bluuebunny/crossref_metadata_2025 huggingface dataset:
A recursive method for computing expected kinship and inbreeding in complex and dynamic breeding programmes
Authors: Sitzenstock F. , Ytournel F. , Simianer H.
Published: June 2012

In many livestock breeding programmes, the development of inbreeding is of critical importance. Thus, the assessment of the expected development of inbreeding should be an essential element in the design of breeding programmes. We propose a new method to deterministically predict the rate of inbreeding based on the gene‐flow method in well‐defined complex and dynamic breeding programmes. In the suggested approach, a breeding programme has to be structured in homogeneous age‐sex‐groups, so called cohorts, with a defined origin of genes. Starting from an initial setup (usually an unrelated and non‐inbred base population), transition rules to calculate the kinship within and between cohorts originating from reproduction or ageing, respectively, are defined. Using this approach recursively provides the expected development of kinship within and between all cohorts over time, which can be combined into average kinships for the whole population or defined subsets. From these quantities, relevant parameters like the inbreeding rate or the effective population size are easily derived. We illustrate the method with a simple static example breeding programme in sheep. Based on this reference breeding programme, we demonstrate the use of our approach for dynamic breeding programmes, in which cohort sizes or vectors of gene origin change over time: here, we model the situation of exponential population growth and a bottleneck situation, respectively. The suggested approach does not account for the effect of selection on the development of inbreeding, but ideas to overcome this limitation are discussed.
Molecular Typing and Genetic Characterization of Pathogenic Variants of Xanthomonas axonopodis pv. citri in Taiwan
Authors: Lin Hsin‐Cheng , Feng Chun‐Yu , Chang Yu‐An , Chang Hsiang
Published: June 2012

Molecular typing was applied and optimized for genetic characterization for three pathogenic variants of Xanthomonas axonopodis pv. citri (Xac) from Taiwan. These three novel variants of atypical symptom–producing X. axonopodis pv. citri were designated as Xac‐Af, Xac‐Ap and Xac‐Ar. Based on polymerase chain reaction (PCR) with primers specific to X. axonopodis pv. citri, leucine‐responsive regulatory protein (lrp) gene assay and DNA fingerprintings generated by repetitive‐sequence PCR (rep‐PCR) and amplified fragment length polymorphism (AFLP) were used to compare strains including the three types of atypical symptom–producing strains Xac‐Af, Xac‐Ap and Xac‐Ar, and additional reference strains from pathotypes Xac‐A, Xac‐A*, Xac‐Aw, X. axonopodis pv. auruantifolii and X. axonopodis pv. citrumelo. These three types of X. axonopodis pv. citri variants can be detected with six sets of primer specific for X. axonopodis pv. citri. Cluster analyses by lrp sequence assay, AFLP and combing the band patterns of rep‐PCR clearly grouped the atypical symptom–producing variants in types Xac‐ Af, Xac‐Ar and Xac‐Ap into the same cluster with typical symptom‐producing strains in pathotype Xac‐A. These three types of X. axonopodis pv. citri variants could be excluded from strains of Xac‐A* and Xac‐Aw in these genotypic analyses. Strains of Xac‐A* and Xac‐Aw were closely related to Xac‐A strains in our results. No Taiwan isolate was related to X. axonopodis pv. auruantifolii or X. axonopodis pv. citrumelo. The results further confirmed the atypical symptom–producing variants of X. axonopodis pv. citri in Taiwan belong to pathotype Xac‐A.
Genetic polymorphism of copper transporter protein 1 is related to platinum resistance in Chinese non‐small cell lung carcinoma patients
Authors: Xu Xiaojing , Duan Li , Zhou Boting , Ma Rui , Zhou Honghao , Liu Zhaoqian
Published: June 2012

Chemotherapeutic resistance to platinum‐based anticancer drugs is a major obstacle in the successful treatment of lung cancer. Cellular uptake and platinum accumulation are considered the most important factors contributing to platinum resistance. The copper transporter family is the major plasma membrane transporter for platinum uptake. Copper transporter protein 1 (CTR1) plays an essential role in cisplatin influx and is closely related to platinum resistance by influencing platinum uptake and accumulation. The aim of the present study was to determine whether CTR1 polymorphisms are associated with platinum resistance in non‐small cell lung carcinoma (NSCLC) patients.

A total of 282 incident Chinese Han NSCLC patients were enrolled in the study and followed up at three different institutions. All patients underwent at least two cycles of platinum‐based chemotherapy. Twenty single‐nucleotide polymorphisms of CTR1 were detected from genomic DNA samples.

Genetic polymorphisms of CTR1 at rs7851395 and rs12686377 were associated with platinum resistance in NSCLC patients. Patients with a GT haplotype presented with increased susceptibility to platinum resistance (P < 0.05), whereas an AG haplotype contributed to longer survival (P < 0.05).

In conclusion, a significant relationship was found between rs7851395 and rs12686377 polymorphisms and platinum resistance, as well as clinical outcomes, in Chinese NSCLC patients. Thus, CTR1 plays an essential role in platinum resistance and could be considered a predictive marker for the pretreatment evaluation of NSCLC patients.
Motor Vehicle Collision–related Emergency Department Visits by Older Adults in the United States
Authors: Platts‐Mills Timothy F. , Hunold Katherine M. , Esserman Denise A. , Sloane Philip D. , McLean Samuel A.
Published: June 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:821–827 © 2012 by the Society for Academic Emergency Medicine

Objectives:  Motor vehicle collisions (MVCs) are the second most common cause of nonfatal injury among U.S. adults age 65 years and older. However, the frequency of emergency department (ED) visits, disposition, pain locations, and pain severity for older adults experiencing MVCs have not previously been described. The authors sought to determine these characteristics using information from two nationally representative data sets.

Methods:  Data from the 2008 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample (NEDS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) were used to estimate MVC‐related ED visits and ED disposition for patients 65 years and older. NHAMCS data from 2004 through 2008 were used to further characterize MVC‐related ED visits.

Results:  In 2008, the NEDS contained 28,445,564 patient visits, of which 760,356 (2.7%) were due to MVCs. The NHAMCS contained 34,134 patient visits, of which 1,038 (3.0%) were due to MVCs. National estimates of MVC‐related ED visits by patients 65 years and older in 2008 are 226,000 (95% confidence interval [CI] = 210,000 to 240,000) for NEDS and 270,000 (95% CI = 185,000 to 355,000) for NHAMCS. Most older adults with MVC‐related ED visits were sent home from the ED (proportion discharged NEDS 78%, 95% CI = 78% to 79%; NHAMCS 77%, 95% CI = 66% to 86%). During the years 2004 through 2008, of MVC‐related ED visits by older adults not resulting in hospital admission, moderate or severe pain was reported in 61% (95% CI = 52% to 70%) of those with recorded pain scores. Older patients sent home after MVC‐related ED visits were less likely than younger patients to receive analgesics (35%, 95% CI = 26% to 43% vs. 47%, 95% CI = 44% to 50%) during their ED evaluations or as discharge prescriptions (52%, 95% CI = 41% to 62% vs. 65%, 95% CI = 61% to 68%).

Conclusions:  In 2008, adults age 65 years or older made more than 200,000 MVC‐related ED visits. Approximately 80% of these visits were discharged home from the ED, but the majority of discharged patients reported moderate or severe pain. Further studies of pain and functional outcomes in this population are needed.
Gender‐specific Medicine: Yesterday’s Neglect, Tomorrow’s Opportunities
Authors: McGregor Alyson J. , Choo Esther
Published: June 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:861–865 © 2012 by the Society for Academic Emergency Medicine

The Institute of Medicine has stated that analyzing data according to sex and gender may change practices used by clinicians and taught in medical education. Gender‐specific medicine embraces the concept that differences between men and women encompass the entire organism, not just their reproductive biology, and that recognizing these differences will improve the precision and quality of health care for both men and women. Research conducted to date has deepened our scientific understanding of sex and gender differences in the etiology, diagnosis, progression, outcomes, treatment, and prevention of many conditions that affect both women and men.

The rapid growth and maturation of emergency medicine (EM) research provides a major opportunity to make an impact in this broad area of scientific inquiry. However, recent evidence suggests that barriers to the recognition of gender in funded and published research persist. Without systematic inclusion in research, and medical school and residency curricula, gender‐based medicine cannot be translated into widespread clinical practice. Collaborations between women’s health researchers across fields of medicine will be essential, given the large knowledge deficits to be addressed and the gender‐based issues that span all specialties. We provide one model for a multifaceted initiative targeting improvements in gender medicine for the specialty of EM. If emergency health services are to meet the needs of both women and men at modern‐day standards, then they must acknowledge the emerging science demonstrating that sex and gender differences influence the delivery of high‐quality clinical care.
Pediatric Emergency Department Crowding Is Associated With a Lower Likelihood of Hospital Admission
Authors: Michelson Kenneth A. , Monuteaux Michael C. , Stack Anne M. , Bachur Richard G.
Published: June 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:816–820 © 2012 by the Society for Academic Emergency Medicine

Objectives:  Emergency department (ED) crowding may affect disposition decision‐making. The objective was to measure the effect of ED crowding on probability of admission and return visit to the ED after discharge.

Methods:  The authors studied a historical cohort at a large pediatric ED over 40 months. Each patient was assigned a score on arrival based on the ED occupancy rate (the ratio of patients to beds). Patients were divided into quintiles by occupancy rate. The proportion admitted for each quintile was compared to the least crowded quintile adjusting for acuity, hospital occupancy, and time of arrival. The same analysis was performed for return visits to the ED within 48 hours. The analyses were repeated for the subsets of patients with asthma and with gastroenteritis and/or dehydration.

Results:  From the 40 months of historical data, 198,778 visits were analyzed. The adjusted odds ratio (aOR) for admission among the whole cohort was 0.85 (95% confidence interval [CI] = 0.81 to 0.89) comparing the highest to the lowest crowding quintiles (occupancy rate > 1.17 and < 0.54, respectively). For asthma patients, aOR = 0.93 (95% CI = 0.72 to 1.20), and for gastroenteritis patients, aOR = 0.87 (95% CI = 0.65 to 1.17). The aOR of return visits comparing the highest to the lowest crowding quintiles for all patients was aOR = 0.87 (95% CI = 0.79 to 0.97), for asthma patients was aOR = 1.52 (95% CI = 0.95 to 2.46), and for gastroenteritis patients was aOR = 0.83 (95% CI = 0.54 to 1.28).

Conclusions:  Increasing ED crowding is associated with a lower likelihood of hospital admission and lower frequency of return visits within 48 hours.
Ultrasound‐guided, Bougie‐assisted Cricothyroidotomy: A Description of a Novel Technique in Cadaveric Models
Authors: Curtis Keith , Ahern Matthew , Dawson Matthew , Mallin Michael
Published: June 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:876–879 © 2012 by the Society for Academic Emergency Medicine

Background:  Ultrasound (US) has well‐documented utility in critical procedures performed in the emergency department. It has been described as a “skill integral to the practice of emergency medicine” in the 2007 Model of Clinical Practice of Emergency Medicine. One of the ideal uses for US in critical care may be in the performance of emergent cricothyroidotomy. To the best of our knowledge there is currently no description of how to perform an US‐guided open cricothyroidotomy in the literature.

Objectives:  This study aimed to develop and describe an US‐guided technique for emergent open cricothyroidotomy and evaluate the time to completion and failure rate of this technique.

Methods:  This study was performed in a cadaver lab on 21 cadavers. The procedure was performed by two independent operators with US guidance using a linear transducer in the longitudinal orientation placed on the anterior midline of the neck. The cricothyroid membrane was incised with a No. 20 scalpel and a bougie with a coude tip was inserted into the trachea. A 6.0 endotracheal tube was then advanced over the bougie and the cuff was inflated. Endotracheal tube placement was confirmed by dissection. The procedure was timed to evaluate the length of time to identification of the cricothyroid membrane and completion of the procedure. There was no control group for this study.

Results:  There were 12 female and nine male cadavers. The mean body mass index (BMI) was 21.9 (range = 12.2 to 44.9). There was a median time to identification of the cricothyroid membrane of 3.6 seconds (interquartile range [IQR] = 1.9 to 15.3 seconds) and median time to completion of the procedure of 26.2 seconds (IQR = 10.7 to 50.7 seconds). The failure rate was 1 out of 21, with one incision placed between the cricoid cartilage and the first tracheal ring. In this case, the trachea was still cannulated. Similar completion times were obtained with high‐ and low‐BMI cadavers.

Conclusions:  Ultrasound‐guided bougie‐assisted cricothyroidotomy is a novel technique that may be beneficial in emergent open cricothyroidotomy. The data suggest that this technique is rapid, with a median time to completion of 26.2 seconds. The data also suggest that the procedure may have a low failure rate, with 20 of 21 cadavers undergoing successful cricothyroidotomy.
Insurance Status and the Care of Adult Patients 19 to 64 Years of Age Visiting the Emergency Department
Authors: Mannix Rebekah , Stack Anne M. , Chiang Vincent
Published: June 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:808–815 © 2012 by the Society for Academic Emergency Medicine

Objectives:  The objective was to determine whether insurance status is associated with the care of patients presenting to the emergency department (ED).

Methods:  This was a retrospective cross‐sectional analysis of ED visits using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS; 1999 through 2008). Patients 19 to 64 years of age were categorized as having private insurance, public insurance, or no insurance as their primary insurance. Six components of ED care were assessed: wait time, left prior to discharge, use of diagnostic testing, treatment, instructions for follow‐up, and whether the patient had been seen in the past 72 hours.

Results:  Nonprivate insurance status was associated with all six components of ED care, including higher proportions of leaving before discharge of patients with public insurance (4.1%, 95% confidence interval [CI] = 3.8% to 4.5%) versus patients with no insurance (4.7%, 95% CI = 4.2% to 5.1%) or private insurance (2.2%, 95% CI = 2.0% to 2.4%; p < 0.001). It was also associated with a higher proportion of return visits with 5.1% (95% CI = 4.6% to 5.6%) of patients with public insurance versus 4.7% (95% CI = 4.1% to 4.6%) of patients with no insurance versus 3.8% (95% CI = 3.5% to 4.2%) of patients with private insurance (p < 0.001). Patients with public or no insurance also had decreased odds of ED testing compared to those with private insurance (adjusted odds ratio [AOR] for public = 0.84, 95% CI = 0.80 to 0.88; and AOR for none = 0.82, 95% CI = 0.79 to 0.86).

Conclusions:  Nonprivate insurance status is associated with different care patterns in adults aged 19 to 64 years visiting the ED. Further studies are needed to evaluate how these disparate care patterns affect health outcomes.
Association between prolonged breast‐feeding and early childhood caries: a hierarchical approach
Authors: Nunes Ana Margarida Melo , Alves Claudia Maria Coelho , Borba de Araújo Fernando , Ortiz Tânia Mara Lopes , Ribeiro Marizélia Rodrigues Costa , Silva Antônio Augusto Moura da , Ribeiro Cecília Claudia Costa
Published: June 2012

Objectives

This study was conducted to investigate the association between prolonged breastfeeding and early childhood caries(ECC) with adjustment for important confounders, using hieraschical approach.

Methods

This retrospective cohort study involved 260 low‐income children (18–42 months). The number of decayed teeth was used as a measure of caries. Following a theoretical framework, the hierarchical model was built in a forward fashion, by adding the following levels in succession: level 1: age; level 2: social variables; level 3: health variables; level 4: behavioral variables; level 5: oral hygiene–related variables; level 6: oral hygiene quality measured by visible plaque; and level 7: contamination by mutans streptococci. Sequential forward multiple Poisson regression analysis was employed.

Results

Breast‐feeding was not a risk factor for ECC after adjustment for some confounders (incidence density ratio, 1.15; 95% confidence interval, 0.84–1.59, P = 0.363).

Conclusion

Prolonged breast‐feeding was not a risk factor for ECC while age, high sucrose comption between main meals and the quality of oral higiene were associated with disease in children.
Expression of cancer stem cell markers ALDH1 and Bmi1 in oral erythroplakia and the risk of oral cancer
Authors: Feng Jin‐Qiu , Xu Zi‐Yuan , Shi Lin‐Jun , Wu Lan , Liu Wei , Zhou Zeng‐Tong
Published: June 2012

J Oral Pathol Med (2013)42: 148–153

Background:  Oral erythroplakia (OE) is a notoriously aggressive oral pre‐malignant lesion with a high tendency to oral cancer development, but its biological behavior is largely unknown. The objective of this study was to determine the expression of cancer stem cell markers ALDH1 and Bmi1 in OE and their correlation with malignant transformation of OE.

Methods:  In a retrospective case–control study, expression patterns of ALDH1 and Bmi1 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n = 17) and patients with malignant transformed lesions (n = 17).

Results:  ALDH1 and Bmi1 expression was observed in 19 (55.9%) and 20 (58.8%) of 34 patients with OE, respectively. Multivariate analysis revealed that ALDH1 expression was significantly associated with increased risk of transformation (P < 0.05), but Bmi1 expression was not a significant marker (P > 0.05). Notably, the coexpression of both ALDH1 and Bmi1 was a strong indicator associated with 8.56‐fold (95% confidence interval [CI], 1.74–42.17; P < 0.01) for malignant transformation. Point prevalence analysis revealed that 78.6% (95% CI, 54.0–100) of the patient with coexpression of both ALDH1 and Bmi1 developed oral cancer.

Conclusion:  Our data indicated that the expression patterns of ALDH1 and Bmi1 in OE were associated with malignant transformation, suggesting that they may be valuable predictors for evaluating the risk of oral cancer.
Contemporary Spiritualities and Christianity: Is There an Authentic Christian Gnosis?
Authors: White Dominic
Published: June 2012

The growing non-religious spiritualities are markedly neo-Gnostic in their interest in cosmologies and their opposition to institutional religion. Gnostic cosmologies, specifically their teachings on the cosmic significance of the Cross, angelology and multiple heavens in fact all have counterparts in Irenaeus and Christian apocrypha. Clement of Alexandria asserts an authentic Christian gnosis communicated by Christ to Peter, James and John. The use of Richard Bauckham's “eyewitness” Biblical exegetical method shows that most of the Christian cosmological traditions can be credibly held as teachings of the apostles and “deepening” (Daniélou) interpretations of Scripture. Gnosticism appropriated but distorted them. The existence of an inner circle among the disciples, the patristic and liturgical traditions and the teachings of Paul indicate that for the early Church, gnosis was the Holy Spirit's gift of knowledge, God's knowledge of the cosmos. This knowledge could not be understood outside the Church. To enable application of Christian gnosis to dialogue with contemporary spirituality, renewal of Christian theology and practice in the light of the gnosis is proposed, particularly in the areas of liturgy, fundamental and natural theology and evangelisation.
Hans Urs von Balthasar and Adrienne von Speyr's Ecclesial Relationship
Authors: Sutton Matthew Lewis
Published: June 2012

Many systematic theologians acknowledge the relationship between Hans Urs von Balthasar, the significant twentieth‐century Catholic theologian, and Adrienne von Speyr, the Swiss physician and Catholic mystic. There is, however, difficulty understanding the actual character and purpose of this relationship. I argue in this paper that Paul's theology of charism, particularly dealing with double mission charisms, will help us understand correctly the ecclesial relationship between von Balthasar and von Speyr. After an overview of von Balthasar's statements regarding the relationship and the three main interpretations of it, I offer my own interpretation of this relationship by using Paul's theology of charism. The ramifications will be a reinterpretation of central aspects of von Balthasar's theology including but not limited to his theology of Holy Saturday, Trinitarian theology, and theology of the communion of saints.
A Determined and Subjective Love: Agreeing with Luther's Evangelical Reading of Hosea 2
Authors: Muhlhan Brett
Published: June 2012

A close reading of Hosea 2 seems to reveal some inconsistencies in a feminist approach to this particular text. This essay challenges a particular feministic reading of Hosea 2 with an analysis that contends for the hearing of Yahweh's voice as he addresses Israel with a determined and subjective love. The relationship between Hosea and Gomer is used by Yahweh as a sign-act and in no way should the psychology of Hosea and Gomer take centre stage in the reading of this text. When the text speaks, it reveals that Yahweh's love is enduring, proactive and emotional. It also sets the tone for how we may continue to understand the tension between command and promise which may give cause to reshape the responsibility of today's theologians and church leaders. Eventually this text rests on the promise of Yahweh, by way of command, that there will in fact be a great day of blessing to come for his people (Hos 1:11; 3:5).
Ecclesia de Trinitate
Authors: Dadosky John
Published: June 2012

This paper addresses the foundations of the Church systematically as it originates in the Triune God's plan of salvation. The Church is an extension of the missions of the Son and Spirit in history. Analogies are invoked to help ground the nature and the mission of the of the Church. The paper further explores the implications of Ecclesia de Trinitate in light of Vatican II, the visible and invisible missions of the Son and the Spirit, the role of Mary and the multi‐religious context.
Toward a Liturgical Existentialism
Authors: Rivera Joseph
Published: June 2012

A liturgical existentialism attempts to situate Christian spirituality in view of a post‐Heideggerian world. To this end, French phenomenologist Jean‐Yves Lacoste has undertaken what is perhaps the most sustained analysis of Heideggerian existential phenomenology from a theological‐mystical point of view, and this paper highlights his major achievement: the liturgical reduction. Certainly existentialism, after Heidegger, makes the “world” an object of inquiry, and yet Lacoste's reduction is problematic precisely because it privileges an ascetic spirituality that desires to “bracket” the world. Both the temporality and topology of the liturgical reduction are exposed to view in order to show that a liturgical existentialism properly conceived, does not bracket the world, but is realized carefully in and through the world‐horizon itself.
DISTINGUISHING FOUR TRADITIONAL VINEGARS BY SENSORY ANALYSIS AND COLORIMETRIC SENSORS
Authors: ZOU X.B. , SHI J.Y. , HAO L.M. , ZHAO J.W. , SUN Z.B. , HUANG X.Y.
Published: June 2012

The aim of this research was to use sensory analysis and colorimetric sensors to evaluate four Chinese traditional vinegars. Firstly, sensory analysis was performed by descriptive tests. An evaluation card for vinegar sensory analysis was set up. Four traditional vinegar groups can be clearly identified by sensory panelists from principal component analysis results. Secondly, 23 chemoresponsive dyes and seven pH dyes were selected, and a 5 × 6 colorimetric sensor array was used to measure the four traditional vinegars. With cluster analysis, all samples were assembled “Zhenjiang Vinegar,”“Shanxi Vinegar,”“Sichuan Vinegar” and “Zhejiang Vinegar” when the similarity was 12. Thirdly, the correlation between the sensory analysis and the colorimetric sensor analysis was taken into account. These works showed that sensory analysis and colorimetric sensor analysis were both good in identifying different vinegars although they did not correlate with each other.

PRACTICAL APPLICATIONS

An evaluation card was set up for sensory evaluation. Thirteen descriptive attributes belong to three distinct classes and their scores were first reported in this article. The evaluation card could be used for quality control of vinegar by sensory analysis in Vinegar Company in China. The colorimetric sensor array system which was set up in this article could also be used in the Chinese vinegar quality control. This article also gives an approach for studying the traditional food in China.
Discovering Novel α‐aminoacyl‐Containing Proline Derivatives with Potent and Selective Inhibitory Activity Against Dipeptidyl Peptidase IV: Design, Synthesis, Biological Evaluation, and Molecular Modeling
Authors: Zhang Xiaodong , Wang Jiang , Su Mingbo , Li Zeng , Li Jingya , Li Jia , Liu Hong
Published: June 2012

On the basis of the enzyme‐binding features of known potent inhibitors of dipeptidyl peptidase IV, novel α‐aminoacyl‐containing proline analogs (8Aa–8Ak, 8Ba–8Bj, 8Ca–8Ck, and 8Da–8Di) with the S configuration were designed, synthesized, and their activity profiled. Their structural features were determined by nuclear magnetic resonance (NMR) spectroscopy, low‐ and high‐resolution mass spectroscopy. Five compounds (8Aa, 8Aj, 8Ch, 8Ck, and 8Dc) were shown to have promising inhibitory activities against dipeptidyl peptidase IV. Two of them, compounds 8Aa and 8Aj inhibited dipeptidyl peptidase IV with IC50 values of 4.56 and 8.4 μm, respectively, and displayed no inhibition at other dipeptidyl peptidase IV. The possible binding modes of compounds 6, 7, 8Aa, and 8Aj with dipeptidyl peptidase IV were also explored by molecular docking simulation. This study provides promising new templates for the further development of antidiabetic agents.
Neoflavonoids and Tetrahydroquinolones as Possible Cancer Chemopreventive Agents
Authors: Luqman Suaib , Meena Abha , Singh Pragya , Kondratyuk Tamara P. , Marler Laura E. , Pezzuto John M. , Negi Arvind S.
Published: June 2012

Several lactone‐ and lactam‐based neoflavonoids and tetrahydroquinolones were synthesized and evaluated for cancer chemopreventive studies using cell and molecular target‐based in vitro bioassays, namely NFκB, aromatase, and quinone reductase 1. These analogs blocked TNF‐α‐induced NFκB activation in a dose‐dependent manner with IC50 values in the range of 0.11–3.2 μm. In addition, compound 8 inhibited aromatase activity with an IC50 value of 12.12 μm, and compound 10 affected quinone reductase 1 induction (IR, 3.6; CD, 19.57 μm). Neoflavonoids 8 and 10 exhibiting good results can further be optimized for improved therapeutic profiles. However, investigations into the actions of neoflavonoids and tetrahydroquinolones, especially those related to the NFκB signaling pathway, aromatase inhibition, induction of quinone reductase 1 expression, and in vivo studies could provide new insights into the cancer chemopreventive ability of these molecules.
The Effects of UV Emission from Compact Fluorescent Light Exposure on Human Dermal Fibroblasts and Keratinocytes In Vitro
Authors: Mironava Tatsiana , Hadjiargyrou Michael , Simon Marcia , Rafailovich Miriam H.
Published: June 2012

Compact fluorescent light (CFL) bulbs can provide the same amount of lumens as incandescent light bulbs, using one quarter of the energy. Recently, CFL exposure was found to exacerbate existing skin conditions; however, the effects of CFL exposure on healthy skin tissue have not been thoroughly investigated. In this study, we studied the effects of exposure to CFL illumination on healthy human skin tissue cells (fibroblasts and keratinocytes). Cells exposed to CFLs exhibited a decrease in the proliferation rate, a significant increase in the production of reactive oxygen species, and a decrease in their ability to contract collagen. Measurements of UV emissions from these bulbs found significant levels of UVC and UVA (mercury [Hg] emission lines), which appeared to originate from cracks in the phosphor coatings, present in all bulbs studied. The response of the cells to the CFLs was consistent with damage from UV radiation, which was further enhanced when low dosages of TiO2 nanoparticles (NPs), normally used for UV absorption, were added prior to exposure. No effect on cells, with or without TiO2 NPs, was observed when they were exposed to incandescent light of the same intensity.
Biodistribution and Pharmacokinetic Studies of a Porphyrin Dimer Photosensitizer (Oxdime) by Fluorescence Imaging and Spectroscopy in Mice Bearing Xenograft Tumors
Authors: Khurana Mamta , Ulrich Sébastien , Kim Anthony , Moriyama Yumi , Netchev George , Akens Margarete K. , Anderson Harry L. , Wilson Brian C.
Published: June 2012

Herein, we present a study of the pharmacokinetics and biodistribution of a butadiyne‐linked conjugated porphyrin dimer (Oxdime) designed to have high near‐infrared (NIR) 2‐photon absorption cross‐section for photodynamic therapy (PDT). Changes in biodistribution over time were monitored in mice carrying B16‐F10 melanoma xenografts, following intravenous injection. Using fluorescence imaging of live animals and analyzing isolated organs ex vivo at different time points between 30 min and 24 h after injection, accumulation of Oxdime was measured in several organs (heart, kidney and liver) and in tumor. The concentration in the plasma was about 5–10 times higher than in other tissues. The fluorescence signal peaked at 3–12 h after injection in most tissues, including the tumor and the plasma. The change in the fluorescence emission spectrum of the sensitizer over time was also monitored and a shift in the maximum from 800 to 740 nm was observed over 24 h, showing that the Oxdime is metabolized. Significant quantities accumulated in the tumor, indicating that this PDT sensitizer may be promising for cancer treatment.
Rates of assay success and genotyping error when single nucleotide polymorphism genotyping in non‐model organisms: a case study in the Antarctic fur seal
Authors: HOFFMAN J. I. , TUCKER R. , BRIDGETT S. J. , CLARK M. S. , FORCADA J. , SLATE J.
Published: June 2012

Although single nucleotide polymorphisms (SNPs) are increasingly being recognized as powerful molecular markers, their application to non‐model organisms can bring significant challenges. Among these are imperfect conversion rates of assays designed from in silico resources and the enhanced potential for genotyping error relative to pre‐validated, highly optimized human SNPs. To explore these issues, we used Illumina’s GoldenGate assay to genotype 480 Antarctic fur seal (Arctocephalus gazella) individuals at 144 putative SNPs derived from a 454 transcriptome assembly. One hundred and thirty‐five polymorphic SNPs (93.8%) were automatically validated by the program GenomeStudio, and the initial genotyping error rate, estimated from nine replicate samples, was 0.004 per reaction. However, an almost tenfold further reduction in the error rate was achieved by excluding 31 loci (21.5%) that exhibited unclear clustering patterns, manually editing clusters to allow rescoring of ambiguous or incorrect genotypes, and excluding 18 samples (3.8%) with unreliable genotypes. After stringent quality filtering, we also found a counter‐intuitive negative relationship between in silico minor allele frequency and the conversion rate, suggesting that some of our assays may have been designed from paralogous loci. Nevertheless, we obtained over 45 000 individual SNP genotypes with a final error rate of 0.0005, indicating that the GoldenGate assay is eminently capable of generating large, high‐quality data sets for non‐model organisms. This has positive implications for future studies of the evolutionary, behavioural and conservation genetics of natural populations.
Sexing the Sciuridae: a simple and accurate set of molecular methods to determine sex in tree squirrels, ground squirrels and marmots
Authors: GORRELL JAMIESON C. , BOUTIN STAN , RAVEH SHIRLEY , NEUHAUS PETER , CÔTÉ STEEVE D. , COLTMAN DAVID W.
Published: June 2012

We determined the sequence of the male‐specific minor histocompatibility complex antigen (Smcy) from the Y chromosome of seven squirrel species (Sciuridae, Rodentia). Based on conserved regions inside the Smcy intron sequence, we designed PCR primers for sex determination in these species that can be co‐amplified with nuclear loci as controls. PCR co‐amplification yields two products for males and one for females that are easily visualized as bands by agarose gel electrophoresis. Our method provides simple and reliable sex determination across a wide range of squirrel species.
Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors
Authors: Anforth Rachael , Tembe Varsha , Blumetti Tatiana , Fernandez‐Peñas Pablo
Published: June 2012

B‐RAF inhibitors (BRAFi) have been shown to improve rates of overall and progression‐free survival in patients with stage IV metastatic melanoma positive for the BRAF V600E mutation. However, the main drawback is the development of verrucal keratosis (hyperkeratotic papules with verruca‐like characteristics with benign histological findings) and cutaneous squamous cell carcinomas (cuSCC). We have found upstream mutations in RAS as well as PIK3CA in both verrucal keratosis and cuSCC. This suggests that verrucal keratosis is an early clinical presentation of cuSCC in patients on BRAFi.
Intraventricular pressure gradients throughout the cardiac cycle: effects of ischaemia and modulation by afterload
Authors: Guerra Miguel , Amorim Mário Jorge , Brás‐Silva Cármen , Leite‐Moreira Adelino F.
Published: June 2012

New Findings

What is the central question of this study?

The aim of the present study was to characterize the intraventricular pressure gradients (IVPGs) along the cardiac cycle, to correlate them with myocardial segmental asynchrony and to evaluate their response to regional myocardial ischaemia and ventricular afterload.

What is the main finding and its importance?

We showed the existence of diastolic and systolic IVPGs in the left ventricle (LV) and demonstrated for the first time that normal gradient pattern is related to physiological asynchrony between basal and apical myocardial segments. Moreover, we showed that IVPG, a marker of normal left ventricular function, can be attenuated, lost entirely, or even reversed after regional acute ischaemia and afterload elevations.

The aim of the present study was to characterize the intraventricular pressure gradients (IVPGs) througout the cardiac cycle, to correlate them with myocardial segmental asynchrony and to evaluate the effects of ischaemia and modulation by afterload. Open‐chest anaesthetized rabbits (n= 6) were instrumented with pressure‐tip micromanometers placed in the apex and outflow tract of the left ventricular (LV) cavity and with sonomicrometer crystals placed in the apex and base of the LV free wall to measure IVPGs and myocardial segment length changes during basal, afterloaded (aortic cross‐clamping) and ischaemic conditions (left anterior descending coronary artery ligation). During early diastole (rapid filling), we recorded an IVPG (4.6 ± 0.7 mmHg) from the cardiac base towards the apex followed by an apex‐to‐outflow pressure gradient (3.6 ± 0.2 mmHg). During systole, we recorded an IVPG (0.6 ± 0.1 mmHg) from apex to outflow during early rapid ejection, which inverted during late slow ejection. Interestingly, the maximal rate of LV pressure fall occurred earlier and relaxation rate was faster in the base than in the apex. While shortening of basal segments was complete at the end of ejection, apical segments always showed a significant amount of postsystolic shortening. The IVPGs were entirely lost during ischaemia and attenuated by afterload elevations. During ischaemia, systolic shortening of the apical segment decreased, while postsystolic shortening increased. The present study confirms the existence of diastolic and systolic IVPGs in the LV and demonstrates, for the first time, that this normal gradient pattern is related to physiological asynchrony between basal and apical myocardial segments. Moreover, we show that the IVPG, a marker of normal left ventricular function, can be attenuated, lost entirely or even reversed after regional acute ischaemia and afterload elevations.
Increased activity of the renin–angiotensin and sympathetic nervous systems is required for regulation of the blood pressure in rats fed a low‐protein diet
Authors: Gomide Joelma M. C. , de Menezes Rodrigo C. , Fernandes Luciano G. , Silva Fernanda C. , Cardoso Leonardo M. , Miranda Pedro H. , da Silva Jr Luiz Gonzaga , Lima Mercia P. , Pesquero Jorge L. , Foureaux Giselle , Ferreira Anderson J. , Chianca‐Jr Deoclécio A.
Published: June 2012

New Findings

What is the central question of this study?

Is the increase in blood pressure observed in rats fed a low protein diet due to overactivation of sympathetic and renin angiontensin systems?

What is the main finding and its importance?

The data show an increase in the expression of angiotensin II type 1 receptors and an incrased sympathetic activity in this experimental model, suggesting that both systems are contributing to the high blood pressure observed in these animals.

Previous studies have shown that postweaning protein restriction induces changes in the sympathetic nervous system in rats, leading to alterations in cardiovascular parameters. In addition, the renin–angiotensin system is also affected in these animals. Here, we hypothesized that adjustments in the interaction between the RAS and SNS underlie the cardiovascular adaptations observed in rats fed a low‐protein diet. Thus, we evaluated the alterations in the mean arterial pressure (MAP) and heart rate of Fisher rats fed a protein‐deficient diet before and after systemic administration of the angiotensin‐converting enzyme inhibitor enalapril and the angiotensin II (Ang II) type 1 (AT1) receptor antagonist losartan alone or in combination with the α1‐adrenergic receptor antagonist prazosin. Administration of enalapril or losartan decreased the MAP only of rats under protein restriction. Prazosin injection after the infusion of losartan caused a further decrease in the MAP of malnourished rats. In contrast, only the administration of prazosin elicited a reduction in the MAP of control animals. When the sequence of administration of the antagonists was inverted, infusion of prazosin in animals fed the standard or the low‐protein diet induced a reduction in the MAP that was further decreased by the subsequent injection of losartan. Importantly, in both protocols the responses of malnourished animals to losartan were markedly greater when compared with the control group. Moreover, these animals presented lower levels of circulating Ang II and a reduced responsiveness to Ang II. In contrast, the expression of AT1 receptors in the aorta of malnourished animals was increased. Thus, our data suggest that the renin–angiotensin system is an important factor supporting blood pressure in rats fed a low‐protein diet and that the sympathetic nervous system activity in these animals is under strong influence of Ang II acting via AT1 receptors.
Regulatory properties of O-acetyl-L-serine sulfhydrylase of Cephalosporium acremonium: evidence of an isoenzyme and its importance in cephalosporin C biosynthesis
Authors: Döbeli H , Nüesch J
Published: June 2012

O-Acetyl-L-serine sulfhydrylase catalyzes the final step in the biosynthesis of cysteine from H2S and O-acetyl-L-serine in the fungus Cephalosporsium acremonium, a cephalosporin C-producing organism. We separated this enzyme from the closely related but less specific O-acetyl-L-homoserine sulfhydrylase and showed that O-acetyl-L-homoserine sulfhydrylase also catalyzes the formation of cysteine from O-acetyl-L-serine and H2S. The expression of O-acetyl-L-serine sulfhydrylase was regulated by exogenous methionine. In addition, this enzyme was inhibited by S-adenosyl-L-methionine and 5-formylpteroyl monoglutamic acid. The inhibition of both S-adenosyl-L-methionine and 5-formylpteroyl monoglutamic acid was noncompetitive. Results obtained with gel filtraton experiments in various buffer systems indicate an association-dissociation behavior of O-acetyl-L-serine sulfhydrylase.
Plasmid-determined resistance to fosfomycin in Serratia marcescens
Authors: Mendoza C , Garcia J M , Llaneza J , Mendez F J , Hardisson C , Ortiz J M
Published: June 2012

Multiple-antibiotic-resistant strains of Serratia marcescens isolated from hospitalized patients were examined for their ability to transfer antibiotic resistance to Escherichia coli by conjugation. Two different patterns of linked transferable resistance were found among the transconjugants. The first comprised resistance to carbenicillin, streptomycin, and fosfomycin; the second, and more common, pattern included resistance to carbenicillin, streptomycin, kanamycin, gentamicin, tetracycline, chloramphenicol, sulfonamide, and fosfomycin. The two types of transconjugant strains carried a single plasmid of either 57 or 97 megadaltons in size. Both of these plasmids are present in parental S. marcescens strains resistant to fosfomycin. The 57-megadalton plasmid was transformed into E. coli.
How partially inhibitory concentrations of chloramphenicol affect the growth of Escherichia coli
Authors: Harvey R J , Koch A L
Published: June 2012

In the presence of up to 6 microM chloramphenicol, balanced exponential growth of Escherichia coli occurred at a reduced rate after an adjustment period. The inhibition of ribosome function by chloramphenicol within growing cells was inferred from measurements of growth rate and cell composition during balanced growth and of pulse-labeling of cells by radioactive proline after a 10-min exposure to chloramphenicol. In each case the results were consistent with simple noncompetitive inhibition of protein synthesis, with 50% inhibition occurring at 2 microM chloramphenicol, the concentration that gave 50% binding of chloramphenicol to purified ribosomes in vitro. The differences between these results and those obtained with cell-free protein synthesizing systems were shown to be in part due to slow binding of chloramphenicol and in part due to the slow rate and lack of saturation of the cell-free protein-synthesizing systems now available. During balanced growth in concentrations of chloramphenicol 1 microM or higher, the net rate of maturation of ribosomal ribonucleic acid was also inhibited (50% at 2.8 microM). The specific growth rate during balanced growth was inhibited by 50% at 1.8 microM chloramphenicol, but at higher concentrations inhibition was greater than expected from the simple noncompetitive dose-response observed for inhibition of polypeptide synthesis. However, the inhibition of maturation of ribosomal ribonucleic acid plus the inhibition of protein synthesis quantitatively accounted for the observed inhibition of growth. Thus, we have presented for the first time an essentially complete account of the effects of partially inhibitory concentrations of an antibiotic on the growth physiology of a bacterium.
Microbial transformation of N-methylcolchiceinamide
Authors: Davis P J
Published: June 2012

Seventy-seven microorganisms were examined for their ability to metabolize the antineoplastic agent N-methylcolchiceinamide, an analog of colchicine. Five streptomycetes exhibited significant metabolism, and Streptomyces griseus NRRL B-599 completely converted the substrate to three metabolites. In preparative-scale studies, N-dealkylation resulted in the production of colchiceinamide, the major metabolite (65%), which was characterized by chemical, spectroscopic, and chromatographic comparisons with the standard compound. Two phenolic metabolites resulting from )-dealkylation were also isolated and identified as 2 and 3-O-demethyl-N-methylcolchiceinamide.
Aminocyclitol-modifying enzymes specified by chromosomal genes in Staphylococcus aureus
Authors: Kayser F H , Homberger F , Devaud M
Published: June 2012

A genetic analysis of aminocyclitol resistance in two strains of Staphylococcus aureus was performed. Resistance of strain FK170, isolated in Zurich, was due to the production of a 3'-phosphotransferase [APH(3')]. Strain 5532, isolated in London, produced a 2"-phosphotransferase [APH(2")] and a 6'-N-acetyltransferase [AAC(6')]. Plasmid deoxyribonucleic acid (DNA) was isolated by isopycnic centrifugation from the two parent strains, as well as from susceptible variants and from resistant transductants of both strains. Comparative analysis of plasmid and from resistant transductants of both strains. Comparative analysis of plasmid DNA by centrifugation in sucrose gradients revealed that strain FK170 harbored a 2.7-megadalton tetracycline R-plasmid and a 36-megadalton cryptic plasmid. Strain 5532 contained an 18.5-megadalton penicillinase plasmid. No evidence for plasmid location of the markers for aminocyclitol resistance could be obtained.
In vitro and in vivo morphological response of Klebsiella pneumoniae to cefotiam and cefazolin
Authors: Nakao M , Nishi T , Tsuchiya K
Published: June 2012

The effect of cefotiam and cefazolin on the ultrastructure of Klebsiella pneumoniae DT-S in vitro and in experimental pneumonia in mice was examined by electron microscopy. The action of both cephalosporins against K. pneumoniae DT-S was bactericidal, and a dose response in the action was definite. At the minimal inhibitory concentration of each cephalosporin, filamentation of the cells was induced and the cytoplasm became sparse during the course of incubation. With elevation of the concentration of the cephalosporins, spheroplasts were formed; they subsequently collapsed. In the lungs of mice, the infecting organisms localized in the alveolar space, and each cell was connected by a threadlike material. A fibrous matrix, located on the cell surface of the infecting organisms, was observed in ultrathin sections. By administration of each cephalosporin to mice, several morphological changes, similar to those noted in vitro, were observed in the infecting organisms.
Occurrence of transposable trimethoprim resistance in clinical isolates of Escherichia coli devoid of self-transmissible resistance plasmids
Authors: Towner K J , Venning B M , Pinn P A
Published: June 2012

Fifty trimethoprim-resistant clinical isolates of Escherichia coli, devoid of self transmissible trimethoprim resistance plasmids, were examined for the presence of trimethoprim resistance transposons. Trimethoprim resistance was mobilized from 12 strains by transposition onto plasmid RP4. The trimethoprim resistance transposons isolated comprised two groups: those with and without linked streptomycin resistance.