bluuebunny/crossref_metadata_2025 huggingface dataset:
Palaeogeography and diachronous infill of an ancient deep‐marine foreland basin, Upper Cretaceous Cerro Toro Formation, Magallanes Basin
Authors: Bernhardt Anne , Jobe Zane R. , Grove Marty , Lowe Donald R.
Published: October 2011

The details of how narrow, orogen‐parallel ocean basins are filled with sediment by large axial submarine channels is important to understand because these depositional systems commonly form in through‐like basins in various tectonic settings. The Magallanes foreland basin is an excellent location to study an orogen‐parallel deep‐marine system. Conglomerate lenses of the Upper Cretaceous Cerro Toro Formation have been previously interpreted to represent the fill of a single submarine channel (4–8 km wide, >100 km long) that funneled coarse detritus southward along the basin axis. This interpretation was based on lithologic correlations. New U/Pb dating of zircons from volcanic ashes and sandstones, coupled with strontium isotope stratigraphy, refine the controls on depositional ages and provenance. Results demonstrate that north‐south oriented conglomerate lenses are contemporaneous within error limits (ca. 84–82 Ma) supporting that they represent parts of an axial channel belt. Channel deposits 20 km west of the axial location are 87–82 Ma in age. These channels are partly contemporaneous with the ones within the axial channel belt, making it likely that they represent feeders to the axial channel system. The northern Cerro Toro Formation spans a Turonian to Campanian interval (ca. 90–82 Ma) whereas the formation top, 70 km to the south, is as young as ca. 76 Ma. Kolmogorov–Smirnoff statistical analysis on detrital zircon age distributions shows that the northern uppermost Cerro Toro Formation yields a statistically different age distribution than other samples from the same formation but shows no difference relative to the overlying Tres Pasos Formation. These results suggest the partly coeval deposition of both formations. Integration of previously acquired geochronologic and stratigraphic data with new data show a pronounced southward younging pattern in all four marine formations in the Magallanes Basin. Highly diachronous infilling may be an important depositional pattern for narrow, orogen‐parallel ocean basins.
CD22 Exon 12 deletion is a characteristic genetic defect of therapy‐refractory clones in paediatric acute lymphoblastic leukaemia
Authors: Ma Hong , Qazi Sanjive , Ozer Zahide , Gaynon Paul , Reaman Gregory H. , Uckun Fatih M.
Published: October 2011

Gene expression profiling (GEP) of primary leukaemic cells (PLC) from 157 paediatric B‐lineage acute lymphoblastic leukaemia (ALL) patients, including a direct comparison of matched pair initial diagnosis versus first relapse leukaemic specimens, provided previously unknown evidence that relapse clones are characterized by significantly higher expression levels of a CD22 exon 12 deletion (CD22ΔE12)‐associated signature transcriptome than the PLC from newly diagnosed patients. In agreement with and validating these GEP results, reverse transcription polymerase chain reaction and Western blot analysis of PLC from 19 of 19 paediatric ALL patients in first bone marrow relapse occurring within 12 months of the completion of primary therapy confirmed them to be CD22ΔE12+. Likewise, PLC in diagnostic initial bone marrow specimens from seven of seven therapy‐refractory newly diagnosed paediatric B‐lineage ALL patients with <7 months event‐free survival (EFS), including four patients with induction failures and three patients with early relapses, were CD22ΔE12+, whereas PLC from only one of five newly diagnosed paediatric B‐lineage ALL patients with >18 months EFS was CD22ΔE12+. CD22ΔE12+ could be detected in PLC of therapy‐refractory patients both at the time of initial diagnosis as well as at the time of documented treatment failure. Our study implicates the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy‐refractory paediatric B‐lineage ALL.
Developmental screening in context: adaptation and standardization of the Denver Developmental Screening Test‐II (DDST‐II) for Sri Lankan children
Authors: Wijedasa D.
Published: October 2011

Background Developmental problems in children can be alleviated to a great extent with early detection and intervention through periodic screening for developmental delays during pre‐school ages. Currently, there is no established system for developmental screening of children in Sri Lanka. Although some developmental norms, which are similar to those of Denver Developmental Screening Test‐II (DDST‐II), have been introduced into the Sri Lankan Child Health Developmental Record (CHDR), those norms have not been standardized to the Sri Lankan child population. The aim of this research was to establish Sri Lankan norms for DDST‐II and to test the universal and regional applicability of developmental screening tests by comparing the Sri Lankan norms with the norms of DDST‐II and DDST‐Singapore norms, the geographically nearest standardization of DDST‐II. The norms were also compared with the milestones already available in the CHDR.

Methods DDST‐II was adapted and standardized on a sample of 4251 Sri Lankan children aged 0–80 months. Thirteen public health nursing sisters were trained to collect the data as part of their routine work. The 25th, 50th, 75th and 90th percentile ages of acquiring each developmental milestone were then calculated using logistic regression.

Results The Denver Developmental Screening Test for Sri Lankan Children (DDST‐SL) was created. Most of the established DDST‐SL norms were different to the comparable norms in DDST‐II, DDST‐Singapore and the CHDR.

Conclusions In view of the results of the study, it is imperative that developmental screening tests are used in context and are adapted and standardized to the populations in question before utilization.
A riverscape perspective of Pacific salmonids and aquatic habitats prior to large‐scale dam removal in the Elwha River, Washington, USA
Authors: BRENKMAN S. J. , DUDA J. J. , TORGERSEN C. E. , WELTY E. , PESS G. R. , PETERS R. , MCHENRY M. L.
Published: October 2011

Abstract  Dam removal has been increasingly proposed as a river restoration technique. In 2011, two large hydroelectric dams will be removed from Washington State’s Elwha River. Ten anadromous fish populations are expected to recolonise historical habitats after dam removal. A key to understanding watershed recolonisation is the collection of spatially continuous information on fish and aquatic habitats. A riverscape approach with an emphasis on biological data has rarely been applied in mid‐sized, wilderness rivers, particularly in consecutive years prior to dam removal. Concurrent snorkel and habitat surveys were conducted from the headwaters to the mouth (rkm 65–0) of the Elwha River in 2007 and 2008. This riverscape approach characterised the spatial extent, assemblage structure and patterns of relative density of Pacific salmonids. The presence of dams influenced the longitudinal patterns of fish assemblages, and species richness was the highest downstream of the dams, where anadromous salmonids still have access. The percent composition of salmonids was similar in both years for rainbow trout, Oncorhynchus mykiss (Walbaum), coastal cutthroat trout, Oncorhynchus clarkii clarkii (Richardson) (89%; 88%), Chinook salmon, Oncorhynchus tshawytscha (Walbaum) (8%; 9%), and bull trout, Salvelinus confluentus (Suckley) (3% in both years). Spatial patterns of abundance for rainbow and cutthroat trout (r = 0.76) and bull trout (r = 0.70) were also consistent between years. Multivariate and univariate methods detected differences in habitat structure along the river profile caused by natural and anthropogenic factors. The riverscape view highlighted species‐specific biological hotspots and revealed that 60–69% of federally threatened bull trout occurred near or below the dams. Spatially continuous surveys will be vital in evaluating the effectiveness of upcoming dam removal projects at restoring anadromous salmonids.
Acclimation to ocean acidification during long‐term CO2 exposure in the cold‐water coral Lophelia pertusa
Authors: Form Armin U. , Riebesell Ulf
Published: October 2011

Ocean acidity has increased by 30% since preindustrial times due to the uptake of anthropogenic CO2 and is projected to rise by another 120% before 2100 if CO2 emissions continue at current rates. Ocean acidification is expected to have wide‐ranging impacts on marine life, including reduced growth and net erosion of coral reefs. Our present understanding of the impacts of ocean acidification on marine life, however, relies heavily on results from short‐term CO2 perturbation studies. Here, we present results from the first long‐term CO2 perturbation study on the dominant reef‐building cold‐water coral Lophelia pertusa and relate them to results from a short‐term study to compare the effect of exposure time on the coral's responses. Short‐term (1 week) high CO2 exposure resulted in a decline of calcification by 26–29% for a pH decrease of 0.1 units and net dissolution of calcium carbonate. In contrast, L. pertusa was capable to acclimate to acidified conditions in long‐term (6 months) incubations, leading to even slightly enhanced rates of calcification. Net growth is sustained even in waters sub‐saturated with respect to aragonite. Acclimation to seawater acidification did not cause a measurable increase in metabolic rates. This is the first evidence of successful acclimation in a coral species to ocean acidification, emphasizing the general need for long‐term incubations in ocean acidification research. To conclude on the sensitivity of cold‐water coral reefs to future ocean acidification further ecophysiological studies are necessary which should also encompass the role of food availability and rising temperatures.
The effect of sowing date and nitrogen on the dry‐matter yield and nitrogen content of forage rape (Brassica napus L.) and stubble turnips (Brassica rapa L.) in Ireland
Authors: Keogh B. , McGrath T. , Grant J.
Published: October 2011

Two field experiments were conducted at Teagasc, Moorepark, Ireland, to determine the effect of sowing date and nitrogen application on the dry‐matter (DM) yield and crude protein (CP) content of forage rape and stubble turnips. The first experiment consisted of three sowing dates (1 August, 15 August and 31 August) with four rates of fertilizer N (0, 40, 80 and 120 kg N ha−1) on forage rape DM yields. The second experiment consisted of three sowing dates (1 August, 15 August and 31 August) with four rates of fertilizer N (0, 40, 80 and 120 kg N ha−1) over two soil sites (fertile or nitrogen depleted) on forage rape and stubble turnip DM yields. A delay in sowing from 1 to 31 August characterized a 74·5% decrease in forage rape DM yield, while stubble turnip DM yield decreased by 55·5%. Forage rape DM yields increased positively up to 120 kg N ha−1 at the first two sowing dates over both sites. In contrast, stubble turnips showed less response beyond 40 kg N ha−1 on site 1 in the first two sowing dates, while DM yield increased positively up to 120 kg N ha−1 on the less fertile site. The results indicate that the optimal sowing time for forage rape and a stubble turnip in Ireland was early August.
People’s experiences of the impact of transient ischaemic attack and its consequences: qualitative study
Authors: Gibson Josephine , Watkins Caroline
Published: October 2011

gibson j. & watkins c. (2011) People’s experiences of the impact of transient ischaemic attack and its consequences: qualitative study. Journal of Advanced Nursing68(6), 1707–1715.

Aim.  This paper is a report of a study of how people’s experiences of transient ischaemic attack affect their perception of their health and their uptake of health maintenance measures.

Background.  Transient ischaemic attack is a well‐recognized warning sign of subsequent stroke, but early diagnosis and management of risk factors can substantially reduce this risk. Even though the physical effects of a transient ischaemic attack are transient, it is known to negatively affect quality of life. However, no qualitative studies have explored the impact of transient ischaemic attack on people’s everyday lives.

Methods.  Sixteen participants were recruited from a vascular surgery clinic in a district general hospital in North West England. All had a recent transient ischaemic attack. A qualitative grounded theory study using detailed interviews (n = 21) was conducted.

Findings.  Participants experienced conflict between acknowledgement of the transient ischaemic attack as a significant illness episode with implications for their long‐term health, and denial of its seriousness. Although they often ignored the initial signs, participants also experienced fear due to increased awareness of their risk of stroke. Often, they believed that they were having a permanent stroke. Many participants were prompted to seek medical advice by a family member or acquaintance. Having a transient ischaemic attack negatively changed their perception of their health and their quality of life, but some also viewed it as a positive event that had warned of their stroke risk and enabled them to take up health maintenance measures.

Conclusions.  Having a transient ischaemic attack permanently changes people’s quality of life and their perception of their health, despite the transience of the symptoms. The ability of people to make positive health changes after a transient ischaemic attack to some extent ameliorates the negative effects of being aware of their heightened stroke risk. Their appreciation of their quality of life may also be enhanced. The transience of the symptoms and lack of knowledge of transient ischaemic attacks lead to delays in seeking medical advice.
Lack of regeneration and climatic vulnerability to fire of Scots pine may induce vegetation shifts at the southern edge of its distribution
Authors: Vilà‐Cabrera Albert , Rodrigo Anselm , Martínez‐Vilalta Jordi , Retana Javier
Published: October 2011

Aim  Forest ecosystems dominated by fire‐sensitive species could suffer shifts in composition under altered crown fire regimes mediated by climate change. The aims of this study were to: (1) study the spatio‐temporal patterns and the climatic distribution of fires in Scots pine (Pinus sylvestris) forests during the last 31 years in north‐eastern Spain, (2) evaluate the climatic vulnerability to fire of these forests in Spain, (3) analyse the regeneration of Scots pine after fire, and (4) predict the mid‐term maintenance or replacement of Scots pine in burned areas.

Location  Catalonia (north‐eastern Spain): the southern distribution limit of Scots pine.

Methods  We characterized the spatio‐temporal and the climatic distribution of fires that occurred in Catalonia between 1979 and 2009. We used a generalized linear model to characterize the climatic vulnerability to fire of Scots pine in the whole of Spain. We assessed the regeneration of the species after crown fires in nine burned areas in Catalonia. The resulting data were integrated into a stochastic matrix model to predict the mid‐term maintenance or replacement of Scots pine in burned areas.

Results  During the last three decades, Scots pine forests distributed in dry sites were most affected by fire. Our assessment of the vulnerability to fire of Scots pine forests in Spain as a whole, based on climatic and topographical variables, showed that 32% of these forests are vulnerable to fire, and that this proportion could increase to 66% under a conservative climate change scenario. Field data showed almost no regeneration of Scots pine after crown fires, and a limited capacity to recolonize from unburned edges, even in relatively old fires, with 90% of recruits located in the first 25 m from the edge. This process could be delayed by the elapsed time for new recruits to achieve reproductive maturity, which we estimated to be c. 15 years. Finally, our matrix model predicted the replacement of burned Scots pine forests by oak (Quercus sp.) forests, shrublands or mixed resprouter forests.

Main conclusions  Increased vulnerability to fire of Scots pine forests under future, warmer conditions may result in vegetation shifts at the southern edge of the distribution of the species.
A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis
Authors: Hamrefors V. , Hedblad B. , Engström G. , Almgren P. , Sjögren M. , Melander O.
Published: October 2011

Abstract.  Hamrefors V, Hedblad B, Engström G, Almgren P, Sjögren M, Melander O (Lund University, Malmö, Sweden). A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis. J Intern Med 2012; 271: 271–281.

Objective.  To assess whether or not a genetic risk score that was previously shown to be associated with myocardial infarction (MI) and coronary artery disease (CAD) is also associated with markers of carotid atherosclerosis.

Design.  A total of 4022 middle‐aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single‐nucleotide polymorphisms (SNPs), previously associated with MI and CAD. The genetic score (Score‐MI) was then related to carotid bulb intima–media thickness (IMT), common carotid artery (CCA) IMT and to the occurrence of carotid plaques in the study population.

Results.  Score‐MI was associated with IMT of the bulb (P < 0.001) and the CCA (P < 0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P = 0.003). The effect size of Score‐MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score‐MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score‐MI = 1.11; 95% confidence interval 1.04–1.18; P = 0.001). In addition to SNPs with known effects on LDL levels, Score‐MI showed nominal associations with increasing systolic blood pressure and decreasing C‐reactive protein levels.

Conclusions.  This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic MI risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether or not assessing the genetic score could be valuable for early treatment decisions in these subjects.
Polydactyly in the largest New World fruit bat, Artibeus lituratus
Authors: GONÇALVES Fernando , FISCHER Erich , CARVALHO Luiz Felipe Alves da Cunha , FERREIRA Cláudia Márcia Marily
Published: October 2011

Polydactyly in bats has rarely been observed; a few cases are recorded for insectivorous molossid and vespertilionid species in North America. Here we report polydactyly in the foliage‐roosting phyllostomid Artibeus lituratus, in the southern Pantanal floodplain and adjacent uplands, Brazil. Bats were mist‐netted in six populations, and capture rate per population was estimated. Of 444 A. lituratus individuals sampled, one female and one male exhibited supernumerary toes. These cases occurred in the two densest populations, in sites where forests are distributed in small disconnected fragments. This situation could favour increased inbreeding in A. lituratus and, indirectly, the manifestation of polydactyly.
Mycobacterium smegmatis RNase J is a 5′‐3′ exo‐/endoribonuclease and both RNase J and RNase E are involved in ribosomal RNA maturation
Authors: Taverniti Valerio , Forti Francesca , Ghisotti Daniela , Putzer Harald
Published: October 2011

The presence of very different sets of enzymes, and in particular the presence of RNase E and RNase J, has been used to explain significant differences in RNA metabolism between the two model organisms Escherichia coli and Bacillus subtilis. However, these studies might have somewhat polarized our view of RNA metabolism. Here, we identified a RNase J in Mycobacterium smegmatis that has both 5′‐3′ exo‐ and endonucleolytic activity. This enzyme coexists with RNase E in this organism, a configuration that enabled us to study how these two key nucleases collaborate. We demonstrate that RNase E is responsible for the processing of the furA‐katG transcript in M. smegmatis and that both RNase E and RNase J are involved in the 5′ end processing of all ribosomal RNAs. In contrast to B. subtilis, the activity of RNase J, although required in vivo for 23S rRNA maturation, is not essential in M. smegmatis. We show that the pathways for ribosomal RNA maturation in M. smegmatis are quite different from those observed in E. coli and in B. subtilis. Studying organisms containing different combinations of key ribonucleases can thus significantly broaden our view of the possible strategies that exist to direct RNA metabolism.
Type 4 metallothionein genes are involved in regulating Zn ion accumulation in late embryo and in controlling early seedling growth in Arabidopsis
Authors: REN YUJUN , LIU YANG , CHEN HONGYU , LI GANG , ZHANG XUELIAN , ZHAO JIE
Published: October 2011

Type 4 metallothionein (MT) genes are recognized for their specific expression in higher plant seeds, but their functions are still unclear. In this study, the functions of two Arabidopsis metallothionein genes, AtMT4a and AtMT4b, are investigated in seed development, germination and early seedling growth. Transcriptional analysis showed that these two genes are specifically expressed in late embryos. Subcellular localization displayed that both AtMT4a and AtMT4b are widespread distributed in cytoplasm, nucleus and membrane. Co‐silencing RNAi of AtMT4a and AtMT4b reduced seed weight and influenced the early seedling growth after germination, whereas overexpression of these two genes caused the opposite results. Detailed analysis showed clearly the correlation of AtMT4a and AtMT4b to the accumulation of some important metal ions in late embryos, especially to Zn ion storing in seeds, which then serves as part of early Zn ion resources for post‐germinated seedling growth. Furthermore, phytohormone abscisic acid (ABA) and gibberellic acid (GA) may play roles in regulating the expression and function of AtMT4a and AtMT4b during seed development; and this may influence Zn accumulation in seeds and Zn ion nutrient supplementation in the early seedling growth after germination.
Array‐Based Sequence Capture and Next‐Generation Sequencing for the Identification of Primary Immunodeficiencies
Authors: Ghosh S. , Krux F. , Binder V. , Gombert M. , Niehues T. , Feyen O. , Laws H.‐J. , Borkhardt A. ,   on behalf of PID‐NET: German Network on Primary Immunodeficiency Diseases
Published: October 2011

Primary immunodeficiencies are genetic disorders in which components of immunological pathways are either missing or dysregulated. With the advent of next‐generation sequencing, testing for genes in conditions with a heterogeneous genetic background seems more promising. We designed a custom microarray with 385K probe capacity to capture exons of 395 human genes, known or predicted to be associated with primary immunodeficiency and immune regulation. Enriched target DNA was sequenced using a GS FLX Titanium 454 platform. The patients selected were likely to have an underlying immunodeficiency. In one patient with hepatosplenomegaly, recurrent infections and an elevated IgM level, sequence analysis of the patient and his two unaffected parents identified ATM (ataxia telangiectasia mutated) as the underlying defect. In a second child with a clinical SCID phenotype, we detected a mutation in the ARTEMIS gene after focusing on SCID‐associated genes. 454 sequencing yielded 152,000–397,000 high‐quality reads per patient. 78–99% of the targeted nucleotides were covered at least one time, 76–82% at least five times. Array‐based sequence capture expands our capacities to sequence large targeted DNA regions in a less laborious and time‐consuming approach. Our array was capable to find the underlying genetic defect in two patients with suspected primary immunodeficiency. Upcoming whole‐exome sequencing definitely will add more valuable data, but bioinformatical analysis and validation of variants already pose major challenges.
Establishment of a Lotus japonicus gene tagging population using the exon‐targeting endogenous retrotransposon LORE1
Authors: Fukai Eigo , Soyano Takashi , Umehara Yosuke , Nakayama Shinobu , Hirakawa Hideki , Tabata Satoshi , Sato Shusei , Hayashi Makoto
Published: October 2011

We established a gene tagging population of the model legume Lotus japonicus using an endogenous long terminal repeat (LTR) retrotransposon Lotus Retrotransposon 1 (LORE1). The population was composed of 2450 plant lines, from which a total of 4532 flanking sequence tags of LORE1 were recovered by pyrosequencing. The two‐dimensional arrangement of the plant population, together with the use of multiple identifier sequences in the primers used to amplify the flanking regions, made it possible to trace insertions back to the original plant lines. The large‐scale detection of new LORE1 insertion sites revealed a preference for genic regions, especially in exons of protein‐coding genes, which is an interesting feature to consider in the interaction between host genomes and chromoviruses, to which LORE1 belongs, a class of retrotransposon widely distributed among plants. Forward screening of the symbiotic mutants from the population succeeded to identify five symbiotic mutants of known genes. These data suggest that LORE1 is robust as a genetic tool.
ARVs and cash too: caring and supporting people living with HIV/AIDS with the Malawi Social Cash Transfer
Authors: Miller C. , Tsoka M. G.
Published: October 2011

Objectives  The Malawian Social Cash Transfer Scheme (SCT) is a social protection programme for ultra poor and labour‐constrained households, including people living with HIV/AIDS (PLWHA). We aimed to gain insight into respondents’ circumstances prior to becoming transfer beneficiaries and to examine how PLWHA used transfers to support themselves and their families.

Methods  We conducted 24 semi‐structured qualitative interviews with PLWHA who were also SCT beneficiaries and living in villages where the scheme was operational in 2008.

Results  Respondents were destitute and lacked food and basic necessities prior to the transfer. As cash recipients, the majority of respondents reported positive impacts on health, food security and economic well‐being as well as an improved ability to care for their families.

Conclusion  Important unanswered programmatic questions persist, such as ‘What is the appropriate transfer level?’ And ‘Should recipients graduate from the scheme?’ Moreover, the scheme’s long‐term sustainability is still unclear. Nevertheless, this analysis presents evidence describing how PLWHA used cash transfers to improve their situation and mitigate the impact of HIV/AIDS on families.
Valuing gene testing in children with possible neurofibromatosis 1
Authors: Tsang E , Birch P , Friedman JM
Published: October 2011

Tsang E, Birch P, Friedman JM. Valuing gene testing in children with possible neurofibromatosis 1.

With the growing number of clinical guidelines recommending genetics tests in routine clinical care, the value of these tests should be evaluated. We examined the economic value of offering genetic testing to children with possible neurofibromatosis 1 (NF1) in British Columbia. Diagnosis of NF1 is usually made based on diagnostic clinical criteria, but molecular diagnostic testing, currently offered on a case‐by‐case basis in BC, now reliably diagnoses NF1 in 95% of cases. Children who present with some clinical features but whose findings are insufficient to meet the diagnostic criteria are labelled as having ‘possible NF1’. Current guidelines call for these children to be followed as they have NF1, leading to annual ophthalmologic examinations and screening for complications; thus, there are increased costs to health care system. We created a model to account for these costs to the health care system, comparing the current protocol with one that would offer all children diagnosed with possible NF1 with genetic testing. Focusing on the incremental cost allowed us to determine that genetic testing provides good value, and patient interviews provided insight into the qualitative benefits of an earlier firm diagnosis. These findings may be helpful in guiding health policy decision‐making.
Serum TARC and CTACK concentrations in children with atopic dermatitis, allergic asthma, and urticaria
Authors: Machura Edyta , Rusek‐Zychma Małgorzata , Jachimowicz Magdalena , Wrzask Magdalena , Mazur Bogdan , Kasperska‐Zajac Alicja
Published: October 2011

To cite this article: Machura E, Rusek‐Zychma M, Jachimowicz M, Wrzask M, Mazur B, Kasperska‐Zajac A. Serum TARC and CTACK concentrations in children with atopic dermatitis, allergic asthma, and urticaria. Pediatr Allergy Immunol 2012: 23: 278–284.

Background:  Thymus and activation–regulated chemokine (TARC/CCL17) and cutaneous T cell‐attracting chemokine (CTACK/CCL27) belong to the CC chemokine family, which plays an important role in immune‐inflammatory processes. It has been demonstrated that serum concentrations of TARC and CTACK are increased in patients with various allergic diseases.

Aim:  To compare serum TARC and CTACK concentrations between children with different clinical manifestation of mast cell–dependent diseases, such as atopic allergy and urticaria.

Methods:  A total of 87 children including 26 with mild to severe atopic dermatitis (AD), 43 children with controlled allergic asthma symptoms (treated and untreated with anti‐inflammatory drugs), and 18 children with urticaria were recruited into the study. The control group consisted of 31 healthy non‐atopic children.

Results:  Serum concentrations of TARC and CTACK were significantly higher in children with AD than in healthy controls. No significant differences in serum concentrations of the chemokines between asthmatics, urticaria patients, and healthy controls were found. The severity of AD symptoms significantly correlated with serum CTACK and TARC concentrations.

Conclusion:  These findings, in conjunction with earlier data, indicate that differences may exist in circulating concentrations of TARC and CTACK, between patients with atopic allergy and urticaria.
The transcription factor SP4 is reduced in postmortem cerebellum of bipolar disorder subjects: control by depolarization and lithium
Authors: Pinacho Raquel , Villalmanzo Nuria , Lalonde Jasmin , Haro Josep Maria , Meana J Javier , Gill Grace , Ramos Belén
Published: October 2011

Pinacho R, Villalmanzo N, Lalonde J, Haro JM, Meana JJ, Gill G, Ramos B. The transcription factor SP4 is reduced in postmortem cerebellum of bipolar disorder subjects: control by depolarization and lithium. Bipolar Disord 2011: 13: 474–485. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S.

Objectives:  Regulation of gene expression is important for the development and function of the nervous system. However, the transcriptional programs altered in psychiatric diseases are not completely characterized. Human gene association studies and analysis of mutant mice suggest that the transcription factor specificity protein 4 (SP4) may be implicated in the pathophysiology of psychiatric diseases. We hypothesized that SP4 levels may be altered in the brain of bipolar disorder (BD) subjects and regulated by neuronal activity and drug treatment.

Methods:  We analyzed messenger RNA (mRNA) and protein levels of SP4 and SP1 in the postmortem prefrontal cortex and cerebellum of BD subjects (n = 10) and controls (n = 10). We also examined regulation of SP4 mRNA and protein levels by neuronal activity and lithium in rat cerebellar granule neurons.

Results:  We report a reduction of SP4 and SP1 proteins, but not mRNA levels, in the cerebellum of BD subjects. SP4 protein and mRNA levels were also reduced in the prefrontal cortex. Moreover, we found in rat cerebellar granule neurons that under non‐depolarizing conditions SP4, but not SP1, was polyubiquitinated and degraded by the proteasome while lithium stabilized SP4 protein.

Conclusions:  Our study provides the first evidence of altered SP4 protein in the cerebellum and prefrontal cortex in BD subjects supporting a possible role of transcription factor SP4 in the pathogenesis of the disease. In addition, our finding that SP4 stability is regulated by depolarization and lithium provides a pathway through which neuronal activity and lithium could control gene expression suggesting that normalization of SP4 levels could contribute to treatment of affective disorders.
Four mood stabilizers commonly induce FEZ1 expression in human astrocytes
Authors: Yu Zhiqian , Ono Chiaki , Kim Helen B , Komatsu Hiroshi , Tanabe Yoichiro , Sakae Nobutaka , Nakayama Keiichi I , Matsuoka Hiroo , Sora Ichiro , Bunney William E , Tomita Hiroaki
Published: October 2011

Yu Z, Ono C, Kim HB, Komatsu H, Tanabe Y, Sakae N, Nakayama KI, Matsuoka H, Sora I, Bunney WE, Tomita H. Four mood stabilizers commonly induce FEZ1 expression in human astrocytes. Bipolar Disord 2011: 13: 486–499. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S.

Objectives:  Mood stabilizers influence the morphology, chemotaxis, and survival of neurons, which are considered to be related to the mood‐stabilizing effects of these drugs. Although previous studies suggest glial abnormalities in patients with bipolar disorder and an effect of mood stabilizers on certain genes in astrocytes, less is known about the effects of mood stabilizers in astrocytes than in neurons. The present study identifies a common underlying response to mood stabilizers in astrocytes.

Methods:  Human astrocyte‐derived cells (U‐87 MG) were treated with the four most commonly used mood stabilizers (lithium, valproic acid, carbamazepine, and lamotrigine) and subjected to microarray gene expression analyses. The most prominently regulated genes were validated by qRT‐PCR and western blot analysis. The intercellular localization of one of these regulated genes, fasciculation and elongation protein zeta 1 (FEZ1), was evaluated by immunofluorescence staining.

Results:  The microarray data indicated that FEZ1 was the only gene commonly induced by the four mood stabilizers in human astrocyte‐derived cells. An independent experiment confirmed astrocytic FEZ1 induction at both the transcript and protein levels following mood stabilizer treatments. FEZ1 localized to the cytoplasm of transformed and primary astrocytes from the human adult brain.

Conclusions:  Our data suggest that FEZ1 may play important roles in human astrocytes, and that mood stabilizers might exert their cytoprotective and mood‐stabilizing effects by inducing FEZ1 expression in astrocytes.
Could the use of energy drinks induce manic or depressive relapse among abstinent substance use disorder patients with comorbid bipolar spectrum disorder?
Authors: Rizkallah Élie , Bélanger Michèle , Stavro Katherine , Dussault Maxime , Pampoulova Tania , Chiasson Jean‐Pierre , Potvin Stéphane
Published: October 2011

Rizkallah É, Bélanger M, Stavro K, Dussault M, Pampoulova T, Chiasson J‐P, Potvin S. Could the use of energy drinks induce manic or depressive relapse among abstinent substance use disorder patients with comorbid bipolar spectrum disorder? Bipolar Disord 2011: 13: 578–580. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S.

Objective:  The potential harmful effects of excessive caffeine consumption remain largely unknown among psychiatric populations. Energy drinks have particularly high levels of caffeine content and have previously been shown to induce psychotic relapse. Clinical observations of three bipolar disorder patients with comorbid substance use disorder revealed an excessive consumption of energy drinks prior to manic or depressive relapse.

Background:  Three patients with bipolar spectrum disorder and comorbid substance use disorder were assessed by a psychiatrist upon re‐admission to a rehabilitation centre following manic or depressive relapse. The assessment was based on DSM‐IV criteria and performed by a psychiatrist who specialized in bipolar spectrum disorder and comorbidities to determine the presence of manic or depressive relapse. Two patients were diagnosed with bipolar disorder type I, and the third with bipolar disorder type II. All three patients were diagnosed with comorbid substance use disorders and all three abused cocaine.

Results:  In all three cases, relapse occurred following at least one week of excessive binging on energy drinks, with a maximum daily consumption of nine cans. Following cessation of energy drink consumption, two of the patients remained abstinent from drug use and maintained psychiatric stability. One patient relapsed three months post‐treatment and resumed consuming cocaine and energy drinks.

Conclusions:  These clinical observations support other case reports that suggest the existence of a potential correlation between excessive energy drink consumption and relapse among psychiatric populations.
The expression of pectin methylesterase in onion flower buds is associated with the dominant male‐fertility restoration allele
Authors: Huo Yumeng , Miao Jun , Liu Bingjiang , Yang Yanyan , Zhang Yihui , Tahara Yasuki , Meng Qingwei , He Qiwei , Kitano Hidemi , Wu Xiong
Published: October 2011

With 6 figures and 2 tables

In this study, we investigated differential gene expression in the flower buds of male‐fertile and male‐sterile pools by using the cDNA‐sequence‐related amplified polymorphism (SRAP) method and discovered a fragment that was specifically expressed in male‐fertile pool. Cloning and sequence analysis revealed that this differentially expressed sequence corresponded to a pectin methylesterase gene in Allium cepa (AcPME). This sequence was deposited in GenBank (GU384209). In male‐fertility‐restored line, AcPME was specifically expressed in tiny buds but not in roots, leaves and bulbs. In male‐sterile line and maintainer line, AcPME was not expressed in roots, leaves, bulbs or tiny buds. AcPME was differentially expressed during different flowering stages (I, II, III, IV and V). We developed a PCR‐based marker (WHR240) associated with the expression of AcPME. This marker was validated in six other onion lines; in each case, the male‐fertility‐restored onion was reliably identified. WHR240 therefore permits the efficient marker‐assisted selection of maintainer individuals in onion breeding programmes.
Effects of Cumulus Cells on In Vitro Maturation of Oocytes and Development of Cloned Embryos in the Pig
Authors: Ju S , Rui R
Published: October 2011

Contents

The purpose of this study was to investigate the role of porcine cumulus cells (CC) in oocyte maturation and somatic cell nuclear transfer (SCNT) embryo development in vitro. Denuded pig oocytes were co‐cultured with CC or routinely cultured in maturation medium without a feeder layer. Porcine CC inactivated with mitomycin C or non‐inactivated were used for the feeder layer in co‐culture with porcine SCNT embryos to investigate comparatively the developmental competence of cloned embryos. The DNA damage aspects of apoptosis and expression pattern of genes implicated in apoptosis (Fas/FasL) as well as the mRNA expression of DNA methyltransferase (Dnmt1, Dnmt3a) of porcine SCNT embryos were also evaluated by comet assay or real‐time RT‐PCR, respectively. The results showed that co‐culture with CC improved the extrusion rate of pbI (49.3% vs 31.5%, p < 0.05) and survival rate (75.7% vs 53.3%, p < 0.05) of denuded oocytes, but had no effects on blastocyst developmental rate or 2‐cell‐stage survival rate of in vitro fertilization embryos. Co‐culture with CC inactivated by mitomycin C improved the blastocyst developmental rate (26.6% vs 13.0%, p < 0.05) and decreased the apoptotic incidence (27.6% vs 46.2%, p < 0.05) of porcine cloned embryos. Co‐culture with inactivated CC reduced Fas and FasL mRNA expression of cloned embryos at the blastocyst stage compared with NT controls (p < 0.05), but there were no differences in Dnmt1 and Dnmt3a mRNA expression among groups. Co‐culture with inactivated cumulus cell monolayer significantly increased blastocyst formation and decreased the apoptotic incidence in porcine cloned embryos during in vitro development.
Immunohistochemical and functional studies on calcium‐sensing receptors in rat uterine smooth muscle
Authors: Pistilli Marc J , Petrik James J , Holloway Alison C , Crankshaw Denis J
Published: October 2011

1. Activation of calcium‐sensing receptors (CaS) leads to relaxation of vascular smooth muscle. However, the role of CaS in uterine smooth muscle is unknown. Therefore the aim of the present study was to investigate the expression and function of CaS in the uterus.

2. The expression of CaS in the oestrogen‐dominated rat uterus was investigated using immunohistochemistry. The effects of putative CaS ligands on oxytocin‐induced contractions of longitudinally orientated uterine strips from oestrogen‐dominated rats were determined at reduced extracellular Ca2+concentrations using conventional organ bath techniques.

3. Immunohistochemical evidence showed the presence of CaS in the endometrium and smooth muscle layers of the rat uterus. Oxytocin‐induced contractions were inhibited by cations (Gd3+ > Ca2+ = Mg2+), polyamines (spermine > spermidine) and the positive allosteric modulators cinacalcet and calindol. However (R)‐ and (S)‐cinacalcet were equipotent, indicating a lack of stereoselectivity, and the negative allosteric modulator calhex‐231 also caused dose‐dependent relaxation. In addition, although intermediate‐conductance calcium‐activated potassium channels and cytochrome P450‐dependent signal transduction have been implicated in CaS‐induced relaxation of vascular smooth muscle, neither Tram‐34 nor miconazole (1 μmol/L), which block these pathways, respectively, had any effect on the ability of cinacalcet to inhibit oxytocin‐induced contractions.

4. Calcium‐sensing receptors are expressed in smooth muscle layers of the rat uterus and their ligands produce potent relaxation of longitudinally orientated uterine strips. However, the pharmacological profile of inhibition of contractility by CaS ligands is not consistent with a role for CaS in the regulation of uterine contractility in the rat.
Cardiorenal syndrome: Pathophysiology, preclinical models, management and potential role of uraemic toxins
Authors: Liu Shan , Lekawanvijit Suree , Kompa Andrew R , Wang Bing H , Kelly Darren J , Krum Henry
Published: October 2011

1. Cardiorenal syndrome (CRS) describes the primary dysfunction in either the kidney or heart that initiates the combined impairment of both organs. The heart and kidney exert reciprocal control of the respective function to maintain constant blood volume and organ perfusion under continuously changing conditions.

2. The pathophysiology of CRS is not fully understood, but appears to be caused by a complex combination of haemodynamic, neurohormonal, immunological and biochemical feedback pathways. Of these pathways, the contributory role of uraemic toxins that accumulate in CRS has been underexplored. One such toxin, namely indoxyl sulphate, has been found to have direct adverse effects on relevant cardiac cells.

3. Early diagnosis by assessing cardiac and renal injury biomarkers may be critical for timely therapeutic intervention. Such therapies are directed at attenuation of neurohormonal activation, control of elevated blood pressure, correction of anaemia and relief of hypervolaemia. Reduction of non‐dialysable uraemic toxins is a further potentially beneficial therapeutic strategy.
Age‐related changes in two‐pore domain acid‐sensitive K+ channel expression in rat dorsal root ganglion neurons
Authors: Kim Gyu‐Tae , Cho Young‐Woo , Tak Hyun‐Min , Lee Jeong‐Soon , Kim Eun‐Jin , Han Jaehee , Kang Dawon
Published: October 2011

1. Two‐pore domain K+ (K2P) channel expression influences brain development. The K2P channels, including two‐pore domain acid‐sensitive K+ (TASK) channels, contribute to the setting of the resting membrane potential of neurons. In addition to neurons in the brain, dorsal root ganglion (DRG) neurons also express K2P channels. The aim of the present study was to identify postnatal changes in the expression of TASK channels in DRG neurons.

2. Expression of TASK channels (TASK‐1, TASK‐2 and TASK‐3) was compared between neonatal (postnatal Day (P) 1 or P2) and adult (P120) rat DRG using semiquantitative polymerase chain reaction, western blot analysis, immunostaining and the patch‐clamp technique.

3. In adult (P120) rat DRG, expression of TASK‐2 mRNA and protein was downregulated, whereas TASK‐3 mRNA and protein expression was upregulated. There were no consistent changes in TASK‐1 mRNA and protein expression. Single‐channel recordings showed very low TASK‐2‐ and TASK‐3‐like channel expression in P1–P2 DRG neurons (∼10% in TASK‐2 and ∼3% in TASK‐3). In P120 DRG, there was a reduction in the detection of TASK‐2‐like channels, whereas the detection of TASK‐3‐like channels increased.

4. These results show that TASK‐2 and TASK‐3 mRNA and protein expression undergoes age‐related changes in DRG neurons, indicating that TASK‐2 and TASK‐3 channels are likely to contribute to the setting of the resting membrane potential of DRG neurons in neonates and adults, separately or together, during DRG development.
Extended newborn screening: An update for the general paediatrician
Authors: Coman David , Bhattacharya Kaustuv
Published: October 2011

Extended newborn screening (ENBS) with the use of tandem mass spectrometry technology is well established in all Australian states and in New Zealand. ENBS has afforded a marked reduction in morbidity and mortality in select conditions such as medium‐chain acyl‐CoA dehydrogenase deficiency. While this technology has been of great benefit to newborn screening, it comes with many inherent and unforeseen challenges. In this review, we discuss the successes and challenges associated with ENBS.
Gene therapy: Progress in childhood disease
Authors: Ginn Samantha L , Alexander Ian E
Published: October 2011

The recent sequencing of the human genome combined with the development of massively high throughput genetic analysis technologies is driving unprecedented growth in our knowledge of the molecular basis of disease. While this has already had a major impact on our diagnostic power, the therapeutic benefits remain largely unrealised. This review examines progress in the exciting and challenging field of gene therapy. In particular we focus on the treatment of genetic disease in infants and children where the most significant successes have been observed to date, despite the majority of trial participants being adults. Notably, gene transfer to the haematopoietic compartment has provided the clearest examples of therapeutic benefit, particularly in the context of primary immunodeficiencies. The triumphs and tribulations of these successes are explored, and the key challenges confronting researchers as they seek to further advance the field are defined and discussed.