bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1
Authors: Yang Shen-Hsi , Sharrocks Andrew D.
Published: August 2015

The ETS-domain transcription factor Elk-1 is regulated by phosphorylation in response to activation of the MAPK (mitogen-activated protein kinase) pathways. This phosphorylation triggers a series of molecular events that convert Elk-1 from a transcriptionally silent state into a highly active state and then back to a basal level. At the same time, activation of the ERK (extracellular-signal-regulated kinase) MAPK pathway leads to loss of modification of Elk-1 by SUMO (small ubiquitin-related modifier). As SUMO imparts repressive properties on Elk-1, ERK-mediated SUMO loss leads to de-repression at the same time as the ERK pathway promotes activation of Elk-1. Thus a two-step mechanism is employed to convert Elk-1 into its fully activated state. Here, the molecular events underlying these changes in Elk-1 status, and the role of PIASxα [protein inhibitor of activated STAT (signal transducer and activator of transcription) xα] as a co-activator that facilitates this process, are discussed.
Substrate specificity and acute regulation of the tumour suppressor phosphatase, PTEN
Authors: Downes C. Peter , Perera Nevin , Ross Sarah , Leslie Nick R.
Published: August 2015

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumour suppressor that functions as a PtdIns(3,4,5)P3 3-phosphatase to inhibit cell proliferation, survival and growth by antagonizing PI3K (phosphoinositide 3-kinase)-dependent signalling. Recent work has begun to focus attention on potential biological functions of the protein phosphatase activity of PTEN and on the possibility that some of its functions are phosphatase-independent. We discuss here the structural and regulatory mechanisms that account for the remarkable specificity of PTEN with respect to its PtdIns substrates and how it avoids the soluble headgroups of PtdIns that occur commonly in cells. Secondly we discuss the concept of PTEN as a constitutively active enzyme that is subject to negative regulation both physiologically and pathologically. Thirdly, we review the evidence that PTEN functions as a dual specificity phosphatase with discrete lipid and protein substrates. Lastly we present a current model of how PTEN may participate in the control of cell migration.
PtdIns5P: a little phosphoinositide with big functions?
Authors: Coronas Sophie , Ramel Damien , Pendaries Caroline , Gaits-Iacovoni Frédérique , Tronchère Hélène , Payrastre Bernard
Published: August 2015

Phosphoinositides are minor constituents of cell membranes playing a critical role in the regulation of many cellular functions. Recent discoveries indicate that mutations in several phosphoinositide kinases and phosphatases generate imbalances in the levels of phosphoinositides, thereby leading to the development of human diseases. Although the roles of phosphoinositide 3-kinase products and PtdIns(4,5)P2 were largely studied these last years, the potential role of phosphatidylinositol monophosphates as direct signalling molecules is just emerging. PtdIns5P, the least characterized phosphoinositide, appears to be a new player in cell regulation. This review will summarize the current knowledge on the mechanisms of synthesis and degradation of PtdIns5P as well as its potential roles.
Plant steroid hormones
Authors: GEUNS JAN M. C.
Published: August 2015

After a brief survey of the literature on the recently discovered brassinolide, some of our results with corticosteroids are given. A number of structural requirements of corticosteroids were deduced in a bioassay involving elongation growth and lateral root formation. To explain the activity of glucocorticoids, the involvement of a receptor protein is suggested as well as an enhanced RNA synthesis. However, the structural requirements found are not applicable to experiments on adventitious root formation, implying a different mode of action of corticosteroids in this test system.
Biosynthesis of abscisic acid
Authors: HORGAN R. , NEILL S. J. , WALTON D. C. , GRIFFIN D.
Published: August 2015

The fungus Cercospora rosicola has been studied as a model system for abscisic acid biosynthesis. 1′-Deoxyabscisic acid and 4′-hydroxy-α-ionylidene acetic acid have been identified as endogenous compounds in this fungus. The results of feeding these and other putative intermediates suggest that abscisic acid biosynthesis proceeds via the successive oxidations of a 3 -methyl- 5 - (2′,6′,6′- trimethylcyclohex-2′-en-1′-yl)- 2,4-pentadienyl intermediate. Preliminary results suggest that a similar pathway may operate in plants.
Sex equity in French newspaper photographs: A content analysis of 2012 Olympic Games by L'Equipe
Authors: Delorme Nicolas , Testard Nadège
Published: August 2015

The aim of this article was to examine sex equity in the photographic coverage of the London 2012 Olympic Games by a French sports daily newspaper. A sample of 1073 photographs was collected and analysed. A content analysis was carried out focusing on the number of photographs, the space they cover, their location and position, the type and colour of shot and the sport they depict. A significant under‐representation of female athletes’ photographs was found. However, contrary to most of previous research in this field, the other quantitative and qualitative variables do not show any differences. Furthermore, a significant positive correlation between the number of photographs for each sport and the number of French medals was found (for women, for men and for the whole sample), suggesting that the photographic coverage of this event is mainly based on the success of French athletes independently of their sex.
Does social capital enhance political participation of older adults? A multi-level analysis of older Finns and Swedes
Authors: Nygård Mikael , Nyqvist Fredrica , Steenbeek Wouter , Jakobsson Gunborg
Published: August 2015

This article contributes to the literature on political gerontology by analysing the role that social capital plays in the political participation of older adults. More specifically, the aim is to test the importance of individual-level and contextual-level social capital for different types of political participation of older adults in a Scandinavian setting by using survey data from Finland and Sweden (N= 6838). The results show that even though membership in voluntary associations, intense social networks and high levels of interpersonal trust tend to be positively correlated with political participation of older adults as a whole, the explanative logic differs between them depending on the kind of political engagement. The only type of social capital with a robust positive impact on all dimensions of political participation was individual-level membership in voluntary associations.
Politicization and the Two Modes of Evaluating Judicial Decisions
Authors: Woodson Benjamin
Published: August 2015

Since courts lack control of the purse and the sword, understanding what causes the public to accept court decisions is essential. Using three studies, this paper shows that the public’s perception of the process judges use to make decisions changes the determinants of acceptance. When judges are perceived as using a principled decision-making process, institutional loyalty determines acceptance. When judges are perceived as using a politicized decision-making process, agreement with the policy implications of a decision determines acceptance. These results emphasize the importance of decision-making process perceptions in ensuring that courts can induce voluntary acceptance of their decisions.
Partnering for real world learning, sustainability, tourism education
Authors: Jennings Gayle , Cater Carl I. , Hales Rob , Kensbock Sandra , Hornby Glen
Published: August 2015

Purpose

– The purpose of this article is to study how real world learning was used to engender and enhance sustainability principles and practices with 11 micro-, small- and medium-tourism business enterprises and 101 university tourism students enrolled across three university courses.

Design/methodology/approach

– Action research processes were used to focus curricula on “education about and for sustainability”. A participatory paradigm informed the action research processes. The key methodology was qualitative. Empirical materials were generated through lived experiences, reflexive team conversations, team journals, reflexive journals and student learning materials. Reflexive conversations and reflective dialogue framed interpretations.

Findings

– The action research process found that pedagogies, andragogies and ethnogogies that emphasize social processes of meaning making and sensemaking enhance and engender “education about sustainability” and “education for sustainability”, especially when coupled with real world learning as a platform for social and profession-building processes between university students, course teaching staff and industry, in this case, micro-, small- and medium-tourism entrepreneurs.

Research limitations/implications

– The qualitative findings of this action research study are specific to the participants involved. Generalizability to other university and business settings and goodness of fit require further study.

Practical implications

– Insights are provided with regard to implementing real world learning in university undergraduate and postgraduate courses by partnering with industry and focusing on education for sustainability (EfS). A demonstration of the effectiveness of action research as a tool for changing curricula is provided.

Social implications

– Learning is a social process of meaning making. Time for real world social interaction is critical for learning. Partnering with industry complements student learning and facilitates the translation of theory into practice.

Originality/value

– EfS is engendered and enhanced when learning-teaching engagements are predicated on real world settings, circumstances and experiences.
Mercury exposure, stress and prolactin secretion in an Arctic seabird: an experimental study
Authors: Tartu Sabrina , Bustamante Paco , Angelier Frédéric , Lendvai Ádám Z. , Moe Børge , Blévin Pierre , Bech Claus , Gabrielsen Geir W. , Bustnes Jan Ove , Chastel Olivier
Published: August 2015

Life‐history theory predicts that long‐lived organisms should reduce parental effort under inclement environmental conditions in order to favour long‐term survival.

Seabirds are long‐lived top predators often exposed to environmental endocrine disrupting chemicals such as mercury (Hg). Hg‐contaminated birds show disrupted parental behaviour.

Avian parental behaviour is governed by two key hormones in birds: corticosterone (CORT, a glucocorticoid hormone) and prolactin (PRL, a pituitary hormone involved in parental care). Any disruption of these hormones may alter the ability of an individual to adjust parental behaviour to environmental conditions.

The first aim of this study was to describe the relationships between blood Hg concentrations, plasma PRL and reproductive performance in Arctic black‐legged kittiwakes (Rissa tridactyla). We a found negative relationship between plasma initial PRL and blood Hg concentrations in males. Moreover, Hg concentration was negatively related to breeding success in chick‐rearing males.

Secondly, to study the effect of a chronic increase in CORT levels on the Hg–PRL relationship, we experimentally increased stress with CORT pellet implantation. We predicted that Hg and CORT would act synergistically on PRL and an increase in CORT concentration would steepen the Hg–PRL relationship. However, adding CORT did not steepen the Hg–PRL relationship. Hatching success was significantly lower in CORT‐implanted males than in controls, and breeding success was not reduced in CORT‐implanted male kittiwakes with high levels of blood Hg.

Our results suggest that Hg may impair reproductive performance through a disruption of PRL secretion. Contrary to our prediction, Hg and CORT did not act synergistically and the underlying mechanisms associating CORT and Hg with PRL might be more complex than a single interaction between two factors.
Secondary health conditions experienced by people with spinal cord injury within community living: Implications for a National Disability Insurance Scheme
Authors: Callaway Libby , Barclay Linda , McDonald Rachael , Farnworth Louise , Casey Jackie
Published: August 2015

Background

Australia's National Disability Insurance Scheme (NDIS) provides supports for individuals, delivered through a personalised participant planning process, to influence choice and goal attainment.

Aim

This study aimed to use both quantitative and qualitative methods to examine the impact of secondary health conditions on the experiences of people with spinal cord injury (SCI) who have returned to community living, in the context of Australia's National Disability Strategy and recently launched NDIS. Exploration of lived experience of health conditions following SCI utilising this mixed methods approach may offer important insights for effective planning within an NDIS.

Methods

A cross‐sectional survey using the Spinal Cord Injury Secondary Conditions Scale (SCISCS), demographic questionnaire and in‐depth interview was undertaken with 33 people with SCI living in the community. Demographic and SCISCS data were reported using descriptive statistics. Interviews were audio‐taped, transcribed and analysed thematically.

Results

Participants were on average 58.5 years of age and 20 years post‐injury. Five key themes emerged relating to (i) spasm and pain; (ii) sexual dysfunction; (iii) pressure areas; (iv) fatigue; and (v) the impact of secondary health conditions on life role participation and choice of supports and equipment.

Conclusion

Secondary health conditions can significantly impact occupational participation following SCI. Appropriate intervention, including customised equipment and direct support, if delivered as part of an effective NDIS, may prevent or reduce the severity of these conditions and offer the potential to influence health and participation outcomes of people who have returned to community living.
Financial Strain and Medication Adherence among Diabetes Patients in an Integrated Health Care Delivery System: The Diabetes Study of Northern California (DISTANCE)
Authors: Lyles Courtney R. , Seligman Hilary K. , Parker Melissa M. , Moffet Howard H. , Adler Nancy , Schillinger Dean , Piette John D. , Karter Andrew J.
Published: August 2015

Objective

To examine self‐reported financial strain in relation to pharmacy utilization adherence data.

Data Sources/Study Setting

Survey, administrative, and electronic medical data from Kaiser Permanente Northern California.

Study Design

Retrospective cohort design (2006, n = 7,773).

Data Collection/Extraction Methods

We compared survey self‐reports of general and medication‐specific financial strain to three adherence outcomes from pharmacy records, specifying adjusted generalized linear regression models.

Principal Findings

Eight percent and 9 percent reported general and medication‐specific financial strain. In adjusted models, general strain was significantly associated with primary nonadherence (RR = 1.37; 95 percent CI: 1.04–1.81) and refilling late (RR = 1.34; 95 percent CI: 1.07–1.66); and medication‐specific strain was associated with primary nonadherence (RR = 1.42, 95 percent CI: 1.09–1.84).

Conclusions

Simple, minimally intrusive questions could be used to identify patients at risk of poor adherence due to financial barriers.
Modeling Area‐Level Health Rankings
Authors: Courtemanche Charles , Soneji Samir , Tchernis Rusty
Published: August 2015

Objective

Rank county health using a Bayesian factor analysis model.

Data Sources

Secondary county data from the National Center for Health Statistics (through 2007) and Behavioral Risk Factor Surveillance System (through 2009).

Study Design

Our model builds on the existing county health rankings (CHRs) by using data‐derived weights to compute ranks from mortality and morbidity variables, and by quantifying uncertainty based on population, spatial correlation, and missing data. We apply our model to Wisconsin, which has comprehensive data, and Texas, which has substantial missing information.

Data Collection Methods

The data were downloaded fromwww.countyhealthrankings.org.

Principal Findings

Our estimated rankings are more similar to theCHRs for Wisconsin than Texas, as the data‐derived factor weights are closer to the assigned weights for Wisconsin. The correlations between theCHRs and our ranks are 0.89 for Wisconsin and 0.65 for Texas. Uncertainty is especially severe for Texas given the state's substantial missing data.

Conclusions

The reliability of comprehensiveCHRs varies from state to state. We advise focusing on the counties that remain among the least healthy after incorporating alternate weighting methods and accounting for uncertainty. Our results also highlight the need for broader geographic coverage in health data.
Globus Pallidus Necrosis Unrelated to Carbon Monoxide Poisoning: Retrospective Analysis of 27 Cases of Basal Ganglia Necrosis
Authors: Yarid Nicole A. , Harruff Richard C.
Published: August 2015

Bilateral globus pallidus necrosis is said to be characteristic of carbon monoxide (CO) poisoning. However, there has been no scientific test of this hypothesis. To examine the assertion that globus pallidus necrosis is typical of CO poisoning, this study examined autopsy cases from the King County Medical Examiner's Office (KCMEO) between 1994 and 2013. Twenty‐seven cases with bilateral basal ganglia lesions were identified and examined for associated or causative disease or injury with the following results: 10 cases of drug overdose, seven heart disease, three asphyxia, two chronic ethanolism, two Huntington‐like disorder, and one case each of remote trauma, rheumatic heart disease, and cerebral artery gas embolism. Additionally, review of all known cases at KCMEO of CO poisoning found no evidence of globus pallidus or basal ganglia necrosis. Thus, this study provides no support for the assertion that globus pallidus necrosis is characteristic of CO poisoning.
Giant Diaphragmatic Lipoma: Two Autopsy Case Reports and Review of the Literature
Authors: Margiotta Gabriele , Carlini Luigi , Carnevali Eugenia , Lancia Massimo , Gabbrielli Mario , Bacci Mauro
Published: August 2015

Lipomas are common benign tumors most frequently found within the subcutaneous areas of the body. Deep‐seated lipomas are rare and tend to be larger than cutaneous ones. Lipomas are rarely seen in the thoracic cavity, and they are usually located in the mediastinum, bronchiole, and lungs. Diaphragmatic lipomas have been occasionally reported in the literature, the first being described by Clark et al. in 1886. The authors report two rare cases of giant diaphragmatic lipoma incidentally found during forensic autopsies. In the first case, a Caucasian 85‐year‐old woman burned to death with another passenger, after her methane‐fueled car collided with another car on a highway near Terni, Umbria, Italy. In the second case, a Caucasian 45‐year‐old man collapsed while walking through the countryside of Perugia. In either case, a large mass in the thorax was observed. The definitive pathologic diagnosis was giant intrathoracic diaphragmatic lipoma without evidence of malignancy. The authors also review the relevant literature and discuss differential diagnoses. These case reports contribute to the establishment of the actual incidence of diaphragmatic lipomas.
Attempted Serial Neonaticides: Case Report and a Brief Review of the Literature
Authors: Barros Alcina Juliana Soares , Rosa Regis Goulart , Telles Lisieux Elaine de Borba , Taborda José Geraldo Vernet
Published: August 2015

Neonaticide is an infant murder occurring on the day of birth. The case reports found in the literature are often focused on the mother as the agent in the context of pregnancy denial, dissociative symptoms, or psychosis. However, this report describes a rare case of attempted serial neonaticides, in which the acts were committed by a nurse at the nursery of a referral hospital inBrazil. The authors describe a forensic psychiatric evaluation for criminal responsibility and correlate the information from this particular case with relevant forensic themes, namely neonaticide,Munchausen by proxy syndrome, and serial healthcare killers.
A Longitudinal Study on Human Outdoor Decomposition in Central Texas
Authors: Suckling Joanna K. , Spradley M. Katherine , Godde Kanya
Published: August 2015

The development of a methodology that estimates the postmortem interval (PMI) from stages of decomposition is a goal for which forensic practitioners strive. A proposed equation (Megyesi et al. 2005) that utilizes total body score (TBS) and accumulated degree days (ADD) was tested using longitudinal data collected from human remains donated to the Forensic Anthropology Research Facility (FARF) at Texas State University‐San Marcos. Exact binomial tests examined the rate of the equation to successfully predict ADD. Statistically significant differences were found between ADD estimated by the equation and the observed value for decomposition stage. Differences remained significant after carnivore scavenged donations were removed from analysis. Low success rates for the equation to predict ADD from TBS and the wide standard errors demonstrate the need to re‐evaluate the use of this equation and methodology for PMI estimation in different environments; rather, multivariate methods and equations should be derived that are environmentally specific.
Quantification of Maxillary Dental Arcade Curvature and the Estimation of Biological Ancestry in Forensic Anthropology
Authors: Clark Melissa A. , Guatelli‐Steinberg Debbie , Hubbe Mark , Stout Sam
Published: August 2015

Previous studies suggest that palate shape is a useful indicator of biological ancestry in human remains. This study evaluates interobserver error in ancestry estimation using palate shape and explores palate shape variation in Gullah (descendants of West Africans) and Seminole (Indigenous American) population samples using geometric morphometric analysis. Ten participants were asked to ascribe biological ancestry and shape to 28 dental casts based on a classification scheme employed in previous studies. The mean correct classification was 42.0%, indicating that the likelihood of assigning the correct ancestry is very poor and not significantly different from random assignment (p = 0.12). The accuracy analysis based on categorical classification of the casts was complemented by geometric morphometric analysis of nine 3D landmarks reflecting palate shape of 158 casts. Principal component analysis results show no difference between populations regarding palate shape, and cross‐validated discriminant function analysis correctly classified only 62.0% of the specimens. Combined, these results show that previous methods to estimate ancestry are inaccurate and that this inaccuracy is probably due to a lack of palate shape differences between groups, rather than limitation of the analytical method per se. Therefore, we recommend caution should be used when choosing to apply the analysis of palate shape in forensically relevant contexts.
Physical Properties, Volatiles Compositions and Sensory Descriptions of the Aromatized Hazelnut Oil‐Wax Organogels
Authors: Yılmaz Emin , Öğütcü Mustafa , Yüceer Yonca Karagül
Published: August 2015

The purpose of this study was to determine the physicochemical, thermal and sensorial features of vitamin enriched and aromatized hazelnut oil‐beeswax and sunflower wax organogels. Another objective was to monitor the influence of storage on textural and oxidative stability and volatile composition of the organogels. The results show that organogels with beeswax had lower levels of solid fat content, melting point and firmness than sunflower wax counterparts. The microphotographs revealed that beeswax organogels had spherical crystals while sunflower wax organogels continued need‐like crystals, but both organogels continued crystallized β’ polymorph. All organogels maintained their oxidative stability during storage. Quantitative descriptive analysis results were consistent with these findings that the organogel structure and properties were similar to breakfast margarine. The main volatile components of the organogels with added strawberry aroma were ethyl acetate, ethyl butanoate, ethyl‐2‐methyl butanoate, D‐limonene, ethyl caproate; banana‐aroma were isoamyl acetate, isoamyl valerianate, ethyl acetate; and butter‐aroma were 2,3‐butanedione, 3‐hydroxy‐2‐butanone. These volatile components were not only detected in the fresh samples but also at the end of the storage period. Sensory definition terms were matched with the sensory descriptors of the detected volatiles. In conclusion, the new organogels were shown to be suitable for food product applications.
High respiratory rate is associated with early reduction of lung edema clearance in an experimental model of ARDS
Authors: Retamal J. , Borges J. B. , Bruhn A. , Cao X. , Feinstein R. , Hedenstierna G. , Johansson S. , Suarez‐Sipmann F. , Larsson A.
Published: August 2015

Background

The independent impact of respiratory rate on ventilator‐induced lung injury has not been fully elucidated. The aim of this study was to investigate the effects of two clinically relevant respiratory rates on early ventilator‐induced lung injury evolution and lung edema during the protective ARDSNet strategy. We hypothesized that the use of a higher respiratory rate during a protective ARDSNet ventilation strategy increases lung inflammation and, in addition, lung edema associated to strain‐induced activation of transforming growth factor beta (TGF‐β) in the lung epithelium.

Methods

Twelve healthy piglets were submitted to a two‐hit lung injury model and randomized into two groups: LRR (20 breaths/min) and HRR (40 breaths/min). They were mechanically ventilated during 6 h according to the ARDSNet strategy. We assessed respiratory mechanics, hemodynamics, and extravascular lung water (EVLW). At the end of the experiment, the lungs were excised and wet/dry ratio, TGF‐β pathway markers, regional histology, and cytokines were evaluated.

Results

No differences in oxygenation, PaCO2 levels, systemic and pulmonary arterial pressures were observed during the study. Respiratory system compliance and mean airway pressure were lower in LRR group. A decrease in EVLW over time occurred only in the LRR group (P < 0.05). Wet/dry ratio was higher in the HRR group (P < 0.05), as well as TGF‐β pathway activation. Histological findings suggestive of inflammation and inflammatory tissue cytokines were higher in LRR.

Conclusion

HRR was associated with more pulmonary edema and higher activation of the TGF‐β pathway. In contrast with our hypothesis, HRR was associated with less lung inflammation.
The skull of the Chinese sturgeon, Acipenser sinensis (Acipenseridae)
Authors: Hilton Eric J. , Dillman Casey B. , Zhang Tao , Zhang Longzhen , Zhuang Ping
Published: August 2015

The Chinese sturgeon, Acipenser sinensis, is a large member of Acipenseridae now found only in the Yangtze River and the Yellow and East China seas. The goal of this paper was to describe the skull of A. sinensis in the context of recent anatomical and systematic studies of sturgeons. Five specimens (354–670 mm standard length) were prepared as skeletons. The left and right parietals and frontals are broadly separated by a median fontanelle. The lateral‐most lateral extrascapular variably supports the confluence of the supratemporal, occipital and trunk lateral lines. There is no distinct ventral supraorbital process as found in other sturgeons. The anterodorsal portion of the snout is unique among Acipenseridae by having a single large anamestic dorsal rostral bone instead of a series of separate dorsal rostral bones. There are 0–2 lateral rostral bones on each side positioned anterior to but not in contact with the horizontal arm of the jugal. The dorsal surface of the neurocranium lacks a pineal opening, and its anterior tip is sharply pointed in the smaller specimens examined and gently curved in larger specimens. The anteromedial arm of the palatopterygoid is broad relative to other acipenserids. These new morphological data are discussed and compared among Acipenseridae.
CYP3A5 polymorphism affects the increase in CYP3A activity after living kidney transplantation in patients with end stage renal disease
Authors: Suzuki Yosuke , Fujioka Takashi , Sato Fuminori , Matsumoto Kunihiro , Muraya Nanako , Tanaka Ryota , Sato Yuhki , Ohno Keiko , Mimata Hiromitsu , Kishino Satoshi , Itoh Hiroki
Published: August 2015

Aims

It has been reported that cytochrome P450 (CYP)3A activity increases significantly in patients with end stage renal disease (ESRD) after kidney transplantation, with wide interindividual variability in the degree of increase. The aim of this study was to evaluate the influence of CYP3A5 polymorphism on the increase in CYP3A activity after living kidney transplantation, by measuring the plasma concentration of 4β‐hydroxycholesterol.

Methods

This prospective study recruited 22 patients with ESRD who underwent a first living kidney allograft transplantation, comprising 12 patients with CYP3A5*1 allele (CYP3A5*1/*1 or *1/*3) and 10 patients without CYP3A5*1 allele (CYP3A5*3/*3).

Results

No significant difference in estimated glomerular filtration rate over time was observed between patients with the CYP3A5*1 allele and patients without the CYP3A5*1 allele, suggesting that the degrees of recovery in renal function after living kidney transplantation were similar in the two groups. However, plasma concentrations of 4β‐hydroxycholesterol on days 90 (57.1 ± 13.4 vs. 39.5 ± 10.8 ng ml−1) and 180 (55.0 ± 14.5 vs. 42.4 ± 12.6 ng ml−1) after living kidney transplantation were significantly higher in the presence of the CYP3A5*1 allele than in the absence of the CYP3A5*1 allele [P = 0.0034 (95% confidence interval of difference 6.55, 28.6) and P = 0.043 (95% confidence interval of difference 0.47, 24.8), respectively], suggesting that CYP3A activity may increase markedly associated with recovery of renal function in patients with the CYP3A5*1 allele.

Conclusions

These findings suggest that the presence of the CYP3A5*1 allele contributes to marked elevation of CYP3A activity associated with recovery of renal function after kidney transplantation.
Phase II study of HCVIDD/MA in patients with newly diagnosed peripheral T‐cell lymphoma
Authors: Chihara Dai , Pro Barbara , Loghavi Sanam , Miranda Roberto N. , Medeiros L. Jeffrey , Fanale Michelle A. , Hagemeister Fredrick B. , Fayad Luis E. , Romaguera Jorge E. , Samaniego Felipe , Neelapu Sattva S. , Younes Anas , Fowler Nathan H. , Rodriguez M. Alma , Wang Michael , Kwak Larry W. , McLaughlin Peter , Dang Nam H. , Oki Yasuhiro
Published: August 2015

A phase II study was performed to evaluate the efficacy of hyper‐fractionated cyclophosphamide, vincristine, pegylated liposomal doxorubicin and dexamethasone alternating with methotrexate/cytarabine (HCVIDD/MA) in patients with newly diagnosed peripheral T‐cell lymphoma (PTCL), excluding ALK‐positive anaplastic large cell lymphoma. Fifty‐three patients were enrolled. Treatment was planned for up to 8 cycles but only 9% of patients received more than 6 cycles due primarily to disease progression (n = 13) or prolonged thrombocytopenia (n = 12). The overall response rate was 66% with a complete response rate of 57%. Median progression‐free survival (PFS) was 7·5 months. With a median follow‐up of 7·6 years, 5‐year PFS and overall survival (OS) were 21% and 48%, respectively. The patients with extranodal Natural Killer‐cell lymphoma had a shorter PFS (median, 2·4 months) than other subtypes. Grade 3/4 anaemia, neutropenia and thrombocytopenia were observed in 66%, 74% and 79% of patients, respectively. Of note, 23% of patients discontinued therapy due to prolonged thrombocytopenia. In conclusion, HCVIDD/MA for the first‐line treatment of PTCL patients is associated with significant myelosuppression leading to poor treatment adherence, and the response and survival outcomes with this regimen are similar to standard CHOP. This study was registered at www.clinicaltrials.gov as #NCT00290433.
Hierarchical Multiview Rigid Registration
Authors: Tang Yizhi , Feng Jieqing
Published: August 2015

Registration is a key step in the 3D reconstruction of real‐world objects. In this paper, we propose a hierarchical method for the rigid registration of multiple views. The multiview registration problem is solved via hierarchical optimization defined on an undirected graph. Each node or edge in this graph represents a single view or a connection between two overlapped views, respectively. The optimizations are performed hierarchically on the edges, the loops, and the entire graph. First, each overlapped pair of views is locally aligned. Then, a loop‐based incremental registration algorithm is introduced to refine the initial pairwise alignments. After a loop is registered, the views in the loop are merged into a metaview in the graph. Finally, global error diffusion is applied to the entire graph to evenly distribute the accumulated errors to all views. In addition, a new objective function is defined to describe the loop closure problem; it improves the accuracy and robustness of registration by simultaneously considering transformation and registration errors. The experimental results show that the proposed hierarchical approach is accurate, efficient and robust for initial view states that are not well posed.
Perfect Laplacians for Polygon Meshes
Authors: Herholz Philipp , Kyprianidis Jan Eric , Alexa Marc
Published: August 2015

A discrete Laplace‐Beltrami operator is called perfect if it possesses all the important properties of its smooth counterpart. It is known which triangle meshes admit perfect Laplace operators and how to fix any other mesh by changing the combinatorics. We extend the characterization of meshes that admit perfect Laplacians to general polygon meshes. More importantly, we provide an algorithm that computes a perfect Laplace operator for any polygon mesh without changing the combinatorics, although, possibly changing the embedding. We evaluate this algorithm and demonstrate it at applications.
Can bi‐cubic surfaces be class A?
Authors: Karčiauskas Kęstutis , Peters Jörg
Published: August 2015

'Class A surface’ is a term in the automotive design industry, describing spline surfaces with aesthetic, non‐oscillating highlight lines. Tensor‐product B‐splines of degree bi‐3 (bicubic) are routinely used to generate smooth design surfaces and are often the de facto standard for downstream processing. To bridge the gap, this paper explores and gives a concrete suggestion, how to achieve good highlight line distributions for irregular bi‐3 tensor‐product patch layout by allowing, along some seams, a slight mismatch of normals below the industry‐accepted tolerance of one tenth of a degree. Near the irregularities, the solution can be viewed as transforming a higher‐degree, high‐quality formally smooth surface into a bi‐3 spline surface with few pieces, sacrificing formal smoothness but qualitatively retaining the shape.
Methylisothiazolinone in selected consumer products in Belgium: Adding fuel to the fire?
Authors: Aerts Olivier , Meert Hans , Goossens An , Janssens Sighile , Lambert Julien , Apers Sandra
Published: August 2015

Background

Methylisothiazolinone (MI) contact allergy is severely affecting consumers with allergic contact dermatitis, owing to its presence in cosmetics, household detergents, and water‐based paints, in particular. Data on the true isothiazolinone concentrations in these products are scarce, and labelling may be incorrect.

Objectives

To report on the MI concentrations in such products marketed in Belgium, in order to verify the accuracy of labelling (when applicable) and compliance with EU regulations.

Materials and methods

Thirty cosmetics (18 leave‐on and 12 rinse‐off), eight detergents and four paints were analysed for MI by the use of high‐performance liquid chromatography with ultraviolet detection.

Results

The analysed leave‐on, and to a lesser extent the rinse‐off, cosmetics, contained MI at concentrations far exceeding the permitted 100 ppm use concentration. Household detergents contained high concentrations of MI, and mislabelling occurred for both cosmetics and detergents. The (limited) data on paints are in line with the existing literature.

Conclusion

Cosmetics and detergents may facilitate contact sensitization because of a (too) high MI concentration, and mislabelling may make its avoidance extremely difficult. Safer use concentrations and correct labelling should be ensured by adequate quality control.
Monocyte nadir is a possible indicator for neutrophil nadir during lung cancer chemotherapy
Authors: Moriyama Yusuke , Horita Nobuyuki , Kudo Makoto , Shinkai Masaharu , Fujita Hiroyuki , Yamanaka Takeharu , Ishigatsubo Yoshiaki , Kaneko Takeshi
Published: August 2015

Introduction

No previous study clearly demonstrated the association between the absolute neutrophil count (ANC) nadir and the absolute monocyte count (AMC) nadir among patients undergoing chemotherapy.

Methods

We retrospectively reviewed patients with an incurable lung cancer in two university hospital who were treated with platinum doublet or triplet. In this study, the nadir was defined as the lowest value during days 1–22.

Results

We observed 75 patients: 61 men (81%) and 14 women (19%), median age of 69 years. The number of days that elapsed between the first day of chemotherapy and the median ANC nadir of 12 days was longer than that for AMC nadir of 6 (Wilcoxon signed rank test: P < 0.001). The number of days that elapsed between the first day of chemotherapy and the AMC nadir was the only factor that had a significant correlation with that for ANC nadir (Spearman's rank correlation: r = 0.34, P = 0.003). Among 75 patients, 23 (31%) had an ANC at nadir <1000/μL. AMC at nadir of 100/μL predicted an ANC at nadir <1000/μL with a sensitivity of 83% and a specificity of 56%.

Conclusion

Both neutrophils and monocytes are differentiated from a common progenitor, a granulocyte macrophage colony forming cell, which can provide good explanation for the association between ANC and AMC nadirs. We would like to recommend physicians to observe the AMC nadir to predict the timing and severity of the ANC nadir.
Colorectal cancer screening by colonoscopy: putting it into perspective
Authors: Vleugels Jasper L.A. , van Lanschot Meta C.J. , Dekker Evelien
Published: August 2015

Implementation of nationwide screening programs aims to decrease the disease burden of colorectal cancer (CRC) in the general population. Globally, most population screening programs for CRC are carried out by either fecal occult blood test, flexible sigmoidoscopy or colonoscopy. For screening programs with colonoscopy as the primary method, only circumstantial evidence from observational studies is available to prove its effectiveness, suggesting that colonoscopy effectively reduces CRC incidence and mortality. Currently, large randomized trials are being conducted to corroborate these findings. Besides the direct effect of a screening program for CRC, its protective effect is further enhanced by enrolment of patients that underwent polypectomy in surveillance programs. However, despite CRC screening and surveillance colonoscopies, interval CRC still occur. Those are predominantly located in the right‐sided colon and potential explanations, besides unfavorable tumor characteristics, are preventable operator‐dependent factors relating to the quality of the colonoscopy procedure. In an effort to reduce differences in endoscopists’ performance and thereby the occurrence of interval CRC, quality indicators of colonoscopy have been introduced. In addition, emerging advanced colonoscopy techniques might contribute to improvement in polyp detection and removal. Meticulous inspection of the colonic mucosa not only results in the detection of advanced and relevant lesions, but also in the removal of many diminutive and small lesions leading to an increasing number of surveillance colonoscopies, known as the ‘high‐detection paradox’. More data on the cost‐effectiveness of high‐quality colonoscopy as a primary screening method and surveillance programs with intervals based on optimal risk stratification are eagerly awaited.
BT‐benzo‐29 inhibits bacterial cell proliferation by perturbing FtsZ assembly
Authors: Ray Shashikant , Jindal Bhavya , Kunal Kishore , Surolia Avadhesha , Panda Dulal
Published: August 2015

We have identified a potent antibacterial agent N‐(4‐sec‐butylphenyl)‐2‐(thiophen‐2‐yl)‐1H‐benzo[d]imidazole‐4‐carboxamide (BT‐benzo‐29) from a library of benzimidazole derivatives that stalled bacterial division by inhibiting FtsZ assembly. A short (5 min) exposure of BT‐benzo‐29 disassembled the cytokinetic Z‐ring in Bacillus subtilis cells without affecting the cell length and nucleoids. BT‐benzo‐29 also perturbed the localization of early and late division proteins such as FtsA, ZapA and SepF at the mid‐cell. Further, BT‐benzo‐29 bound to FtsZ with a dissociation constant of 24 ± 3 μm and inhibited the assembly and GTPase activity of purified FtsZ. A docking analysis suggested that BT‐benzo‐29 may bind to FtsZ at the C‐terminal domain near the T7 loop. BT‐benzo‐29 displayed significantly weaker inhibitory effects on the assembly and GTPase activity of two mutants (L272A and V275A) of FtsZ supporting the prediction of the docking analysis. Further, BT‐benzo‐29 did not appear to inhibit DNA duplication and nucleoid segregation and it did not perturb the membrane potential of B. subtilis cells. The results suggested that BT‐benzo‐29 exerts its potent antibacterial activity by inhibiting FtsZ assembly. Interestingly, BT‐benzo‐29 did not affect the membrane integrity of mammalian red blood cells. BT‐benzo‐29 bound to tubulin with a much weaker affinity than FtsZ and exerted significantly weaker effects on mammalian cells than on the bacterial cells indicating that the compound may have a strong antibacterial potential.
SH3 domain of c‐Src governs its dynamics at focal adhesions and the cell membrane
Authors: Machiyama Hiroaki , Yamaguchi Tomoyuki , Sawada Yasuhiro , Watanabe Tomonobu M. , Fujita Hideaki
Published: August 2015

We studied the role of the Src SH3 domain in its dynamics at the cell membrane using site‐directed mutagenesis and live cell imaging. Physiologically, cell proliferation and migration require the expression of Src family kinases. Hyperactivation of Src molecules has been detected in various cancer cells. Although the activation mechanism of Src has been intensively studied, the dynamics of Src at the cell membrane are still unclear. Although Src molecules also exist at various cellular locations, we found that activated Src molecules are mainly localized at peripheral cell adhesion sites. Src phosphorylation status and subdomain conformations are thought to regulate Src activation and translocation. In this study, we analyzed the single‐molecule dynamics of wild‐type Src and SH2‐ and SH3‐mutated Src at the cell membrane. Introducing mutations in the SH3 domain resulted in reduced Src motility at the cell membrane, both inside and outside of focal adhesions. Disruption of the actin cytoskeleton resulted in less diffusive Src movement at the cell membrane. We demonstrate that, inside focal adhesions, the SH3 domain enhanced dissociation of Src from the adhesion site and disruption of the SH3 domain altered the distribution of Src at the cell membrane. Inside focal adhesions, kinase activity of Src was essential for the Src mobility reduction by SH3 domain mutation, suggesting that rapid mobility of Src at focal adhesions mediated by the SH3 domain is catalytic‐activity‐dependent. These findings show that the SH3 domain of Src governs the dynamics of Src at the cell membrane and may be involved in rapid signal transduction in cells.
Angiotensin type 1a receptors on corticotropin‐releasing factor neurons contribute to the expression of conditioned fear1
Authors: Hurt R. C. , Garrett J. C. , Keifer O. P. , Linares A. , Couling L. , Speth R. C. , Ressler K. J. , Marvar P. J.
Published: August 2015

Although generally associated with cardiovascular regulation, angiotensin II receptor type 1a (AT1aR) blockade in mouse models and humans has also been associated with enhanced fear extinction and decreased post‐traumatic stress disorder (PTSD) symptom severity, respectively. The mechanisms mediating these effects remain unknown, but may involve alterations in the activities of corticotropin‐releasing factor (CRF)‐expressing cells, which are known to be involved in fear regulation. To test the hypothesis that AT1aR signaling in CRFergic neurons is involved in conditioned fear expression, we generated and characterized a conditional knockout mouse strain with a deletion of the AT1aR gene from its CRF‐releasing cells (CRF‐AT1aR(−/−)). These mice exhibit normal baseline heart rate, blood pressure, anxiety and locomotion, and freeze at normal levels during acquisition of auditory fear conditioning. However, CRF‐AT1aR(−/−) mice exhibit less freezing than wild‐type mice during tests of conditioned fear expression—an effect that may be caused by a decrease in the consolidation of fear memory. These results suggest that central AT1aR activity in CRF‐expressing cells plays a role in the expression of conditioned fear, and identify CRFergic cells as a population on which AT1R antagonists may act to modulate fear extinction.
Spatial scaling of temporal changes in avian communities
Authors: Jarzyna Marta A. , Zuckerberg Benjamin , Porter William F. , Finley Andrew O. , Maurer Brian A.
Published: August 2015

Aim

Biodiversity patterns and the mechanisms driving these patterns are inherently scale dependent. Studies investigating biodiversity scaling have focused mostly on evaluating community turnover without taking into consideration its underlying processes of local extinction (hereafter, extinction) and colonization. Our goal was to evaluate the spatial scaling of change in avian assemblages through time and identify environmental drivers of community‐wide dynamics across a range of spatial scales, with a focus on extinction and colonization.

Location

NewYorkState.

Methods

We analysed community dissimilarity, temporal turnover, extinction and colonization as measures of temporal change in avian communities at five spatial resolutions (5 × 5, 10 × 10, 20 × 20, 40 × 40 and 80 km × 80 km). We evaluated the relationships between community change and change in climatic conditions, landscape fragmentation and elevation at each spatial grain usingBayesian spatially varying intercept models.

Results

We found that the decline in colonization with increasing spatial scale was less steep than the decline in community dissimilarity, temporal turnover or extinction. We also found that the importance of environmental drivers to community change was dependent on both scale and metric, though we did not find optimal spatial scales at which either landscape or climatic processes consistently drove patterns of community change. Landscape characteristics were the most important correlate of extinction at all spatial scales, while colonization was not predicted well by any of the environmental factors.

Main conclusions

The slower decline in colonization across spatial grains is probably a consequence of the high mobility and dispersal abilities of birds. We further conclude that the two processes underlying community change – extinction and colonization – are driven by different factors. Landscape characteristics strongly affect the rates of extinctions in avian communities. On the contrary, patterns of colonization are likely to be a result of intrinsic characteristics of birds – specifically, high dispersal ability – that allow them to colonize new sites, regardless of the environmental context.