bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of nucleotide excision repair and p53 in zidovudine (AZT)‐induced centrosomal deregulation
Authors: Momot Dariya , Nostrand Terri A. , John Kaarthik , Ward Yvona , Steinberg Seth M. , Liewehr David J. , Poirier Miriam C. , Olivero Ofelia A.
Published: July 2014

The nucleoside reverse transcriptase inhibitor zidovudine (AZT) induces genotoxic damage that includes centrosomal amplification (CA > 2 centrosomes/cell) and micronucleus (MN) formation. Here we explored these end points in mice deficient in DNA repair and tumor suppressor function to evaluate their effect on AZT‐induced DNA damage. We used mesenchymal‐derived fibroblasts cultured from C57BL/6J mice that were null and wild type (WT) for Xpa, and WT, haploinsufficient and null for p53 (6 different genotypes). Dose‐responses for CA formation, in cells exposed to 0, 10, and 100 μM AZT for 24 hr, were observed in all genotypes except the Xpa(+/+)p53(+/−) cells, which had very low levels of CA, and the Xpa(−/−)p53(−/−) cells, which had very high levels of CA. For CA there was a significant three‐way interaction between Xpa, p53, and AZT concentration, and Xpa(−/−) cells had significantly higher levels of CA than Xpa(+/+) cells, only for p53(+/−) cells. In contrast, the MN and MN + chromosomes (MN + C) data showed a lack of AZT dose response. The Xpa(−/−) cells, with p53(+/+) or (+/−) genotypes, had levels of MN and MN + C higher than the corresponding Xpa(+/+) cells. The data show that CA is a major event induced by exposure to AZT in these cells, and that there is a complicated relationship between AZT and CA formation with respect to gene dosage of Xpa and p53. The loss of both genes resulted in high levels of damage, and p53 haploinsufficicency strongly protected Xpa(+/+) cells from AZT‐induced CA damage. Environ. Mol. Mutagen. 55:719–726, 2014. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Targeting Perfectionism in Anorexia Nervosa Using a Group‐Based Cognitive Behavioural Approach: A Pilot Study
Authors: Lloyd Samantha , Fleming Caroline , Schmidt Ulrike , Tchanturia Kate
Published: July 2014

Objective

This study aimed to explore whether a six session cognitive behavioural group intervention targeting perfectionism is efficacious in reducing perfectionism in adults with anorexia nervosa in an inpatient setting.

Method

Adults with anorexia nervosa received a group perfectionism intervention in an inpatient setting. Self‐report and patient satisfaction questionnaires were completed at the beginning of the first session and end of the last session.

Results

Significant changes of moderate effect size were observed for overall perfectionism, concern over mistakes and personal standards dimensions of perfectionism following participation in the group. These changes were found to be independent of change in body mass index.

Conclusions

A group cognitive behavioural approach appears to be efficacious in reducing perfectionism in adults with anorexia nervosa. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
A cystoid with two left facets: the significance of Tetracystis in the evolution and classification of the Callocystitidae (Echinodermata, Glyptocystitoida)
Authors: Paul Christopher R. C.
Published: July 2014

Revision of some North American Silurian callocystitid cystoids shows that Tetracystis Schuchert has the first two brachioles to the left in ambulacra B and D (B D different pattern), whereas Troosticystis Paul and Lovenicystis Regéll have only the first brachiole to the left in all four ambulacra (B–E the same pattern). ‘Apiocystites’ elegans Hall is transferred to Tetracystis because it has the B D different pattern. Lovenicystis kopfi sp. nov. is characterized by four short ambulacra. Salirocystis gen. nov. has the B D different pattern and two hydropores. All callocystitids that lack ambulacrum A are assigned to a new subfamily, the Tetracystinae; those with five ambulacra are referred to informally as ‘lepadocystines’. The previously recognized subfamily Callocystitinae is reduced in rank to a tribe within the ‘lepadocystines’. Preliminary character analysis suggests that the loss of ambulacrum A was the most significant evolutionary event within the family Callocystitidae, but has been overlooked in taxonomy. Character analysis also shows that all ‘lepadocystines’ had the B D different pattern of primary brachioles, which is retained in four tetracystine genera, Lepocrinites Conrad, Sphaerocystites Hall, Tetracystis and Salirocystis. Since Salirocystis has the plesiomorphic B D different pattern plus the apomorphic double hydropore, one cannot define a monophyletic taxon characterized by the B–E the same pattern plus one characterized by a double hydropore. Both alternatives are equally parsimonious. Here a new monophyletic tribe Lipsanocystini is defined characterized by a double hydropore. The B–E the same pattern evolved independently twice. Among current characters the loss of ambulacrum A, development of the B–E the same pattern and development of two hydropores are the most significant evolutionary events. Number of periproct border plates, length and structure of ambulacra are less significant. Copyright © 2014 John Wiley & Sons, Ltd.
Polymorphisms in melanoma differentiation‐associated gene 5 link protein function to clearance of hepatitis C virus
Authors: Hoffmann Franziska S. , Schmidt Andreas , Dittmann Chevillotte Meike , Wisskirchen Christian , Hellmuth Johannes , Willms Simone , Gilmore Rachel H. , Glas Jürgen , Folwaczny Matthias , Müller Tobias , Berg Thomas , Spengler Ulrich , Fitzmaurice Karen , Kelleher Dermot , Reisch Nicole , Rice Charles M. , Endres Stefan , Rothenfusser Simon
Published: July 2014

Among patients newly infected with hepatitis C virus (HCV), only 20‐30% clear the infection spontaneously. In the remaining 70% the infection persists, causing chronic liver inflammation and disease. It is well established that polymorphisms in host genes, especially in components of the innate immune response, contribute to the phenomenon of spontaneous HCV clearance. Retinoic acid inducible gene‐I (RIG‐I)‐like helicases such as melanoma differentiation‐associated gene 5 (MDA‐5) are cytoplasmic sensors of viral RNA that are critical for triggering innate immune responses after infection with RNA viruses. We analyzed 14 nonsynonymous single‐nucleotide polymorphisms in RIG‐I‐like helicase‐pathway‐genes comparing European patients who spontaneously cleared HCV (n = 285) or had persistent infection (n = 509). We found that polymorphic haplotypes in the MDA‐5 gene IFIH1 encoding histidine at position 843 and threonine at position 946 strongly correlate with the resolution of HCV infection (odds ratio [OR]: 16.23; 95% confidence interval [CI]: 3.67‐71.87; P = 1.1 × 10−6). Overexpression of MDA‐5 genetic variants in HEK 293 cells and in a tissue culture model of HCV infection revealed that the histidine 843/threonine 946 variant leads to increased baseline and ligand‐induced expression of interferon‐induced genes and confers an increased ability to suppress HCV replication. Conclusion: These data suggest that MDA‐5 plays a significant role in the defense against HCV and that polymorphisms in MDA‐5 can influence the outcome of HCV infection. (Hepatology 2015;61:460‐470)
Bisphenol a regulates the estrogen receptor alpha signaling in developing hippocampus of male rats through estrogen receptor
Authors: Xu Xiao‐Bin , He Ye , Song Chen , Ke Xin , Fan Shi‐Jun , Peng Wei‐Jie , Tan Ruei , Kawata Mitsuhiro , Matsuda Ken‐Ichi , Pan Bing‐Xing , Kato Nobumasa
Published: July 2014

Bisphenol A (BPA), one of the most common environmental endocrine disruptors, has been recognized to have wide adverse effects on the brain development and behavior. These adversities are related to its ability to bind estrogen receptor (ER) with subsequent alteration of its expression in the target areas. However, very little is known about whether BPA exposure also affects ER phosphorylation and its translocation to nucleus during postnatal development, two critical steps for its function. Here, we found that during development from postnatal day 7 (P7) to P21, the alpha subtype of ER (ERα) in the hippocampus of male rats experienced remarkable alterations in terms of its expression, phosphorylation and translocation to nucleus. Exposure to low level of BPA had bidirectional, development‐dependent effects on the expression of ERα mRNA and protein, but decreased ERα phosphorylation and impaired its translocation to nucleus throughout the period investigated. Treatment with low dose of ICI 182,780 (ICI), an ER antagonist to block the binding of ER with BPA, reversed the altered ERα following BPA exposure, highlighting critical involvement of ER. Moreover, ICI treatment rescued the hippocampus‐dependent behavioral deficits in the adult rats experiencing early‐life BPA exposure. Overall, our results indicate that BPA interferes with the ERα signaling in the developing hippocampus in an ER‐dependent manner, which may underlie its adverse behavioral and cognitive outcomes in adult animals. © 2014 Wiley Periodicals, Inc.
CBFβ and the Leukemogenic Fusion Protein CBFβ‐SMMHC Associate With Mitotic Chromosomes to Epigenetically Regulate Ribosomal Genes
Authors: Lopez‐Camacho Cesar , van Wijnen Andre J. , Lian Jane B. , Stein Janet L. , Stein Gary S.
Published: July 2014

Mitotic bookmarking is an epigenetic control mechanism that sustains gene expression in progeny cells; it is often found in genes related to the maintenance of cellular phenotype and growth control. RUNX transcription factors regulate a broad spectrum of RNA Polymerase (Pol II) transcribed genes important for lineage commitment but also regulate RNA Polymerase I (Pol I) driven ribosomal gene expression, thus coordinating control of cellular identity and proliferation. In this study, using fluorescence microscopy and biochemical approaches we show that the principal RUNX co‐factor, CBFβ, associates with nucleolar organizing regions (NORs) during mitosis to negatively regulate RUNX‐dependent ribosomal gene expression. Of clinical relevance, we establish for the first time that the leukemogenic fusion protein CBFβ‐SMMHC (smooth muscle myosin heavy chain) also associates with ribosomal genes in interphase chromatin and mitotic chromosomes to promote and epigenetically sustain regulation of ribosomal genes through RUNX factor interactions. Our results demonstrate that CBFβ contributes to the transcriptional regulation of ribosomal gene expression and provide further understanding of the epigenetic role of CBFβ‐SMMHC in proliferation and maintenance of the leukemic phenotype. J. Cell. Biochem. 115: 2155–2164, 2014. © 2014 Wiley Periodicals, Inc.
Non‐Random Patterns in the Distribution of NOR‐Bearing Chromosome Territories in Human Fibroblasts: A Network Model of Interactions
Authors: Pliss Artem , Fritz Andrew J. , Stojkovic Branislav , Ding Hu , Mukherjee Lopamudra , Bhattacharya Sambit , Xu Jinhui , Berezney Ronald
Published: July 2014

We present a 3‐D mapping in WI38 human diploid fibroblast cells of chromosome territories (CT) 13,14,15,21, and 22, which contain the nucleolar organizing regions (NOR) and participate in the formation of nucleoli. The nuclear radial positioning of NOR‐CT correlated with the size of chromosomes with smaller CT more interior. A high frequency of pairwise associations between NOR‐CT ranging from 52% (CT13–21) to 82% (CT15–21) was detected as well as a triplet arrangement of CT15–21‐22 (72%). The associations of homologous CT were significantly lower (24–36%). Moreover, singular contacts between CT13–14 or CT13–22 were found in the majority of cells, while CT13–15 or CT13–21 predominantly exhibited multiple interactions. In cells with multiple nucleoli, one of the nucleoli (termed “dominant”) always associated with a higher number of CT. Moreover, certain CT pairs more frequently contributed to the same nucleolus than to others. This nonrandom pattern suggests that a large number of the NOR‐chromosomes are poised in close proximity during the postmitotic nucleolar recovery and through their NORs may contribute to the formation of the same nucleolus. A global data mining program termed the chromatic median determined the most probable interchromosomal arrangement of the entire NOR‐CT population. This interactive network model was significantly above randomized simulation and was composed of 13 connections among the NOR‐CT. We conclude that the NOR‐CT form a global interactive network in the cell nucleus that may be a fundamental feature for the regulation of nucleolar and other genomic functions. J. Cell. Physiol. 230: 427–439, 2015. © 2014 Wiley Periodicals, Inc.
Runx1 Activities in Superficial Zone Chondrocytes, Osteoarthritic Chondrocyte Clones and Response to Mechanical Loading
Authors: LeBlanc Kimberly T. , Walcott Marie E. , Gaur Tripti , O'Connell Shannon L. , Basil Kirti , Tadiri Christina P. , Mason‐Savas April , Silva Jason A. , van Wijnen Andre J. , Stein Janet L. , Stein Gary S. , Ayers David C. , Lian Jane B. , Fanning Paul J.
Published: July 2014

Runx1, the hematopoietic lineage determining transcription factor, is present in perichondrium and chondrocytes. Here we addressed Runx1 functions, by examining expression in cartilage during mouse and human osteoarthritis (OA) progression and in response to mechanical loading. Spared and diseased compartments in knees of OA patients and in mice with surgical destabilization of the medial meniscus were examined for changes in expression of Runx1 mRNA (Q‐PCR) and protein (immunoblot, immunohistochemistry). Runx1 levels were quantified in response to static mechanical compression of bovine articular cartilage. Runx1 function was assessed by cell proliferation (Ki67, PCNA) and cell type phenotypic markers. Runx1 is enriched in superficial zone (SZ) chondrocytes of normal bovine, mouse, and human tissues. Increasing loading conditions in bovine cartilage revealed a positive correlation with a significant elevation of Runx1. Runx1 becomes highly expressed at the periphery of mouse OA lesions and in human OA chondrocyte ‘clones’ where Runx1 co‐localizes with Vcam1, the mesenchymal stem cell (MSC) marker and lubricin (Prg4), a cartilage chondroprotective protein. These OA induced cells represent a proliferative cell population, Runx1 depletion in MPCs decreases cell growth, supporting Runx1 contribution to cell expansion. The highest Runx1 levels in SZC of normal cartilage suggest a function that supports the unique phenotype of articular chondrocytes, reflected by upregulation under conditions of compression. We propose Runx1 co‐expression with Vcam1 and lubricin in murine cell clusters and human ‘clones’ of OA cartilage, participate in a cooperative mechanism for a compensatory anabolic function. J. Cell. Physiol. 230: 440–448, 2015. © 2014 Wiley Periodicals, Inc.
Proteomic Characterization of Pig Sperm Anterior Head Plasma Membrane Reveals Roles of Acrosomal Proteins in ZP3 Binding
Authors: Kongmanas Kessiri , Kruevaisayawan Hathairat , Saewu Arpornrad , Sugeng Clarissa , Fernandes Jason , Souda Puneet , Angel Jonathan B. , Faull Kym F. , Aitken R. John , Whitelegge Julian , Hardy Daniel , Berger Trish , Baker Mark A. , Tanphaichitr Nongnuj
Published: July 2014

The sperm anterior head plasma membrane (APM) is the site where sperm first bind to the zona pellucida (ZP). This binding reaches the maximum following the sperm capacitation process. To gain a better understanding of the sperm‐ZP binding mechanisms, we compared protein profiles obtained from mass spectrometry of APM vesicles isolated from non‐capacitated and capacitated sperm. The results revealed that ZP‐binding proteins were the most abundant group of proteins, with a number of them showing increased levels in capacitated sperm. Blue native gel electrophoresis and far‐western blotting revealed presence of high molecular weight (HMW) protein complexes in APM vesicles of both non‐capacitated and capacitated sperm, but the complexes (∼750–1300 kDa) from capacitated sperm possessed much higher binding capacity to pig ZP3 glycoprotein. Proteomic analyses indicated that a number of proteins known for their acrosome localization, including zonadhesin, proacrosin/acrosin and ACRBP, were components of capacitated APM HMW complexes, with zonadhesin being the most enriched protein. Our immunofluorescence results further demonstrated that a fraction of these acrosomal proteins was transported to the surface of live acrosome‐intact sperm during capacitation. Co‐immunoprecipitation indicated that zonadhesin, proacrosin/acrosin and ACRBP interacted with each other and they may traffic as a complex from the acrosome to the sperm surface. Finally, the significance of zonadhesin in the binding of APM HMW complexes to pig ZP3 was demonstrated; the binding ability was decreased following treatment of the complexes with anti‐zonadhesin antibody. Our results suggested that acrosomal proteins, especially zonadhesin, played roles in the initial sperm‐ZP binding during capacitation. J. Cell. Physiol. 230: 449–463, 2015. © 2014 Wiley Periodicals, Inc.
Neoadjuvant Chemotherapy in Breast Cancer Patients Induces miR‐34a and miR‐122 Expression
Authors: Frères Pierre , Josse Claire , Bovy Nicolas , Boukerroucha Meriem , Struman Ingrid , Bours Vincent , Jerusalem Guy
Published: July 2014

Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti‐cancer drugs on their expression levels. In this article, we describe the modifications of circulating miRNAs profile after neoadjuvant chemotherapy (NAC) for breast cancer. The expression of 188 circulating miRNAs was assessed in the plasma of 25 patients before and after NAC by RT‐qPCR. Two miRNAs, miR‐34a and miR‐122, that were significantly increased after NAC, were measured in tumor tissue before and after chemotherapy in 7 patients with pathological partial response (pPR) to NAC. These two chemotherapy‐induced miRNAs were further studied in the plasma of 22 patients with adjuvant chemotherapy (AC) as well as in 12 patients who did not receive any chemotherapy. Twenty‐five plasma miRNAs were modified by NAC. Among these miRNAs, miR‐34a and miR‐122 were highly upregulated, notably in pPR patients with aggressive breast cancer. Furthermore, miR‐34a level was elevated in the remaining tumor tissue after NAC treatment. Studying the kinetics of circulating miR‐34a and miR‐122 expression during NAC revealed that their levels were especially increased after anthracycline‐based chemotherapy. Comparisons of the plasma miRNA profiles after NAC and AC suggested that chemotherapy‐induced miRNAs originated from both tumoral and non‐tumoral compartments. This study is the first to demonstrate that NAC specifically induces miRNA expression in plasma and tumor tissue, which might be involved in the anti‐tumor effects of chemotherapy in breast cancer patients. J. Cell. Physiol. 230: 473–481, 2015. © 2014 Wiley Periodicals, Inc.
Furin mediates brain‐derived neurotrophic factor upregulation in cultured rat astrocytes exposed to oxygen–glucose deprivation
Authors: Chen Yan , Zhang Junjian , Deng Min
Published: July 2014

This study investigated the changes in brain‐derived neurotrophic factor (BDNF) expression and the role of furin in BDNF maturation in reactive astrocytes from rats exposed to oxygen–glucose deprivation (OGD). Furin, a proprotein convertase, is upregulated and cleaves certain substrates during hypoxia in cancer cells. In addition, during hypoxia in the central nervous system, astrocytes become reactive and release BDNF to protect neurons. Maturation of BDNF in astrocytes requires furin‐mediated endoproteolytic processing of the precursor protein pro‐BDNF to BDNF. To expand our knowledge about the role of furin in BDNF maturation in astrocytes, these cells were exposed to OGD, and expression of furin and BDNF was detected by Western blot analysis. Changes in BDNF expression were observed when furin activity was inhibited by furin prosegment. We found that protein expression of BDNF and furin was upregulated, and this upregulation correlated with OGD stimulation. Furin inhibition reduced BDNF maturation and secretion. These results indicate that furin mediates the upregulation of BDNF in reactive astrocytes exposed to OGD and that furin may impact the biological effect of reactive astrocytes. © 2014 Wiley Periodicals, Inc.
TGF‐β signaling regulates fibrotic expression and activity in carpal tunnel syndrome
Authors: Gingery Anne , Yang Tai‐Hua , Passe Sandra M. , An Kai‐Nan , Zhao Chunfeng , Amadio Peter C.
Published: July 2014

Fibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of carpal tunnel syndrome (CTS). While the nature of CTS has been extensively studied, little is known about the etiology of this disease. We investigated SSCT tissue from patients with CTS and control subjects using fibrosis arrays and cell culture analysis. Twofold changes in fibrotic gene expression were found in multiple genes from patient SSCT using fibrosis arrays. This data was confirmed via qRT‐PCR on a subset of genes; collagen I (Col1), collagen III (Col3), connective tissue growth factor (CTGF), transforming growth factor β (TGF‐β), and SMAD3 (P < 0.05) which significantly corroborate the fold changes found in the fibrosis arrays. To further explore the nature of SSCT fibrosis, cells were isolated from patient and control tissue. Col1, Col3, TGF‐β, and SMAD3 were highly expressed in patient SSCT fibroblasts as compared to control (P < 0.05). Further, fibrotic genes expression was decreased by inhibiting TGF‐β receptor I (TβRI) activity (P < 0.05). TGF‐β second messenger SMAD activity was significantly activated in SSCT fibroblasts from patients and this activation was abrogated by inhibiting TβRI signaling (P < 0.05). These findings suggest that blocking TGF‐β signaling may be an important therapeutic approach to treating the underlying fibrosis of SSCT in CTS patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1444–1450, 2014.
A Longitudinal Investigation of Changes to Social Resources Associated With Psychological Distress Among Kurdish Torture Survivors Living in Northern Iraq
Authors: Hall Brian J. , Bonanno George A. , Bolton Paul A. , Bass Judith K.
Published: July 2014

Social resources can buffer against psychological distress following potentially traumatic events. Psychological distress can also lead to social resource deterioration. This longitudinal study evaluated whether baseline psychological distress symptoms and changes in these symptoms were associated with changes in social resources 5 months later among 96 adult male (52.6%) and female treatment‐seeking torture survivors residing in Kurdistan, Iraq. Adapted versions of the Hopkins Symptom Checklist‐25, Harvard Trauma Questionnaire, and a traumatic grief measure were used. Locally derived scales measured perceived social support, social integration, and frequency of social contact. Multinomial logistic regression models assessed the association between symptoms and loss or gain in social resources. We hypothesized that higher mental health symptoms would relate to decreased social resources. Higher baseline depression (adjusted conditional odds ratio [ACOR] = 1.14), posttraumatic stress disorder (PTSD; ACOR = 1.09), and traumatic grief symptoms (ACOR = 1.14) increased the odds of loss of social integration. For some, higher traumatic grief symptoms were associated with increased social integration (ACOR = 1.17). Increased anxiety (ACOR = 1.23) and PTSD symptoms (ACOR = 1.07) was associated with declines in social contact; decreased depression (ACOR = 1.06) and PTSD symptoms (ACOR = 1.04) were related to gaining social contact. This study highlights the complex relationship between mental health symptoms and losses and gains in social resources among torture survivors.
Effect of distractions on operative performance and ability to multitask—A case for deliberate practice
Authors: Ahmed Aadil , Ahmad Mueen , Stewart C. Matthew , Francis Howard W. , Bhatti Nasir I.
Published: July 2014

Objectives/Hypothesis

To measure the effect of distractions on the operative performance and analyze if practice and experience are the factors that can help to overcome the distractions.

Study Design

Prospective observational study.

Methods

Ten postgraduate year (PGY) 2‐6 residents and two faculty members from Johns Hopkins' otolaryngology department were recruited and asked to deepen the dissection at the sinodural angle on the Voxel‐man mastoidectomy simulator. They were asked to perform the task under four conditions: 1) no distractors, 2) differentiation and counting of a specific alarm sound among different sounds played in the background while performing the surgical task, 3) simultaneous performance of simple arithmetic task of moderate difficulty, and 4) simultaneous performance of the task with both sets of distractors combined.

Results

Time taken for the task (P = .02) and error scores (P = .002) increased under the third and fourth conditions. The ability to multitask and response to surgical and cognitive tasks improved with increasing level of experience of the participants.

Conclusions

Distractions lead to impaired dexterity and an increase in the incidence of errors. However, experience and deliberate practice can help achieve the ability to multitask without compromising the operative performance.

Level of Evidence

NA Laryngoscope, 125:837–841, 2015
Vascular patterns in mature hypertrophic burn scars treated with fractional CO2 laser
Authors: Connolly Karen L. , Chaffins Marsha , Ozog David
Published: July 2014

Background and Objective

Fractional CO2 laser has recently emerged as a promising therapeutic modality to improve the texture and appearance of burn scars. An issue in many burn scars is persistent erythema, which traditionally has been treated with vascular lasers. Interestingly, fractional CO2 lasers have been shown to improve the appearance of burn scars, including erythema, but no mechanism has been proposed for this change.

Our objective is to evaluate the histopathologic changes in vasculature in burn scars treated with fractionated CO2 laser, and to attempt to describe the mechanism behind reduced erythema following treatment.

Study Design/Materials and Methods

Uncontrolled, prospective study of ten patients with mature burn scars, from a clinical and histological perspective. Biopsy specimens were obtained before and 2 months after 3 treatment sessions. Anti‐CD31 immunostaining was performed to highlight vascular patterns in biopsy specimens.

Results

In histological analysis, an increase in vascular density, particularly of small caliber vessels, was seen following treatment, with an 82.6% average increase in vasculature (P = 0.028). This increase in vascularity correlated with a decrease in clinical erythema and vascularity scores, measured using the Vancouver Scar Scale.

Conclusion

Mature hypertrophic burn scars treated with a fractional CO2 laser showed a statistically significant increase in vascular density in the superficial dermis. A non‐statistical decrease in clinically perceived erythema and improvement of overall appearance was seen. To our knowledge, this is the first report of increased vascular density in burn scars treated with fractional CO2 laser and suggests our prior assumptions on causes of erythema in mature hypertrophic scars may need to be challenged. Lasers Surg. Med. 46:597–600, 2014. © 2014 Wiley Periodicals, Inc.
Vascularized bone transplant chimerism mediated by vascular endothelial growth factor
Authors: Willems Wouter F. , Larsen Mikko , Friedrich Patricia F. , Bishop Allen T.
Published: July 2014

Background

Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF‐treated bone allotransplants results from repopulation with circulation‐derived autogenous cells or survival of allogenic transplant‐derived cells.

Methods

Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1a) to male Piebald Viral Glaxo (PVG;RT1c). Arteriovenous bundle implantation and short‐term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection of bone remodeling areas was performed at the inner and outer cortex. Sex‐mismatched genes were quantified with reverse transcription‐polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER).

Results

At 4 weeks, rER was significantly higher at the inner cortex in VEGF‐treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF‐treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups.

Conclusions

These in vivo findings suggest a chemotactic effect of intramedullary applied VEGF on recipient‐derived bone and could imply that more rapid angiogenesis of vascularized allotransplants can be established with microencapsulated VEGF. © 2014 Wiley Periodicals, Inc. Microsurgery 35:45–51, 2015.
On the lorentzian versus Gaussian character of time‐domain spin‐echo signals from the brain as sampled by means of gradient‐echoes: Implications for quantitative transverse relaxation studies
Authors: Mulkern Robert V. , Balasubramanian Mukund , Mitsouras Dimitrios
Published: July 2014

Purpose

To determine whether Lorentzian or Gaussian intra‐voxel frequency distributions are better suited for modeling data acquired with gradient‐echo sampling of single spin‐echoes for the simultaneous characterization of irreversible and reversible relaxation rates. Clinical studies (e.g., of brain iron deposition) using such acquisition schemes have typically assumed Lorentzian distributions.

Theory and Methods

Theoretical expressions of the time‐domain spin‐echo signal for intra‐voxel Lorentzian and Gaussian distributions were used to fit data from a human brain scanned at both 1.5 Tesla (T) and 3T, resulting in maps of irreversible and reversible relaxation rates for each model. The relative merits of the Lorentzian versus Gaussian model were compared by means of quality of fit considerations.

Results

Lorentzian fits were equivalent to Gaussian fits primarily in regions of the brain where irreversible relaxation dominated. In the multiple brain regions where reversible relaxation effects become prominent, however, Gaussian fits were clearly superior.

Conclusion

The widespread assumption that a Lorentzian distribution is suitable for quantitative transverse relaxation studies of the brain should be reconsidered, particularly at 3T and higher field strengths as reversible relaxation effects become more prominent. Gaussian distributions offer alternate fits of experimental data that should prove quite useful in general. Magn Reson Med 74:51–62, 2015. © 2014 Wiley Periodicals, Inc.
Paradoxical effect of the signal‐to‐noise ratio of GRAPPA calibration lines: A quantitative study
Authors: Ding Yu , Xue Hui , Ahmad Rizwan , Chang Ti‐chiun , Ting Samuel T. , Simonetti Orlando P.
Published: July 2014

Purpose

Intuitively, GRAPPA auto‐calibration signal (ACS) lines with higher signal‐to‐noise ratio (SNR) may be expected to boost the accuracy of kernel estimation and increase the SNR of GRAPPA reconstructed images. Paradoxically, Sodickson and his colleagues pointed out that using ACS lines with high SNR may actually lead to lower SNR in the GRAPPA reconstructed images. A quantitative study of how the noise in the ACS lines affects the SNR of the GRAPPA reconstructed images is presented.

Methods

In a phantom, the singular values of the GRAPPA encoding matrix and the root‐mean‐square error of GRAPPA reconstruction were evaluated using multiple sets of ACS lines with variant SNR. In volunteers, ACS lines with high and low SNR were estimated, and the SNR of corresponding TGRAPPA reconstructed images was evaluated.

Results

We show that the condition number of the GRAPPA kernel estimation equations is proportional to the SNR of the ACS lines. In dynamic image series reconstructed with TGRAPPA, high SNR ACS lines result in reduced SNR if appropriate regularization is not applied.

Conclusion

Noise has a similar effect to Tikhonov regularization. Without appropriate regularization, a GRAPPA kernel estimated from ACS lines with higher SNR amplifies random noise in the GRAPPA reconstruction. Magn Reson Med 74:231–239, 2015. © 2014 Wiley Periodicals, Inc.
Boveri at 100: Theodor Boveri and genetic predisposition to cancer
Authors: Hansford Samantha , Huntsman David G
Published: July 2014

One hundred years have passed since the publication of Theodore Boveri's Zur Frage der Entstehung maligner Tumouren [Concerning the Origin of Malignant Tumours]. This prescient publication created the foundations for much of our understanding of the origins of cancer and in particular the genetic basis of some cancers. In his work, Boveri suggested that loss of key cellular attributes, now known as tumour suppressor genes, are a key driver event in the development of cancer and inheritance could play a role in cancer susceptibility. He also predicted that chromosomal (genomic) instability as a key hallmark of cancer. Whilst these key insights that still inform the practice of cancer genetics, they were not the main theme of Boveri's text, which was to describe the role of chromosomal abnormalities in the development of cancer. In making his case he also suggested that genetic information could be contained in distinct packages (genes) that are linearly arranged along chromosomes and that cancers arise from single cells. These remarkably accurate hypotheses add weight to the need to celebrate this landmark publication for its accurate prediction of so much that we take for granted. Here we focus on Boveri's contributions to our understanding of hereditary cancers, which, alongside the astute clinical observations of Paul Broca and Aldred Scott Warthin, were published decades before the field became respectable, yet could still inform anyone studying hereditary cancers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Discoidin domain receptor 2 (DDR2) promotes breast cancer cell metastasis and the mechanism implicates epithelial–mesenchymal transition programme under hypoxia
Authors: Ren Tingting , Zhang Wei , Liu Xinping , Zhao Hu , Zhang Jian , Zhang Jing , Li Xia , Zhang Yan , Bu Xin , Shi Man , Yao Libo , Su Jin
Published: July 2014

A wide range of genes involved in breast cancer metastasis have been reported to be related to the microenvironment. We studied the role of discoidin domain receptor 2 (DDR2), a collagen‐binding receptor, in breast cancer progression under hypoxic conditions. We showed that DDR2 protein expression closely correlated with the expression of hypoxic marker HIF‐1α in clinical breast cancer specimens. The in vitro data demonstrated that hypoxia treatment increased the levels of both expression and phosphorylation of DDR2 in human breast cancer cell lines. In vivo, orthotopic breast tumour xenografts with DDR2 knockdown displayed reduced dissemination and significant prevention in pulmonary and lymphatic metastasis; conversely, these processes were significantly facilitated by the enforced expression of the activated form of DDR2. Further mechanism studies indicated that DDR2 plays an indispensable role in a series of hypoxia‐induced behaviours of breast cancer cells, including migration, invasion, and epithelial–mesenchymal transition (EMT). The transcription factor Snail was found to mediate DDR2‐induced down‐regulation of the cell–cell adhesion molecule E‐cadherin. It was also documented that there is a correlation between DDR2 and E‐cadherin expression with the presence of lymph node metastases in 160 cases of invasive human breast carcinoma. In addition, we provided evidence that DDR2 silencing in breast cancer cells prevents the hypoxia‐induced activation of ERK MAPK, suggesting its potential involvement in mediating the effect of DDR2 on hypoxia‐induced signalling. Based on the results of this study, we conclude that DDR2 participates in hypoxia‐induced breast cancer metastasis through the regulation of cell migration, invasion, and EMT, and thus may serve as an accessible therapeutic target for the treatment of breast cancer.Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Remaining Useful Life Estimation for Systems with Time‐varying Mean and Variance of Degradation Processes
Authors: Zhang Jian‐xun , Hu Chang‐hua , Si Xiao‐sheng , Zhou Zhi‐jie , Du Dang‐bo
Published: July 2014

This paper focuses on the problem of how to estimate remaining useful life (RUL) for a class of systems with high fluctuating dagradation caused by time‐varying mean and variance. In engineering practice, the fluctuation of the degradation data can reflect the system stability, and hence it can serve as an additional indicator for the system's health state in addition to the degradation observations. To estimate the RUL for this class of systems, three issues should be considered jointly: (i) how to model the degradation data with high fluctuation, (ii) how to define an indicator denoting the fluctuation's level, and (iii) how to combine the degradation path and the fluctuation for the RUL estimating task. In responses to the above issues, this paper characterizes the degree of the fluctuation by the standard deviation of the stochastic degradation process and defines the standard deviation as an additional performance variable. Moreover, a stochastic degradation model is proposed to reflect the high fluctuating degradation data, in which the standard deviation is time dependent. To obtain the marginal distribution of the RUL derived by the standard deviation, the failure threshold of the standard deviation is given according to its influence on the degradation process. Another marginal distribution derived by the degradation data is also obtained by the time distribution of the degradation process crossing the degradation threshold. Then, through deriving the correlation between the two marginal distributions based on the probability theory, the joint distribution of the RUL is obtained. Finally, a practical case study for gyro is conducted. The results demonstrate the feasibility and applicability of the proposed model. Copyright © 2014 John Wiley & Sons, Ltd.
Incorporating sustainable development principles into building design: a review from a structural perspective including case study
Authors: Miller Dane , Doh Jeung‐Hwan
Published: July 2014

The incorporation of sustainable development (SD) principles into all industries is increasingly important. The contribution of the building industry to a wide range of environmental impacts is extensive with the construction, operation and maintenance of buildings accounting for approximately 50% of all energy usage and anthropogenic greenhouse gas (GHG) emissions globally. In the building design process, structural engineers play a limited role in the sustainability of a design. The decisions on the incorporation of such aspects are usually at the mercy of the architect and client. A literature review was conducted to record and present the variability in research on issues directly related to the environmental performance of structures. There are inconsistencies in the published contribution of embodied energy (EE) and proportion of life cycle energy usage in structures. Outcomes demonstrate that due to this variability, environmental performance of structures is difficult to validate. A systematic approach beginning with standardized calculation procedure and database generation for EE of building materials is essential for practitioners to deliver sustainable structural designs. An analysis of a typical concrete office structure indicates potential benefits through the use of quantifiable environmental performance measures, delivering efficient solutions. Comparisons of slab construction techniques indicate overall EE reductions up to 40% being achievable. Copyright © 2014 John Wiley & Sons, Ltd.
Thinking outside the box: A review of artificial roosts for bats
Authors: Mering Elisabeth D. , Chambers Carol L.
Published: July 2014

Artificial roosts designed to attract bats have been used to increase populations, aid seed dispersal, and control insects. More important from a conservation perspective, artificial roosts provide habitat where natural roosts have been lost. Although artificial roosts have been widely used, much of the information on species that use artificial roosts, roost design, and placement is anecdotal and poorly reported. We reviewed the existing literature on artificial roosts to summarize current research and inform research and management decisions. From 47 publications and reports, we identified 48 types of structures used by 59 species. Roosts were constructed from wood (66.7%), concrete (8.3%), or other materials (25.0%) and varied in size and shape from small‐volume wood boxes (0.002 m3) to large (6 m tall) free‐standing structures. Variables most often considered in the context of attracting bats were aspect, substrate, and mount location; few studies measured height or microclimate. Colonization rates ranged from 7% to 100%. Bats commonly used structures as solitary (21 species) or social (breeding or maternity; 21 species) roosts. Most species documented to use artificial roosts are vespertilionids (73%), have the International Union for Conservation of Nature's designation of least concern (93%), and roost in tree cavities or buildings. Three species are designated as endangered (Myotis sodalis) or near threatened (M. bechsteinii, M. dasycneme). Artificial roosts should be constructed and installed to mimic natural roosts, emphasize requirements of target species, and exclude non‐target species. Monitoring species composition and identifying effects of roost density will help determine conservation impacts of artificial roosts. © 2014 The Wildlife Society.
Performance feedback in the audit environment: A review and synthesis of research on the behavioral effects✩
Authors: Andiola Lindsay M.
Published: July 2014

This paper synthesizes the extant feedback literature, focusing on how feedback affects an auditor’s learning, performance, and motivation. Performance feedback is an important component in the auditing environment for ensuring quality control and for developing and coaching staff auditors. However, the literature on feedback in the audit environment is fragmented and limited making it difficult to assess its behavioral effects on auditors. This paper has three main objectives. The first is to review some of the influential research in psychology and management to identify key variables and issues that appear to be critical in the study of behavioral consequences of feedback in organizational settings. The second is to review performance feedback research specifically in auditing to identify the areas previously examined and synthesize the findings. The third is to suggest a variety of future research opportunities that may assist in developing an understanding and knowledge of the behavioral effects of feedback on auditors. The literature analysis has significant implications for audit research and practice. In particular, the analysis provides important insights into understanding who, how, and when performance feedback should be given to improve its effectiveness in the audit environment.
Outcome of pregnancy following second‐ or third‐trimester intrauterine fetal death
Authors: Maignien Chloé , Nguyen Amélie , Dussaux Chloé , Cynober Evelyne , Gonzales Marie , Carbonne Bruno
Published: July 2014

Objective

To investigate the outcomes of a pregnancy after a second‐ or third‐trimester intrauterine fetal death (IUFD).

Methods

A prospective observational study was conducted at Trousseau Hospital (Paris, France) between 1996 and 2011. The first ongoing pregnancy in women who had had a previous IUFD was monitored. Management of their treatment was according to a standardized protocol. Recurrence of fetal death was the main outcome criterion.

Results

The subsequent pregnancies of 87 women who had experienced at least one previous IUFD were followed up. The cause of previous IUFD was placental in 50 (57%) women, unknown in 19 (22%), adnexal in 12 (14%), metabolic in 2 (2%), and malformative in 4 (5%). Three (3%) participants had another stillbirth. Overall, obstetric complications occurred in 34 (39%) pregnancies (including 22 [25%] preterm births, 5 [6%] small for gestational age, and 6 [7%] maternal vascular complications). Obstetric complications were significantly more common among women whose previous stillbirth had been due to placental causes than among those affected by other causes (P = 0.02).

Conclusion

Most pregnancies after IUFD resulted in a live birth; however, adverse obstetric outcomes were more common when the previous stillbirth was due to placental causes.
Individual differences in interpersonal touch: On the development, validation, and use of the “comfort with interpersonal touch” (CIT) scale
Authors: Webb Andrea , Peck Joann
Published: July 2014

This research details the development of the “comfort with interpersonal touch” (CIT) scale designed to measure individual differences in interpersonal touch tendencies and preferences. The CIT construct is defined as the degree to which an individual is comfortable with intentional interpersonal touch from or to another person. The scale incorporates the distinction between initiating touch, which is the act of touching someone else, and receiving touch, which is the act of being touched by someone else. Investigation of this construct includes scale development, measure purification, and validation. We situate CIT‐initiating and CIT‐receiving within an approach–avoidance framework and demonstrate that comfort with initiating touch is more related to approach tendencies such as assertiveness while comfort with receiving touch is more related to avoidant tendencies such as avoiding crowded spaces. While previous research generally finds positive effects of interpersonal touch, we find that these effects, at least in part, depend on an individual's comfort with interpersonal touch. We discuss theoretical and managerial implications as well as future research opportunities using the CIT scale.