bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissection of the Head Cuticle and Sheath of Living Flies for Whole-Cell Patch-Clamp Recordings in the Brain
Authors: Murthy Mala , Turner Glenn
Published: February 2013

Whole-cell patch-clamp recording has been applied to neurons in the central nervous system of Drosophila, allowing researchers to study the function of neurons of interest within native circuits in a genetically tractable model system. Here, we present a method to expose neurons in the fly brain for such recording. The fly is inserted into an opening in a piece of tinfoil in a recording platform and fixed in place. This immobilizes the fly’s head and permits the exposed neurons to be bathed in saline above the surface of the foil, while the sensory structures (antennae, proboscis, and much of the eyes) remain dry below the surface of the foil. The tinfoil is within a well that allows external saline to be perfused over the fly, and the walls of the well adapted so the ground wire (connected to the amplifier head stage) can be securely positioned within the saline bath. Our method to construct a recording platform, presented here, makes use of materials in the laboratory. Once the fly is mounted in the platform, the head cuticle and sheath covering the brain are removed. We describe how to mount the fly and open up the head cuticle to access the mushroom body Kenyon cells (KCs), whose somata are located on the dorsal/posterior surface of the brain. To record from neuronal cell bodies located in other brain regions, the approach to mount the fly must be modified to provide consistent access to the cells of interest.
Isolation of Mouse Mammary Organoids for Long-Term Time-Lapse Imaging
Authors: Ewald Andrew J.
Published: February 2013

Many epithelial tissues develop deep within the animal and are inaccessible to high-resolution optical imaging with visible wavelengths. Protocols for culturing whole epithelial organs have existed since the 1950s, but the use of three-dimensional (3D) organotypic cultures of epithelial fragments has advanced dramatically in recent years. Here we describe the practical details involved in isolating mammary epithelial tissue and culturing organoids embedded within 3D gels. Mammary glands are mechanically disrupted and enzymatically digested, and the epithelial cell fragments are separated from stromal cells by differential centrifugation. The organoids are cultured in BD Matrigel in the absence or presence of growth factor.
Metabolic Effectors Secreted by Bacterial Pathogens: Essential Facilitators of Plastid Endosymbiosis?
Authors: Ball Steven G. , Subtil Agathe , Bhattacharya Debashish , Moustafa Ahmed , Weber Andreas P.M. , Gehre Lena , Colleoni Christophe , Arias Maria-Cecilia , Cenci Ugo , Dauvillée David
Published: February 2013

Under the endosymbiont hypothesis, over a billion years ago a heterotrophic eukaryote entered into a symbiotic relationship with a cyanobacterium (the cyanobiont). This partnership culminated in the plastid that has spread to forms as diverse as plants and diatoms. However, why primary plastid acquisition has not been repeated multiple times remains unclear. Here, we report a possible answer to this question by showing that primary plastid endosymbiosis was likely to have been primed by the secretion in the host cytosol of effector proteins from intracellular Chlamydiales pathogens. We provide evidence suggesting that the cyanobiont might have rescued its afflicted host by feeding photosynthetic carbon into a chlamydia-controlled assimilation pathway.
WUSCHEL-RELATED HOMEOBOX4Is Involved in Meristem Maintenance and Is Negatively Regulated by the CLE GeneFCP1in Rice
Authors: Ohmori Yoshihiro , Tanaka Wakana , Kojima Mikiko , Sakakibara Hitoshi , Hirano Hiro-Yuki
Published: February 2013

The shoot apical meristem is the ultimate source of the cells that constitute the entire aboveground portion of the plant body. In Arabidopsis thaliana, meristem maintenance is regulated by the negative feedback loop of WUSCHEL-CLAVATA (WUS-CLV). Although CLV-like genes, such as FLORAL ORGAN NUMBER1 (FON1) and FON2, have been shown to be involved in maintenance of the reproductive meristems in rice (Oryza sativa), current understanding of meristem maintenance remains insufficient. In this article, we demonstrate that the FON2-LIKE CLE PROTEIN1 (FCP1) and FCP2 genes encoding proteins with similar CLE domains are involved in negative regulation of meristem maintenance in the vegetative phase. In addition, we found that WUSCHEL-RELATED HOMEOBOX4 (WOX4) promotes the undifferentiated state of the meristem in rice and that WOX4 function is associated with cytokinin action. Consistent with similarities in the shoot apical meristem phenotypes caused by overexpression of FCP1 and downregulation of WOX4, expression of WOX4 was negatively regulated by FCP1 (FCP2). Thus, FCP1/2 and WOX4 are likely to be involved in maintenance of the vegetative meristem in rice.
ArabidopsisPhytochrome B Promotes SPA1 Nuclear Accumulation to Repress Photomorphogenesis under Far-Red Light
Authors: Zheng Xu , Wu Suowei , Zhai Huqu , Zhou Peng , Song Meifang , Su Liang , Xi Yulin , Li Zhiyong , Cai Yingfan , Meng Fanhua , Yang Li , Wang Haiyang , Yang Jianping
Published: February 2013

Phytochrome A (phyA) is the primary photoreceptor mediating deetiolation under far-red (FR) light, whereas phyB predominantly regulates light responses in red light. SUPPRESSOR OF PHYA-105 (SPA1) forms an E3 ubiquitin ligase complex with CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), which is responsible for the degradation of various photomorphogenesis-promoting factors, resulting in desensitization to light signaling. However, the role of phyB in FR light signaling and the regulatory pathway from light-activated phytochromes to the COP1-SPA1 complex are largely unknown. Here, we confirm that PHYB overexpression causes an etiolation response with reduced ELONGATED HYPOCOTYL5 (HY5) accumulation under FR light. Notably, phyB exerts its nuclear activities and promotes seedling etiolation in both the presence and absence of phyA in response to FR light. PhyB acts upstream of SPA1 and is functionally dependent on it in FR light signaling. PhyB interacts and forms a protein complex with SPA1, enhancing its nuclear accumulation under FR light. During the dark-to-FR transition, phyB is rapidly imported into the nucleus and facilitates nuclear SPA1 accumulation. These findings support the notion that phyB plays a role in repressing FR light signaling. Activity modulation of the COP1-SPA E3 complex by light-activated phytochromes is an effective and pivotal regulatory step in light signaling.
An Arabidopsis Cell Wall Proteoglycan Consists of Pectin and Arabinoxylan Covalently Linked to an Arabinogalactan Protein
Authors: Tan Li , Eberhard Stefan , Pattathil Sivakumar , Warder Clayton , Glushka John , Yuan Chunhua , Hao Zhangying , Zhu Xiang , Avci Utku , Miller Jeffrey S. , Baldwin David , Pham Charles , Orlando Ronald , Darvill Alan , Hahn Michael G. , Kieliszewski Marcia J. , Mohnen Debra
Published: February 2013

Plant cell walls are comprised largely of the polysaccharides cellulose, hemicellulose, and pectin, along with ∼10% protein and up to 40% lignin. These wall polymers interact covalently and noncovalently to form the functional cell wall. Characterized cross-links in the wall include covalent linkages between wall glycoprotein extensins between rhamnogalacturonan II monomer domains and between polysaccharides and lignin phenolic residues. Here, we show that two isoforms of a purified Arabidopsis thaliana arabinogalactan protein (AGP) encoded by hydroxyproline-rich glycoprotein family protein gene At3g45230 are covalently attached to wall matrix hemicellulosic and pectic polysaccharides, with rhamnogalacturonan I (RG I)/homogalacturonan linked to the rhamnosyl residue in the arabinogalactan (AG) of the AGP and with arabinoxylan attached to either a rhamnosyl residue in the RG I domain or directly to an arabinosyl residue in the AG glycan domain. The existence of this wall structure, named ARABINOXYLAN PECTIN ARABINOGALACTAN PROTEIN1 (APAP1), is contrary to prevailing cell wall models that depict separate protein, pectin, and hemicellulose polysaccharide networks. The modified sugar composition and increased extractability of pectin and xylan immunoreactive epitopes in apap1 mutant aerial biomass support a role for the APAP1 proteoglycan in plant wall architecture and function.
ArabidopsisPaired Amphipathic Helix Proteins SNL1 and SNL2 Redundantly Regulate Primary Seed Dormancy via Abscisic Acid–Ethylene Antagonism Mediated by Histone Deacetylation
Authors: Wang Zhi , Cao Hong , Sun Yongzhen , Li Xiaoying , Chen Fengying , Carles Annaick , Li Yong , Ding Meng , Zhang Cun , Deng Xin , Soppe Wim J.J. , Liu Yong-Xiu
Published: February 2013

Histone (de)acetylation is a highly conserved chromatin modification that is vital for development and growth. In this study, we identified a role in seed dormancy for two members of the histone deacetylation complex in Arabidopsis thaliana, SIN3-LIKE1 (SNL1) and SNL2. The double mutant snl1 snl2 shows reduced dormancy and hypersensitivity to the histone deacetylase inhibitors trichostatin A and diallyl disulfide compared with the wild type. SNL1 interacts with HISTONE DEACETYLASE19 in vitro and in planta, and loss-of-function mutants of SNL1 and SNL2 show increased acetylation levels of histone 3 lysine 9/18 (H3K9/18) and H3K14. Moreover, SNL1 and SNL2 regulate key genes involved in the ethylene and abscisic acid (ABA) pathways by decreasing their histone acetylation levels. Taken together, we showed that SNL1 and SNL2 regulate seed dormancy by mediating the ABA-ethylene antagonism in Arabidopsis. SNL1 and SNL2 could represent a cross-link point of the ABA and ethylene pathways in the regulation of seed dormancy.
A DEAD Box RNA Helicase Is Critical for Pre-mRNA Splicing, Cold-Responsive Gene Regulation, and Cold Tolerance inArabidopsis
Authors: Guan Qingmei , Wu Jianmin , Zhang Yanyan , Jiang Changhua , Liu Renyi , Chai Chenglin , Zhu Jianhua
Published: February 2013

Cold stress resulting from chilling and freezing temperatures substantially reduces crop production worldwide. To identify genes critical for cold tolerance in plants, we screened Arabidopsis thaliana mutants for deregulated expression of a firefly luciferase reporter gene under the control of the C-REPEAT BINDING FACTOR2 (CBF2) promoter (CBF2:LUC). A regulator of CBF gene expression1 (rcf1-1) mutant that is hypersensitive to cold stress was chosen for in-depth characterization. RCF1 encodes a cold-inducible DEAD (Asp-Glu-Ala-Asp) box RNA helicase. Unlike a previously reported DEAD box RNA helicase (LOW EXPRESSION OF OSMOTICALLY RESPONSIVE GENES4 [LOS4]) that regulates mRNA export, RCF1 does not play a role in mRNA export. Instead, RCF1 functions to maintain proper splicing of pre-mRNAs; many cold-responsive genes are mis-spliced in rcf1-1 mutant plants under cold stress. Functional characterization of four genes (PSEUDO-RESPONSE REGULATOR5 [PRR5], SHAGGY-LIKE SERINE/THREONINE KINASE12 [SK12], MYB FAMILY TRANSCRIPTION FACTOR CIRCADIAN1 [CIR1], and SPFH/PHB DOMAIN-CONTAINING MEMBRANE-ASSOCIATED PROTEIN [SPFH]) that are mis-spliced in rcf1-1 revealed that these genes are cold-inducible positive (CIR1 and SPFH) and negative (PRR5 and SK12) regulators of cold-responsive genes and cold tolerance. Together, our results suggest that the cold-inducible RNA helicase RCF1 is essential for pre-mRNA splicing and is important for cold-responsive gene regulation and cold tolerance in plants.
Mechanistic models of animal migration behaviour – their diversity, structure and use
Authors: Bauer Silke , Klaassen Marcel
Published: February 2013

Migration is a widespread phenomenon in the animal kingdom, including many taxonomic groups and modes of locomotion. Developing an understanding of the proximate and ultimate causes for this behaviour not only addresses fundamental ecological questions but has relevance to many other fields, for example in relation to the spread of emerging zoonotic diseases, the proliferation of invasive species, aeronautical safety as well as the conservation of migrants.

Theoretical methods can make important contributions to our understanding of migration, by allowing us to integrate findings on this complex behaviour, identify caveats in our understanding and to guide future empirical research efforts. Various mechanistic models exist to date, but their applications seem to be scattered and far from evenly distributed across taxonomic units.

Therefore, we provide an overview of the major mechanistic modelling approaches used in the study of migration behaviour and characterize their fundamental features, assumptions and limitations and discuss their typical data requirements both for model parameterization and for scrutinizing model predictions.

Furthermore, we review 155 studies that have used mechanistic models to study animal migration and analyse them with regard to the approaches used and the focal species, and also explore their contribution to advancing current knowledge within six broad migration ecology research themes.

This identifies important gaps in our present knowledge, which should be tackled in future research using existing and to‐be developed theoretical approaches.
Quantitative physiology of Lactococcus lactis at extreme low‐growth rates
Authors: Ercan Onur , Smid Eddy J. , Kleerebezem Michiel
Published: February 2013

This paper describes the metabolic adaptation of Lactococcus lactis during the transition from a growing to a non‐growing state using retentostat cultivation. Under retentostat cultivation, the specific growth rate decreased from 0.025 h−1 to 0.0001 h−1 in 42 days, while doubling time increased to more than 260 days. Viability of the overall culture was maintained above 90% but included approximately 20% damaged cells, which had lost their colony forming capacity on solid media. Although culture biomass and viability had reached a steady‐state after 14 days of retentostat cultivation, the morphology of the cells changed from coccus‐to‐rod shape at later stages of retentostat cultivation, by which the cell's surface to volume ratio was estimated to increase 2.4‐fold. Furthermore, the metabolic patterns switched between homolactic and mixed‐acid fermentation during the retentostat cultivation. Retentostat cultivation enabled the calculation of accurate substrate‐ and energy‐related maintenance coefficients and biomass yields under non‐growing conditions, which were in good agreement with those calculated by extrapolation from chemostat cultivations at high dilution rates. In this study, we illustrate how retentostat cultivation allows decoupling of growth and non‐growth associated processes in L. lactis, enabling the analysis of quantitative physiological responses of this bacterium to near zero‐specific growth rates.
Diabetes nurse case management and motivational interviewing for change (DYNAMIC): Results of a 2‐year randomized controlled pragmatic trial (糖尿病护士病例管理以及促进改变的动机性会谈（DYNAMIC）：一项为期2年的实用随机对照研究)
Authors: Gabbay Robert A. , Añel‐Tiangco Raquel M. , Dellasega Cheryl , Mauger David T. , Adelman Alan , Van Horn Deborah H.A.
Published: February 2013

Background

The aim of the present study was to determine whether the addition of nurse case managers (NCMs) trained in motivational interviewing (MI) to usual care would result in improved outcomes in high‐risk type 2 diabetes patients.

Methods

A 2‐year randomized controlled pragmatic trial randomized 545 patients to usual care control (n = 313) or those who received the intervention (n = 232) with additional practice‐embedded NCM care, including MI‐guided behavior change counseling. The NCMs received intensive MI training with ongoing fidelity assessment.

Results

Systolic blood pressure (SBP) was better in the intervention than usual care group (131 ± 15 vs. 135 ± 18 mmHg, respectively; P < 0.05). Improvements were seen in both the control and intervention groups in terms of HbA1c (from 9.1% to 8.0% and from 8.8% to 7.8%, respectively), low‐density lipoprotein (LDL; from 127 to 100 mg/dL and from 128 to 102 mg/dL, respectively), and diastolic blood pressure (from 78 to 74 mmHg and from 80 to 74 mmHg, respectively). Depression symptom scores were better in the intervention group. The reduction in diabetes‐related distress approached statistical significance.

Conclusions

The NCMs and MI improved SBP and complications screening. The large decrease in HbA1C and LDL in the control group may have obscured any further intervention effect. Although nurses prompted providers for medication titration, strategies to reduce provider clinical inertia may also be needed.
Comparison of autoantibody‐positive and autoantibody‐negative pediatric participants enrolled in the T1D Exchange clinic registry (在1型糖尿病交流中心临床登记的自身抗体阳性与自身抗体阴性的儿科参与者的比较)
Authors: Gerard‐Gonzalez Andrea , Gitelman Stephen E. , Cheng Peiyao , Dubose Stephanie N. , Miller Kellee M. , Olson Beth A. , Redondo Maria J. , Steck Andrea K. , Beck Roy W.
Published: February 2013

Objective

To compare characteristics of autoantibody (aAb)‐positive and ‐negative cases of type 1 diabetes (T1D) <18 years old in the T1D Exchange clinic registry.

Methods

An aAb‐positive status (n = 6239) required at least one of the aAbs to be positive; an aAb‐negative status (n = 485) required negative results on testing of at least two different aAbs.

Results

The percentage of males was higher (58% vs 51%; P = 0.002) and total daily insulin dose lower (P = 0.003) in aAb‐negative compared with aAb‐positive groups, but both groups had similar distributions of race–ethnicity, diagnosis age, family history of T1D, ketoacidosis at diagnosis, body mass index at diagnosis and at most recent office visit, and current HbA1c.

Conclusions

Male gender and lower total daily insulin dose were more likely in aAb‐negative than aAb‐positive children with T1D, but no other distinguishing characteristics were identified. Further examination of characteristics of aAb‐negative cases may help characterize the heterogeneous nature of T1D.
Restricted variation in plant barcoding markers limits identification in closely related bryophyte species
Authors: Hassel Kristian , Segreto Rossana , Ekrem Torbjørn
Published: February 2013

Species‐level identification and delimitation of bryophytes using the proposed general barcode markers for land plants has been challenging. Bryophyta (mosses) is the second most species‐rich group of land plants after angiosperms, and it is thus of great importance to find useful barcoding regions also for this group of plants. We investigated how the plastid regions atpF–atpH, rbcL and trnH–psbA and the nuclear ITS2 region performed as barcode markers on closely related bryophyte taxa of selected moss (Bartramia, Distichium, Fissidens, Meesia and Syntrichia) and liverwort (Blepharostoma) genera from boreal and arctic regions. We also evaluated how sequencing success of herbarium specimens is related to length of the sequenced fragment, specimen age and taxonomic group. Sequencing success was higher for shorter fragments and younger herbarium specimens, but was lower than expected in the genera Distichium and Fissidens, indicating imperfect universality of the primers used. None of the studied DNA barcode regions showed a consistent barcode gap across the studied genera. As a single locus, the region atpF–atpH performed slightly better than rbcL and ITS2 and much better than trnH–psbA in terms of grouping conspecific sequences in monophyletic groups. This marker also gave a higher percentage of correct hits when conducting blast searches on a local database of identified sequences. Concatenated data sets of two and three markers grouped more conspecific sequences in monophyletic groups, but the improvement was not great compared with atpF–atpH alone. A discussion of recent studies testing barcode regions for bryophytes is given. We conclude that atpF–atpH, rbcL and ITS2 are to be the most promising barcode markers for mosses.
Molecular mapping of stomatal‐conductance‐related traits in durum wheat (Triticum turgidum ssp. durum)
Authors: Panio G. , Motzo R. , Mastrangelo A.M. , Marone D. , Cattivelli L. , Giunta F. , De Vita P.
Published: February 2013

The most promising traits identified in wheat to raise yield potential via an increase in biomass accumulation are stomatal conductance and stomatal‐conductance‐related traits, such as carbon isotope discrimination (CID) and photosynthetic rate. The evaluation of the extent of genetic variation and the mapping of chromosomal regions controlling these traits are essential for the development of effective breeding strategies in durum wheat. A population of 161 F2‐derived, F8–F9 recombinant inbred lines obtained from a cross between durum wheat (Triticum turgidum ssp. durum) cultivars Ofanto and Cappelli was phenotyped for heading date, plant height, leaf porosity, CID and chlorophyll concentration (estimated through the SPAD index) for 2007/2008 and 2008/2009 seasons, at Ottava, Sardinia (Italy) under irrigated conditions. The genotype mean heritability for leaf porosity, CID and chlorophyll concentration was moderate in size. Six quantitative trait loci were detected for leaf porosity, four for chlorophyll concentration, but only one for CID, because of the small variation expressed in the population for this trait under these experimental conditions. The quantitative trait loci for leaf porosity located on chromosome 3B appear to be more stable with respect to the others, and different microsatellite markers are positioned within the interval of the quantitative trait loci, or in their vicinity, that represent useful tools in programmes for selection assisted by molecular markers.
A new clade of Dickeya spp. plays a major role in potato blackleg outbreaks in North Finland
Authors: Degefu Yeshitila , Potrykus Marta , Golanowska Malgorzata , Virtanen Elina , Lojkowska Ewa
Published: February 2013

Until recently Dickeya was regarded as a pathogen not established in Finland. As a result the blackleg symptom observed on potato was often associated with Pectobacterium atrosepticum. The occurrence of Dickeya spp. on potato in Finland was first reported in 2004. Since then the prevalence of Dickeya has been monitored through surveys and routine test of seed lots produced in the country. The results of monitoring of Dickeya spp. in seed lots produced in Finland between the years 2004 and 2008 indicated a steady increase in the incidence of Dickeya spp. The highest incidence was observed in samples from the 2006 growing season where about 37% were positive for Dickeya spp. The summer in 2006 was one of the warmest summers recorded in 100 years in Finland. The majority of infected lots were imported varieties. Since recently heavy blackleg outbreaks have occurred in production fields in the High Grade (HG) zone. A detailed study of these incidents of blackleg outbreaks in North Finland during the years 2008 and 2010 indicated that Dickeya spp. was the major component in the observed blackleg complex. It was detected and isolated from almost all symptomatic plants investigated. Repetitive sequences PCR (REP‐PCR) and Pulsed Field Gel Electrophoresis (PFGE) analysis of strains isolated in Finland showed identical pattern with those isolated recently in other European countries with a proposed name ‘Dickeya solani’. Moreover, the dnaX gene sequence of the representative strains isolated in Finland indicated 100% similarity to the dnaX sequences of ‘D. solani’. The study presents the first report of a detailed analysis of bacteria involved in potato blackleg complex from natural field outbreaks in North Finland HG zone and characterisation of the ‘D. solani’ strains playing the major role in the disease complex.
Sources of momentum profits in international stock markets
Authors: Park Kyung‐In , Kim Dongcheol
Published: February 2013

This paper examines the sources of momentum profits of countries exhibiting and not exhibiting momentum and compares the differences in the underlying factors determining momentum profits between these two groups of countries. We find remarkable differences in the decomposed components between these two groups of countries. Countries exhibiting momentum show that the cross‐sectional dispersion in unconditional mean returns dominates the negative contribution from the component reflecting the intertemporal behaviour of asset returns. However, this is not the case in countries exhibiting no momentum. Furthermore, countries with greater relative contribution from the cross‐sectional variance in unconditional mean returns tend to have greater momentum profits. Our results may support risk‐based explanations for the momentum phenomenon rather than behavioural finance‐based explanations.
Intercoalescence Time Distribution of Incomplete Gene Genealogies in Temporally Varying Populations, and Applications in Population Genetic Inference
Authors: Chen Hua
Published: February 2013

Tracing back to a specific time T in the past, the genealogy of a sample of haplotypes may not have reached their common ancestor and may leave m lineages extant. For such an incomplete genealogy truncated at a specific time T in the past, the distribution and expectation of the intercoalescence times conditional on T are derived in an exact form in this paper for populations of deterministically time‐varying sizes, specifically, for populations growing exponentially. The derived intercoalescence time distribution can be integrated to the coalescent‐based joint allele frequency spectrum (JAFS) theory, and is useful for population genetic inference from large‐scale genomic data, without relying on computationally intensive approaches, such as importance sampling and Markov Chain Monte Carlo (MCMC) methods. The inference of several important parameters relying on this derived conditional distribution is demonstrated: quantifying population growth rate and onset time, and estimating the number of ancestral lineages at a specific ancient time. Simulation studies confirm validity of the derivation and statistical efficiency of the methods using the derived intercoalescence time distribution. Two examples of real data are given to show the inference of the population growth rate of a European sample from the NIEHS Environmental Genome Project, and the number of ancient lineages of 31 mitochondrial genomes from Tibetan populations.
Bladder and bowel dysfunction and the resolution of urinary incontinence with successful management of bowel symptoms in children
Authors: Borch Luise , Hagstroem Søren , Bower Wendy F , Siggaard Rittig Charlotte , Rittig Søren
Published: February 2013

Aim

To investigate the effect of treating defecation problems on urinary incontinence in children suffering from combined urinary bladder and bowel dysfunction (BBD).

Methods

We established a clinical database from medical records of all children referred to the urinary incontinence and gastroenterology outpatient clinics with BBD. The following variables were extracted: symptoms of constipation, faecal incontinence, urinary incontinence, age at onset of symptoms, treatment, including duration and response. All children went through the same treatment protocol. Faecal disorders were treated primarily and once relieved, the daytime incontinence was managed and followed by intervention for nocturnal enuresis.

Results

In total, 73 children were included in the study. The treatment regimen resulted in resolution of the defecation disorder in 96% of the patients. Of the children with daytime urinary incontinence, 68% had at least a 50% reduction in number of daytime incontinence episodes by successful relief of bowel dysfunction and 27% became completely continent during daytime. Only 17% of the children suffering from enuresis had a significant reduction in number of wet nights after relief of their faecal problem.

Conclusion

The empirical treatment approach of managing bowel symptoms before intervening for bladder dysfunction in children with BBD is found to be appropriate.
The likelihood of having flood insurance increases with social expectations
Authors: Lo Alex Y
Published: February 2013

Flood insurance can reduce potentially disastrous economic losses to households. As climatic uncertainties grow, governments have increasingly found the social costs of non‐insurance prohibitive. Attempts to improve insurance coverage could benefit from a characterisation of the insured and uninsured households. The dominant view holds that the insured household is more risk aware and more likely to consider the costs of insurance to be affordable. In a survey of residents of Brisbane, Australia, however, the risk and income effects were found to be not significant. Instead, perception of social response predicted insurance status. The likelihood of insuring against flooding increases if individuals expect the same action from other people or affirmation from family members or friends. Adoption of flood insurance is associated with perceived social expectations. Flood managers, policymakers and insurers should address these social determinants head‐on in order to improve insurance coverage.
Postoperative complication rates and invasiveness of laparoscopy‐assisted distal gastrectomy and open distal gastrectomy based on the American Society of Anesthesiologists classification system
Authors: Kawamura Hideki , Tanioka Toshiro , Tahara Munenori , Takahashi Masahiro
Published: February 2013

Introduction

We investigated potential advantages of laparoscopy‐assisted distal gastrectomy (LADG) in high‐risk gastric cancer patients. We examined the differences among various risk groups by comparing the incidence of postoperative complications and invasiveness of LADG with those of open distal gastrectomy (ODG) based on the American Society of Anesthesiologists (ASA) criteria.

Methods

A total of 639 patients with stage IA or IB gastric cancer were included in this study. ODG was performed between 2003 and 2005, and LADG was performed between 2006 and 2011.

Results

The incidence of postoperative complications in the LADG group (ASA1, 5.6%; ASA2, 3.8%; and ASA3, 5.7%) was significantly lower than that in the ODG group in all the ASA classes (ASA1, 16.9%; ASA2, 12.5%; and ASA3, 20%). Changes in the pain scores, body temperatures and blood analyses revealed that LADG was less invasive than ODG in all ASA classes. However, as the ASA class increased, the less invasive nature of LADG decreased.

Conclusion

LADG may be less invasive than ODG, even in ASA3 patients. Hence, LADG may reduce the incidence of postoperative complications in ASA1, ASA2, and ASA3 patients.
Cytogenetics of extramedullary manifestations in multiple myeloma
Authors: Billecke Lisa , Murga Penas Eva M. , May Annette M. , Engelhardt Monika , Nagler Arnon , Leiba Merav , Schiby Ginette , Kröger Nicolaus , Zustin Jozef , Marx Andreas , Matschke Jakob , Tiemann Markus , Goekkurt Eray , Heidtmann Hans‐Heinrich , Vettorazzi Eik , Dierlamm Judith , Bokemeyer Carsten , Schilling Georgia
Published: February 2013

Extramedullary disease in patients with multiple myeloma is a rare event, occurring mostly in advanced disease or relapse. Outcome is poor and prognostic factors predicting the development of extramedullary disease have not been defined. We investigated cytogenetic alterations of myeloma cells in different extramedullary manifestations by adapting the fluorescence in situ hybridization (FISH) technique in combination with cytoplasmic immunoglobulin staining to study the cytogenetics of plasma cell tumours on paraffin embedded material. Thirty six patients were investigated: 19 with extramedullary disease, 11 with skeletal extramedullary disease and six with solitary extramedullary plasmacytoma. The first two groups showed the following results: del(17p13) 32% vs. 27%, del(13q14) 35% vs. 27%, MYC‐overrepresentation 28% vs. 18% and t(4;14) 37% vs. 18%. We detected an overall higher incidence of del(17p13) in both groups compared to data from bone marrow samples of multiple myeloma reported to date (range 7–16%). The solitary extramedullary plasmacytomas presented overall less cytogenetic aberrations than the other groups. Most important, three patients with extramedullary disease and one with skeletal extramedullary disease presented different FISH findings in the extramedullary tumour compared to their bone marrow plasma cells. del(17p13), occurring additional in three of four cases, seems a strong marker for extramedullary progression of myeloma.
Outcome after first relapse in adult patients with Philadelphia chromosome‐negative acute lymphoblastic leukaemia
Authors: Kako Shinichi , Kanamori Heiwa , Kobayashi Naoki , Shigematsu Akio , Nannya Yasuhito , Nakamae Mika , Shigeno Kazuyuki , Suzukawa Kazumi , Takeuchi Masahiro , Tsuzuki Motohiro , Usuki Kensuke , Hatanaka Kazuo , Ogawa Kazuei , Mitani Kinuko , Nawa Yuichiro , Hatta Yoshihiro , Mizuno Ishikazu , Kanda Yoshinobu
Published: February 2013

To analyse the outcome of adult patients who developed a first relapse of acute lymphoblastic leukaemia (ALL), we collected the clinical data of 332 patients with Philadelphia‐chromosome (Ph) negative ALL, aged 16–65 years, who relapsed after first complete remission (CR1) between 1998 and 2008 in 69 institutions all over Japan, including 58 patients who relapsed after allogeneic haematopoietic stem cell transplantation (Allo‐HSCT) in CR1. The overall survival (OS) was 43·4% at 1 year, and 16·3% at 5 years from relapse in patients who received chemotherapy alone in CR1. Among patients who relapsed after chemotherapy alone in CR1, 123 (52·5%) achieved a second remission (CR2) following salvage chemotherapy, of whom 62 subsequently underwent Allo‐HSCT during CR2. Allo‐HSCT in CR2 was significantly associated with better OS. Moreover, the type of salvage chemotherapy influenced OS from relapse. A doxorubicin, vincristine, and predonisone‐based (AdVP‐type) regimen was related to better OS in patients with longer CR1 (more than 1 year), but was related to worse OS in patients with shorter CR1. In conclusion, the prognosis of patients with relapsed Ph‐negative ALL is poor. Allo‐HSCT after a first relapse could improve the prognosis. Selection of the optimal salvage chemotherapy might depend on the duration of CR1.
Identifying and describing feelings and psychological flexibility predict mental health in men with HIV
Authors: Landstra Jodie M. B. , Ciarrochi Joseph , Deane Frank P. , Hillman Richard J.
Published: February 2013

Background

Difficulty identifying and describing feelings (DIDF) and psychological flexibility (PF) predict poor emotional adjustment.

Objective

To examine the relationship between DIDF and PF and whether DIDF and low PF would put men undergoing cancer screening at risk for poor adjustment.

Design

Longitudinal self‐report survey.

Methods

Two hundred and one HIV‐infected men who have sex with men participated in anal cancer screening at two time points over 14 weeks. Psychological flexibility was assessed by the Acceptance and Action Questionnaire II and DIDF by the Toronto Alexithymia Scale‐20. We also measured depression, anxiety, stress (DASS) and health‐related quality of life (QOL; SF‐12).

Results

Both DIDF and PF were reliable predictors of mental health. When levels of baseline mental health were controlled, greater DIDF predicted increases in Time 2 depression, anxiety and stress and decreases in mental and physical QOL. The link between PF and mental health was entirely mediated by DIDF.

Conclusions

Being chronically low in PF could lead to greater DIDF and thereby worse mental health. Having more PF promotes the ability to identify and differentiate the nuances of pleasant and unpleasant emotions, which enhances an individual's mental health. Intentionally enhancing men's ability to identify and describe feelings or PF may assist them to better manage a range of difficult life experiences such as health screenings and other potentially threatening information.

Statement of contribution

What is already known on this subject? Difficulties identifying and describing feelings (DIDF); components of alexithymia and psychological flexibility (PF) both predict emotional adjustment. A cross‐sectional study has identified that alexithymia and PF are related concepts. Cancer screening programmes can have difficult psychological impacts.

What does this study add? The longitudinal design supported cross‐sectional findings that DIDF and PF are related concepts. The link between PF and mental health was mediated by DIDF. Enhancing DIDF or PF may assist psychological responses to health screening.
Ecological, evolutionary, and conservation implications of incubation temperature‐dependent phenotypes in birds
Authors: DuRant Sarah E. , Hopkins William A. , Hepp Gary R. , Walters J. R.
Published: February 2013

Incubation is a vital component of reproduction and parental care in birds. Maintaining temperatures within a narrow range is necessary for embryonic development and hatching of young, and exposure to both high and low temperatures can be lethal to embryos. Although it is widely recognized that temperature is important for hatching success, little is known about how variation in incubation temperature influences the post‐hatching phenotypes of avian offspring. However, among reptiles it is well known that incubation temperature affects many phenotypic traits of offspring with implications for their future survival and reproduction. Although most birds, unlike reptiles, physically incubate their eggs, and thus behaviourally control nest temperatures, variation in temperature that influences embryonic development still occurs among nests within a population. Recent research in birds has primarily been limited to populations of megapodes and waterfowl; in each group, incubation temperature has substantial effects on hatchling phenotypic traits important for future development, survival, and reproduction. Such observations suggest that incubation temperature (and incubation behaviours of parents) is an important but underappreciated parental effect in birds and may represent a selective force instrumental in shaping avian reproductive ecology and life‐history traits. However, much more research is needed to understand how pervasive phenotypic effects of incubation temperature are among birds, the sources of variation in incubation temperature, and how effects on phenotype arise. Such insights will not only provide foundational information regarding avian evolution and ecology, but also contribute to avian conservation.
Androgenic pathway in triple negative invasive ductal tumors: Its correlation with tumor cell proliferation
Authors: McNamara Keely M. , Yoda Tomomi , Miki Yasuhiro , Chanplakorn Niramol , Wongwaisayawan Sansanee , Incharoen Pimpin , Kongdan Youwanush , Wang Lin , Takagi Kiyoshi , Mayu Takagi , Nakamura Yasuhiro , Suzuki Takashi , Nemoto Noriko , Miyashita Minoru , Tamaki Kentaro , Ishida Takanori , Ohuchi Noriaki , Sasano Hironobu
Published: February 2013

Triple negative breast cancer (TNBC) is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity. Patients with TNBC frequently undergo an aggressive clinical course due to the unavailability of specific targeted therapies. Androgen receptor (AR) was reported to be expressed in up to 60% of TNBC cases but there have been controversies as to the roles of androgen signaling through AR in TNBC. Therefore, in this study, we analyzed the status of AR in combination with androgen synthesizing enzymes (5α‐reductase type 1 (5αR1) and 17β‐hydroxysteroid dehydrogenase type 5 (17βHSD5)] in order to further understand androgenic actions in TNBC. Androgen receptor, 5αR1, and 17βHSD5 were immunolocalized in a cohort of 203 TNBC patients from Thailand and Japan. We then correlated the findings with clinicopathological characteristics (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki‐67 labeling index, disease‐free survival, and overall survival) of the patients. Univariate analysis revealed that AR+/enzyme+ cases were associated with a significantly lower Ki‐67 labeling index than AR−/enzyme− samples. Multivariate analysis indicated the presence of significant positive correlations between AR and enzyme status in tumor cells, and between tumor diameter, lymph node invasion, and distant metastasis. Significant negative correlations were also detected between Ki‐67 labeling index and AR status (P = 0.04) or 5αR1 (P < 0.001). Cox proportional hazards analysis showed that Ki‐67 labeling index and stage were the only factors predicting disease‐free and overall survival of the patients, although univariate Kaplan–Meier analysis revealed AR/5αR1 negativity suggested a more adverse clinical course up to 80 months after surgery. These results suggest that the presence of androgen synthesizing pathways in addition to AR expression in tumor cells could confer a better clinical outcome through suppression of cell proliferation.
Activity Cliffs: Facts or Artifacts?
Authors: Medina‐Franco José L.
Published: February 2013

The fact that similar compounds may have very different properties has a large impact in several areas of chemistry. In drug discovery, almost every medicinal chemist working on lead optimization has faced unexpected large ‘jumps’ in activity due to small changes in structure, that is, activity cliffs. A number of computational approaches have been developed to detect and quantify activity cliffs and help to understand, and eventually predict, structure–activity relationships (SAR) in compound data sets. Although activity cliffs do exist, the identification and quantification of cliffs have to proceed with caution because one may identify ‘false positive cliffs’. In addition to apparent cliffs due to inaccurate determinations of activity, computationally identified cliffs can be artifacts attributed to the molecular representation and quantitative definition of ‘high’ structural similarity. This paper brings together and discusses, in a brief and integrated manner, some of the major aspects that raise the question whether all the activity cliffs detected in compound data sets are facts or artifacts.
What is the evidence in humans that DNA methylation changes link events in utero and later life disease?
Authors: Reynolds Rebecca M. , Jacobsen Greta H. , Drake Amanda J.
Published: February 2013

Development in utero is now recognized as crucial to determining later life disease susceptibility. Whilst mechanisms are poorly understood, there has been considerable interest in the potential role of epigenetic processes in intra‐uterine programming of disease. Epigenetic modifications include various mechanisms that influence chromatin structure and gene expression. Here, we review emerging data from human studies that altered DNA methylation links intra‐uterine events with later life disease. Further research in this field is needed to determine whether altered DNA methylation in target tissues can be used as a biomarker for the early identification of and intervention in individuals most at risk of later life disease.
Incidence of −93 MLH1 promoter polymorphism in familial and sporadic colorectal cancer
Authors: Martínez‐Urueña N. , Macías L. , Pérez‐Cabornero L. , Infante M. , Lastra E. , Cruz J. J. , Miner C. , González R. , Durán M.
Published: February 2013

Aim

The MLH1 promoter contains a common single nucleotide polymorphism (−93 guanine > adenine) located in an essential region for maximum transcriptional activity. This has been associated with an increased risk of microsatellite instability (MSI) colorectal cancer. The aim of the study was to compare the distribution of MLH1 −93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects.

Method

We genotyped 200 familial colon samples, 183 cases of sporadic colon cancer and 236 control subjects. MSI was analysed.

Results

The GA genotype was under‐represented in patients with familial colon cancer, whereas the AA genotype was over‐represented in cases of sporadic colon cancer. A greater frequency of the MLH1 GA genotype was found in the cancer cases with MLH1 focal immunohistochemistry (IHC) for anti‐MLH1 antibody. When we compared genotype distribution in the familial colorectal cancer cases with and without MSI, we failed to detect any correlation, although the GA genotype is more frequent in cases with MSI.

Conclusion

There is a relationship between the MLH1 −93G>A polymorphism in the homozygous state and the risk of sporadic colorectal cancer. The variant MLH1 −93G>A appears to be related to cases with focal IHC activity more than to complete absence of the MLH1 protein in the tumour tissue.
Long‐term efficacy of dextranomer in stabilized hyaluronic acid (NASHA/Dx) for treatment of faecal incontinence
Authors: La Torre F. , de la Portilla F.
Published: February 2013

Aim

Randomized, controlled trials have demonstrated the efficacy and safety of injectable bulking agents for the treatment of faecal incontinence (FI), although the long‐term outcome has not been assessed. NASHA/Dx gel, a biocompatible, nonallergenic bulking agent consisting of nonanimal stabilized hyaluronic acid and dextranomer microspheres, has demonstrated efficacy and safety for up to 12 months after treatment. The objective of this study was to evaluate the long‐term efficacy and safety of NASHA/Dx, assessed 24 months after treatment.

Method

This study was a 24‐month follow‐up assessment of patients treated with NASHA/Dx under open‐label conditions. Data on FI episodes and quality of life measures were collected from diaries over the 28‐day period immediately preceding the 24‐month assessment. Adverse events were collected.

Results

Eighty‐three of 115 patients completed the 24‐month follow‐up assessment. At 24 months, 62.7% of patients were considered responders and experienced a ≥ 50% reduction in the total number of FI episodes. The median number of FI episodes declined by 68.8% (P < 0.001). Episodes of both solid and liquid stool incontinence decreased. The mean number of incontinence‐free days increased from 14.6 at baseline to 21.7 at 24 months (P < 0.001). Incontinence scores and FI quality of life scores also showed significant improvements. The most common adverse events (AEs) were proctalgia (13.3%) and pyrexia (9.6%). The majority of AEs were mild to moderate, self‐limited and resolved within 1 month of the injection.

Conclusion

NASHA/Dx is safe, effective and durable over a 24‐month period with a majority of patients experiencing significant improvement in multiple symptoms associated with FI.
The persistent challenge of parastomal herniation: a review of the literature and future developments
Authors: Hotouras A. , Murphy J. , Thaha M. , Chan C. L.
Published: February 2013

Aim

The aim of this review article was to outline current evidence relating to the treatment and prevention of parastomal herniation with a view to guide surgeons dealing with patients potentially affected by this complication.

Method

Medline and PubMed databases were searched using the keywords ‘parastomal hernia/herniation’, ‘stoma hernia/herniation’ and ‘stoma complications’. Evidence was obtained from randomized and non‐randomized studies. Case reports and articles not written in English were excluded. Qualitative assessment of all included studies was performed using the Oxford Centre for Evidence‐Based Medicine 2011 levels of evidence.

Results

The search revealed a total of 228 publications of which 115 fulfilled the selection criteria. Stoma formation through the rectus muscle is complicated by parastomal herniation in up to 50% of cases. There is no conclusive evidence that alternative techniques (e.g. extraperitoneal, lateral rectus abdominis positioned stoma) are superior. Open and laparoscopic parastomal hernia repair have similar recurrence rates up to 50%. The ‘Sugarbaker’ technique appears to be superior to the ‘keyhole’ technique when a laparoscopic approach is used. Prophylactic mesh reinforcement of the stoma trephine appears to reduce the herniation rate to approximately 15% and is accompanied by a decrease in symptomatic hernias requiring repair without any difference in stoma‐related morbidity.

Conclusion

Large prospective controlled trials are required to compare surgical techniques of stoma formation in reducing the incidence of parastomal herniation. Despite limited evidence, routine prophylactic mesh reinforcement of the stoma trephine should be offered to all patients undergoing permanent stoma formation.