non-response to physiotherapy on completion of the physiotherapy treatment programme as defined by the Osteoarthritis Research Society International treatment responder criteria. A principal component analysis will identify measures related to pain sensitisation to include in the predictive model. Regression analyses will explore the relationship between responder status and pain sensitisation while accounting for confounders.

Ethics and dissemination

This study has been approved by St James’ Hospital/AMNCH Research Ethics Committee and by the St Vincent's Healthcare Group Ethics and Medical Research Committee. The results will be presented at international conferences and published in a peer review journal.

Trial registration number

NCT02310945.
Temporal trends in out-of-hospital cardiac arrest survival outcomes between two metropolitan communities: Seoul-Osaka resuscitation study
Authors: Ro Young Sun , Shin Sang Do , Kitamura Tetsuhisa , Lee Eui Jung , Kajino Kentaro , Song Kyoung Jun , Nishiyama Chika , Kong So Yeon , Sakai Tomohiko , Nishiuchi Tatsuya , Hayashi Yasuyuki , Iwami Taku ,   for Seoul-Osaka Resuscitation Study (SORS) Group
Published: June 2015

Objectives

The objective of this study was to compare the temporal trends in survival after out-of-hospital cardiac arrest (OHCA) between two large metropolitan communities in Asia and evaluate the factors affecting survival after OHCA.

Design

A population-based prospective observational study.

Setting

The Cardiovascular Disease Surveillance (CAVAS) project in Seoul and the Utstein Osaka Project in Osaka.

Participants

A total of 36 292 resuscitation-attempted OHCAs with cardiac aetiology from 2006 to 2011 in Seoul and Osaka (11 082 in Seoul and 25 210 in Osaka).

Primary outcome measures

The primary outcome was neurologically favourable survival. Trend analysis and multivariable Poisson regression models were conducted to evaluate the temporal trends in survival of two communities.

Results

During the study period, the overall neurologically favourable survival was 2.6% in Seoul and 4.6% in Osaka (p<0.01). In both communities, bystander cardiopulmonary resuscitation (CPR) rates increased significantly from 2006 to 2011 (from 0.1% to 13.1% in Seoul and from 33.3% to 41.7% in Osaka). OHCAs that occurred in public places increased in Seoul (12.5% to 20.1%, p for trend <0.01) and decreased in Osaka (13.5% to 10.5%, p for trend <0.01). The proportion of OHCAs defibrillated by emergency medical service (EMS) providers was only 0.4% in 2006 but increased to 17.5% in 2011 in Seoul, whereas the proportion in Osaka decreased from 17.7% to 13.7% (both p for trend <0.01). Age-adjusted and gender-adjusted rates of neurologically favourable survival increased significantly in Seoul from 1.4% in 2006 to 4.3% in 2011 (adjusted rate ratio per year, 1.17; p for trend <0.01), whereas no significant improvement was observed in Osaka (3.6% in 2006 and 5.1% in 2011; adjusted rate ratio per year, 1.03; p for trend=0.08).

Conclusions

Survivals after OHCA were increased in Seoul while remained constant in Osaka, which may have been affected by the differences and improvements of patient, community, and EMS system factors.
Reducing hospital acquired pressure ulcers in intensive care
Authors: Cullen Gill Emma
Published: June 2015

Pressure ulcers are a definite problem in our health care system and are growing in numbers. Unfortunately, it is usually the most weak and vulnerable of our culture that faces these complications, causing the patient and their families discomfort, anguish, and economic hardship due to their expensive treatment.

Data collected by the tissue viability department showed high incidence of hospital acquire pressure ulcers in the intensive care unit in March 2013. An action plan was initiated and implemented by the tissue viability team, senior nursing management, pressure ulcer prevention (PUP) team and respiratory therapists (RT’s) within the ICU. Our objective was to reduce hospital acquired pressure ulcers in the intensive care unit using the plan, do, check, act quality improvement process.
Reducing Door to- Balloon- Time for Acute ST Elevation Myocardial Infarction In Primary Percutaneous Intervention: Transformation using Robust Performance Improvement
Authors: Ellahham, MD Samer , Aljabbari Samir , Harold Mananghaya Tristan , J. Raji Salama , Al Zubaidi Abdulmajeed
Published: June 2015

Cardiovascular diseases (CVDs) are the leading causes of death in the UAE. Prompt reperfusion access is essential for patients who have Myocardial Infarction (MI) with ST-segment elevation as they are at a relatively high risk of death.This risk may be reduced by primary percutaneous coronary intervention (PCI), but only if it is performed in a timely manner. Guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation (door-to-balloon (D2B) time) during primary PCI should be 90 minutes or less. The earlier therapy is initiated, the better the outcome. Our aim was to decrease the door-to-balloon time for patients with ST segment elevation myocardial infarction (STEMI) who come through the emergency department (ED) in Sheikh Khalifa Medical City,a tertiary hospital in UAE, to meet the standard of less than 90 minutes. A multidisciplinary team was formed including interventional cardiologists, catheterization laboratory personnel, emergency department caregivers and quality staff. The project utilized the Lean Six Sigma Methodology which provided a powerful approach to quality improvement. The process minimized waste and variation, and a decreased median door-to-balloon time from 75.9 minutes to 60.1 minutes was noted. The percentage of patients who underwent PCI within 90 minutes increased from 73% to 96%. In conclusion, implementing the Lean Six Sigma methodology resulted in having processes that are leaner, more efficient and minimally variable. While recent publication failed to provide evidence of better outcome, the lessons learned were extrapolated to other primary percutaneous coronary intervention centers in our system.This would have marked impact on patient safety, quality of care and patient experience.
Quality improvement in resident education: a pilot project to mitigate metabolic side effects from atypical antipsychotic medications in youth
Authors: Jeffrey Jessica
Published: June 2015

This resident physician-led quality improvement project was conducted with aims to improve the health of youth prescribed atypical antipsychotic medications by increasing physician monitoring for metabolic side effects, while simultaneously educating trainees in quality improvement methodology.

The plan, do, study, act quality improvement framework was utilized. Baseline metabolic monitoring rates of patients prescribed atypical antipsychotic medications in the two psychiatry resident outpatient clinics were obtained. Rates were stratified based on time on medication (<1 year, ≥1 year) and parameter monitored. Metabolic monitoring rates subsequent to targeted changes were obtained. Problem solving with residents revealed barriers to monitoring, such as limited awareness of specific guideline recommendations and lack of convenient access to medical equipment (calibrated scales). Residents received education about atypical antipsychotic monitoring guidelines and side effect treatment. Residents were provided with calibrated scales. Atypical antipsychotic monitoring templates were introduced. Online surveys using were conducted to determine self-reported baseline-monitoring rates and comfort with guidelines following targeted change.

The baseline metabolic monitoring rates of patients prescribed atypical antipsychotic medications was 9% (range: 0 to 17.6%) for youth in their first year taking an atypical antipsychotic medication and 58.9% (range: 29% to 100%) in subsequent years on medication. The results of relatively easy changes resulted in modest improvement in monitoring rates. The metabolic monitoring rate of a patient initiated on an atypical antipsychotic medication was 29% after targeted quality improvement measures were employed. Following quality improvement changes, residents reported increased knowledge about guidelines and increased monitoring for side effects. Use of a standardized data collection instrument to track monitoring of patients increased from 0% to 70% (range: 30% to 90%).

Quality improvement projects provide an avenue with which to improve atypical antipsychotic monitoring rates. Through active participation in quality improvement projects, psychiatry residents may be taught to employ quality improvement methodology.
Menstrual cycle could affect Ki67 expression in estrogen receptor-positive breast cancer patients
Authors: Horimoto Yoshiya , Arakawa Atsushi , Tanabe Masahiko , Kuroda Keiji , Matsuoka Joe , Igari Fumie , Himuro Takanori , Yoshida Yuko , Tokuda Emi , Shimizu Hideo , Hino Okio , Saito Mitsue
Published: June 2015

Background

Ki67 is a potent prognostic marker for determining systemic treatment of patients with hormone receptor-positive breast cancer. However, evaluation of Ki67 expression can be difficult, due mostly to its heterogeneity. The Ki67 expression level, which indicates that a cell is undergoing division (cell cycle), rises when proliferation activity increases. Thus, Ki67 expression might be affected by hormonal stimuli. We hypothesised that Ki67 expression level might change during the menstrual cycle. We examined pairs of biopsy and surgical specimens from individual patients to evaluate this hypothesis.

Methods

First, the effects of estradiol on Ki67 expression in breast cancer cell lines were examined employing immunocytochemistry and Western blotting. Next, differences in Ki67 expression between biopsy and surgical specimens from 131 patients with estrogen receptor-positive tumours were retrospectively examined.

Results

In vitro experiments showed Ki67 expression in estrogen receptor-positive cancer cells to be dependent on estradiol stimulation. Ki67 expression was higher in biopsy samples collected in the luteal phase than in those from other phases. When biopsy and surgical samples were obtained at different times during the menstrual cycle in the same individual, there were differences in Ki67 expression between these samples. Those collected in the luteal phase showed higher Ki67 expression than samples obtained during other phases (p<0.01).

Conclusions

Ki67 expression varied in the same patients according to menstrual cycle phase. Our results suggest that Ki67 expression in estrogen receptor-positive breast cancer should be carefully assessed bearing in mind the patient's menstrual cycle, since the interpretation of expression could affect treatment decisions.
Towards silvicultural mitigation of the European ash (Fraxinus excelsior) dieback: the importance of acclimated trees in retention forestry
Authors: Rosenvald Raul , Drenkhan Rein , Riit Taavi , Lõhmus Asko
Published: June 2015

The European ash (Fraxinus excelsior L.) dieback is an acute forest pathology problem caused by the invasive ascomycete Hymenoscyphus fraxineus (T. Kowalski) Baral, Queloz, Hosoya. There are no practical solutions yet, but selection for resistant genotypes and intensive care have been highlighted as options. Our aim was to assess the disease mitigation potential of silvicultural harvests, which influence stress levels in retained trees. We annually monitored 577 retention trees on Estonian cut areas for 13 years, including 9 years impacted by the dieback. Sixty-five percent of the trees survived and 15% retained healthy crown, despite all sampled trees being infected. The damage was smallest in the trees retained near precut edges. Former forest-interior trees that were left in central parts of the cut areas suffered high initial damage but smaller disease progression than trees near postcut edges. Tree size and secondary infection by Armillaria spp. were not related to disease progression, but rapid decline was observed in the region with the highest density of ash trees retained. Our results indicate a significant silvicultural potential for tree resistance. Ash trees tend to be healthiest in open conditions, which probably inhibit the pathogen and provide better resources for the tree. Location near precut edges is an important tree retention criterion, which can mitigate initial harvest-induced stress.
Armand-Frappier Outstanding Student Award — The emerging role of 25-hydroxycholesterol in innate immunity
Authors: Singaravelu Ragunath , Srinivasan Prashanth , Pezacki John Paul
Published: June 2015

The metabolic interplay between hosts and viruses plays a crucial role in determining the outcome of viral infection. Viruses reorchestrate the host’s primary metabolic gene networks, including genes associated with mevalonate and isoprenoid synthesis, to acquire the necessary energy and structural components for their viral life cycles. Recent work has demonstrated that the interferon-mediated antiviral response suppresses the sterol pathway through production of a signalling molecule, 25-hydroxycholesterol (25HC). This oxysterol has been shown to exert multiple effects, both through incorporation into host cellular membranes as well as through transcriptional control. Herein, we summarize our current understanding of the multifunctional roles of 25HC in the mammalian innate antiviral response.
Identification and expression analysis of theLRR-RLKgene family in tomato (Solanum lycopersicum) Heinz 1706
Authors: Wei Zhirong , Wang Jiehua , Yang Shaohui , Song Yingjin
Published: June 2015

As the largest subfamily of receptor-like kinases (RLKs), leucine-rich repeat receptor-like kinases (LRR-RLKs) regulate the growth, development, and stress responses of plants. Through a reiterative process of sequence analysis and re-annotation, 234 LRR-RLK genes were identified in the genome of tomato (Solanum lycopersicum) ‘Heinz 1706’, which were further grouped into 10 major groups based on their sequence similarity. In comparison to the significant role of tandem duplication in the expansion process of this gene family in other species, only approximately 12% (29 out of 234) of SlLRR-RLK genes arose from tandem duplication. Using the multiple expectation maximization for motif elicitation (MEME) method, the motif composition and arrangement were found to be variably conserved within each SlLRR-RLK group, indicating their different extent of functional divergence. Expression profiling analyses by qRT-PCR data revealed that SlLRR-RLK genes were differentially expressed in various tomato organs and tissues, and some SlLRR-RLK genes exhibited preferential expression in fruits at distinct developmental stages, suggesting that SlLRR-RLK may take important roles in fruit development and ripening process. The results of this study provide an overview of the LRR-RLK gene family in tomato Heinz 1706, one important species of Solanaceae, and will be helpful for future functional analysis of this important protein family in fleshy fruit-bearing species.
PARALLEL IMPLEMENTATION OF THE BOX COUNTING ALGORITHM IN OPENCL
Authors: MUKUNDAN RAMAKRISHNAN
Published: June 2015

The box counting algorithm is a well-known method for the computation of the fractal dimension of an image. It is often implemented using a recursive subdivision of the image into a set of regular tiles or boxes. Parallel implementations often try to map the boxes to different compute units, and combine the results to get the total number of boxes intersecting a shape. This paper presents a novel and highly efficient method using Open Computing Language (OpenCL) kernels to perform the computation on a per-pixel basis. The mapping and reduction stages are performed in a single pass, and therefore require the enqueuing of only a single kernel. Each instance of the kernel updates the information pertaining to all the boxes containing the pixel, and simultaneously increments the box counters at multiple levels, thereby eliminating the need for another pass to perform the summation. The complete implementation and coding details of the proposed method are outlined. The performance of the method on different processors are analyzed with respect to varying image sizes.
Extraction of Whole-Body Affordances for Loco-Manipulation Tasks
Authors: Kaiser Peter , Vahrenkamp Nikolaus , Schültje Fabian , Borràs Júlia , Asfour Tamim
Published: June 2015

Humanoid robots that have to operate in cluttered and unstructured environments, such as man-made and natural disaster scenarios, require sophisticated sensorimotor capabilities. A crucial prerequisite for the successful execution of whole-body locomotion and manipulation tasks in such environments is the perception of the environment and the extraction of associated environmental affordances, i.e., the action possibilities of the robot in the environment. We believe that such a coupling between perception and action could be a key to substantially increase the flexibility of humanoid robots.

In this paper, we approach the affordance-based generation of whole-body actions for stable locomotion and manipulation. We incorporate a rule-based system to assign affordance hypotheses to visually perceived environmental primitives in the scene. These hypotheses are then filtered using extended reachability maps that carry stability information, for identifying reachable affordance hypotheses. We then formulate the hypotheses in terms of a constrained inverse kinematics problem in order to find whole-body configurations that utilize a chosen set of hypotheses.

The proposed methods are implemented and tested in simulated environments based on RGB-D scans as well as on a real robotic platform.
Central effects of humanin on hepatic triglyceride secretion
Authors: Gong Zhenwei , Su Kai , Cui Lingguang , Tas Emir , Zhang Ting , Dong H. Henry , Yakar Shoshana , Muzumdar Radhika H.
Published: June 2015

Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the β-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism.
Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis
Authors: Grant Ryan W. , Stephens Jacqueline M.
Published: June 2015

Adipose tissue has the largest capacity to store energy in the body and provides energy through the release of free fatty acids during times of energy need. Different types of immune cells are recruited to adipose tissue under various physiological conditions, indicating that these cells contribute to the regulation of adipose tissue. One major pathway influenced by a number of immune cells is the release of free fatty acids through lipolysis during both physiological (e.g., cold stress) and pathophysiological processes (e.g., obesity, type 2 diabetes). Adipose tissue expansion during obesity leads to immune cell infiltration and adipose tissue remodeling, a homeostatic process that promotes inflammation in adipose tissue. The release of proinflammatory cytokines stimulates lipolysis and causes insulin resistance, leading to adipose tissue dysfunction and systemic disruptions of metabolism. This review focuses on the interactions of cytokines and other inflammatory molecules that regulate adipose tissue lipolysis during physiological and pathophysiological states.
Issues Affecting the Synthetic Scalability of Ternary Metal Ferrite Nanoparticles
Authors: Morrow Lauren , Barron Andrew R.
Published: June 2015

Ternary Mn-Zn ferrite (MnxZn1-xFe2O4) nanoparticles (NPs) have been prepared by the thermal decomposition of an oleate complex, sodium dodecylbenzenesulfonate (SDBS) mediated hydrazine decomposition of the chloride salts, and triethylene glycol (TREG) mediated thermal decomposition of the metal acetylacetonates. Only the first method was found to facilitate the synthesis of uniform, isolable NPs with the correct Mn : Zn ratio (0.7 : 0.3) as characterized by small angle X-ray scattering (SAXS), transmission electron microscopy (TEM), and inductively coupled plasma-optical emission spectroscopy (ICP-OES). Scaling allowed for retention of the composition and size; however, attempts to prepare Zn-rich ferrites did not result in NP formation. Thermogravimetric analysis (TGA) indicated that the incomplete decomposition of the metal-oleate complexes prior to NP nucleation for Zn-rich compositions is the cause.
The Beginnings of Pancreatology as a Field of Experimental and Clinical Medicine
Authors: Ceranowicz Piotr , Cieszkowski Jakub , Warzecha Zygmunt , Kuśnierz-Cabala Beata , Dembiński Artur
Published: June 2015

This review presents the history of discoveries concerning the pancreas. In antiquity and the Middle Ages knowledge about the anatomy of the pancreas was very limited and its function was completely unknown. Significant progress was first made in the seventeenth and eighteenth centuries. Johann Georg Wirsüng, the prosector of the University of Padua, discovered the main pancreatic duct, and Giovanni Santorini discovered the accessory duct. Regnier de Graaf was the first to perform pancreatic exocrine studies, and Paul Langerhans’s 1869 discovery of pancreatic islets was the first step toward recognizing the pancreas as an endocrine gland. The twentieth century brought the discovery of insulin and other pancreatic hormones. To date, histochemical staining, transmission electron microscopy, and immunohistochemistry enabled the discovery of five cell types with identified hormonal products in adult human pancreatic islets. Twentieth-century pancreatic studies led to crucial advances in scientific knowledge and were recognized, among other things, with seven Nobel Prizes. The first of these went to Ivan Pavlov in 1904 for his work on the physiology of digestion. The most recent was awarded to Günter Blobel in 1999 for discovering signaling mechanisms that govern the transport and localization of proteins within pancreatic acinar cells.
Biotechnological Aspects and Perspective of Microbial Keratinase Production
Authors: Gopinath Subash C. B. , Anbu Periasamy , Lakshmipriya Thangavel , Tang Thean-Hock , Chen Yeng , Hashim Uda , Ruslinda A. Rahim , Arshad M. K. Md.
Published: June 2015

Keratinases are proteolytic enzymes predominantly active when keratin substrates are available that attack disulfide bridges in the keratin to convert them from complex to simplified forms. Keratinases are essential in preparation of animal nutrients, protein supplements, leather manufacture, textile processing, detergent formulation, feather meal processing for feed and fertilizer, the pharmaceutical and biomedical industries, and waste management. Accordingly, it is necessary to develop a method for continuous production of keratinase from reliable sources that can be easily managed. Microbial keratinase is less expensive than conventionally produced keratinase and can be obtained from fungi, bacteria, and actinomycetes. In this overview, the expansion of information about microbial keratinases and important considerations in keratinase production are discussed.
Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth
Authors: Declercq Jeroen , Brouwers Bas , Pruniau Vincent P. E. G. , Stijnen Pieter , Tuand Krizia , Meulemans Sandra , Prat Annik , Seidah Nabil G. , Khatib Abdel-Majid , Creemers John W. M.
Published: June 2015

Proprotein convertases are subtilisin-like serine endoproteases that cleave and hence activate a variety of proproteins, including growth factors, receptors, metalloproteases, and extracellular matrix proteins. Therefore, it has been suggested that inhibition of the ubiquitously expressed proprotein convertase FURIN might be a good therapeutic strategy for several tumor types. Whether this is also the case for hepatocellular carcinoma (HCC) is currently not clear. In a mouse model for HCC expression ofFurinwas not altered in the tumors, while those of PC7, PC5/6, and PACE4 significantly decreased, at least at some time points. To investigate the impact ofFurininhibition on the development and progression of HCC in this model,Furinwas genetically ablated in the liver.Furininactivation resulted in an increased tumor mass after 5 weeks. This was not caused by decreased apoptosis, since no differences in the apoptosis index could be observed. However, it could at least partially be explained by increased hepatocyte proliferation at 5 weeks. The tumors of theFurinknockout mice were histologically similar to those in wild type mice. In conclusion, liver-specificFurininhibition in HCC enhances the tumor formation and will not be a good therapeutic strategy for this tumor type.
Removal of Organic Dyes by Nanostructure ZnO-Bamboo Charcoal Composites with Photocatalysis Function
Authors: Yu Xinliang , Qin Aimiao , Liao Lei , Du Rui , Tian Ning , Huang Song , Wei Chun
Published: June 2015

Composites of nanostructure zinc oxide (nano-ZnO) and bamboo charcoal (BC) were successfully prepared via impregnation-precipitation method. The products were characterized by XRD, SEM, and EDS. Rhodamine B (RhB) and acid fuchsin (AF) were selected as the organic dyes of photocatalysis degradation under the irradiation of ultraviolet light (UV). The influence of particle size of BC, irradiation time, pH value of the solution, and additive amount of H2O2on removal of the dyes has been studied. The results show that smaller particle size of BC in the composites has a better removal effect. The composites possess the highest removal capacity for RhB and AF under the conditions of pH = 2 and pH = 5.4, respectively. The optimum additive amount of H2O2for 5 mL RhB and AF was 0.050 mL and 0.1 mL, with a removal rate of 93% and 99%, respectively.
HPV Testing from Dried Urine Spots as a Tool for Cervical Cancer Screening in Low-Income Countries
Authors: Frati Elena Rosanna , Martinelli Marianna , Fasoli Ester , Colzani Daniela , Bianchi Silvia , Binda Sandro , Olivani Pierfranco , Tanzi Elisabetta
Published: June 2015

Nowadays, several screening strategies are available to prevent cervical cancer, but inadequate resources, sociocultural barriers, and sampling issues impede their success in low-income countries. To overcome these issues, this study aimed to evaluate the performance of human papillomavirus (HPV) testing from dried urine spots (DUS). Eighty-eight urine samples (including 56 HPV DNA positive specimens) were spotted on filter paper, dried, and stored in paper-bags. HPV DNA was detected from the DUS after 1 week and 4 weeks of storage using a polymerase chain reaction (PCR) assay. The sensitivity, specificity, and concordance of the DUS-based HPV test were evaluated by comparing the results with those of HPV testing on fresh urine samples as the gold standard. The sensitivity of the test was 98.21% (95% CI: 90.56–99.68) for DUS stored for 1 week and 96.42% (95% CI: 87.88–99.01) for DUS stored for 4 weeks. The specificity was 100% (95% CI: 89.28–100) at both time points. The concordance between DUS and fresh urine HPV testing was “almost perfect” using theκstatistic. These preliminary data suggest that a DUS-based assay could bypass sociocultural barriers and sampling issues and therefore could be a suitable, effective tool for epidemiological surveillance and screening programs, especially in low-income countries.
An Airway Network Flow Assignment Approach Based on an Efficient Multiobjective Optimization Framework
Authors: Guan Xiangmin , Zhang Xuejun , Zhu Yanbo , Sun Dengfeng , Lei Jiaxing
Published: June 2015

Considering reducing the airspace congestion and the flight delay simultaneously, this paper formulates the airway network flow assignment (ANFA) problem as a multiobjective optimization model and presents a new multiobjective optimization framework to solve it. Firstly, an effective multi‐island parallel evolution algorithm with multiple evolution populations is employed to improve the optimization capability. Secondly, the nondominated sorting genetic algorithm II is applied for each population. In addition, a cooperative coevolution algorithm is adapted to divide the ANFA problem into several low‐dimensional biobjective optimization problems which are easier to deal with. Finally, in order to maintain the diversity of solutions and to avoid prematurity, a dynamic adjustment operator based on solution congestion degree is specifically designed for the ANFA problem. Simulation results using the real traffic data from China air route network and daily flight plans demonstrate that the proposed approach can improve the solution quality effectively, showing superiority to the existing approaches such as the multiobjective genetic algorithm, the well‐known multiobjective evolutionary algorithm based on decomposition, and a cooperative coevolution multiobjective algorithm as well as other parallel evolution algorithms with different migration topology.
Long Term Exposure to Polyphenols of Artichoke (Cynara scolymusL.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line
Authors: Mileo Anna Maria , Di Venere Donato , Abbruzzese Claudia , Miccadei Stefania
Published: June 2015

Polyphenolic extracts from the edible part of artichoke (Cynara scolymusL.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associatedβ-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes,p16INK4aandp21Cip1/Waf1in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.
Ab Initio Theoretical Investigation on the Geometrical and Electronic Structures of Gallium Aurides: Ga Aun0/- and Ga2Aun0/-  (n = 1–4)
Authors: Yao Wen-Zhi , Yao Jian-Bin , Li Si-Dian
Published: June 2015

This study presents a systematic investigation of the geometric and electronic properties of GaA and Ga2A (n = 1–4) clusters based on density functional theory and wave function theory. Detailed orbital analyses, adaptive natural density partitioning, and electron localization function analyses are performed and relevant results are discussed. GaA (n = 1–4) clusters with n‐Au terminals and Ga2A (n = 1–4) clusters with bridged Au atoms possess geometric structures and bonding patterns similar to those of the corresponding gallium hydrides Ga and Ga2. Ga–Au interaction is predicted to occur through highly polar covalent bonds in monogallium aurides. In contrast to the highly symmetric ground states of C2v Ga2Au, C2v Ga2Au2, and D3h Ga2Au3, C3v Ga2Au4 is composed of strong interactions between a Ga+ cation and the face of a tetrahedral GaA anion. The adiabatic and vertical detachment energies of the anions under study are calculated to facilitate their experimental characterization. Geometric and electronic structural comparisons with the corresponding gallium hydrides are conducted to establish an isolobal analogy between gold and hydrogen atoms.