bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscopic origins for stabilizing room-temperature ferromagnetism in ultrathin manganite layers
Authors: Kourkoutis L. Fitting , Song J. H. , Hwang H. Y. , Muller D. A.
Published: June 2010

La
0.7
Sr
0.3
MnO
3
is a conducting ferromagnet at room temperature. Combined with thin SrTiO
3
layers, the resulting heterostructures could be used as highly spin-polarized magnetic-tunnel-junction memories. However, when shrunk to dimensions below an apparent critical thickness, the structures become insulating and ferromagnetic ordering is suppressed. Interface spin and charge modulations are thought to create an interfacial dead layer, thus fundamentally limiting the use of this material in atomic-scale devices. The thickness of this dead layer, and whether it is intrinsic, is still controversial. Here we use atomic-resolution electron spectroscopy to demonstrate that the degradation of the magnetic and transport properties of La
0.7
Sr
0.3
MnO
3
/SrTiO
3
multilayers correlates with atomic intermixing at the interfaces, and the presence of extended two-dimensional cation defects in the La
0.7
Sr
0.3
MnO
3
layers (in contrast to three-dimensional precipitates in thick films). When these extrinsic defects are eliminated, metallic ferromagnetism at room temperature can be stabilized in five-unit-cell-thick manganite layers in superlattices, placing the upper limit for any intrinsic dead layer at two unit cells per interface.
Kinesin’s light chains inhibit the head- and microtubule-binding activity of its tail
Authors: Wong Yao Liang , Rice Sarah E.
Published: June 2010

Kinesin-1 is a microtubule-based motor comprising two heavy chains (KHCs) and two light chains (KLCs). Motor activity is precisely regulated to avoid futile ATP consumption and to ensure proper intracellular localization of kinesin-1 and its cargoes. The KHC tail inhibits ATPase activity by interacting with the enzymatic KHC heads, and the tail also binds microtubules. Here, we present a role for the KLCs in regulating both the head- and microtubule-binding activities of the kinesin-1 tail. We show that KLCs reduce the affinity of the head-tail interaction over tenfold and concomitantly repress the tail’s regulatory activity. We also show that KLCs inhibit tail-microtubule binding by a separate mechanism. Inhibition of head-tail binding requires steric and electrostatic factors. Inhibition of tail-microtubule binding is largely electrostatic, pH dependent, and mediated partly by a highly negatively charged linker region between the KHC-interacting and cargo-binding domains of the KLCs. Our data support a model wherein KLCs promote activation of kinesin-1 for cargo transport by simultaneously suppressing tail-head and tail-microtubule interactions. KLC-mediated inhibition of tail-microtubule binding may also influence diffusional movement of kinesin-1 on microtubules, and kinesin-1’s role in microtubule transport/sliding.
Economic aspects of global warming in a post-Copenhagen environment
Authors: Nordhaus William D.
Published: June 2010

The science of global warming has reached a consensus on the high likelihood of substantial warming over the coming century. Nations have taken only limited steps to reduce greenhouse gas emissions since the first agreement in Kyoto in 1997, and little progress was made at the Copenhagen meeting in December 2009. The present study examines alternative outcomes for emissions, climate change, and damages under different policy scenarios. It uses an updated version of the regional integrated model of climate and the economy (RICE model). Recent projections suggest that substantial future warming will occur if no abatement policies are implemented. The model also calculates the path of carbon prices necessary to keep the increase in global mean temperature to 2 °C or less in an efficient manner. The carbon price for 2010 associated with that goal is estimated to be $59 per ton (at 2005 prices), compared with an effective global average price today of around $5 per ton. However, it is unlikely that the Copenhagen temperature goal will be attained even if countries meet their ambitious stated objectives under the Copenhagen Accord.
Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses
Authors: Welters Marij J. P. , Kenter Gemma G. , de Vos van Steenwijk Peggy J. , Löwik Margriet J. G. , Berends-van der Meer Dorien M. A. , Essahsah Farah , Stynenbosch Linda F. M. , Vloon Annelies P. G. , Ramwadhdoebe Tamara H. , Piersma Sytse J. , van der Hulst Jeanette M. , Valentijn A. Rob P. M. , Fathers Lorraine M. , Drijfhout Jan W. , Franken Kees L. M. C. , Oostendorp Jaap , Fleuren Gert Jan , Melief Cornelis J. M. , van der Burg Sjoerd H.
Published: June 2010

One half of a group of 20 patients with human papillomavirus type 16 (HPV16)-induced vulvar intraepithelial neoplasia grade 3 displayed a complete regression (CR) after therapeutic vaccination with HPV16 E6/E7 synthetic long peptides. Patients with relatively larger lesions generally did not display a CR. To investigate immune correlates of treatment failure, patients were grouped according to median lesion size at study entry, and HPV16-specific immunity was analyzed at different time points by complementary immunological assays. The group of patients with smaller lesions displayed stronger and broader vaccine-prompted HPV16-specific proliferative responses with higher IFNγ (P= 0.0003) and IL-5 (P< 0.0001) levels than patients with large lesions. Characteristically, this response was accompanied by a distinct peak in cytokine levels after the first vaccination. In contrast, the patient group with larger lesions mounted higher frequencies of HPV16-specific CD4+CD25+Foxp3+T cells (P= 0.005) and displayed a lower HPV16-specific IFNγ/IL-10 ratio after vaccination (P< 0.01). No disparity in T memory immunity to control antigens was found, indicating that the differences in HPV-specific immunity did not reflect general immune failure. We observed a strong correlation between a defined set of vaccine-prompted specific immune responses and the clinical efficacy of therapeutic vaccination. Notably, a high ratio of HPV16-specific vaccine-prompted effector T cells to HPV16-specific CD4+CD25+Foxp3+T cells was predictive of clinical success. Foxp3+T cells have been associated previously with impaired immunity in malignancies. Here we demonstrate that the vaccine-prompted level of this population is associated with early treatment failure.
Nominally hydrous magmatism on the Moon
Authors: McCubbin Francis M. , Steele Andrew , Hauri Erik H. , Nekvasil Hanna , Yamashita Shigeru , Hemley Russell J.
Published: June 2010

For the past 40 years, the Moon has been described as nearly devoid of indigenous water; however, evidence for water both on the lunar surface and within the lunar interior have recently emerged, calling into question this long-standing lunar dogma. In the present study, hydroxyl (as well as fluoride and chloride) was analyzed by secondary ion mass spectrometry in apatite [Ca
5
(PO
4
)
3
(F,Cl,OH)] from three different lunar samples in order to obtain quantitative constraints on the abundance of water in the lunar interior. This work confirms that hundreds to thousands of ppm water (of the structural form hydroxyl) is present in apatite from the Moon. Moreover, two of the studied samples likely had water preserved from magmatic processes, which would qualify the water as being indigenous to the Moon. The presence of hydroxyl in apatite from a number of different types of lunar rocks indicates that water may be ubiquitous within the lunar interior, potentially as early as the time of lunar formation. The water contents analyzed for the lunar apatite indicate minimum water contents of their lunar source region to range from 64 ppb to 5 ppm H
2
O. This lower limit range of water contents is at least two orders of magnitude greater than the previously reported value for the bulk Moon, and the actual source region water contents could be significantly higher.
New immature hominin fossil from European Lower Pleistocene shows the earliest evidence of a modern human dental development pattern
Authors: Bermúdez de Castro José María , Martinón-Torres María , Prado Leyre , Gómez-Robles Aida , Rosell Jordi , López-Polín Lucía , Arsuaga Juan Luís , Carbonell Eudald
Published: June 2010

Here we present data concerning the pattern of dental development derived from the microcomputed tomography (microCT) study of a recently discovered immature hominin mandible with a mixed dentition recovered from the TD6 level of the Gran Dolina Lower Pleistocene cave site in Sierra de Atapuerca, northern Spain. These data confirm our previous results that nearly 1 million years ago at least one European hominin species had a fully modern pattern of dental development with a clear slowdown in the development of the molar field regarding the anterior dental field. Furthermore, using available information about enamel formation times and root extension rates in chimpanzees, early hominins, and modern humans, we have estimated that the formation time of the upper and lower first molars of individual 5 (H5) from TD6, which had just erupted at the time of the death of this individual, ranges between 5.3 and 6.6 y. Therefore, the eruption time of the first permanent molars (M1) in the TD6 hominins was within the range of variation of modern human populations. Because the time of M1 eruption in primates is a robust marker of life history, we suggest, as a working hypothesis, that these hominins had a prolonged childhood in the range of the variation of modern humans. If this hypothesis is true, it implies that the appearance in
Homo
of this important developmental biological feature and an associated increase in brain size preceded the development of the neocortical areas leading to the cognitive capabilities that are thought to be exclusive to
Homo sapiens
.
Consolation as possible expression of sympathetic concern among chimpanzees
Authors: Romero Teresa , Castellanos Miguel A. , de Waal Frans B. M.
Published: June 2010

Chimpanzees are known to spontaneously provide contact comfort to recent victims of aggression, a behavior known as consolation. Similar behavior in human children is attributed to empathic or sympathetic concern. In line with this empathy hypothesis, chimpanzee consolation has been shown to reduce the recipient's state of arousal, hence to likely alleviate distress. Other predictions from the empathy hypothesis have rarely been tested, however, owing to small sample sizes in previous studies. An exceptionally large database of spontaneous consolation in two outdoor-housed groups of chimpanzees lends further support to the empathy hypothesis in that consolation occurred disproportionally between individuals that are socially close (i.e., kin and affiliation partners) and was more typical of females than males, which differences are also known of human empathy. These effects were demonstrated using generalized linear mixed models, which control multiple variables at once. An exception to the above pattern was formed by the highest-ranking males, which frequently offered consolation to victims of aggression, probably as part of their general policing function in chimpanzee society. Consolation occurred more frequently in the absence of reconciliation between former opponents, suggesting that actors are sensitive to the contact need of victims of aggression, which may be greater if the aggressor ignores them. That consolation is an integrated part of close mutual relationships is supported by the tendency for it being reciprocated.
MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs
Authors: Frost Robert J. A. , Hamra F. Kent , Richardson James A. , Qi Xiaoxia , Bassel-Duby Rhonda , Olson Eric N.
Published: June 2010

Piwi-interacting RNAs (piRNAs) comprise a broad class of small noncoding RNAs that function as an endogenous defense system against transposable elements. Here we show that the putative DExD-box helicase MOV10-like-1 (MOV10L1) is essential for silencing retrotransposons in the mouse male germline.Mov10l1is specifically expressed in germ cells with increasing expression from gonocytes/type A spermatogonia to pachytene spermatocytes. Primary spermatocytes ofMov10l1−/−mice show activation of LTR and LINE-1 retrotransposons, followed by cell death, causing male infertility and a complete block of spermatogenesis at early prophase of meiosis I. Despite the early expression ofMov10l1, germline stem cell maintenance appears unaffected inMov10l1−/−mice. MOV10L1 interacts with the Piwi proteins MILI and MIWI. MOV10L1 also interacts with heat shock 70-kDa protein 2 (HSPA2), a testis-enriched chaperone expressed in pachytene spermatocytes and also essential for male fertility. These studies reveal a crucial role of MOV10L1 in male fertility and piRNA-directed retrotransposon silencing in male germ cells and suggest that MOV10L1 functions as a key component of a safeguard mechanism for the genetic information in male germ cells of mammals.
Identification of a novel antigen-presenting cell population modulating antiinfluenza type 2 immunity
Authors: Yoo Jae-Kwang , Galligan Carole L. , Virtanen Carl , Fish Eleanor N.
Published: June 2010

Antiinfluenza type 2 (T2) immunity contributes to both immunopathology and immunoprotection, yet the underlying mechanisms modulating T2 immunity remain ill defined. We describe a novel mouse antigen (Ag)-presenting cell (APC), designated late-activator APC (LAPC). After pulmonary influenza A (H1N1) virus infection, LAPCs enter the lungs, capture viral Ag, and subsequently migrate to the draining lymph node (DLN) and spleen, with delayed kinetics relative to dendritic cells (DCs). In the DLN, influenza virus–activated LAPCs present Ag and selectively induce T helper type 2 (Th2) effector cell polarization by cell–cell contact–mediated modulation of GATA-3 expression. In adoptive transfer experiments, influenza virus–activated LAPCs augmented Th2 effector T cell responses in the DLN, increased production of circulating antiinfluenza immunoglobulin, and increased levels of T2 cytokines in bronchoalveolar lavage fluid in recipient influenza virus–infected mice. LAPC-recipient mice exhibited exacerbated pulmonary pathology, with delayed viral clearance and enhanced pulmonary eosinophilia. Collectively, our results identify and highlight the importance of LAPCs as immunomodulators of T2 immunity during influenza A virus infection.
Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiency
Authors: Walter Jolan E. , Rucci Francesca , Patrizi Laura , Recher Mike , Regenass Stephan , Paganini Tiziana , Keszei Marton , Pessach Itai , Lang Philipp A. , Poliani Pietro Luigi , Giliani Silvia , Al-Herz Waleed , Cowan Morton J. , Puck Jennifer M. , Bleesing Jack , Niehues Tim , Schuetz Catharina , Malech Harry , DeRavin Suk See , Facchetti Fabio , Gennery Andrew R. , Andersson Emma , Kamani Naynesh R. , Sekiguchi JoAnn , Alenezi Hamid M. , Chinen Javier , Dbaibo Ghassan , ElGhazali Gehad , Fontana Adriano , Pasic Srdjan , Detre Cynthia , Terhorst Cox , Alt Frederick W. , Notarangelo Luigi D.
Published: June 2010

The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations.
Homeostatic expansion of autoreactive immunoglobulin-secreting cells in the Rag2 mouse model of Omenn syndrome
Authors: Cassani Barbara , Poliani Pietro Luigi , Marrella Veronica , Schena Francesca , Sauer Aisha V. , Ravanini Maria , Strina Dario , Busse Christian E. , Regenass Stephan , Wardemann Hedda , Martini Alberto , Facchetti Fabio , van der Burg Mirjam , Rolink Antonius G. , Vezzoni Paolo , Grassi Fabio , Traggiai Elisabetta , Villa Anna
Published: June 2010

Hypomorphic RAG mutations, leading to limited V(D)J rearrangements, cause Omenn syndrome (OS), a peculiar severe combined immunodeficiency associated with autoimmune-like manifestations. Whether B cells play a role in OS pathogenesis is so far unexplored. Here we report the detection of plasma cells in lymphoid organs of OS patients, in which circulating B cells are undetectable. Hypomorphic Rag2R229Q knock-in mice, which recapitulate OS, revealed, beyond severe B cell developmental arrest, a normal or even enlarged compartment of immunoglobulin-secreting cells (ISC). The size of this ISC compartment correlated with increased expression of Blimp1 and Xbp1, and these ISC were sustained by elevated levels of T cell derived homeostatic and effector cytokines. The detection of high affinity pathogenic autoantibodies toward target organs indicated defaults in B cell selection and tolerance induction. We hypothesize that impaired B cell receptor (BCR) editing and a serum B cell activating factor (BAFF) abundance might contribute toward the development of a pathogenic B cell repertoire in hypomorphic Rag2R229Q knock-in mice. BAFF-R blockade reduced serum levels of nucleic acid-specific autoantibodies and significantly ameliorated inflammatory tissue damage. These findings highlight a role for B cells in OS pathogenesis.
A new method for designing degenerate primers and its use in the identification of sequences in Brachiaria showing similarity to apomixis-associated genes
Authors: Gorrón Eduardo , Rodríguez Fausto , Bernal Diana , Rodriguez-Rojas Luis Miguel , Bernal Adriana , Restrepo Silvia , Tohme Joe
Published: June 2010

Motivation: We developed a technique and a tool for degenerate primer design based on multiple local alignments employing the MEME algorithm supported with electronic PCR. The objective is to find adequate primers starting from sequences with poor global similarity. We show an example of its application in our laboratory to find sequences in Brachiaria with similarity to ESTs related to apomixis.

Contact:  srestrep@uniandes.edu.co; j.tohme@cgiar.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Black Rot of Orchids Caused by Phytophthora cactorum and Phytophthora palmivora in Florida
Authors: Cating R. A. , Palmateer A. J. , Stiles C. M. , Rayside P. A.
Published: June 2010

Several species of Phytophthora have been reported to cause economic damage on orchids worldwide. Of these, P. cactorum and P. palmivora have the widest host range across orchid genera, and they are the most common species affecting commercial orchid production in Florida. The objective of this guide is to provide a practical diagnostic resource for black rot on orchids in Florida.

Accepted for publication 27 April 2010. Published 14 June 2010.
Resistance to Dodine in Populations of Venturia inaequalis in Quebec, Canada
Authors: Carisse Odile , Jobin Tristan
Published: June 2010

Dodine was introduced in the USA and Canada in the early 1960s for the control of apple scab. Following control failure, growers stopped using dodine in the mid-1970s. Despite the curtailment of dodine use more than 30 years ago, persistent resistance to the fungicide was suspected in V. inaequalis populations. The dodine sensitivity was determined for two populations that were not exposed to dodine for at least 30 years – a wild type population (25 monoconidial isolates) and a population constructed with isolates collected in orchards managed for apple scab (156 isolates). The sensitivity to dodine was determined by monitoring growth of these isolates on agar Petri dishes amended with 0, 0.01, 0.1, 1.0, or 10.0 μg/ml of dodine. Sensitivity to fungicide was evaluated based on ED50 values. Both populations showed a lognormal distribution of ED50 values. The ED50 means were 0.525 μg/ml and 1.735 μg/ml for the wild type and managed orchards populations, respectively. In managed orchard, 31.4% of the isolates were resistant to dodine (ED50 > 1.0 μg/ml). Cross-resistance with myclobutanil and with kresoxim-methyl was tested and found not to be significant. The results of this study suggest that resistance to dodine is still present in the populations of V. inaequalis from Quebec and that reintroduction of dodine should only be done along with an appropriate resistance management strategy.

Accepted for publication 27 April 2010. Published 14 June 2010.
Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells
Authors: Choi Seung H. , Wright Jason B. , Gerber Scott A. , Cole Michael D.
Published: June 2010

Rapid Myc protein turnover is critical for maintaining basal levels of Myc activity in normal cells and a prompt response to changing growth signals. We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)–CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus. TRPC4AP/TRUSS suppresses Myc-mediated transactivation and transformation in a dose-dependent manner. Finally, we found that TRPC4AP/TRUSS expression is strongly down-regulated in most cancer cell lines, leading to Myc protein stabilization. These studies identify a novel pathway targeting Myc degradation that is suppressed in cancer cells.
Cdx2 regulates endo-lysosomal function and epithelial cell polarity
Authors: Gao Nan , Kaestner Klaus H.
Published: June 2010

In contrast to our significant understanding of signaling cascades that determine cell polarity in lower eukaryotic or immortalized cells, little is known about the transcriptional program that governs mammalian epithelial polarization in vivo. Here we show, using conditional gene ablation and three-dimensional tissue culture, that the homeobox transcription factor Cdx2 controls apical–basolateral polarity in mouse enterocytes and human colonic epithelial cells. Cdx2 regulates a comprehensive gene network involved in endo-lysosomal maturation and protein transport. In the absence of Cdx2, defective protein trafficking impairs apical–basal transport and induces ectopic lumen formation. These defects are partially recapitulated by suppression of key apical transport components, Rab11a and Kif3b, which are regulated by Cdx2. Furthermore, Cdx2 deficiency affects components that control the organization of microvillus actin cytoskeleton, leading to severe microvillus atrophy. These results demonstrate that Cdx2 regulates epithelial cell polarity and morphogenesis through control of apical protein transport and endo-lysosomal function.
How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?
Authors: Labib Karim
Published: June 2010

Chromosome replication occurs precisely once during the cell cycle of almost all eukaryotic cells, and is a highly complex process that is still understood relatively poorly. Two conserved kinases called Cdc7 (cell division cycle 7) and cyclin-dependent kinase (CDK) are required to establish replication forks during the initiation of chromosome replication, and a key feature of this process is the activation of the replicative DNA helicase in situ at each origin of DNA replication. A series of recent studies has shed new light on the targets of Cdc7 and CDK, indicating that chromosome replication probably initiates by a fundamentally similar mechanism in all eukaryotes.
Evolutionary conservation of meiotic DSB proteins: more than just Spo11
Authors: Cole Francesca , Keeney Scott , Jasin Maria
Published: June 2010

Meiotic recombination is initiated by programmed DNA double-strand breaks (DSBs) generated by the Spo11 protein. In budding yeast, five other meiotic-specific proteins are also required for DSB formation, but, with rare exception, orthologs had not been identified in other species. In this issue of Genes & Development, Kumar and colleagues (pp. 1266–1280) used a phylogenomic approach to identify two of these proteins across multiple clades, and confirmed that one of these, MEI4, is a functional ortholog in mouse.
Phenotypic annotation of the mouse X chromosome
Authors: Cox Brian J. , Vollmer Marion , Tamplin Owen , Lu Mei , Biechele Steffen , Gertsenstein Marina , van Campenhout Claude , Floss Thomas , Kühn Ralf , Wurst Wolfgang , Lickert Heiko , Rossant Janet
Published: June 2010

Mutational screens are an effective means used in the functional annotation of a genome. We present a method for a mutational screen of the mouse X chromosome using gene trap technologies. This method has the potential to screen all of the genes on the X chromosome without establishing mutant animals, as all gene-trapped embryonic stem (ES) cell lines are hemizygous null for mutations on the X chromosome. Based on this method, embryonic morphological phenotypes and expression patterns for 58 genes were assessed, ∼10% of all human and mouse syntenic genes on the X chromosome. Of these, 17 are novel embryonic lethal mutations and nine are mutant mouse models of genes associated with genetic disease in humans, including BCOR and PORCN. The rate of lethal mutations is similar to previous mutagenic screens of the autosomes. Interestingly, some genes associated with X-linked mental retardation (XLMR) in humans show lethal phenotypes in mice, suggesting that null mutations cannot be responsible for all cases of XLMR. The entire data set is available via the publicly accessible website (http://xlinkedgenes.ibme.utoronto.ca/).
Outcome of children with sickle cell disease admitted to intensive care – a single institution experience
Authors: Bartram Jack L. , Thein Swee L. , Gardner Kate , Egberongbe Yaya , D’Silva Pam , Height Susan E. , Dick Moira C. , O’Driscoll Sandra , Rees David C.
Published: June 2010

We retrospectively audited children with sickle cell disease (SCD) admitted to paediatric intensive care (PICU) at King’s College Hospital between January 2000 and December 2008. Forty‐six children with SCD were admitted, on 49 separate occasions. Ages ranged from 4 months to 15 years (median 7·6 years). Three children died in PICU, however two presented to hospital in cardiorespiratory arrest; overall mortality was 6%. The most common reason for admission was acute chest syndrome (43%). 88% of admissions required blood transfusion, of which 74% had exchange blood transfusions. The mortality among children with SCD admitted to PICU is low.
Oxidative stress and inflammation modulate peroxisome proliferator‐activated receptors with regional discrepancy in diabetic heart
Authors: Lee Ting‐I. , Kao Yu‐Hsun , Chen Yao‐Chang , Pan Nan‐Hung , Chen Yi‐Jen
Published: June 2010

Eur J Clin Invest 2010; 40 (8): 692–699

Background  Peroxisome proliferator‐activated receptors (PPARs) play a pivotal role in myocardial lipid and glucose homeostasis. We investigated the effects of diabetes on PPAR isoforms in different cardiac regions and explored whether proinflammatory cytokines or oxidative stress modulate PPARs in diabetic hearts.

Materials and methods  Male Wistar rats were separated into control, diabetes and ascorbate‐treated diabetes groups. Real‐time PCR and Western blot analysis were performed on PPAR isoforms, tumour necrosis factor (TNF)‐α and interleukin (IL)‐6, from left and right atria and ventricles. Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase activity was quantified through photometric measurements.

Results  In control hearts, PPAR‐α was most expressed, and PPAR‐γ least expressed in mRNA and protein levels. Diabetes decreased the protein and mRNA levels of PPAR‐α and PPAR‐δ. Ascorbate attenuated the diabetes‐induced down‐regulations of PPAR‐α and PPAR‐δ proteins in all cardiac regions and down‐regulation of PPAR‐α mRNA in the left atrium. In PPAR‐γ, the protein and mRNA levels were increased in diabetic atria and ventricles, which were decreased by ascorbate. Moreover, diabetes increased the TNF‐α and IL‐6 protein levels, and NAD(P)H oxidase activities in atria and ventricles. Ascorbate attenuated the increase of TNF‐α, IL‐6 protein levels and NAD(P)H oxidase activity in the atria, but only attenuated the increase of NAD(P)H oxidase activities in the ventricles.

Conclusions  Peroxisome proliferator‐activated receptor isoforms are differentially expressed in the atria and ventricles. Diabetes can modulate PPARs through increased inflammatory cytokines and oxidative stress, which are attenuated by ascorbate treatment.
Novel method for isolating untouched rat natural killer cells with higher purity compared with positive selection and fluorescence‐activated cell sorting
Authors: Poli Aurélie , Brons Nicolaas H. C. , Ammerlaan Wim , Michel Tatiana , Hentges François , Chekenya Martha , Zimmer Jacques
Published: June 2010

Natural killer (NK) cells are important effectors of both innate and adaptive immune responses. Although human and mouse NK cells are extensively characterized, much less is known about the rat cells, partly because of the current lack of reliable isolation techniques. We aimed to develop a method for isolating highly pure ‘untouched’ rat NK cells by negative selection from splenocytes. Thereafter, we characterized them phenotypically and functionally in comparison with those isolated by positive selection targeting the NKR‐P1 receptor. Our novel method isolated highly pure untouched NK cells reproducibly with 97 ± 0·7% (n = 7), 96·6 ± 0·8% (n = 3) and 88·3 ± 1·5% (n = 9) in LEWIS, Fischer and athymic nude rats, respectively. The positively selected NK cells were less homogeneous and exhibited undesired method‐related activation profiles. Resting negatively selected NK cells were less proliferative and less robust compared with positively selected NK cells. Although resting positively selected NK cells were more cytotoxic, interleukin‐2 (IL‐2) activation increased the cytotoxicity of negatively selected cells three‐fold. The negatively selected NK cells responded to cross‐linking of the NKR‐P1 receptor by calcium mobilization from intracellular stores. However, combined IL‐2 and IL‐12 activation resulted in significantly more interferon‐γ release from positively selected NK cells. This new NK‐cell isolation method will allow a deeper insight into rat NK‐cell phenotypes and the roles of their receptors in the biology of these cells.
A role for interleukin‐5 in promoting increased immunoglobulin M at the site of disease in leprosy
Authors: Ochoa Maria T. , Teles Rosane , Haas Blake E. , Zaghi Danny , Li Huiying , Sarno Euzenir N. , Rea Thomas H. , Modlin Robert L. , Lee Delphine J.
Published: June 2010

Leprosy is an infectious disease in which the clinical manifestations correlate with the type of immune response mounted to the pathogen, Mycobacterium leprae. To investigate which biological pathways or gene sets are over‐represented in lepromatous (L‐Lep) versus tuberculoid (T‐Lep) patients that might be relevant in disease pathogenesis, we compared the gene expression profiles of L‐lep versus T‐lep skin lesions using knowledge‐guided bioinformatic analysis, incorporating data on likely biological functions, including gene ontology information and regulatory data. Analysis of probe sets comparatively increased in expression in L‐lep versus T‐lep revealed multiple pathways and functional groups involving B‐cell genes (P values all < 0·005) relevant to the dataset. Further pathways analysis of B‐cell genes comparatively increased in expression in L‐lep versus T‐lep lesions revealed a potential network linking the expression of immunoglobulin M (IgM) and interleukin‐5 (IL‐5). Analysis of the leprosy lesions by immunohistology indicated that there was approximately 8% more IgM‐positive cells in L‐lep lesions than in T‐lep lesions. Furthermore, IL‐5 synergized in vitro with M. leprae to enhance total IgM secretion from peripheral blood mononuclear cells. This pathways analysis of leprosy in combination with our in vitro studies implicates a role for IL‐5 in the increased IgM at the site of disease in leprosy.
Adaptive evolution in subterranean termite antifungal peptides
Authors: Bulmer M. S. , Lay F. , Hamilton C.
Published: June 2010

We identified and analysed mRNA sequences of two immune proteins from the subterranean termites Reticulitermes flavipes and Reticulitermes virginicus. These proteins correspond to two immune proteins described in the distantly related termite genus Nasutitermes; termicin, which is a small antifungal peptide, and GNBP2, which functions both as a broad pattern recognition receptor and a direct antifungal effector. A population genetic analysis of nucleotide intraspecific polymorphism and interspecific divergence indicates that a selective sweep has reduced polymorphism in the termicins. Moreover, this selective sweep appears to have been driven by the positive selection of beneficial amino acid changes in the antifungal peptide. In contrast, the pattern of polymorphism and divergence in GNBP2 corresponds to the standard neutral model of evolution.
Decreased detoxification genes and genome size make the human body louse an efficient model to study xenobiotic metabolism
Authors: Lee S. H. , Kang J. S. , Min J. S. , Yoon K. S. , Strycharz J. P. , Johnson R. , Mittapalli O. , Margam V. M. , Sun W. , Li H.‐M. , Xie J. , Wu J. , Kirkness E. F. , Berenbaum M. R. , Pittendrigh B. R. , Clark J. M.
Published: June 2010

The human body louse,Pediculus humanus humanus, has one of the smallest insect genomes, containing ∼10 775 annotated genes. Annotation of detoxification [cytochrome P450 monooxygenase (P450), glutathione‐S‐transferase (GST), esterase (Est) and ATP‐binding cassette transporter (ABC transporter)] genes revealed that they are dramatically reduced inP. h. humanuscompared to other insects except forApis mellifera. There are 37 P450, 13 GST and 17 Est genes present inP. h. humanus, approximately half the number found inDrosophila melanogasterandAnopheles gambiae. The number of putatively functional ABC transporter genes inP. h. humanusandAp. melliferaare the same (36) but both have fewer thanAn. gambiae(44) orDr. melanogaster(65). The reduction of detoxification genes inP. h. humanusmay be a result of this louse's simple life history, in which it does not encounter a wide variety of xenobiotics. Neuronal component genes are highly conserved across different insect species as expected because of their critical function. Although reduced in number,P. h. humanusstill retains at least a minimum repertoire of genes known to confer metabolic or toxicokinetic resistance to xenobiotics (eg Cyp3 clade P450s, Delta GSTs, B clade Ests and B/C subfamily ABC transporters), suggestive of its high potential for resistance development.
Histology, immunocytochemistry and qRT‐PCR analysis of Atlantic salmon, Salmo salar L., post‐smolts following infection with infectious pancreatic necrosis virus (IPNV)
Authors: Ellis A E , Cavaco A , Petrie A , Lockhart K , Snow M , Collet B
Published: June 2010

Infectious pancreatic necrosis (IPN) is a very serious viral disease in terms of its impact on production of Atlantic salmon, Salmo salar L., fry and post‐smolts. Post‐smolts of Atlantic salmon were injected with infectious pancreatic necrosis virus (IPNV) and cohabited with naive fish to produce natural infection. Cohabitant fish were sampled every 2 days, up to day 36 post‐infection (p.i.). From 90 cohabitant fish, 11 (12.2%) were positive by immunohistochemistry (IHC). The first detection of IPNV by IHC occurred on day 16 p.i. which coincided with the onset of mortality in this group. Besides the pancreas, the liver was found to be a key target organ for IPNV. For the first time, the virus was observed in the islets of Langerhans and in the kidney corpuscles of Stannius which suggests that the virus could affect the fish’s metabolism. The liver of two fish, which showed the most widespread presence of IPNV by IHC, had a pathology including focal necrosis and widespread presence of apoptotic hepatocytes, many of which did not stain for virus by IHC. Up‐regulation of cytokine gene expression was found only in the IHC‐positive (IHC+ve) fish and reflected the level of infection as determined by IHC positivity of the liver. In most fish, interferon (IFN), Mx, γIFN and γIP were up‐regulated in liver and kidney, while only IFN and Mx were up‐regulated in gill. IL1β and TNFα were not induced in any tissue. The gill showed variable levels of constitutive expression of IL1β and γIFN. The two fish with liver pathology had the highest level of IFN expression, especially relative to the level of Mx expression, in the liver compared with the other IHC+ve fish which did not have a liver pathology. The results suggest that following widespread infection of hepatocytes, the cells may over‐produce IFN, resulting in apoptosis of neighbouring cells with subsequent death from liver failure.
Diet and nutritional status of children with food allergies
Authors: Flammarion Sophie , Santos Clarisse , Guimber Dominique , Jouannic Lyne , Thumerelle Caroline , Gottrand Frédéric , Deschildre Antoine
Published: June 2010

To cite this article:Flammarion S, Santos C, Guimber D, Jouannic L, Thumerelle C, Gottrand F, Deschildre A. Diet and nutritional status of children with food allergies.Pediatr Allergy Immunol2011;22: 161–165.

The aim of the present study was to assess the food intakes and nutritional status of children with food allergies following an elimination diet. We conducted a cross sectional study including 96 children (mean age 4.7 ± 2.5 years) with food allergies and 95 paired controls (mean age 4.7 ± 2.7 years) without food allergies. Nutritional status was assessed using measurements of weight and height and Z scores for weight‐for‐age, height‐for‐age and weight‐for‐height. Nutrient intakes assessment was based on a 3‐day diet record. Children with food allergies had weight‐for‐age and height‐for‐age Z scores lower than controls (0.1 versus 0.6 and 0.2 versus 0.8 respectively). Children with 3 or more food allergies were smaller than those with 2 or less food allergies (p = 0.04). A total of 62 children with food allergies and 52 controls completed usable diet records. Energy, protein and calcium intakes were similar in the two groups. Children with food allergies were smaller for their age than controls even when they received similar nutrient intakes. Nutritional evaluation is essential for the follow up of children with food allergies.
Maternal B vitamin intake during pregnancy and wheeze and eczema in Japanese infants aged 16–24 months: The Osaka Maternal and Child Health Study
Authors: Miyake Yoshihiro , Sasaki Satoshi , Tanaka Keiko , Hirota Yoshio
Published: June 2010

To cite this article: Miyake Y, Sasaki S, Tanaka K, Hirota Y. Maternal B vitamin intake during pregnancy and wheeze and eczema in Japanese infants aged 16–24 months: The Osaka Maternal and Child Health Study. Pediatric Allergy Immunology 2011: 22: 69–74.

It is uncertain whether B group vitamins are risk or preventive factors for allergic disorders. We prospectively investigated the association between maternal intake of folate and vitamins B12, B6, and B2 during pregnancy and the risk of wheeze and eczema in the infants aged 16–24 months. Subjects were 763 Japanese mother–child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire (DHQ). Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood. Among 763 infants, 169 (22.1%) and 142 (18.6%) had symptoms of wheeze and eczema, respectively. There were no evident relationships between maternal consumption of folate, vitamin B12, vitamin B6, and vitamin B2 during pregnancy and the risk of wheeze or eczema in the offspring after adjustment for maternal age, gestation at baseline, residential municipality at baseline, family income, maternal and paternal education, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, changes in maternal diet in the previous 1 month, season when data at baseline were collected, maternal smoking during pregnancy, baby’s older siblings, baby’s sex, baby’s birth weight, household smoking in the same room as the infant, breastfeeding duration, age at which solid foods were introduced, age of infant at the third survey, and maternal intake of docosahexaenoic acid, n‐6 polyunsaturated fatty acids, vitamin D, calcium, vitamin E, and β‐carotene during pregnancy. Further investigation is warranted to draw conclusions as to the question of whether maternal B vitamin intake during pregnancy is related to the risk of childhood allergic disorders.
Lactate concentrations in the rectal lumen in patients in early septic shock
Authors: IBSEN M. , TENHUNEN J. , WIIS J. , WALDAU T. , LAURITSEN A. Ø. , THORNBERG K. , JOENSEN H. , Perner A.
Published: June 2010

Background: Previously, we observed that rectal luminal lactate was higher in non‐survivors compared with survivors of severe sepsis or septic shock persisting >24 h. The present study was initiated to further investigate this tentative association between rectal luminal lactate and mortality in a larger population of patients in early septic shock.

Methods: A prospective observational multicentre study of 130 patients with septic shock at six general ICU's of university hospitals. Six to 24 h after the onset of septic shock, the concentration of lactate in the rectal lumen was estimated by a 4‐h equilibrium dialysis. Dialysate concentrations of lactate were determined using an auto‐analyser.

Results: The overall 30‐day mortality was 32%, with age and Simplified acute physiology scores II and sequential organ failure assessment scores being significantly higher in non‐survivors. In contrast, there were no differences in concentrations of lactate in the rectal lumen [2.2 (1.4–4.1) and 2.8 (1.6–5.1) mmol/l (P=0.34)] (medians and 25th–75th percentiles) or arterial blood [2.1 (1.4–4.2) and 2.0 (1.3–3.2) mmol/l (P=0.15)] between non‐survivors and survivors. The rectal–arterial difference of the lactate concentration was higher in survivors. There were no differences in blood pressure, noradrenaline dose or central venous oxygen saturation between the groups.

Conclusion: In this prospective, observational study of unselected patients with early septic shock, there was no difference in the concentration of lactate in the rectal lumen between non‐survivors and survivors.

Trial Registration: Clinicaltrials.gov (no: NCT00197938).
Usefulness of endoscopic ultrasound for the prediction of intraoperative bleeding of endoscopic submucosal dissection for gastric neoplasms
Authors: Kikuchi Daisuke , Iizuka Toshiro , Hoteya Shu , Yamashita Satoshi , Nakamura Masanori , Kuroki Yuichiro , Mitani Toshihumi , Fujimoto Ai , Matsui Akira , Nishida Noriko , Yahagi Naohisa
Published: June 2010

Background and Aim:  Intraoperative bleeding is an important determining factor for the technical difficulty and safety of endoscopic submucosal dissection (ESD) for gastric neoplasms, which was previously difficult to predict before ESD. In the present study, we investigated whether endoscopic ultrasound (EUS) could be used to preoperatively predict intraoperative bleeding.

Methods:  The study included 106 patients who underwent EUS before ESD. EUS was used to evaluate the submucosal vascular structure. Patients who had at least 10 vascular structures per field of view or a vessel at least 500 µm in diameter were classified into the rich group (Group R), and others were classified into the non‐rich group (Group N). The two groups were compared retrospectively with respect to procedure time, degree of anemia, frequency of clip use, and others.

Results:  There were 24 patients in Group R and 82 patients in Group N. Submucosal caner was found in 54.2% of patients in Group R and 18.3% in Group N. The reduction in hemoglobin was 5.8% in Group R and 3.45% in Group N. The procedure time was 151 min in Group R and 100 min in Group N. The frequency of clip use was 79.2% in Group R and 31.7% in Group N. A multivariate analysis revealed a significant difference in the depth of invasion and frequency of clip use between the two groups.

Conclusions:  The results suggest that identification of submucosal vascular structure by EUS might allow prediction of intraoperative bleeding during ESD.
Correlation of serum pepsinogens and gastrin‐17 with atrophic gastritis in gastroesophageal reflux patients: A matched‐pairs study
Authors: Peitz Ulrich , Wex Thomas , Vieth Michael , Stolte Manfred , Willich Stefan , Labenz Joachim , Jaspersen Daniel , Lind Tore , Malfertheiner Peter
Published: June 2010

Background and Aim:  An algorithm (GastroPanel) for the non‐invasive diagnosis of atrophic gastritis has been previously proposed, based on serum pepsinogen‐I, gastrin‐17, and Helicobacter pylori (H. pylori) antibodies. The aim of the present study was to evaluate whether serum markers correlate with and predict gastric atrophy in gastroesophageal reflux disease (GERD) patients.

Methods:  The baseline data of the prospective ProGERD study, a study on the long‐term course of GERD (n = 6215 patients), served to select patients with atrophic gastritis diagnosed in biopsies from gastric antrum and corpus, and control cases without atrophy. A total of 208 pairs were matched for age, sex, GERD status (erosive vs non‐erosive), presence of Barrett's esophagus, and histological H. pylori status were retrieved. Serum pepsinogen‐I, gastrin‐17, and H. pylori antibodies were determined using specific enzyme immunoassays.

Results:  A significant negative correlation was found between the degree of corpus atrophy and the level of serum pepsinogen‐I. A previously‐reported negative correlation between the degree of antral atrophy and serum gastrin‐17 could not be confirmed. The low sensitivity (0.32) and specificity (0.70) of the GastroPanel algorithm were mainly due to over diagnosis and under diagnosis of advanced atrophy in the antrum.

Conclusion:  The diagnostic validity of the GastroPanel algorithm to diagnose gastric atrophy non‐invasively is not sufficient for general use in GERD patients.