bluuebunny/crossref_metadata_2025 huggingface dataset:
A hidden Markov model to identify combinatorial epigenetic regulation patterns for estrogen receptor α target genes
Authors: Bonneville Russell , Jin Victor X.
Published: October 2012

Motivation: Many studies have shown that epigenetic changes, such as altered DNA methylation and histone modifications, are linked to estrogen receptor α (ERα)-positive tumors and disease prognoses. Several recent studies have applied high-throughput technologies such as ChIP-seq and MBD-seq to interrogate the altered architectures of ERα regulation in tamoxifen (Tam)-resistant breast cancer cells. However, the details of combinatorial epigenetic regulation of ERα target genes in breast cancers with acquired Tam resistance have not yet been fully examined.

Results: We developed a computational approach to identify and analyze epigenetic patterns associated with Tam resistance in the MCF7-T cell line as opposed to the Tam-sensitive MCF7 cell line, with the goal of understanding the underlying mechanisms of epigenetic regulatory influence on resistance to Tam treatment in breast cancer. In this study, we used ChIP-seq of ERα, RNA polymerase II, three histone modifications and MBD-seq data of DNA methylation in MCF7 and MCF7-T cells to train hidden Markov models (HMMs). We applied the Bayesian information criterion to determine that a 20-state HMM was best, which was reduced to a 14-state HMM with a Bayesian information criterion score of 1.21291 × 107. We further identified four classes of biologically meaningful states in this breast cancer cell model system, and a set of ERα combinatorial epigenetic regulated target genes. The correlated gene expression level and gene ontology analyses showed that different gene ontology terms were enriched with Tam-resistant versus sensitive breast cancer cells. Our study illustrates the applicability of HMM-based analysis of genome-wide high-throughput genomic data to study epigenetic influences on E2/ERα regulation in breast cancer.

Contact:  victor.jin@osumc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
SPSens: a software package for stochastic parameter sensitivity analysis of biochemical reaction networks
Authors: Sheppard Patrick W. , Rathinam Muruhan , Khammash Mustafa
Published: October 2012

Summary: SPSens is a software package for the efficient computation of stochastic parameter sensitivities of biochemical reaction networks. Parameter sensitivity analysis is a valuable tool that can be used to study robustness properties, for drug targeting, and many other purposes. However its application to stochastic models has been limited when Monte Carlo methods are required due to extremely high computational costs. SPSens provides efficient, state of the art sensitivity analysis algorithms in a single software package so that sensitivity analysis can be easily performed on stochastic models of biochemical reaction networks. SPSens implements the algorithms in C and estimates sensitivities with respect to both infinitesimal and finite perturbations to system parameters, in many cases reducing variance by orders of magnitude compared to basic methods. Included among the features of SPSens are serial and parallel command line versions, an interface with Matlab, and several example problems.

Availability: SPSens is distributed freely under GPL version 3 and can be downloaded from http://sourceforge.net/projects/spsens/. The software can be run on Linux, Mac OS X and Windows platforms.

Contact:  mustafa.khammash@bsse.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
Effects of a large-scale and offshore marine protected area on the demersal fish assemblage in the Southwest Atlantic
Authors: Alemany Daniela , Iribarne Oscar O. , Acha Eduardo M.
Published: October 2012

Alemany, D., Iribarne, O. O., and Acha, E. M. 2013. Effects of a large-scale and offshore marine protected area on the demersal fish assemblage in the Southwest Atlantic. – ICES Journal of Marine Science, 70:123–134. There are few extensive and offshore located marine protected areas (MPAs) in the world oceans and their performance is still being debated. We evaluated the effects of a large-scale offshore MPA located on the Southwest Atlantic Patagonian Shelf (43°S 63°W) on the demersal fish assemblage. Compliance of the Patagonian MPA was assessed by analysing eight years of satellite vessel monitoring system (VMS; 2000–2008) data, which showed compliance and fishing effort concentrated near the protection boundaries. MPA effects were studied by employing a five year database collected by a scientific research vessel in protected and fishing locations, before and after the MPA establishment. We assessed 152 scientific trawling stations using multivariate analysis of fish assemblage structure, fish abundance (discriminating target and non-target species), and mean size and proportion of juveniles of the target species (Argentine hake, Merluccius hubbsi). The identified MPA effects were a trend towards increasing abundance of the demersal fish assemblage, the target and non-target fish species, and hake juvenile size, and a higher proportion of juveniles aged 2+ inside the MPA. These positive trends support the case for offshore, large-scale MPAs.
Pontimonas salivibrio gen. nov., sp. nov., a new member of the family

Microbacteriaceae

isolated from a seawater reservoir of a solar saltern
Authors: Jang Gwang Il , Cho Yirang , Cho Byung Cheol
Published: October 2012

A Gram-staining-positive, non-motile, strictly aerobic, non-spore-forming, vibrio-shaped bacterial strain, CL-TW6T, was isolated from a reservoir seawater sample from a solar saltern in Korea. Analysis of the 16S rRNA gene sequence of strain CL-TW6T revealed a clear affiliation with the family

Microbacteriaceae

. Strain CL-TW6T showed the closest phylogenetic relationships with the genera

Yonghaparkia

and

Microcella

, with 16S rRNA gene sequence similarity of 94.8–95.3 %. The strain grew in the presence of 1–9 % sea salts, at 15–35 °C and at pH 7.0–9.0. The major cellular fatty acids of strain CL-TW6T were anteiso-C15 : 0 (32.6 %), iso-C16 : 0 (20.4 %), iso-C15 : 0 (13.2 %) and iso-C14 : 0 (11.8 %) and the major menaquinones were MK-9 and MK-10. Cell-wall analysis showed that the peptidoglycan of strain CL-TW6T contained 2,4-diaminobutyric acid, alanine, glycine and glutamic acid. The major polar lipids were diphosphatidylglycerol and phosphatidylglycerol. The genomic DNA G+C content of strain CL-TW6T was 60.0 mol%. The combined phenotypic, chemotaxonomic and phylogenetic data showed clearly that strain CL-TW6T could be distinguished from members of the family

Microbacteriaceae

with validly published names. Thus, strain CL-TW6T should be classified as representing a novel genus and species in the family

Microbacteriaceae

, for which the name Pontimonas salivibrio gen. nov., sp. nov. is proposed. The type strain of Pontimonas salivibrio is CL-TW6T ( = KCCM 90105T  = JCM 18206T).
Starmerella jinningensis sp. nov., a yeast species isolated from flowers of Erianthus rufipilus
Authors: Li Shao-Lan , Li Zhi-Ying , Yang Li-Yuan , Zhou Xin-Li , Dong Ming-Hua , Zhou Pei , Lai Yong-Hong , Duan Chang-Qun
Published: October 2012

Five yeast strains (Ym24403, Ym24404, Ym24408, Ym24409 and Ym24410T) were isolated from different flowers of Erianthus rufipilus (Gramineae), a wild plant growing in the phosphorus-rich region in Yunnan Province, south-western China, and were found to be phenotypically and genetically divergent from currently recognized yeast species. Sequence analysis of the D1/D2 domain of the large subunit rRNA gene revealed that the five strains represented a novel species described as Starmerella jinningensis sp. nov. The type strain is Ym24410T ( = CBS 11864T  = CCTCC AY 2011002T). Phylogenetic analysis based on the D1/D2 region of the large subunit rRNA gene suggested that S. jinningensis sp. nov. is placed within the Starmerella clade.
Falsirhodobacter halotolerans gen. nov., sp. nov., isolated from dry soils of a solar saltern
Authors: Subhash Y. , Tushar L. , Sasikala Ch. , Ramana Ch. V.
Published: October 2012

Two bacterial strains (JA744T and JA745) were isolated from dry soil samples collected from solar salterns at Humma, Odisha, India. Both strains were Gram-stain-negative, catalase- and oxidase-positive, motile rods. Major fatty acids in both strains included C18 : 1ω7c, C18 : 0 and C16 : 0, while minor amounts of C10 : 0 3-OH, C12 : 0, C12 : 0 3-OH, C14 : 0 and C16 : 0 were also present. Diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, an unidentified glycolipid, five unidentified lipids, an unidentified aminolipid and an unidentified phospholipid made up the polar lipids of both strains. Both strains had bacteriohopane derivatives (BHD1,2) and diploptene as major hopanoids. Mean genomic DNA G+C content was 75±1 mol% and the two strains were closely related (mean DNA–DNA hybridization >90 %). Phylogenetic analysis based on the 16S rRNA gene sequence showed that the two strains clustered with species of the genus

Rhodobacter

belonging to the family

Rhodobacteraceae

of the class

Alphaproteobacteria

. The highest sequence similarity was observed with

Rhodobacter sphaeroides

ATH2.4.1T (96 %) and other members of the genera

Rhodobacter

and

Pseudorhodobacter

(<96 %). However, the two strains were positioned distinctly outside the group formed by the other genera of the family

Rhodobacteraceae

. Distinct morphological, physiological and genotypic differences from previously described taxa support the classification of these isolates as representatives of a novel species in a new genus, for which the name Falsirhodobacter halotolerans gen. nov., sp. nov. is proposed. The type strain of Falsirhodobacter halotolerans is JA744T ( = KCTC 32158T  = NBRC 108897T).
Palaeococcus pacificus sp. nov., an archaeon from deep-sea hydrothermal sediment
Authors: Zeng Xiang , Zhang Xiaobo , Jiang Lijing , Alain Karine , Jebbar Mohamed , Shao Zongze
Published: October 2012

A hyperthermophilic, anaerobic, piezophilic archaeon (strain DY20341T) was isolated from a sediment sample collected from an East Pacific Ocean hydrothermal field (1° 37′ S 102° 45′ W) at a depth of 2737 m. The cells were irregular cocci, 0.8–1.5 µm in diameter. Growth was observed between 50 and 90 °C (optimum 80 °C), pH 5.0 and 8.0 (optimum pH 7.0), 1 % and 7 % (w/v) sea salts (Sigma, optimum 3 %), 1 % and 4 % (w/v) NaCl (optimum 3 %) and 0.1 and 80 MPa (optimum 30 MPa). The minimum doubling time was 66 min at 30 MPa and 80 °C. The isolate was an obligate chemoorganoheterotroph, capable of utilizing complex organic compounds and organic acids including yeast extract, peptone, tryptone, casein, starch, Casamino acids, citrate, lactate, acetate, fumarate, propanoate and pyruvate for growth. It was strictly anaerobic and facultatively dependent on elemental sulfur or sulfate as electron acceptors, but did not reduce sulfite, thiosulfate, Fe(III) or nitrate. The presence of elemental sulfur enhanced growth. The G+C content of the genomic DNA was 43.6±1 mol%. 16S rRNA gene sequence analysis revealed that the closest relative of the isolated organism was

Palaeococcus ferrophilus

DMJT (95.7 % 16S rRNA gene similarity). On the basis of its physiological properties and phylogenetic analyses, the isolate is considered to represent a novel species, for which the name Palaeococcus pacificus sp. nov. is proposed. The type strain is strain DY20341T ( = JCM 17873T = DSM 24777T).
Novosphingobium lindaniclasticum sp. nov., a hexachlorocyclohexane (HCH)-degrading bacterium isolated from an HCH dumpsite
Authors: Saxena Anjali , Anand Shailly , Dua Ankita , Sangwan Naseer , Khan Fazlurrahman , Lal Rup
Published: October 2012

A yellow-pigmented, Gram-negative, aerobic, non-motile, non-spore-forming, rod-shaped-bacterium, LE124T, was isolated from a hexachlorocyclohexane (HCH) dumpsite located in Lucknow, India. The type strain LE124T grew well with hexachlorocyclohexane as a sole carbon source, degrading it within 24 h of incubation. Phylogenetic analysis of strain LE124T showed highest 16S rRNA gene sequence similarity to

Novosphingobium barchaimii

LL02T (98.5 %),

Novosphingobium panipatense

SM16T (98.1 %),

Novosphingobium soli

CC-TPE-1T (97.9 %),

Novosphingobium naphthalenivorans

TUT562T (97.6 %),

Novosphingobium mathurense

SM117T (97.5 %) and

Novosphingobium resinovorum

NCIMB 8767T (97.5 %) and lower sequence similarity (<97 %) to all other members of the genus
Novosphingobium
. The DNA–DNA relatedness between strain LE124T and

N. barchaimii

LL02T and other related type strains was found to vary from 15 % to 45 % confirming that it represents a novel species. The genomic DNA G+C content of strain LE124T was 60.7 mol%. The predominant fatty acids were summed feature 8 (C18 : 1ω7c, 49.1 %), summed feature 3 (C16 : 1ω7c/C16 : 1ω6c, 19.9 %), C16 : 0 (6.7 %), C17 : 1ω6c (4.9 %) and a few hydroxyl fatty acids, C14 : 0 2-OH (9.4 %) and C16 : 0 2-OH (2.1 %). Polar lipids consisted mainly of phosphatidyldimethylethanolamine, phosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, sphingoglycolipid and some unidentified lipids. The major respiratory quinone was ubiquinone Q-10. Spermidine was the major polyamine observed. Phylogenetic analysis, DNA–DNA hybridization, chemotaxonomic and phenotypic analysis support the conclusion that strain LE124T represents a novel species within the genus

Novosphingobium

for which we propose the name Novosphingbium lindaniclasticum sp. nov. The type strain is LE124T ( = CCM 7976T = DSM 25409T).
Emendation of the description of the species Corynebacterium propinquum to include strains which produce urease
Authors: Bernard Kathryn , Pacheco Ana Luisa , Cunningham Ian , Gill Navdeep , Burdz Tamara , Wiebe Deborah
Published: October 2012

Corynebacterium propinquumis a Gram-positive rod occasionally recovered from clinical infections which, according to 16S rRNA gene sequencing, is most closely related (>99 % sequence similarity) toCorynebacterium pseudodiphtheriticum. The two species are very similar biochemically, commonly differentiated by a single test, the detection of urease, where strains ofC. propinquumare described as being urease-non-producing and strains ofC. pseudodiphtheriticumare described as urease-producing. In this study, historical and contemporary strains ofC. propinquumandC. pseudodiphtheriticumfrom this laboratory were definitively characterized, which included use ofrpoBsequencing. Urease-producing strains ofC. propinquumas well as typical urease-non-producing isolates were identified afterrpoBsequencing, with six of these being originally identified asC. pseudodiphtheriticum. Based on these observations, we propose emendation of the description ofC. propinquumto include strains which produce urease. MALDI-TOF analysis may be a useful tool to differentiate these taxa. Existing commercial databases should be updated to include urease-positive strains ofC. propinquum.
Candida ecuadorensis sp. nov., an ascomycetous yeast species found in two separate regions of Ecuador
Authors: James Stephen A. , Carvajal Barriga Enrique Javier , Barahona Patricia Portero , Cross Kathryn , Bond Christopher J. , Roberts Ian N.
Published: October 2012

In the course of an on-going study aimed at cataloguing the natural yeast biodiversity found in Ecuador, two strains (CLQCA 13-025 and CLQCA 20-004T) were isolated from samples of cow manure and rotten wood collected in two separate provinces of the country (Orellana and Bolívar). These strains were found to represent a novel yeast species based on the sequences of their D1/D2 domain of the large-subunit (LSU) rRNA gene and their physiological characteristics. Phylogenetic analysis based on LSU D1/D2 sequences revealed this novel species to belong to the Metschnikowia clade and to be most closely related to Candida suratensis, a species recently discovered in a mangrove forest in Thailand. The species name of Candida ecuadorensis sp. nov. is proposed to accommodate these strains, with strain CLQCA 20-004T ( = CBS 12653T = NCYC 3782T) designated as the type strain.
Epigenetic regulation of olfactory receptor gene expression by the Myb–MuvB/dREAM complex
Authors: Sim Choon Kiat , Perry Sarah , Tharadra Sana Khalid , Lipsick Joseph S. , Ray Anandasankar
Published: October 2012

In both mammals and insects, an olfactory neuron will usually select a single olfactory receptor and repress remaining members of large receptor families. Here we show that a conserved multiprotein complex, Myb–MuvB (MMB)/dREAM, plays an important role in mediating neuron-specific expression of the carbon dioxide (CO2) receptor genes (Gr63a/Gr21a) in Drosophila. Activity of Myb in the complex is required for expression of Gr63a/Gr21a and acts in opposition to the histone methyltransferase Su(var)3-9. Consistent with this, we observed repressive dimethylated H3K9 modifications at the receptor gene loci, suggesting a mechanism for silencing receptor gene expression. Conversely, other complex members, Mip120 (Myb-interacting protein 120) and E2F2, are required for repression of Gr63a in inappropriate neurons. Misexpression in mutants is accompanied by an increase in the H3K4me3 mark of active chromatin at the receptor gene locus. Nuclei of CO2 receptor-expressing neurons contain reduced levels of the repressive subunit Mip120 compared with surrounding neurons and increased levels of Myb, suggesting that activity of the complex can be regulated in a cell-specific manner. Our evidence suggests a model in which olfactory receptors are regulated epigenetically and the MMB/dREAM complex plays a critical role in specifying, maintaining, and modulating the receptor-to-neuron map.
Genome-Wide Analysis ofStowaway-Like MITEs in Wheat Reveals High Sequence Conservation, Gene Association, and Genomic Diversification
Authors: Yaakov Beery , Ben-David Smadar , Kashkush Khalil
Published: October 2012

The diversity and evolution of wheat (Triticum-Aegilops group) genomes is determined, in part, by the activity of transposable elements that constitute a large fraction of the genome (up to 90%). In this study, we retrieved sequences from publicly available wheat databases, including a 454-pyrosequencing database, and analyzed 18,217 insertions of 18 Stowaway-like miniature inverted-repeat transposable element (MITE) families previously characterized in wheat that together account for approximately 1.3 Mb of sequence. All 18 families showed high conservation in length, sequence, and target site preference. Furthermore, approximately 55% of the elements were inserted in transcribed regions, into or near known wheat genes. Notably, we observed significant correlation between the mean length of the MITEs and their copy number. In addition, the genomic composition of nine MITE families was studied by real-time quantitative polymerase chain reaction analysis in 40 accessions of Triticum spp. and Aegilops spp., including diploids, tetraploids, and hexaploids. The quantitative polymerase chain reaction data showed massive and significant intraspecific and interspecific variation as well as genome-specific proliferation and nonadditive quantities in the polyploids. We also observed significant differences in the methylation status of the insertion sites among MITE families. Our data thus suggest a possible role for MITEs in generating genome diversification and in the establishment of nascent polyploid species in wheat.
Group III-AXTHGenes of Arabidopsis Encode Predominant Xyloglucan Endohydrolases That Are Dispensable for Normal Growth
Authors: Kaewthai Nomchit , Gendre Delphine , Eklöf Jens M. , Ibatullin Farid M. , Ezcurra Ines , Bhalerao Rishikesh P. , Brumer Harry
Published: October 2012

The molecular basis of primary wall extension endures as one of the central enigmas in plant cell morphogenesis. Classical cell wall models suggest that xyloglucan endo-transglycosylase activity is the primary catalyst (together with expansins) of controlled cell wall loosening through the transient cleavage and religation of xyloglucan-cellulose cross links. The genome of Arabidopsis (Arabidopsis thaliana) contains 33 phylogenetically diverse XYLOGLUCAN ENDO-TRANSGLYCOSYLASE/HYDROLASE (XTH) gene products, two of which were predicted to be predominant xyloglucan endohydrolases due to clustering into group III-A. Enzyme kinetic analysis of recombinant AtXTH31 confirmed this prediction and indicated that this enzyme had similar catalytic properties to the nasturtium (Tropaeolum majus) xyloglucanase1 responsible for storage xyloglucan hydrolysis during germination. Global analysis of Genevestigator data indicated that AtXTH31 and the paralogous AtXTH32 were abundantly expressed in expanding tissues. Microscopy analysis, utilizing the resorufin β-glycoside of the xyloglucan oligosaccharide XXXG as an in situ probe, indicated significant xyloglucan endohydrolase activity in specific regions of both roots and hypocotyls, in good correlation with transcriptomic data. Moreover, this hydrolytic activity was essentially completely eliminated in AtXTH31/AtXTH32 double knockout lines. However, single and double knockout lines, as well as individual overexpressing lines, of AtXTH31 and AtXTH32 did not demonstrate significant growth or developmental phenotypes. These results suggest that although xyloglucan polysaccharide hydrolysis occurs in parallel with primary wall expansion, morphological effects are subtle or may be compensated by other mechanisms. We hypothesize that there is likely to be an interplay between these xyloglucan endohydrolases and recently discovered apoplastic exo-glycosidases in the hydrolytic modification of matrix xyloglucans.
Crystallization and preliminary crystallographic studies of the W2 domain ofDrosophila melanogastereukaryotic translation initiation factor 5C domain-containing protein
Authors: Zhao Hui , Wang Hong , Liu Huihui , Teng Maikun , Li Xu
Published: October 2012

TheDrosophila melanogastereukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space groupI4, with unit-cell parametersa = b = 81.05,c= 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal.
Predator‐induced stress and the ecology of fear
Authors: Clinchy Michael , Sheriff Michael J. , Zanette Liana Y.
Published: October 2012

Predator‐induced stress has been used to exemplify the concept of stress for close to a century because almost everyone can imagine the terror of fleeing for one's life from a lion or a tiger. Yet, because it has been assumed to be acute and transitory, predator‐induced stress has not been much studied by either comparative physiologists or population ecologists, until relatively recently.

The focus in biomedical research has always been on chronic stress in humans, which most comparative physiologists would agree results from ‘sustained psychological stress – linked to mere thoughts’ rather than ‘acute physical crises’ (like surviving a predator attack) or ‘chronic physical challenges’ (such as a shortage of food). Population ecologists have traditionally focused solely on the acute physical crisis of surviving a direct predator attack rather than whether the risk of such an attack may have a sustained effect on other demographic processes (e.g. the birth rate).

Demographic experiments have now demonstrated that exposure to predators or predator cues can have sustained effects that extend to affecting birth and survival in free‐living animals, and a subset of these have documented associated physiological stress effects. These and similar results have prompted some authors to speak of an ‘ecology of fear’, but others object that ‘the cognitive and emotional aspects of avoiding predation remain unknown’.

Recent biomedical studies on animals in the laboratory have demonstrated that exposure to predators or predator cues can induce ‘sustained psychological stress’ that is directly comparable to chronic stress in humans, and this has now in fact become one of the most common stressors used in studies of the animal model of post‐traumatic stress disorder (PTSD).

We review these recent findings and suggest ways the laboratory techniques developed to measure the ‘neural circuitry of fear’ could be adapted for use on free‐living animals in the field, in order to: (i) test whether predator risk induces ‘sustained psychological stress’ in wild animals, comparable to chronic stress in humans and (ii) directly investigate ‘the cognitive and emotional aspects of avoiding predation’ and hence the ‘ecology of fear’.
Immunomodulatory and antioxidative potential of herb (Pueraria tuberosa) in mice using milk as the carrier
Authors: Sawale Pravin Digambar , Singh Ram Ran Bijoy , Kapila Suman , Arora Sumit , Rastogi Subha , Rawat Ajay Kumar Singh
Published: October 2012

Eighteen healthy male mice were divided into three equal groups and given specific diets for a period of 28 days: Group M were fed a normal synthetic diet (NSD) and milk; Group P were fed NSD and Pueraria tuberosa (PT) extract (0.4%), while the diet of group PM was NSD supplemented with PT extract (0.4%) and milk. The phagocytic activity and immunoglobulin A (in intestines) and immunoglobulin G (serum) levels increased significantly in comparison with group M in PT supplemented groups after a period of 28 days. Group P and Group PM showed significantly higher reduced glutathione level and significantly lowered thiobarbituric acid reactive substances levels in liver and red blood cells as compared to control.
Crossing the Indian Ocean before the Periplus: a comparison of pottery assemblages at the sites of Sumhuram (Oman) and Tissamaharama (Sri Lanka)
Authors: Pavan Alexia , Schenk Heidrun
Published: October 2012

There is a long tradition of studies of the Indian Ocean trade focused almost exclusively on the trade between Roman Egypt and India. Less attention has been paid to the formative period of early historical long‐distance trade in the Indian Ocean. The aim of this paper is to discuss some aspects of the development of this trade, based on an analysis of the South Asian pottery found at two different settlements: Sumhuram in the Sultanate of Oman and Tissamaharama in Sri Lanka.
Ease of intrauterine contraceptive device insertion in family planning settings
Authors: Harvey Caroline , Bateson Deborah , Wattimena Jeany , Black Kirsten I.
Published: October 2012

Background

Intrauterine devices (IUDs) provide highly effective contraception for women worldwide. Reluctance to insert IUDs in the primary care setting may relate to concern about potential difficulty and complications, particularly in nulliparous women.

Aims

To determine the practitioner, patient and procedural factors associated with abandoned IUD insertion, practitioner‐reported difficulty of insertion and adverse events during IUD insertions in the family planning setting.

Methods

This was a prospective study over a 12‐month period of consecutive IUD insertions in four family planning clinics across New South Wales and Queensland. Patient, practitioner and device‐related factors associated with abandoned IUD insertion, practitioner‐reported ease of insertion and immediate insertion‐related adverse events were analysed using logistic regression.

Results

Of 996 insertion procedures, successful insertion occurred in 95%, and 90% were reported as easy by the inserting doctor, including 80% of those in nulliparous women. Patient characteristics associated with an abandoned insertion were nulliparity (AOR 5.19; 2.49–10.82) or caesarean section‐only deliveries (AOR 5.38; 2.58–11.22) and with practitioner‐reported difficult insertion, nulliparity alone (AOR 1.98; 1.11–3.54). Practitioners inserting fewer than 100 IUDs over the 12‐month study period more frequently rated insertions as difficult (AOR 1.76; 1.08–2.88). Complications occurred in 34 women and were more likely in nulliparous women (AOR 4.51; 2.16–9.39).

Conclusions

Most IUDs can be successfully inserted, even in nulliparous women, in a primary care setting. Referral to a specialist may be appropriate for some women who are nulliparous or had caesarean section‐only deliveries, depending on the experience of the practitioner.
Spectrum of mutations in gastrointestinal stromal tumor patients – a population‐based study from Slovakia
Authors: Minárik Gabriel , Plank Lukáš , Lasabová Zora , Szemes Tomáš , Burjanivová Tatiana , Szépe Peter , Buzalková Veronika , Porubský David , Šufliarsky Jozef
Published: October 2012

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract and are characterized by presence of mutations in tyrosine kinases cKIT (KIT) and PDGFRα (PDGFRA). Mutations identified are highly heterogeneous, but some mutations are associated with specific clinical features of the tumor. Samples from 278 GIST patients collected during the period 2004–2011 were screened for mutations in exons 9, 11, 13, and 17 of KIT and 12, 14 and 18 of PDGFRA. Results of mutation screening were summarized and tested for possible association with clinical parameters of tumors. Mutations were identified in 83.81% of patients. Most frequent mutations were found in KIT exon 11 reaching frequency of 62.95%. Other exons contributed to the mutation pool with frequencies 8.27%, 7.55%, 2.52%, 1.44%, 1.08%, and 0.00%, in decreasing order KIT exon 9, PDGRFA exons 18 and 12, KIT exon 13, PDGFRA exon 14, and KIT exon 17. General linear model analysis showed no effect of any individual analyzed mutation on the phenotypic variables, but we confirmed association between mutations KIT exon 9 p. 503‐504_dup2, and PDGFRA exon 18 p. D842V and intestinal and gastric localization of tumors.
The rising tide of cholecystectomy for biliary dyskinesia
Authors: Bielefeldt K.
Published: October 2012

Background

Expert consensus defines biliary dyskinesia as a rare disorder of the gall‐bladder characterised by pain and impaired gall‐bladder function.

Aim

To determine trends in cholecystectomy rates for biliary dyskinesia in the United States.

Methods

As biliary dyskinesia does not have a distinct diagnosis code, the narrative diagnoses for patients were reviewed and abstracted for 200 patients treated for the most commonly used diagnosis codes for biliary dyskinesia (validation sample). Time trends in cholecystectomies and hospitalisations for biliary diseases were assessed using the Nationwide Inpatient Sample (Agency for Healthcare Research and Quality) based on codes for cholecystectomy and diagnosis codes for different biliary disorders.

Results

In the validation sample, biliary dyskinesia accounted for 81% of the patients with ICD‐9 code 575.8 (gall‐bladder disease not elsewhere specified). Between 1997 and 2010, admissions for acute cholecystitis and complications of gallstone disease decreased slightly, whereas admissions with the primary diagnosis code ICD‐9 575.8 tripled. This rise was most pronounced in the paediatric population (700% increase), with biliary dyskinesia accounting for more than 10% of cholecystectomies. Compared with acute biliary diseases, significantly more of the elective hospitalisations were covered by private insurances.

Conclusions

Practice patterns differ from expert opinion, with biliary dyskinesia accounting for an increasing fraction of cholecystectomies. The rise in these elective interventions is associated with a shift to a younger, low risk and predominantly privately insured population. Considering the benign nature of biliary dyskinesia, it is time to reassess the need for operative interventions, which have never been compared with active conservative therapy.
Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study
Authors: Papp K.A. , Langley R.G. , Sigurgeirsson B. , Abe M. , Baker D.R. , Konno P. , Haemmerle S. , Thurston H.J. , Papavassilis C. , Richards H.B.
Published: October 2012

Background Conventional systemic therapies for plaque psoriasis have not fully met the needs of patients, and although current biologic treatments are generally well tolerated, concerns exist with respect to long-term safety. Interleukin (IL)-17A is believed to be an important effector cytokine in the pathogenesis of psoriasis and is produced by Th17 cells, a class of helper T cells that act outside the established Th1/Th2 paradigm for regulation of innate and adaptive immunity.

Objectives To assess the efficacy and safety of different doses of secukinumab, a fully human anti-IL-17A IgG1κ monoclonal antibody, in patients with moderate-to-severe plaque psoriasis.

Methods Patients (n = 125) were randomized 1 : 1 : 1 : 1 : 1 to receive subcutaneous doses of placebo (n = 22) or secukinumab [1 × 25 mg (n = 29), 3 × 25 mg (n = 26), 3 × 75 mg (n = 21) or 3 × 150 mg (n = 27)] at weeks 0, 4 and 8. After the 12-week treatment period, patients entered a follow-up period of 24 weeks. The primary efficacy outcome was at least 75% improvement from baseline in the Psoriasis Area and Severity Index score (PASI 75); secondary outcomes included the Investigator’s Global Assessment (IGA) and PASI 90 and 50 response rates.

Results After 12 weeks of treatment, secukinumab 3 × 150 mg and 3 × 75 mg resulted in significantly higher PASI 75 response rates vs. placebo (82% and 57% vs. 9%; P < 0·001 and P = 0·002, respectively). Higher PASI 75 response rates compared with placebo were maintained throughout the follow-up period with these dosages [week 36, 26% (n = 7) and 19% (n = 4) vs. 4% (n = 1), respectively], with a gradual decline of PASI 75 response over time after the dosing period. IGA response rates were significantly higher in the 3 × 150 mg group vs. placebo at week 12 (48% vs. 9%; P = 0·005) and were consistently higher for the 3 × 150 mg and 3 × 75 mg groups vs. placebo at all time points from week 4 onward. The PASI 90 response rate was significantly higher in the 3 × 150 mg group vs. placebo (52% vs. 5%) at week 12 and remained higher during the follow-up period. Secukinumab was well tolerated. Two cases of neutropenia (≤ grade 2) were reported in the 3 × 150 mg cohort.

Conclusions Treatment with subcutaneous secukinumab 3 × 75 mg and 3 × 150 mg met the primary outcome of PASI 75 response achievement after 12 weeks, demonstrating efficacy in moderate-to-severe psoriasis.
Clinical and prognostic implications of β1, 6‐N‐acetylglucosaminyltransferase V in patients with gastric cancer
Authors: Wang Xuefei , He Hongyong , Zhang Heng , Chen Weidong , Ji Yuan , Tang Zhaoqing , Fang Yong , Wang Cong , Liu Fenglin , Shen Zhenbin , Qin Jing , Zhu Yu , Liu Haiou , Xu Jiejie , Gu Jianxin , Qin Xinyu , Sun Yihong
Published: October 2012

Aberrant β1, 6‐N‐acetylglucosaminyltransferase V (MGAT5) expression in malignant tissues has been reported to be involved in the development of various cancers and their progression, through altering N‐glycan branching. We aimed to investigate the clinical and prognostic values of MGAT5 and improve the risk stratification in patients with gastric cancer. MGAT5 expression was retrospectively analyzed by immunohistochemistry in three independent sets comprising 313 patients from China with gastric adenocarcinoma. Results were assessed for association with clinical features and overall survival using Kaplan–Meier analysis. Prognostic values of MGAT5 expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating MGAT5 expression was determined in patients with late‐stage gastric cancer by using receiver operating characteristic analysis. The results show that low intratumoral MGAT5 density, which was associated with poor differentiation, N classification, TNM stage, and Kiel stage, was an independent prognosticator for poor overall survival. The combination of intratumoral MGAT5 expression and TNM or Kiel staging systems had a better predictive power for overall survival. Applying the prognostic value of intratumoral MGAT5 density to TNM stage III+IV and Kiel stage IIIB+IV groups showed a better risk stratification for overall survival in patients with late‐stage gastric cancer. In conclusion, integrating intratumoral MGAT5 density that was recognized as an independent prognostic marker into current clinical staging systems significantly improved prognostic stratification of patients with late‐stage gastric cancer. This refined risk stratification scheme might aid in appropriate therapeutic options and ultimately improve the outcomes of patients with advanced‐stage disease.
Withaferin A suppresses tumor promoter 12‐O‐tetradecanoylphorbol 13‐acetate‐induced decreases in isocitrate dehydrogenase 1 activity and mitochondrial function in skin epidermal JB6 cells
Authors: Li Wenjuan , Zhao Yunfeng
Published: October 2012

Withaferin A (WA) is a bioactive compound derived from Withania somnifera. The antitumor activity of WA has been well studied in human cancer models; however, its chemopreventive potential is unclear. In the present study, we used the skin epidermal JB6 P+ cells, a well‐established model for tumor promotion, and demonstrated that WA suppressed the tumor promoter 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐induced cell transformation and cell proliferation. Interestingly, TPA inactivated isocitrate dehydrogenase 1 (IDH1), which was reversed by WA. Similar results were also observed in mouse skin tissue. Therefore, we focused on metabolism as the potential mechanism of action. We found that mitochondrial functions were downregulated by TPA treatment, as indicated by reduced mitochondrial membrane potential, complex I activity and mitochondrial respiration. However, all of these downregulations were inhibited by WA. In addition, we examined the levels of α‐ketoglutarate, a product of IDH1, and WA blocked its reduction upon TPA treatment. Finally, we detected the lactate level as a glycolysis marker, and WA suppressed its elevation caused by tumor promoter treatment. Altogether, these results suggest that WA might exert its chemopreventive activity via inhibiting not only oncogenic activation, but also IDH1 inactivation and mitochondrial dysfunction in early tumorigenesis.
Arsenic trioxide prevents nitric oxide production in lipopolysaccharide ‐stimulated RAW 264.7 by inhibiting a TRIF‐dependent pathway
Authors: Takahashi Miyuki , Ota Akinobu , Karnan Sivasundaram , Hossain Ekhtear , Konishi Yuko , Damdindorj Lkhagvasuren , Konishi Hiroyuki , Yokochi Takashi , Nitta Masakazu , Hosokawa Yoshitaka
Published: October 2012

Arsenic trioxide (ATO) is one of the most potent drugs in cancer chemotherapy, and is highly effective in treating both newly diagnosed and relapse patients with acute promyelocytic leukemia (APL). Despite a number of reports regarding the molecular mechanisms by which ATO promotes anti‐tumor or pro‐apoptotic activity in hematological and other solid malignancies, the effects of ATO on immune responses remain poorly understood. To further understand and clarify the effects of ATO on immune responses, we sought to examine whether ATO affects the production of nitric oxide (NO) in a lipopolysaccharide (LPS)‐stimulated mouse macrophage cell line, RAW 264.7. Arsenic trioxide was found to prevent NO production in a dose‐dependent manner. Arsenic trioxide significantly inhibited the increase in inducible nitric oxide synthase (iNOS) at both the mRNA and protein levels. Furthermore, our analyses revealed that the inhibitory effect of ATO on iNOS expression was ascribed to the prevention of IRF3 phosphorylation, interferon (IFN)‐β expression, and STAT1 phosphorylation, but not the prevention of the MyD88‐dependent pathway. Taken together, our results indicate that ATO prevents NO production by inhibiting the TIR‐domain‐containing adaptor protein inducing IFN‐β (TRIF)‐dependent pathway, thus highlighting an anti‐inflammatory property of ATO in innate immunity.
Oral hygiene and cardiometabolic disease risk in the survey of the health of Wisconsin
Authors: VanWormer Jeffrey J. , Acharya Amit , Greenlee Robert T. , Nieto Francisco Javier
Published: October 2012

Objectives

Poor oral health is an increasingly recognized risk factor for cardiovascular disease (CVD) and type 2 diabetes (T2D), but little is known about the association between toothbrushing or flossing and cardiometabolic disease risk. The purpose of this study was to examine the degree to which an oral hygiene index was associated with CVD and T2D risk scores among disease‐free adults in the Survey of the Health of Wisconsin.

Methods

All variables were measured in 2008–2010 in this cross‐sectional design. Based on toothbrushing and flossing frequency, an oral hygiene index (poor, fair, good, excellent) was created as the primary predictor variable. The outcomes, CVD and T2D risk score, were based on previous estimates from large cohort studies. There were 712 and 296 individuals with complete data available for linear regression analyses in the CVD and T2D samples, respectively.

Results

After covariate adjustment, the final model indicated that participants in the excellent (β ± SE = −0.019 ± 0.008, P = 0.020) oral hygiene category had a significantly lower CVD risk score as compared to participants in the poor oral hygiene category. Sensitivity analyses indicated that both toothbrushing and flossing were independently associated with CVD risk score, and various modifiable risk factors. Oral hygiene was not significantly associated with T2D risk score.

Conclusions

Regular toothbrushing and flossing are associated with a more favorable CVD risk profile, but more experimental research is needed in this area to precisely determine the effects of various oral self‐care maintenance behaviors on the control of individual cardiometabolic risk factors. These findings may inform future joint medical–dental initiatives designed to close gaps in the primary prevention of oral and systemic diseases.
Lipid transfer proteins: the most frequent sensitizer in Italian subjects with food‐dependent exercise‐induced anaphylaxis
Authors: Romano A. , Scala E. , Rumi G. , Gaeta F. , Caruso C. , Alonzi C. , Maggioletti M. , Ferrara R. , Palazzo P. , Palmieri V. , Zeppilli P. , Mari A.
Published: October 2012

Background

Specific food‐dependent exercise‐induced anaphylaxis (S‐FDEIAn) is a distinct form of food allergy in which symptoms are elicited by exercise performed after ingesting food to which the patient has become sensitised. Non‐specific FDEIAn (NS‐FDEIAn) is a syndrome provoked by exercise performed after ingesting any food.

Objective

We sought to identify the culprit allergenic molecules in patients with FDEIAn, combining ‘classic’ allergy testing with an allergenic molecule‐based microarray approach for IgE detection.

Methods

All subjects were evaluated who reported at least one episode of anaphylaxis in association with physical exercise performed within 4 h after a meal. We performed skin prick tests (SPT) with commercial food extracts, prick plus prick tests (P + P) with fresh foods (P + P), and serum specific IgE assays by means of both the ImmunoCAP (CAP) and the ISAC 89 microarray system (ISAC).

Results

Among our 82 FDEIAn patients, the most frequent suspected foods were tomato, cereals, and peanut. SPT, P + P, and CAP displayed different degrees of sensitivity. Each test disclosed some positivities not discovered by others. Seventy‐nine subjects were positive to at least one food (49 to more than 20), whereas three were negative. All suspected foods were positive to at least one of SPT, P + P, and CAP. When tested using the ISAC, 64 (78%) subjects were positive to Pru p 3 [peach lipid transfer protein (LTP)], 13 were positive to other food allergen molecules, and five displayed negative results to all food allergenic molecules. Overall, 79 patients probably had S‐FDEIAn and the other 3 NS‐FDEIAn.

Conclusions

Multiple food hypersensitivity represents a clinical hallmark of a large percentage of FDEIAn patients. The very high prevalence of IgE to the LTP suggests a role of this allergen group in causing S‐FDEIAn.
Racially restricted contribution of immunoglobulin Fcγ and Fcγ receptor genotypes to humoral immunity to human epidermal growth factor receptor 2 in breast cancer
Authors: Pandey J P , Namboodiri A M , Kistner-Griffin E , Iwasaki M , Kasuga Y , Hamada G S , Tsugane S
Published: October 2012

Tumour-associated antigen human epidermal growth factor receptor 2 (HER2) is over-expressed in 25–30% of breast cancer patients and is associated with poor prognosis. Naturally occurring anti-HER2 antibody responses have been described in patients with HER2 over-expressing tumours. There is significant interindividual variability in antibody responsiveness, but the host genetic factors responsible for this variability are poorly understood. The aim of the present investigation was to determine whether immunoglobulin genetic markers [GM (genetic determinants of γ chains)] and Fcγ receptor (FcγR) alleles contribute to the magnitude of natural antibody responsiveness to HER2 in patients with breast cancer. A total of 855 breast cancer patients from Japan and Brazil were genotyped for several GM and FcγR alleles. They were also characterized for immunoglobulin (Ig)G antibodies to HER2. In white subjects (n = 263), GM 23-carriers had higher levels of anti-HER2 antibodies than non-carriers of this allele (p = 0·004). At the GM 5/21 locus, the homozygotes for the GM 5 allele had higher levels of anti-HER2 antibodies than the other two genotypes (P = 0·0067). In black subjects (n = 42), FcγRIIa-histidine/histidine homozygotes and FcγRIIIa-phenylalanine/valine heterozygotes were associated with high antibody responses (P = 0·0071 and 0·0275, respectively). FcγR genotypes in white subjects and GM genotypes in black subjects were not associated with anti-HER2 antibody responses. No significant associations were found in other study groups. These racially restricted contributions of GM and FcγR genotypes to humoral immunity to HER2 have potential implications for immunotherapy of breast cancer.