bluuebunny/crossref_metadata_2025 huggingface dataset:
The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance
Authors: Cho Joong Youn , Chak Kayam , Andreone Benjamin J. , Wooley Joseph R. , Kolodkin Alex L.
Published: October 2012

The Drosophila transmembrane semaphorin-1a (Sema-1a) is a repulsive guidance cue that uses the Plexin A (PlexA) receptor during neural development. Sema-1a is required in axons to facilitate motor axon defasciculation at guidance choice points. We found that mutations in the trol gene strongly suppress Sema-1a-mediated repulsive axon guidance. trol encodes the phylogenetically conserved secreted heparan sulfate proteoglycan (HSPG) perlecan, a component of the extracellular matrix. Motor axon guidance defects in perlecan mutants resemble those observed in Sema-1a- and PlexA-null mutant embryos, and perlecan mutants genetically interact with PlexA and Sema-1a. Perlecan protein is found in both the CNS and the periphery, with higher expression levels in close proximity to motor axon trajectories and pathway choice points. Restoring perlecan to mutant motor neurons rescues perlecan axon guidance defects. Perlecan augments the reduction in phospho-focal adhesion kinase (phospho-FAK) levels that result from treating insect cells in vitro with Sema-1a, and genetic interactions among integrin, Sema-1a, and FAK in vivo support an antagonistic relationship between Sema-1a and integrin signaling. Therefore, perlecan is required for Sema-1a–PlexA-mediated repulsive guidance, revealing roles for extracellular matrix proteoglycans in modulating transmembrane guidance cue signaling during neural development.
Synaptic vesicle clustering requires a distinct MIG-10/Lamellipodin isoform and ABI-1 downstream from Netrin
Authors: Stavoe Andrea K.H. , Nelson Jessica C. , Martínez-Velázquez Luis A. , Klein Mason , Samuel Aravinthan D.T. , Colón-Ramos Daniel A.
Published: October 2012

The chemotrophic factor Netrin can simultaneously instruct different neurodevelopmental programs in individual neurons in vivo. How neurons correctly interpret the Netrin signal and undergo the appropriate neurodevelopmental response is not understood. Here we identify MIG-10 isoforms as critical determinants of individual cellular responses to Netrin. We determined that distinct MIG-10 isoforms, varying only in their N-terminal motifs, can localize to specific subcellular domains and are differentially required for discrete neurodevelopmental processes in vivo. We identified MIG-10B as an isoform uniquely capable of localizing to presynaptic regions and instructing synaptic vesicle clustering in response to Netrin. MIG-10B interacts with Abl-interacting protein-1 (ABI-1)/Abi1, a component of the WAVE complex, to organize the actin cytoskeleton at presynaptic sites and instruct vesicle clustering through SNN-1/Synapsin. We identified a motif in the MIG-10B N-terminal domain that is required for its function and localization to presynaptic sites. With this motif, we engineered a dominant-negative MIG-10B construct that disrupts vesicle clustering and animal thermotaxis behavior when expressed in a single neuron in vivo. Our findings indicate that the unique N-terminal domains confer distinct MIG-10 isoforms with unique capabilities to localize to distinct subcellular compartments, organize the actin cytoskeleton at these sites, and instruct distinct Netrin-dependent neurodevelopmental programs.
miR-26a is required for skeletal muscle differentiation and regeneration in mice
Authors: Dey Bijan K. , Gagan Jeffrey , Yan Zhen , Dutta Anindya
Published: October 2012

Multiple microRNAs are known to be induced during the differentiation of myoblasts to myotubes. Yet, experiments in animals have not provided clear evidence for the requirement of most of these microRNAs in myogenic differentiation in vivo. miR-26a is induced during skeletal muscle differentiation and is predicted to target a well-known inhibitor of differentiation, the transforming growth factor β/bone morphogenetic protein (TGF-β/BMP) signaling pathway. Here we show that exogenous miR-26a promotes differentiation of myoblasts, while inhibition of miR-26a by antisense oligonucleotides or by Tough-Decoys delays differentiation. miR-26a targets the transcription factors Smad1 and Smad4, critical for the TGF-β/BMP pathway, and expression of microRNA-resistant forms of these transcription factors inhibits differentiation. Injection of antagomirs specific to miR-26a into neonatal mice derepressed both Smad expression and activity and consequently inhibited skeletal muscle differentiation. In addition, miR-26a is induced during skeletal muscle regeneration after injury. Inhibiting miR-26a in the tibialis anterior muscles through the injection of adeno-associated virus expressing a Tough-Decoy targeting miR-26a prevents Smad down-regulation and delays regeneration. These findings provide evidence for the requirement of miR-26a for skeletal muscle differentiation and regeneration in vivo.
The RNA polymerase II CTD coordinates transcription and RNA processing
Authors: Hsin Jing-Ping , Manley James L.
Published: October 2012

The C-terminal domain (CTD) of the RNA polymerase II largest subunit consists of multiple heptad repeats (consensus Tyr1–Ser2–Pro3–Thr4–Ser5–Pro6–Ser7), varying in number from 26 in yeast to 52 in vertebrates. The CTD functions to help couple transcription and processing of the nascent RNA and also plays roles in transcription elongation and termination. The CTD is subject to extensive post-translational modification, most notably phosphorylation, during the transcription cycle, which modulates its activities in the above processes. Therefore, understanding the nature of CTD modifications, including how they function and how they are regulated, is essential to understanding the mechanisms that control gene expression. While the significance of phosphorylation of Ser2 and Ser5 residues has been studied and appreciated for some time, several additional modifications have more recently been added to the CTD repertoire, and insight into their function has begun to emerge. Here, we review findings regarding modification and function of the CTD, highlighting the important role this unique domain plays in coordinating gene activity.
Transmission Electron Microscopy of Thin Sections of Drosophila: Preparation of Embryos Using n-Heptane and Glutaraldehyde
Authors: McDonald Kent L. , Sharp David J. , Rickoll Wayne
Published: October 2012

This protocol describes the simultaneous permeabilization of Drosophila embryos with n-heptane and initial fixation with glutaraldehyde. Even though the vitelline membrane around the embryo is chemically permeabilized, it must be manually removed to achieve infiltration with embedding resins. Once the embryo is embedded, it can be sectioned for transmission electron microscopy (TEM). This procedure can produce excellent preservation for ultrastructural analysis, and is useful for situations where optimal preservation (e.g., by high-pressure freezing) is not required or is not feasible.
In Vivo Microendoscopy of the Hippocampus
Authors: Barretto Robert P.J. , Schnitzer Mark J.
Published: October 2012

Conventional intravital microscopy has generally been limited to superficial brain areas such as the olfactory bulb, the neocortex, or the cerebellar cortex. In vivo optical microendoscopy uses gradient refractive index (GRIN) microlenses that can be inserted into tissue to image cells in deeper areas. This protocol describes in vivo microendoscopy of the mouse hippocampus. The general methodology can be applied to many deep brain regions and other areas of the body.
Imaging Calcium Waves and Sparks in Central Neurons
Authors: Ross William N. , Manita Satoshi
Published: October 2012

Here we describe the use of wide-field charge-coupled device (CCD) camera-based imaging methods to detect the spatial and temporal aspects of calcium release from internal stores in dendrites of neurons in brain slice preparations. This approach is useful for revealing aspects of this signaling system, which is generally invisible to electrical recording. The changes in intracellular calcium ion concentrations, [Ca2+]i, sometimes occur as large-amplitude, propagating Ca2+ waves or as much smaller, localized events (sparks). In this protocol, a cell is loaded with an indicator that responds to Ca2+, waves or sparks are stimulated in the cell, and the spatial and temporal characteristics of calcium release from internal stores in the cell are detected using wide-field CCD camera-based imaging. Such camera systems have some advantages for detecting and analyzing these [Ca2+]i changes because the waves are spatially extended and the sparks do not always occur at the same locations.
Arabidopsis Defense against Botrytis cinerea: Chronology and Regulation Deciphered by High-Resolution Temporal Transcriptomic Analysis
Authors: Windram Oliver , Madhou Priyadharshini , McHattie Stuart , Hill Claire , Hickman Richard , Cooke Emma , Jenkins Dafyd J. , Penfold Christopher A. , Baxter Laura , Breeze Emily , Kiddle Steven J. , Rhodes Johanna , Atwell Susanna , Kliebenstein Daniel J. , Kim Youn-sung , Stegle Oliver , Borgwardt Karsten , Zhang Cunjin , Tabrett Alex , Legaie Roxane , Moore Jonathan , Finkenstadt Bärbel , Wild David L. , Mead Andrew , Rand David , Beynon Jim , Ott Sascha , Buchanan-Wollaston Vicky , Denby Katherine J.
Published: October 2012

Transcriptional reprogramming forms a major part of a plant's response to pathogen infection. Many individual components and pathways operating during plant defense have been identified, but our knowledge of how these different components interact is still rudimentary. We generated a high-resolution time series of gene expression profiles from a single Arabidopsis thaliana leaf during infection by the necrotrophic fungal pathogen Botrytis cinerea. Approximately one-third of the Arabidopsis genome is differentially expressed during the first 48 h after infection, with the majority of changes in gene expression occurring before significant lesion development. We used computational tools to obtain a detailed chronology of the defense response against B. cinerea, highlighting the times at which signaling and metabolic processes change, and identify transcription factor families operating at different times after infection. Motif enrichment and network inference predicted regulatory interactions, and testing of one such prediction identified a role for TGA3 in defense against necrotrophic pathogens. These data provide an unprecedented level of detail about transcriptional changes during a defense response and are suited to systems biology analyses to generate predictive models of the gene regulatory networks mediating the Arabidopsis response to B. cinerea.
Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?
Authors: Hellings P. W. , Fokkens W. J. , Akdis C. , Bachert C. , Cingi C. , Dietz de Loos D. , Gevaert P. , Hox V. , Kalogjera L. , Lund V. , Mullol J. , Papadopoulos N. G. , Passalacqua G. , Rondón C. , Scadding G. , Timmermans M. , Toskala E. , Zhang N. , Bousquet J.
Published: October 2012

State‐of‐the‐art documents like ARIA and EPOS provide clinicians with evidence‐based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so‐called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline‐directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment‐related, diagnosis‐related and/or patient‐related factors. Treatment‐related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom‐oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient‐related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.
Weight misperception and its barriers to keep health weight in Chinese children
Authors: Zhao Min , Zhang Min , Zhou Xiaoqi , Yang Hongying , Yang Yanhong , Yang Nianhong
Published: October 2012

Aims:  To examine the prevalence rate of misperception, assess the relationship between weight perception and weight‐related behaviors in Chinese children.

Methods:  A total of 2708 children aged 7–12 years from five public primary schools and their parents completed questionnaires assessing social demographic background, dietary and activity related factors. Weight and height were measured by trained investigators. The prevalence of misperception was defined by comparing calculated BMI and their perceived weight status. Log‐binomial model yielded adjusted prevalence ratios (PRs) for each behavior by weight misperception in boys and girls separately.

Results:  Misperception was more prevalent in normal weight children 33.3% for girls and 40.5% for boys and boys were more likely to underestimate their weight status than girls. Associations were observed between misperceived thinness and eating before bed, want to eat seeing others eating, eating sugar and snacks frequently, monophagia and choosy in food both in girls and boys. And associations between misperceived fatness and depression and want to eat seeing others eating were found only in girls.

Conclusions:  Our findings underscore the importance of weight perception in shaping realistic body image among normal weight children. Education must be introduced to help children accurately look on their body shape.
Molecular determinants of platelet delta storage pool deficiencies: an update
Authors: Masliah‐Planchon Julien , Darnige Luc , Bellucci Sylvia
Published: October 2012

Delta storage pool deficiency (δ‐SPD) is a rare heterogeneous group of platelet disorders characterized by a reduction in the number or content of dense granules. δ‐SPD causes a mild to moderate bleeding diathesis characterized mainly by mucocutaneous bleeding. Currently, no specific treatment is available and the therapeutic approach is based on prevention of excessive bleeding. However, during the last few years, important insights into the pathophysiology of δ‐SPD have been achieved using mouse models and dense granule deficiency‐associated congenital diseases, such as Hermansky–Pudlak syndrome and Chediak–Higashi syndrome. It thus appears that δ‐SPD represents a genetically heterogeneous group of intracellular vesicle biogenesis and/or trafficking disorders. This review summarizes recent data regarding the molecular mechanisms together with clinical features of the different types of δ‐SPD. Although the molecular basis of isolated inherited δ‐SPD remains currently unknown, next‐generation sequencing strategies should enable researchers to identify the causative genes. Identification of those genes should contribute to our understanding of the pathophysiology, represent useful tools for genetic diagnosis, and eventually lead to new specific therapeutic approaches.
Activation of caspases‐9, ‐3 and ‐8 in human platelets triggered by BH3‐only mimetic ABT‐737 and calcium ionophore A23187: caspase‐8 is activated via bypass of the death receptors
Authors: Mutlu Asuman , Gyulkhandanyan Armen V. , Freedman John , Leytin Valery
Published: October 2012

Platelet apoptosis and activation have been studied in human platelets treated with BH3‐only mimetic ABT‐737 and calcium ionophore A23187, agents triggering apoptosis through the intrinsic mitochondrial pathway. Platelet apoptosis was determined as activation of crucial apoptosis‐associated caspases, initiator caspase‐9 of intrinsic apoptosis pathway, executioner caspase‐3 and initiator caspase‐8 of extrinsic death receptor pathway, and platelet activation was detected by P‐selectin (CD62) exposure on the platelet surface. We found that ABT‐737 predominantly induced activation of caspases‐9, ‐3 and ‐8 rather than CD62 exposure, whereas A23187 induces both caspases activation and CD62 exposure. Caspase‐8 activation was stimulated independently of the extrinsic apoptosis pathway via mitochondrial membrane permeabilization and depolarization. These data suggest that (i) caspase‐8 activation is triggered in ABT‐737‐ and A23187‐treated anucleate platelets through the mitochondria‐initiated caspase activation cascade bypassing the death receptors, and (ii) ABT‐737‐treated platelets are a useful experimental tool for discerning the role of platelet apoptosis in platelet function and survival.
The genotype of RAET1L (ULBP6), a ligand for human NKG2D (KLRK1), markedly influences the clinical outcome of allogeneic stem cell transplantation
Authors: Antoun Ayman , Vekaria Dhruti , Salama Rafik A. , Pratt Guy , Jobson Shirley , Cook Mark , Briggs David , Moss Paul
Published: October 2012

NKG2D (KLRK1) is an activating receptor on natural killer (NK) and T‐cells and binds a diverse panel of polymorphic ligands encoded by the MIC and RAET1 gene families. We studied the clinical importance of retinoic acid early transcript‐1 (RAET1) polymorphism in allogeneic stem cell transplantation (SCT) by determining the frequency of 18 single nucleotide polymorphisms (SNPs) and individual RAET1 alleles in 371 patient‐donor pairs and relating this to clinical outcome. A strong association was observed between the presence of five SNPs within the patient RAET1L (ULBP6) gene and relapse‐free survival and overall survival. Two common alleles of RAET1L were determined and the presence of the protective RAET1L*02 allele in the patient was associated with a relapse‐free survival of 44% at 8 years compared with just 25% in patients who lacked a RAET1L*02 allele (P < 0·001). Overall survival at this time was 55% in those with RAET1L*02 allele compared to 39% in patients who lacked a RAET1L*02 allele (P = 0·003). These novel findings indicate a critical role for NKG2D–RAET1L interactions in determining SCT clinical outcome and show RAET1L may have an important influence on regulating the strength of the alloreactive immune response. The data will be of value in guiding the development of future transplant therapy protocols.
Radiological and micro‐computed tomography analysis of the bone at dental implants inserted 2, 3 and 4 mm apart in a minipig model with platform switching incorporated
Authors: Elian Nicolas , Bloom Mitchell , Dard Michel , Cho Sang‐Choon , Trushkowsky Richard D. , Tarnow Dennis
Published: October 2012

Background

The purpose of this study was to assess the effect of inter‐implant distance on interproximal bone utilizing platform switching. Analysis of interproximal bone usually depends on traditional two‐dimensional radiographic assessment. Although there has been increased reliability of current techniques, there has been an inability to track bone level changes over time and in three dimensions. Micro‐CT has provided three‐dimensional imaging that can be used in conjunction with traditional two‐dimensional radiographic techniques.

Methods

This study was performed on 24 female minipigs. Twelve animals received three implants with an inter‐implant distance of 3 mm on one side of the mandible and another three implants on the contra‐lateral side, where the implants were placed 2 mm apart creating a split mouth design. Twelve other animals received three implants with an inter‐implant distance of 3 mm on one side of the mandible and another three implants on the contra‐lateral side, where the implants were placed 4 mm apart creating a split mouth design too. The quantitative evaluation was performed comparatively on radiographs taken at t 0 (immediately after implantation) and at t 8 weeks (after termination). The samples were scanned by micro‐computed tomography (μCT) to quantify the first bone to implant contact (fBIC) and bone volume/total volume (BV/TV). Mixed model regressions using the nonparametric Brunner–Langer method were used to determine the effect of inter‐implant distance on the measured outcomes.

Results

The change in bone level was determined using radiography and its mean was 0.05 mm for an inter‐implant distance of 3 and 0.00 mm for a 2 mm distance (P = 0.7268). The mean of this outcome was 0.18 mm for the 3 mm and for 4 mm inter‐implant distance (P = 0.9500). Micro‐computed tomography showed that the fBIC was always located above the reference, 0.27 and 0.20 mm for the comparison of 2–3 mm (P = 0.4622) and 0.49 and 0.34 mm for the inter‐implant distance of 3 and 4 mm (P = 0.1699). BV/TV inside the defined parallelepipedic masks reached 82.38% for the 2 mm inter‐implant distance and 85.00% for 3 mm, P = 0.8432. For the comparison of the 3–4 mm inter‐implant distance, the means were 84.69% and 84.38%, respectively, P = 0.8401. Non‐inferiority tests for the smaller inter‐implant distances for both comparisons showed similar differences and similar tolerance ranges.

Conclusion

The effect of a smaller interproximal distances between implants on bone level, fBIC and BV/TV assessed by two convergent investigation methods, radiology and μCT, was similar to that of larger distances. Implants can potentially be placed 2 mm apart instead of 3 mm and 3 mm apart instead of 4 mm when platform switching is utilized. Further research with a conventional platform is warranted.
Has Agency Theory Run its Course?: Making the Theory more Flexible to Inform the Management of Reward Systems
Authors: Cuevas‐Rodríguez Gloria , Gomez‐Mejia Luis R. , Wiseman Robert M.
Published: October 2012

Manuscript Type

Conceptual

Research Question/Issue

In this paper we discuss three assumptions of agency theory: (1) conflicts of interest between principal and agent, (2) nature of risk, and (3) the proposed internal mechanisms to reduce agency costs. We review criticisms of agency theory's pessimistic assumptions of human behavior and its simplistic view about individual risk preferences to argue how the context may influence both the interest and mechanisms for aligning interest of principals and agents.

Research Findings/Insights

We draw on alternative theoretical perspectives from behavioral and organizational sciences to describe circumstances under which honesty, loyalty, and trust in agents' behaviors are possible and also the development of cooperative rather than contentious relationships.

Theoretical/Academic Implications

This study explores the boundary conditions of traditional agency theory in the hope of extending agency theory outside its current contextual boundaries. In doing so, we provide a more robust and exhaustive view of the economic exchange between principals and agents.

Practitioner/Policy Implications

This study offers insights to managers about how intrinsic incentives may provide an alternative mechanism of control over agents' behavior to extrinsic incentives prescribed by traditional agency theory. Indeed, intrinsic incentives of personal satisfaction and identification with organizational objects, combined with implicit social obligations and reciprocity may, under certain circumstances, provide stronger restraints on agent opportunism than the use of traditional extrinsic rewards in the form of incentive alignment.
Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast
Authors: Jing X. , Wey E. , Michael C. W.
Published: October 2012

X. Jing, E. Wey and C. W. Michael

Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast

Objective:  To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma.

Methods:  A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto‐histologically discrepant cases were reviewed.

Results:  Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom–Richardson grade or the number or size of metastases between tumours with true‐positive and false‐negative cytology. Sampling error was the sole factor contributing to cyto‐histological discrepancy.

Conclusions:  ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.
TEASIng apart alien species risk assessments: a framework for best practices
Authors: Leung Brian , Roura‐Pascual Nuria , Bacher Sven , Heikkilä Jaakko , Brotons Lluis , Burgman Mark A. , Dehnen‐Schmutz Katharina , Essl Franz , Hulme Philip E. , Richardson David M. , Sol Daniel , Vilà Montserrat
Published: October 2012

Some alien species cause substantial impacts, yet most are innocuous. Given limited resources, forecasting risks from alien species will help prioritise management. Given that risk assessment (RA) approaches vary widely, a synthesis is timely to highlight best practices. We reviewed quantitative and scoring RAs, integrating > 300 publications into arguably the most rigorous quantitative RA framework currently existing, and mapping each study onto our framework, which combines Transport, Establishment, Abundance, Spread and Impact (TEASI). Quantitative models generally measured single risk components (78% of studies), often focusing on Establishment alone (79%). Although dominant in academia, quantitative RAs are underused in policy, and should be made more accessible. Accommodating heterogeneous limited data, combining across risk components, and developing generalised RAs across species, space and time without requiring new models for each species may increase attractiveness for policy applications. Comparatively, scoring approaches covered more risk components (50% examined > 3 components), with Impact being the most common component (87%), and have been widely applied in policy (> 57%), but primarily employed expert opinion. Our framework provides guidance for questions asked, combining scores and other improvements. Our risk framework need not be completely parameterised to be informative, but instead identifies opportunities for improvement in alien species RA.
Potential for local adaptation in response to an anthropogenic agent of selection: effects of road deicing salts on amphibian embryonic survival and development
Authors: Hopkins Gareth R. , French Susannah S. , Brodie Edmund D.
Published: October 2012

The application of millions of tons of road deicing salts every winter in North America presents significant survival challenges to amphibians inhabiting roadside habitats. While much is known of the effects of NaCl on anuran tadpoles, less is known of effects on amphibian eggs, or any caudate life stage. In addition, little is known of the effects of MgCl2, which is now the 2nd most commonly used road deicer. Most studies have considered amphibians to be helpless victims of deicing salts, and ignore the possibility of the evolution of local adaptation to this stressor. We attempt to address these knowledge gaps and explore this evolutionary potential by examining the effects of NaCl and MgCl2 on the survival and development of eggs from different female rough‐skinned newts (Taricha granulosa) from the same population. We demonstrate that both salts, at environmentally relevant concentrations, severely affect the embryonic survival and development of this amphibian, but that the effects of the salt are dependent on the identity of the mother. This female × treatment interaction results in substantial variation in tolerance to road deicing salts among newt families, providing the raw material necessary for natural selection and the evolution of local adaptation in this amphibian.
The role of AHI1 and CDKN1C in cutaneous T‐cell lymphoma progression
Authors: Litvinov Ivan V. , Kupper Thomas S. , Sasseville Denis
Published: October 2012

Cutaneous T‐cell lymphoma (CTCL) is the most common lymphoma of the skin. Recent reports suggest that AHI1 is overexpressed in a subset of CTCL‐derived cell lines, where it downregulates the expression of CDKN1C tumor suppressor gene. In the current work, we test the expression of these genes in 60 patients with Mycosis Fungoides and Sezary Syndrome by RT‐PCR and correlate our findings with 6 years of clinical follow‐up. These findings reveal that AHI1 and CDKN1C exhibit opposite expression patterns, where AHI1 is expressed in poor and intermediate prognosis patients, while CDKN1C is expressed in favourable prognosis patients. Kaplan–Meier analysis documents that downregulation of CDKN1C is associated with poor disease outcome in patients with CTCL, while upregulation of AHI1 shows a weak association with aggressive disease course.
A novel missense mutation of the CYLD gene identified in a Hungarian family with Brooke–Spiegler syndrome
Authors: Nagy Nikoletta , Farkas Katalin , Kinyo Ágnes , Nemeth Istvan B. , Kis Erika , Varga János , Bata‐Csorgo Zsuzsanna , Kemeny Lajos , Szell Márta
Published: October 2012

Brooke–Spiegler syndrome (BSS; OMIM 605041) is an autosomal dominant disease characterized by skin appendage tumors due to mutations in the cylindromatosis gene (CYLD). We investigated a Hungarian BSS pedigree with two affected members, father and daughter. Direct sequencing demonstrated a novel missense mutation (c.2613C>G; p.His871Gln) in exon 19 within the ubiquitin‐specific protease domain of the encoded protein. We performed preliminary analysis to reveal the functional role of this novel mutation. Our data suggest that this novel CYLD mutation leads to increased ubiquitination of NEMO through influencing deubiquitinating activity of the CYLD protein and thus may result in enhanced NF‐κB signalling.
The response of soil organic carbon of a rich fen peatland in interior Alaska to projected climate change
Authors: Fan Zhaosheng , David McGuire Anthony , Turetsky Merritt R. , Harden Jennifer W. , Michael Waddington James , Kane Evan S.
Published: October 2012

It is important to understand the fate of carbon in boreal peatland soils in response to climate change because a substantial change in release of this carbon as CO2 and CH4 could influence the climate system. The goal of this research was to synthesize the results of a field water table manipulation experiment conducted in a boreal rich fen into a process‐based model to understand how soil organic carbon (SOC) of the rich fen might respond to projected climate change. This model, the peatland version of the dynamic organic soil Terrestrial Ecosystem Model (peatland DOS‐TEM), was calibrated with data collected during 2005–2011 from the control treatment of a boreal rich fen in the Alaska Peatland Experiment (APEX). The performance of the model was validated with the experimental data measured from the raised and lowered water‐table treatments of APEX during the same period. The model was then applied to simulate future SOC dynamics of the rich fen control site under various CO2 emission scenarios. The results across these emissions scenarios suggest that the rate of SOC sequestration in the rich fen will increase between year 2012 and 2061 because the effects of warming increase heterotrophic respiration less than they increase carbon inputs via production. However, after 2061, the rate of SOC sequestration will be weakened and, as a result, the rich fen will likely become a carbon source to the atmosphere between 2062 and 2099. During this period, the effects of projected warming increase respiration so that it is greater than carbon inputs via production. Although changes in precipitation alone had relatively little effect on the dynamics of SOC, changes in precipitation did interact with warming to influence SOC dynamics for some climate scenarios.
Impacts of climate change on paddy rice yield in a temperate climate
Authors: Kim Han‐Yong , Ko Jonghan , Kang Suchel , Tenhunen John
Published: October 2012

The crop simulation model is a suitable tool for evaluating the potential impacts of climate change on crop production and on the environment. This study investigates the effects of climate change on paddy rice production in the temperate climate regions under the East Asian monsoon system using the CERES‐Rice 4.0 crop simulation model. This model was first calibrated and validated for crop production under elevated CO2 and various temperature conditions. Data were obtained from experiments performed using a temperature gradient field chamber (TGFC) with a CO2 enrichment system installed at Chonnam National University in Gwangju, Korea in 2009 and 2010. Based on the empirical calibration and validation, the model was applied to deliver a simulated forecast of paddy rice production for the region, as well as for the other Japonica rice growing regions in East Asia, projecting for years 2050 and 2100. In these climate change projection simulations in Gwangju, Korea, the yield increases (+12.6 and + 22.0%) due to CO2 elevation were adjusted according to temperature increases showing variation dependent upon the cultivars, which resulted in significant yield decreases (−22.1% and −35.0%). The projected yields were determined to increase as latitude increases due to reduced temperature effects, showing the highest increase for any of the study locations (+24%) in Harbin, China. It appears that the potential negative impact on crop production may be mediated by appropriate cultivar selection and cultivation changes such as alteration of the planting date. Results reported in this study using the CERES‐Rice 4.0 model demonstrate the promising potential for its further application in simulating the impacts of climate change on rice production from a local to a regional scale under the monsoon climate system.
Is Neo‐Republicanism Bad for Women?
Authors: Costa M. Victoria
Published: October 2012

The republican revival in political philosophy, political theory, and legal theory has produced an impressive range of novel interpretations of the historical figures of the republican tradition. It has also given rise to a variety of contemporary neo‐republican theories that build on its historical themes. Although there have been some feminist discussions of its historical representatives, neo‐republicanism has not generated a great deal of enthusiasm among feminists. The present paper examines Phillip Pettit's theory of freedom as nondomination in order to assess its potential usefulness for those with feminist goals. It defends Pettit's account of interpersonal domination from certain feminist objections, but argues that his account of state domination needs to be amended if it is fully to protect the interests of women and other groups.
Morphological variation between non‐native lake‐ and stream‐dwelling pumpkinseed Lepomis gibbosusin the Iberian Peninsula
Authors: Naspleda J. , Vila‐Gispert A. , Fox M. G. , Zamora L. , Ruiz‐Navarro A.
Published: October 2012

The objective of this study was to test if morphological differences in pumpkinseed Lepomis gibbosus found in their native range (eastern North America) that are linked to feeding regime, competition with other species, hydrodynamic forces and habitat were also found among stream‐ and lake‐ or reservoir‐dwelling fish in Iberian systems. The species has been introduced into these systems, expanding its range, and is presumably well adapted to freshwater Iberian Peninsula ecosystems. The results show a consistent pattern for size of lateral fins, with L. gibbosus that inhabit streams in the Iberian Peninsula having longer lateral fins than those inhabiting reservoirs or lakes. Differences in fin placement, body depth and caudal peduncle dimensions do not differentiate populations of L. gibbosus from lentic and lotic water bodies and, therefore, are not consistent with functional expectations. Lepomis gibbosus from lotic and lentic habitats also do not show a consistent pattern of internal morphological differentiation, probably due to the lack of lotic–lentic differences in prey type. Overall, the univariate and multivariate analyses show that most of the external and internal morphological characters that vary among populations do not differentiate lotic from lentic Iberian populations. The lack of expected differences may be a consequence of the high seasonal flow variation in Mediterranean streams, and the resultant low‐ or no‐flow conditions during periods of summer drought.
Ipilimumab induces simultaneous regression of melanocytic naevi and melanoma metastases
Authors: Libon F. , Arrese J. E. , Rorive A. , Nikkels A. F.
Published: October 2012

Ipilimumab blocks cytotoxic T-lymphocyte-associated antigen (CTLA)-4, potentiating the antimelanoma T-cell host response. Ipilimumab has been shown to improve overall survival in patients with previously treated metastatic melanoma. CTLA-4 antibodies generate immune responses to the melanoma-associated antigens Melan-A, NY-ESO-1 and glycoprotein (gp)100 in metastatic melanoma. Digital epiluminescence microscopy (DELM) is a noninvasive method permitting the monitoring of the morphology of melanocytic lesions over time. A 50-year-old man with metastatic melanoma received four ipilimumab injections after failure of dacarbazine chemotherapy. Positron emission tomography revealed regression of pulmonary metastases, and simultaneously, DELM showed regression of several melanocytic naevi. On histological examination of the regressing naevi, prominent CD8+, CD4+ and CD45R0 lichenoid lymphohistiocytic infiltrates were seen, whereas nonregressing naevi were almost free of inflammatory infiltrate. Expression of melanoma-associated antigens in benign melanocytic naevi may explain the induction of naevus regression by ipilimumab. DELM could represent a valuable noninvasive method to monitor ipilimumab efficacy.
Effect of grain tef [Eragrostis tef (Zucc.) Trotter] flour substitution with flaxseed on quality and functionality of injera
Authors: Girma Tewodros , Bultosa Geremew , Bussa Negussie
Published: October 2012

Injera from tef substituted with two flaxseed forms at 3%, 6% and 9% and control injera showed substitution had a significant effect on injera proximate, energy, titratable acidity (TA), total phenolics (TP) contents and sensory acceptability. Flaxseed forms had influence on moisture, fibre, total carbohydrate (TC) and TA. With 9% flour and whole flaxseed substitution, percentage energy, moisture, ash, crude protein, fibre and TA increase were 3.5, 27.3, 25.9, 20.4, 114.3 and 10.1, respectively. TC and pH were high for control. In all injera samples, condensed tannins and free fatty acid were insignificant. With an increase in the flaxseed substitution, most sensory acceptance increased, whereas injera eyes and colour decreased and appeared superior for control (100% tef injera). The 9% flaxseed‐substituted injera showed good proximate nutritional and energy contents of functional potential of high in dietary fibre, alpha linolenic acid, lignans, proteins and TP of anti‐oxidant nature.
Controlled and modified atmospheres influence chilling injury, fruit quality and antioxidative system of Japanese plums (Prunus salicina Lindell)
Authors: Singh Sukhvinder Pal , Singh Zora
Published: October 2012

Our objective was to compare the effects of controlled atmosphere (CA) and modified atmosphere packaging (MAP) on fruit quality, chilling injury (CI) and pro‐ and antioxidative systems in ‘Blackamber’ Japanese plums. Matured fruit were stored for 5 and 8 weeks at 0–1 °C in normal air, CA‐1 (1% O2 + 3% CO2), CA‐2 (2.5% O2 + 3% CO2) and MAP (~10% O2 and 3.8% CO2). CA was more effective than MAP in retention of flesh firmness and titratable acidity during cold storage. Fruit stored in CA‐1 showed reduced CI and membrane lipid peroxidation after 5 and 8 weeks of cold storage. Low O2 atmospheres appeared to limit the generation of reactive oxygen species (ROS) and their efficient scavenging through the concerted action of superoxide dismutase and peroxidase. The role of ascorbate–glutathione (AsA–GSH) cycle in the regulation of oxidative stress was also studied during and after storage in different atmospheres. In conclusion, optimum CA conditions delayed fruit ripening and CI through augmentation of antioxidative metabolism and suppression of oxidative processes.
Aggressive continuous passive motion exercise does not improve knee range of motion after total knee arthroplasty
Authors: Chen Lan‐Hui , Chen Chung‐Hwan , Lin Sung‐Yen , Chien Song‐Hsiung , Su Jiing Yuan , Huang Chao‐Yung , Wang Hui‐Yu , Chou Chih‐Liang , Tsai Tsung‐Yu , Cheng Yuh‐Min , Huang Hsuan‐Ti
Published: October 2012

Aims and objectives.  The aim of this study was to evaluate the effects of continuous passive motion on the range of motion, postoperative pain and life quality of patients undergoing total knee arthroplasty within six months after the operation.

Background.  Total knee arthroplasty reduces pain and improves range of motion of the osteoarthritic knee joint. Continuous passive motion increases postoperative movement, but there is some controversy regarding whether aggressive continuous passive motion can improve range of motion or life quality, and whether it induces more pain.

Design.  A prospective controlled study was conducted in a medical centre in Taiwan from January to December 2006.

Methods.  One hundred and seven patients were recruited. The patients underwent the basic rehabilitation protocols (the control group) or the basic rehabilitation protocols and additional daily use of continuous passive motion for more than six hours per day (the experimental group). The range of motion, modified Short Form‐36 (SF‐36) and semi‐quantitative visual analogue scale were recorded.

Results.  Range of motion increased from 109° preoperatively to 125° at six months postoperatively in the treatment group and from 111° preoperatively to 125° at six months postoperatively in the control group. Visual analogue scale decreased from 7·78 preoperatively to 0·37 at six months postoperatively in the treatment group and from 7·92 preoperatively to 0·21 at six months postoperatively in the control group. The SF‐36 improved from 3·76 preoperatively to 1·77 at six months postoperatively in the treatment group and from 3·68 preoperatively to 1·83 at six months postoperatively in the control group. There was no significant difference in range of motion, visual analogue scale and SF‐36 between groups at each visit.

Conclusion.  With the advances in total knee arthroplasty surgical technique, aggressive continuous passive motion does not provide obvious benefits.

Relevance to clinical practice.  Total knee arthroplasty can alleviate pain and improve range of motion, but aggressive continuous passive motion does not provide additional benefits.
Family members’ perceptions of the nursing bedside handover
Authors: Tobiano Georgia , Chaboyer Wendy , McMurray Anne
Published: October 2012

Aims and objectives.  To explore families’ perceptions of shift‐to‐shift bedside handover.

Background.  The potential role families can play in bedside handover is unknown. Understanding family members’ perceptions can provide a foundation for nurses to tailor their bedside handover to family members’ perceptions, encouraging their involvement and potentially improving patient care.

Design.  Qualitative study, using case study methodology.

Methods.  The study was conducted with eight family members in one rehabilitation ward in Queensland, Australia, in 2009. Data included observations of bedside handover, field notes and in‐depth interviews. Thematic analysis of data was conducted to identify unique and common themes indicative of family perceptions.

Results.  Three major themes emerged. The first, understanding the situation, consisted of three subthemes: feeling informed, understanding the patient’s condition and understanding patient’s treatment. The second theme was interacting with nursing staff, with five subthemes, including sharing information, clarifying information, assisting in care, asking questions and interpreting for the patient. The final subtheme was finding value, which contained five subthemes: feeling at ease, feeling included, valuing individualisation, preparing for the future and maintaining patient privacy.

Conclusions.  Bedside handover provides an opportunity to involve family members in patient care and promote family‐centred care core concepts. Family members value the chance to participate and can ultimately improve the accuracy of handover communication.

Relevance to clinical practice.  Bedside handover is beneficial for nurses, patients and family members and embodies patient and family‐centred care. Managers should consider its implementation in hospitals, developing strategies such as standard operating protocols for a more family inclusive approach to communication. Nurses may require further training to best undertake bedside handover and involve family members in care. The study suggests expansion of research into this important area of family‐centred care.
Resistance or Resilience? Tracking the Pathway of Recent Arrivals to a ‘New’ Rural Destination
Authors: McAreavey Ruth
Published: October 2012

Recent patterns of migration indicate that international migrants are not confined to urban gateways. Instead many migrants have settled in new destination areas located in rural and small town areas. While this might appear to be a positive phenomenon for rural areas struggling with decline and stagnation, the reality is that many of these areas are ill‐equipped to manage the rate and pace of change that has been witnessed in recent years. Migration to established, typically urban areas has been the subject of extensive research. However, little is known about the way in which migrants navigate their way through social structures as they settle into destinations with little experience of immigration. Using empirical research, this article considers the way in which migrants navigate their way through social structures to establish life in a so‐called ‘new’ migration destination. It analyses the way in which government and civil society respond to their needs of recent arrivals, showing how both NGO’s and the statutory sector play an important role in this process. It considers the ramifications for these different sectors and the implications for so‐called ‘new’ destinations as they become more established or ‘mature’ areas of immigration.