bluuebunny/crossref_metadata_2025 huggingface dataset:
MethylPCA: a toolkit to control for confounders in methylome-wide association studies
Authors: Chen Wenan , Gao Guimin , Nerella Srilaxmi , Hultman Christina M , Magnusson Patrik KE , Sullivan Patrick F , Aberg Karolina A , van den Oord Edwin JCG
Published: March 2013

Background

In methylome-wide association studies (MWAS) there are many possible differences between cases and controls (e.g. related to life style, diet, and medication use) that may affect the methylome and produce false positive findings. An effective approach to control for these confounders is to first capture the major sources of variation in the methylation data and then regress out these components in the association analyses. This approach is, however, computationally very challenging due to the extremely large number of methylation sites in the human genome.

Result

We introduce MethylPCA that is specifically designed to control for potential confounders in studies where the number of methylation sites is extremely large. MethylPCA offers a complete and flexible data analysis including 1) an adaptive method that performs data reduction prior to PCA by empirically combining methylation data of neighboring sites, 2) an efficient algorithm that performs a principal component analysis (PCA) on the ultra high-dimensional data matrix, and 3) association tests. To accomplish this MethylPCA allows for parallel execution of tasks, uses C++ for CPU and I/O intensive calculations, and stores intermediate results to avoid computing the same statistics multiple times or keeping results in memory. Through simulations and an analysis of a real whole methylome MBD-seq study of 1,500 subjects we show that MethylPCA effectively controls for potential confounders.

Conclusions

MethylPCA provides users a convenient tool to perform MWAS. The software effectively handles the challenge in memory and speed to perform tasks that would be impossible to accomplish using existing software when millions of sites are interrogated with the sample sizes required for MWAS.
Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV β-lactamase on hydrolysis of penicillin and ampicillin
Authors: Rayamajhi Nabin , Joo Jeong Chan , Cha Seung Bin , Pokherl Subarna , Shin Min Kyung , Yoo Young Je , Yoo Han Sang
Published: March 2013

Background

The aim of this study was to analyze the significance of leucine to proline substitution at position 138(Leu138Pro) on the hydrolysis of penicillin and ampicillin that we identified in the bla
SHV gene of clinical Escherichia coli swine isolate.

Results

Kinetic analysis of the mutant proteins showed that K

m
value of the purified L138P mutant was comparatively higher than SHV-1, SHV-33 and SHV-33(L138P) enzyme for penicillin and ampicillin. Docking simulation of the SHV-1 and SHV-(L138P) enzymes also confirmed that β-lactamases preferred penicillin to ampicillin and the SHV-1 had a higher binding affinity for antibiotics compared to the SHV-(L138P) and other mutants.

Conclusions

Our result demonstrated that L138P has a reduced role in penicillin and ampicillin hydrolyzing properties of SHV β-lactamases. These naturally occurring mutations rendering reduced function of the existing protein could trigger the emergence or acquisition of more effective alternative mechanisms for β-lactam hydrolysis.
Comparative transcription analysis and toxin production of two fluoroquinolone-resistant mutants of Clostridium perfringens
Authors: Park Sunny , Park Miseon , Rafii Fatemeh
Published: March 2013

Background

Fluoroquinolone use has been listed as a risk factor for the emergence of virulent clinical strains of some bacteria. The aim of our study was to evaluate the effect of fluoroquinolone (gatifloxacin) resistance selection on differential gene expression, including the toxin genes involved in virulence, in two fluoroquinolone-resistant strains of Clostridium perfringens by comparison with their wild-type isogenic strains.

Results

DNA microarray analyses were used to compare the gene transcription of two wild types, NCTR and ATCC 13124, with their gatifloxacin-resistant mutants, NCTRR and 13124R. Transcription of a variety of genes involved in bacterial metabolism was either higher or lower in the mutants than in the wild types. Some genes, including genes for toxins and regulatory genes, were upregulated in NCTRR and downregulated in 13124R. Transcription analysis by quantitative real-time PCR (qRT-PCR) confirmed the altered expression of many of the genes that were affected differently in the fluoroquinolone-resistant mutants and wild types. The levels of gene expression and enzyme production for the toxins phospholipase C, perfringolysin O, collagenase and clostripain had decreased in 13124R and increased in NCTRR in comparison with the wild types. After centrifugation, the cytotoxicity of the supernatants of NCTRR and 13224R cultures for mouse peritoneal macrophages confirmed the increased cytotoxicity of NCTRR and the decreased cytotoxicity of 13124R in comparison with the respective wild types. Fluoroquinolone resistance selection also affected cell shape and colony morphology in both strains.

Conclusion

Our results indicate that gatifloxacin resistance selection was associated with altered gene expression in two C. perfringens strains and that the effect was strain-specific. This study clearly demonstrates that bacterial exposure to fluoroquinolones may affect virulence (toxin production) in addition to drug resistance.
A threshold method for immunological correlates of protection
Authors: Chen Xuan , Bailleux Fabrice , Desai Kamal , Qin Li , Dunning Andrew J
Published: March 2013

Background

Immunological correlates of protection are biological markers such as disease-specific antibodies which correlate with protection against disease and which are measurable with immunological assays. It is common in vaccine research and in setting immunization policy to rely on threshold values for the correlate where the accepted threshold differentiates between individuals who are considered to be protected against disease and those who are susceptible. Examples where thresholds are used include development of a new generation 13-valent pneumococcal conjugate vaccine which was required in clinical trials to meet accepted thresholds for the older 7-valent vaccine, and public health decision making on vaccination policy based on long-term maintenance of protective thresholds for Hepatitis A, rubella, measles, Japanese encephalitis and others. Despite widespread use of such thresholds in vaccine policy and research, few statistical approaches have been formally developed which specifically incorporate a threshold parameter in order to estimate the value of the protective threshold from data.

Methods

We propose a 3-parameter statistical model called the a:b model which incorporates parameters for a threshold and constant but different infection probabilities below and above the threshold estimated using profile likelihood or least squares methods. Evaluation of the estimated threshold can be performed by a significance test for the existence of a threshold using a modified likelihood ratio test which follows a chi-squared distribution with 3 degrees of freedom, and confidence intervals for the threshold can be obtained by bootstrapping. The model also permits assessment of relative risk of infection in patients achieving the threshold or not. Goodness-of-fit of the a:b model may be assessed using the Hosmer-Lemeshow approach. The model is applied to 15 datasets from published clinical trials on pertussis, respiratory syncytial virus and varicella.

Results

Highly significant thresholds with p-values less than 0.01 were found for 13 of the 15 datasets. Considerable variability was seen in the widths of confidence intervals. Relative risks indicated around 70% or better protection in 11 datasets and relevance of the estimated threshold to imply strong protection. Goodness-of-fit was generally acceptable.

Conclusions

The a:b model offers a formal statistical method of estimation of thresholds differentiating susceptible from protected individuals which has previously depended on putative statements based on visual inspection of data.
Intrarenal resistance index for the assessment of acute renal injury in a rat liver transplantation model
Authors: Kong Hai-Ying , Chen Fen , He Yong , Wu Lin-Jiao , Wang Li-Qing , Zhu Sheng-Mei , Zheng Shu-Sen
Published: March 2013

Background

Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and associated with a high mortality. The renal resistive index (RI) is used to assess early renal function impairment in critical care patients. However, limited data are available concerning changes of renal RI and the development of AKI early after reperfusion. We approached to investigate the changes of renal RI and AKI after reperfusion in a rat liver transplantation model.

Methods

Rats were randomly divided into sham group or LT group. Ten rats in each group were used for the hemodynamic study and twenty for Doppler measurements during the procedure. Ten rats were sacrificed 30 min or 2 h after the reperfusion. We harvested kidneys, serum and urine for further analysis of the renal function.

Results

The intrarenal RI increased significantly in the anhepatic stage and decreased significantly after the reperfusion in the LT group compared with sham group (P < 0.05). AKI was seen after the reperfusion in the LT group. No correlation was noted between the RI and renal function parameters 30 min after reperfusion.

Conclusions

The intrarenal RI increased significantly during the anhepatic stage, and decreased significantly early after the reperfusion. Intrarenal RI was unable to assess renal function in a rat liver transplantation model.
Reduction of the domino effect in osteoporotic vertebral compression fractures through short-segment fixation with intravertebral expandable pillars compared to percutaneous kyphoplasty: a case control study
Authors: Hsieh Jui-Yang , Wu Chung-Ding , Wang Ting-Ming , Chen Hsuan-Yu , Farn Chui-Jia , Chen Po-Quang
Published: March 2013

Background

Osteoporotic vertebral compression fracture is the leading cause of disability and morbidity in elderly people. Treatment of this condition remains a challenge. Osteoporotic vertebral compression fractures can be managed with various approaches, but each has limitations. In this study, we compared the clinical outcomes obtained using short-segment fixation with intravertebral expandable pillars (I-VEP) to those obtained with percutaneous kyphoplasty in patients who had suffered vertebral compression fractures.

Methods

The study included 46 patients with single-level osteoporotic thoracolumbar fractures. Twenty-two patients in Group I underwent short-segment fixation with I-VEP and 24 patients in Group II underwent kyphoplasty. All patients were evaluated pre- and postoperatively using a visual analogue scale, anterior height of the fractured vertebra, and kyphotic angle of the fractured vertebra. The latter 2 radiological parameters were measured at the adjacent segments as well.

Results

There was no significant difference between the groups in terms of gender or fracture level, but the mean age was greater in Group II patients (p = 0.008). At the 1-year follow-up, there were no significant differences in the visual analogue scale scores, anterior height of the fractured vertebra, or the value representing anterior height above the fractured vertebra and kyphotic angle below the fractured vertebra, after adjusting for the patients’ gender, fracture level, and age. When considered separately, the anterior height below the fractured vertebra was significantly higher and the kyphotic angle above the fractured vertebra was significantly smaller in Group I than in Group II (p = 0.029 and p = 0.008, respectively). The kyphotic angle of the fractured vertebra was significantly smaller in Group II than in Group I (p < 0.001).

Conclusions

In older individuals with vertebral compression fractures, kyphoplasty restored and maintained the collapsed vertebral body with less kyphotic deformity than that induced by short-segment fixation with I-VEP. Short-segment fixation with I-VEP was more effective in maintaining the integrity of adjacent segments, which prevented the domino effect often observed in patients with osteoporotic kyphotic spines.
Stem cells: a new paradigm for disease modeling and developing therapies for age-related macular degeneration
Authors: Melville Heather , Carpiniello Matthew , Hollis Kia , Staffaroni Andrew , Golestaneh Nady
Published: March 2013

Age-related macular degeneration (AMD) is the leading cause of blindness in people over age 55 in the U.S. and the developed world. This condition leads to the progressive impairment of central visual acuity. There are significant limitations in the understanding of disease progression in AMD as well as a lack of effective methods of treatment. Lately, there has been considerable enthusiasm for application of stem cell biology for both disease modeling and therapeutic application. Human embryonic stem cells and induced pluripotent stem cells (iPSCs) have been used in cell culture assays and in vivo animal models. Recently a clinical trial was approved by FDA to investigate the safety and efficacy of the human embryonic stem cell-derived retinal pigment epithelium (RPE) transplantation in sub-retinal space of patients with dry AMD These studies suggest that stem cell research may provide both insight regarding disease development and progression, as well as direction for therapeutic innovation for the millions of patients afflicted with AMD.
Planning and adjustments for the control of reach extent in a virtual environment
Authors: Stewart Jill Campbell , Gordon James , Winstein Carolee J
Published: March 2013

Background

Skilled performance of reach actions includes both anticipatory planning and compensatory adjustments made while moving. The execution of reach actions in a virtual environment (VE) demonstrates similar characteristics to reaches performed in the real-world, however, it is unclear whether the VE itself significantly impacts movement planning or compensatory adjustments. The purpose of this study was to directly compare the use of planning and adjustments to control extent for unconstrained reach actions performed in an immersive VE to those performed in an analogous real-world environment (RWE).

Methods

Five non-disabled adults (29 ± 5 years) reached with the dominant, right arm to six targets presented in two directions (+45°, -45°) and three distances (8, 16, 24 cm) in a VE and an analogous RWE. Position data were sampled at 120 Hz from an electromagnetic marker on the index finger and differentiated to determine velocity and acceleration. The control of reach extent was compared between the two environments (paired t-test) as to the use of planning (correlation of peak acceleration with movement distance), compensatory adjustments prior to peak velocity (correlation of time to peak velocity with movement distance), and compensatory adjustments after peak velocity (variance in movement distance accounted for by deterministic statistical model).

Results

Reach movements were relatively fast (<400 msec) and scaled to target distance in both the VE and RWE. Overall, the control of reach extent was similar in all respects between the two environments. In both environments, a hybrid control pattern was observed. That is, individuals utilized a combined strategy that relied on both planning and compensatory adjustments to capture the target. Adjustments to the reach were evident prior to peak velocity through changes in acceleration duration as well as after peak velocity based on target information. The two factor deterministic statistical model (peak velocity, target distance) explained >92% of the variance in movement distance across participants and environments.

Conclusions

The VE did not impact movement planning or subsequent compensatory adjustments for the control of reach extent when directly compared to an analogous RWE. An immersive VE is a valid environment for the study of unconstrained reach actions.
Effect of variations in depth of neuromuscular blockade on rating of surgical conditions by surgeon and anesthesiologist in patients undergoing laparoscopic renal or prostatic surgery (BLISS trial): study protocol for a randomized controlled trial
Authors: Boon Martijn , Martini Christian H , Aarts Leon PHJ , Bevers Rob FM , Dahan Albert
Published: March 2013

Background

Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation. Especially in procedures that are confined to a narrow working field, such as retroperitoneal laparoscopic surgery, deep neuromuscular relaxation may be beneficial. Until recently, though, deep neuromuscular block (NMB) came at the expense of a variety of issues that conflicted with its use. However, with the introduction of sugammadex, rapid reversal of a deep NMB is feasible. In the current protocol, the association between the depth of NMB and rating of surgical conditions by the surgeon and anesthesiologist is studied.

Methods/design

This is a single-center, prospective, randomized, blinded, parallel group and controlled trial. Eligible patients are randomly assigned to one of two groups: (1) deep NMB (post-tetanic count, one or two twitches; n = 12) and (2) moderate NMB (train-of-four, 1 to 2 twitches, n = 12) by administration of high-dose rocuronium in Group 1 and a combination of atracurium and mivacurium in Group 2. The NMB in Group 1 is reversed by 4 mg/kg sugammadex; the NMB in Group 2 by 1 mg neostigmine and 0.5 mg atropine. Patients are eligible if they are over 18 years, willing to sign the informed consent form, and are scheduled to undergo an elective laparoscopic renal procedure or laparoscopic prostatectomy. A single surgeon performs the surgeries and rates the surgical conditions on a five-point surgical rating scale (SRS) ranging from 1 (poor surgical conditions) to 5 (excellent surgical conditions). The intra-abdominal part of the surgeries is captured on video and a group of five anesthesiologists and ten surgical experts will rate the videos using the same SRS. The primary analysis will be an intention-to-treat analysis. Evaluation will include the association between the level of NMB and SRS, as obtained by the surgeon performing the procedure and the agreement between the scoring of the images by anesthesiologists and surgeons.

Discussion

We aim to show that under the right conditions the perceived opposing goals of surgeons and anesthesiologists (optimal surgical conditions vs. optimal postoperative conditions) may be met without compromise to either.

Trial registration

ClinicalTrials.gov identifier NCT01631149.
Attitudes and local ecological knowledge of experts fishermen in relation to conservation and bycatch of sea turtles (reptilia: testudines), Southern Bahia, Brazil
Authors: Braga Heitor de Oliveira , Schiavetti Alexandre
Published: March 2013

Background

The use of ethnoecological tools to evaluate possible damage and loss of biodiversity related to the populations of species under some degree of threat may represent a first step towards integrating the political management of natural resources and conservation strategies. From this perspective, this study investigates fishermen’s ecological knowledge about sea turtles and attitudes towards the conservation and bycatch in Ilhéus, Southern Bahia, Brazil.

Methods

Fishermen experts semi-structured interviews were performed using snowball sampling method. The interviews consisted of a series of questions relating to the fishermen’s profile, structure and work equipment, the local ecological knowledge of fishermen about sea turtles and bycatch, a projective test, attitudes towards turtle conservation and beliefs and taboos regarding turtles. Indicators for quantitative comparisons of respondents in terms of their broad knowledge and attitudes towards turtle conservation were created. Correlation analyses were made between indicators of knowledge and attitude as well as the relationship between education level and knowledge and attitudes.

Results

Thirty experts were interviewed for the study. The local ecological knowledge and attitudes of fishermen towards the conservation of sea turtles were respectively medium (0.43) and moderate (0.69) according to experts (based on Likert scale and Cronbach’s Alpha). Potential areas of spawning were reported from Barra Grande to Una covering the entire coast of Ilhéus. Methods for identifying the animal, behavior, and popular names were described by fishermen. The most recent captures of turtles were attributed to fishing line, but according to the respondents, lobster nets and shrimp traps are more likely to capture turtles. Knowledge and attitudes were weakly inversely correlated (r = −0.38, p = 0.04), and the education level of the respondent showed a positive correlation with positive attitudes towards turtle conservation (H = 8.33; p = 0.04). Life history, habitat, specific and exogenous taboos, beliefs and the use of hawksbill turtle to make glasses and other handcrafts are also reported in the study.

Conclusions

Monitoring of spawning areas, preservation of traditional practices, strategies to moderate the use of fishery resources and the local ecological knowledge/attitudes can provide data to improve the conservation practices and management of sea turtles.
Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety
Authors: Gurka Marie K , Collins Sean P , Slack Rebecca , Tse Gary , Charabaty Aline , Ley Lisa , Berzcel Liam , Lei Siyuan , Suy Simeng , Haddad Nadim , Jha Reena , Johnson Colin D , Jackson Patrick , Marshall John L , Pishvaian Michael J
Published: March 2013

Background

Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC.

Methods

Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires.

Results

Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment.

Conclusions

SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity.
Breast reconstruction and post-mastectomy radiation practice
Authors: Chen Susie A , Hiley Crispin , Nickleach Dana , Petsuksiri Janjira , Andic Fundagul , Riesterer Oliver , Switchenko Jeffrey M , Torres Mylin A
Published: March 2013

Purpose

The goal of this study was to explore the perspectives and practice of radiation oncologists who treat breast cancer patients who have had breast reconstruction.

Methods

In 2010, an original electronic survey was sent to all physician members of the American Society of Radiation Oncology, National Cancer Research Institute-Breast Cancer Studies Group in the United Kingdom, Thai Society of Therapeutic Radiology and Oncology, Swiss Society of Radiation Oncology, and Turkish Radiation Oncology Society. We identified factors associated with radiation oncologists who treat breast cancer patients with reconstruction performed prior to radiation and obtained information regarding radiation management of the breast reconstruction.

Results

358 radiation oncologists responded, and 60% of the physicians were from the United States. While 64% of participants agree or strongly agree that breast image affects a woman’s quality of life during radiation, 57% feel that reconstruction challenges their ability to deliver effective breast radiation. Compared with other countries, treatment within the United States was associated with a high reconstruction rate (>/= 50% of mastectomy patients) prior to radiation (p < 0.05). Delayed-immediate reconstruction with a temporary tissue expander was more common in the United States than in other countries (52% vs. 23%, p = 0.01). Among physicians who treat patients with tissue expanders, the majority (60%) prefer a moderately inflated implant with 150-250 cc of fluid rather than a completely deflated (13%) or inflated expander (28%) during radiation. Among radiation oncologists who treat reconstructions, 49% never use bolus and 40% never boost a breast reconstruction. United States physicians were more likely than physicians from other countries to boost or bolus the reconstruction irrespective of the type of reconstruction seen in their clinic patients (p < 0.01).

Conclusions

Great variation in practice is evident from our study of radiation treatment for breast cancer patients with reconstruction. Further research on the impact and delivery of radiation to a reconstructed breast may validate some of the observed practices, highlight the variability in treatment practice, and help create a treatment consensus.
Novel mutations in the ferritin-L iron-responsive element that only mildly impair IRP binding cause hereditary hyperferritinaemia cataract syndrome
Authors: Luscieti Sara , Tolle Gabriele , Aranda Jessica , Campos Carmen Benet , Risse Frank , Morán Érica , Muckenthaler Martina U , Sánchez Mayka
Published: March 2013

Background

Hereditary Hyperferritinaemia Cataract Syndrome (HHCS) is a rare autosomal dominant disease characterized by increased serum ferritin levels and early onset of bilateral cataract. The disease is caused by mutations in the Iron-Responsive Element (IRE) located in the 5′ untranslated region of L-Ferritin (FTL) mRNA, which post-transcriptionally regulates ferritin expression.

Methods

We describe two families presenting high serum ferritin levels and juvenile cataract with novel mutations in the L-ferritin IRE. The mutations were further characterized by in vitro functional studies.

Results

We have identified two novel mutations in the IRE of L-Ferritin causing HHCS: the Badalona +36C > U and the Heidelberg +52 G > C mutation. Both mutations conferred reduced binding affinity on recombinant Iron Regulatory Proteins (IPRs) in EMSA experiments. Interestingly, the Badalona +36C > U mutation was found not only in heterozygosity, as expected for an autosomal dominant disease, but also in the homozygous state in some affected subjects. Additionally we report an update of all mutations identified so far to cause HHCS.

Conclusions

The Badalona +36C > U and Heidelberg +52 G > C mutations within the L-ferritin IRE only mildly alter the binding capacity of the Iron Regulatory Proteins but are still causative for the disease.
Adenocarcinoma of the seminal vesicles complicated by antineutrophil cytoplasmic antibody vasculitis: a case report and review of the literature
Authors: Lote Hazel , Mannion Ethna , Cook Terence , Cairns Thomas , Savage Philip
Published: March 2013

Introduction

Adenocarcinoma of the seminal vesicles is a very rare malignancy, with less than 100 cases reported worldwide. It is documented to have a poor prognosis, with the majority of patients developing metastatic disease, most commonly in the prostate, bladder and rectum. Currently there is no standard treatment for metastatic disease and the limited reports of treatment with radiotherapy, chemotherapy and hormonal (anti-androgenic) therapy show that they are generally of modest benefit. The association between malignancy and an increased risk of autoimmune vasculitis has been demonstrated in a number of malignancies, but to date there have been no documented cases of adenocarcinoma of the seminal vesicles associated with anti-neutrophil cytoplasmic antibody vasculitis.

Case presentation

In this report we describe the case of a 55-year-old Caucasian man with metastatic adenocarcinoma of the seminal vesicles. He previously had received chemotherapy treatment for advanced testicular cancer and later presented with hemospermia. He subsequently developed c-antineutrophil cytoplasmic antibody vasculitis requiring intensive immunosuppression and renal dialysis.

Conclusion

Adenocarcinoma of the seminal vesicles is a rare diagnosis and our case is more unusual in that our patient previously had chemotherapy treatment for advanced testicular cancer and went on to develop severe antineutrophil cytoplasmic antibody vasculitis when diagnosed with metastatic seminal vesicle cancer. This case illustrates that autoimmune vasculitis can occur in any patient with malignancy and an early referral to the renal team combined with renal biopsy can assist in the earlier diagnosis and more successful management of these rare events. This case should be of interest to oncologists, renal physicians, urologists and general physicians who encounter patients presenting with hemospermia or vasculitis.
Functional heterologous expression of an engineered full length CipA from Clostridium thermocellum in Thermoanaerobacterium saccharolyticum
Authors: Currie Devin H , Herring Christopher D , Guss Adam M , Olson Daniel G , Hogsett David A , Lynd Lee R
Published: March 2013

Background

Cellulose is highly recalcitrant and thus requires a specialized suite of enzymes to solubilize it into fermentable sugars. In C. thermocellum, these extracellular enzymes are present as a highly active multi-component system known as the cellulosome. This study explores the expression of a critical C. thermocellum cellulosomal component in T. saccharolyticum as a step toward creating a thermophilic bacterium capable of consolidated bioprocessing by employing heterologously expressed cellulosomes.

Results

We developed an inducible promoter system based on the native T. saccharolyticum xynA promoter, which was shown to be induced by xylan and xylose. The promoter was used to express the cellulosomal component cipA*, an engineered form of the wild-type cipA from C. thermocellum. Expression and localization to the supernatant were both verified for CipA*. When a ΔcipA mutant C. thermocellum strain was cultured with a CipA*-expressing T. saccharolyticum strain, hydrolysis and fermentation of 10 grams per liter SigmaCell 101, a highly crystalline cellulose, were observed. This trans-species complementation of a cipA deletion demonstrated the ability for CipA* to assemble a functional cellulosome.

Conclusion

This study is the first example of an engineered thermophile heterologously expressing a structural component of a cellulosome. To achieve this goal we developed and tested an inducible promoter for controlled expression in T. saccharolyticum as well as a synthetic cipA. In addition, we demonstrate a high degree of hydrolysis (up to 93%) on microcrystalline cellulose.
Effects of ectopic HER-2/neu gene expression on the COX-2/PGE2/P450arom signaling pathway in endometrial carcinoma cells: HER-2/neu gene expression in endometrial carcinoma cells
Authors: Li Shu , Ma XiaoXin , Ma Li , Wang Cuicui , He YuanQi , Yu ZhiJuan
Published: March 2013

Objectives

To investigate the role of HER-2/neu-mediated COX-2/P450arom signal in estrogen-dependent endometrial carcinoma.

Methods

The recombinant eukaryotic expression vector, pcDNA3.1-HER-2/neu, was constructed and transfect to Ishikawa endometrial carcinoma cells. The expression of COX-2 and P450arom in transfected cells were detected by real-time PCR and western blotting. The levels of estrogen in cell supernatants were detected by ELISA.

Results

Over-expression of HER-2/neu in transfected cells was confirmed by real-time PCR and western blotting. The levels of autocrine estrogen in transfected cells was significantly increased which combination with the enhancement of COX-2 and P450arom expression in transfected cells.

Conclusion

HER-2/neu induced the improvement of autocrine estrogen in endometrial carcinoma cell through triggering the COX-2/P450arom signal.
Consumption of a low glycaemic index diet in late life extends lifespan of Balb/c mice with differential effects on DNA damage
Authors: Nankervis Scott A , Mitchell Jenee M , Charchar Fadi J , McGlynn Maree A , Lewandowski Paul A
Published: March 2013

Background

Caloric restriction is known to extend the lifespan of all organisms in which it has been tested. Consequently, current research is investigating the role of various foods to improve health and lifespan. The role of various diets has received less attention however, and in some cases may have more capacity to improve health and longevity than specific foods alone. We examined the benefits to longevity of a low glycaemic index (GI) diet in aged Balb/c mice and examined markers of oxidative stress and subsequent effects on telomere dynamics.

Results

In an aged population of mice, a low GI diet extended average lifespan by 12%, improved glucose tolerance and had impressive effects on amelioration of oxidative damage to DNA in white blood cells. Telomere length in quadriceps muscle showed no improvement in the dieted group, nor was telomerase reactivated.

Conclusion

The beneficial effects of a low GI diet are evident from the current study and although the impact to telomere dynamics late in life is minimal, we expect that earlier intervention with a low GI diet would provide significant improvement in health and longevity with associated effects to telomere homeostasis.
The severity of experimental arthritis is independent of IL-36 receptor signaling
Authors: Lamacchia Céline , Palmer Gaby , Rodriguez Emiliana , Martin Praxedis , Vigne Solenne , Seemayer Christian A , Talabot-Ayer Dominique , Towne Jennifer E , Gabay Cem
Published: March 2013

Introduction

Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis.

Methods

Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring.

Results

IL-36R, IL-36Ra and IL-36γ mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice.

Conclusions

The development and severity of experimental arthritis are independent of IL-36R signaling.
Cortisol levels and neuropsychiatric diagnosis as markers of postoperative delirium:a prospective cohort study
Authors: Kazmierski Jakub , Banys Andrzej , Latek Joanna , Bourke Julius , Jaszewski Ryszard
Published: March 2013

Introduction

The pathophysiology of delirium after cardiac surgery is largely unknown. Thepurpose of this study was to investigate whether increased concentration ofpreoperative and postoperative plasma cortisol predicts the development ofdelirium after coronary artery bypass graft surgery. A second aim was to assesswhether the association between cortisol and delirium is stress related ormediated by other pathologies, such as major depressive disorder (MDD) orcognitive impairment.

Methods

The patients were examined 1 day preoperatively with the Mini InternationalNeuropsychiatric Interview and the Montreal Cognitive Assessment and the TrailMaking Test to screen for depression and for cognitive impairment, respectively.Blood samples for cortisol levels were collected both preoperatively andpostoperatively. The Confusion Assessment Method for the Intensive Care Unit wasused within the first 5 days postoperatively to screen for a diagnosis ofdelirium.

Results

Postoperative delirium developed in 36% (41 of 113) of participants. Multivariatelogistic regression analysis revealed two groups independently associated with anincreased risk of developing delirium: those with preoperatively raised cortisollevels; and those with a preoperative diagnosis of MDD associated with raisedlevels of cortisol postoperatively. According to receiver operating characteristicanalysis, the most optimal cutoff values of the preoperative and postoperativecortisol concentration that predict the development of delirium were 353.55 nmol/land 994.10 nmol/l, respectively.

Conclusion

Raised perioperative plasma cortisol concentrations are associated with deliriumafter coronary artery bypass graft surgery. This may be an importantpathophysiological consideration in the increased risk of postoperative deliriumseen in patients with a preoperative diagnosis of MDD.
Insulin-Mediated Oxidative Stress and DNA Damage in LLC-PK1 Pig Kidney Cell Line, Female Rat Primary Kidney Cells, and Male ZDF Rat Kidneys In Vivo
Authors: Othman Eman Maher , Kreissl Michael C. , Kaiser Franz R. , Arias-Loza Paula-Anahi , Stopper Helga
Published: March 2013

Hyperinsulinemia, a condition with excessively high insulin blood levels, is related to an increased cancer incidence. Diabetes mellitus is the most common of several diseases accompanied by hyperinsulinemia. Because an elevated kidney cancer risk was reported for diabetic patients, we investigated the induction of genomic damage by insulin in LLC-PK1 pig kidney cells, rat primary kidney cells, and ZDF rat kidneys. Insulin at a concentration of 5nM caused a significant increase in DNA damage in vitro. This was associated with the formation of reactive oxygen species (ROS). In the presence of antioxidants, blockers of the insulin, and IGF-I receptors, and a phosphatidylinositol 3-kinase inhibitor, the insulin-mediated DNA damage was reduced. Phosphorylation of protein kinase B (PKB or AKT) was increased and p53 accumulated. Inhibition of the mitochondrial and nicotinamide adenine dinucleotide phosphatase oxidase-related ROS production reduced the insulin-mediated damage. In primary rat cells, insulin also induced genomic damage. In kidneys from healthy, lean ZDF rats, which were infused with insulin to yield normal or high blood insulin levels, while keeping blood glucose levels constant, the amounts of ROS and the tumor protein (p53) were elevated in the high-insulin group compared with the control level group. ROS and p53 were also elevated in diabetic obese ZDF rats. Overall, insulin-induced oxidative stress resulted in genomic damage. If the same mechanisms are active in patients, hyperinsulinemia might cause genomic damage through the induction of ROS contributing to the increased cancer risk, against which the use of antioxidants and/or ROS production inhibitors might exert protective effects.
Hypoxia-Inducible Factor and Vascular Endothelial Growth Factor Are Targets of Dietary Soy During Acute Stroke in Female Rats
Authors: Ma Yulin , Lovekamp-Swan Tara , Bekele Woube , Dohi Akiko , Schreihofer Derek A.
Published: March 2013

Dietary soy and soy isoflavones are neuroprotective in experimental cerebral ischemia. Because these isoflavones have estrogenic properties, we hypothesized that, like estrogens, they would inhibit acute vascular injury and the detrimental acute increase in hypoxia-induced vascular endothelial growth factor (VEGF) that leads to cerebral edema after stroke. Mature ovariectomized female Sprague Dawley rats were fed soy-free or soy-containing diets for 4 weeks followed by 90 minutes of transient middle cerebral artery occlusion. Similar to estrogens, dietary soy significantly reduced cerebral edema and vascular apoptosis 24 hours after stroke. Soy also inhibited the ischemia-induced increase in cortical VEGF and VEGF receptor (VEGFR)-2 protein expression observed 4 and 24 hours after stroke, although mRNA levels increased. The reduction in VEGF/VEGFR-2 was associated both with decreases in receptor phosphorylation and signaling to AKT and endothelial nitric oxide synthase. Furthermore degradation of the VEGFR-2 was increased with dietary soy. The primary ischemic stimulus for VEGF, hypoxia-inducible factor 1α (HIF1α), was similarly reduced by dietary soy 4 hours after transient middle cerebral artery occlusion in both the cortex and striatum. The inhibition of HIF1α activity was further confirmed by a significant decrease in the HIF1α-activated apoptotic mediator BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Nip3-like protein X). These data suggest that soy isoflavones target events early in the ischemic cascade as part of their neuroprotective actions and counterbalance some of the detrimental effects of the endogenous response to cerebral injury.
Application of a Bis(silylene) Nickel Complex as Precatalyst in C–C Bond Formation Reactions
Authors: Someya Chika I , Haberberger Michael , Wang Wenyuan , Enthaler Stephan , Inoue Shigeyoshi
Published: March 2013

In the present study the catalytic performance of a nickel complex stabilized by an oxygen-bridged bis(silylene) ligand was examined in cross-coupling reactions of aryl halides with organometallic zinc and Grignard reagents. Good to excellent catalytic activity was observed for a variety of substrates with this system.
Expansion of Pore Windows and Interior Spaces of Microporous Porphyrin-based Metal Carboxylate Frameworks: Synthesis and Crystal Structure of [Cu2(ZnBDCBPP)]
Authors: Matsunaga Satoshi , Kato Shigeki , Endo Nanako , Mori Wasuke
Published: March 2013

We successfully synthesized a novel porphyrin-based metal carboxylate framework, [Cu2(ZnBDCBPP)]·5DMF·5H2O, with expanded pore windows and interior spaces, by using a ZnBDCBPP building block. Single-crystal X-ray analysis revealed that the framework of [Cu2(ZnBDCBPP)] formed a three-dimensional network. The cavity was surrounded by a total of 16 accessible metal sites with two distinct metals, and large pore windows were present. These large pore windows appear to be crucial for an enhanced catalytic performance because they facilitate the diffusion of substrates and products.
Structural Control of Carbon Nanotubes due to Magnetic Fields Applied in Preparation
Authors: Sakaguchi Ayumi , Hamasaki Atom , Ozeki Sumio
Published: March 2013

Multi- and single-walled carbon nanotubes (MWCNTs and SWCNTs) were prepared by the chemical vapor deposition from ethanol-saturated Ar gas onto catalytic substrates at 1073 K under magnetic fields of up to 10 T. MWCNTs were aligned in parallel to magnetic fields more than 4 T in the growth process even at 1073 K. Also, the formation of metallic SWCNTs of around 1.0-nm diameter was promoted over 4 T. These results demonstrate that magnetic fields may control the growth of CNTs.
An Electrochemically Surface-modified Porous Granule Developed for Phosphate Removal from Aqueous Solution
Authors: Yang Shengjiong , Ding Dahu , Zhao Yingxin , Zhang Zhenya
Published: March 2013

A porous granule was developed from Kanuma clay, corn starch, iron powder, white cement, and calcium oxide for phosphate removal. An electrochemical surface modification (ESM) process was then adopted during the preparation of the porous granule (PG). The results reflect that PG is a more promising adsorbent than other clay mineral materials for phosphate removal from wastewater, and ESM process is approved to be a novel effective surface modification path.
Size Selective Synthesis of Subnano Pd Clusters Using Core [Poly(propylene imine)]–Shell [Poly(benzyl ether)] Hybrid Dendrimers
Authors: Mizugaki Tomoo , Kibata Takayuki , Mitsudome Takato , Jitsukawa Koichiro , Kaneda Kiyotomi
Published: March 2013

The core–shell hybrid dendrimers consisting of a third generation poly(propylene imine) (PPI) dendrimer as a core and poly(benzyl ether) (PBE) dendrons as shells were synthesized. Fine tuning of the nanovoids of the hybrid dendrimers was achieved by changing the generation of the PBE dendron units, which allows the maximum size of Pd clusters encapsulated within the dendrimer to be controlled.
Preparation of LiClO4-doped Titanium Organodiphosphonates Possessing Oligomeric Ethylene Oxide Chains and Their Ionic Conductivity
Authors: Saito Hitomi , Dobashi Masataka , Naka Hiroki , Momma Toshiyuki , Osaka Tetsuya , Sugahara Yoshiyuki
Published: March 2013

Hybrids possessing both oligomeric ethylene oxide chains and Ti–O–P networks were prepared from TiCl4 and organodiphosphonic acid [(HO)2OP(C2H4O)3C2H4PO(OH)2] via a nonhydrolytic sol–gel process and subsequently treated with a LiClO4 solution. The P/Ti ratio was fixed at 2 and the ethylene oxide unit/Li+ ratio was changed from 5 to 20. Li+ ions are likely to be solvated by ether oxygen atoms. Li+ ion transport in the hybrids with ionic conductivity values in the 10−5 S cm−1 range was observed at ambient temperatures.
Advance Selling in a Supply Chain Under Uncertain Supply and Demand
Authors: Cho Soo-Haeng , Tang Christopher S.
Published: March 2013

We examine three selling strategies of a manufacturer who produces and sells a seasonal product to a retailer under uncertain supply and demand: (1) advance selling—presells the product before observing uncertain supply and demand; (2) regular selling—sells the product after supply and demand are realized; and (3) dynamic selling—combines both advance and regular selling strategies. We model the first two strategies as single-period Stackelberg games, and we model the last strategy as a two-period dynamic Stackelberg game. By comparing the equilibria of these games, we formalize our understanding of several intuitive results. For example, from the manufacturer's perspective, dynamic selling dominates advance selling and regular selling: having more selling opportunities is beneficial to the manufacturer. However, from the retailer's perspective, we find two counterintuitive results: (a) postponing the ordering decision can be detrimental—the retailer can be worse off under regular selling than under advance selling; and (b) more ordering opportunities can be detrimental—the retailer can be worse off under dynamic selling than under advance selling. In addition, we analyze the impact of supply and demand uncertainties under these strategies and find that both types of uncertainties can be beneficial to the retailer.