bluuebunny/crossref_metadata_2025_split huggingface dataset:
The two peptide lantibiotic lacticin 3147 acts synergistically with polymyxin to inhibit Gram negative bacteria
Authors: Draper Lorraine A , Cotter Paul D , Hill Colin , Ross R Paul 
Published: September 2013

Abstract

Background
The emergence of bacterial drug resistance encourages the re-evaluation of the potential of existing antimicrobials. Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity. Here, we focussed on expanding the potential of lacticin 3147, one of the most studied lantibiotics and one which possesses potent activity against a wide range of Gram positive species including many nosocomial pathogens. More specifically, our aim was to investigate if lacticin 3147 activity could be enhanced when combined with a range of different clinical antibiotics.

Results
Initial screening revealed that polymyxin B and polymyxin E (colistin) exhibited synergistic activity with lacticin 3147. Checkerboard assays were performed against a number of strains, including both Gram positive and Gram negative species. The resultant fractional inhibitory concentration (FIC) index values established that, while partial synergy was detected against Gram positive targets, synergy was obvious against Gram negative species, including Cronobacter and E. coli.

Conclusions
Combining lacticin 3147 with low levels of a polymyxin could provide a means of broadening target specificity of the lantibiotic, while also reducing polymyxin use due to the lower concentrations required as a result of synergy.
Exogenous mRNA delivery and bioavailability in gene transfer mediated by piggyBac transposition
Authors: Bire Solenne , Gosset David , Jégot Gwenhael , Midoux Patrick , Pichon Chantal , Rouleux-Bonnin Florence 
Published: September 2013

Abstract

Background
Up to now, the different uptake pathways and the subsequent intracellular trafficking of plasmid DNA have been largely explored. By contrast, the mode of internalization and the intracellular routing of an exogenous mRNA in transfected cells are poorly investigated and remain to be elucidated. The bioavailability of internalized mRNA depends on its intracellular routing and its potential accumulation in dynamic sorting sites for storage: stress granules and processing bodies. This question is of particular significance when a secure transposon-based system able to integrate a therapeutic transgene into the genome is used. Transposon vectors usually require two components: a plasmid DNA, carrying the gene of interest, and a source of transposase allowing the integration of the transgene. The principal drawback is the lasting presence of the transposase, which could remobilize the transgene once it has been inserted. Our study focused on the pharmacokinetics of the transposition process mediated by the piggyBac transposase mRNA transfection. Exogenous mRNA internalization and trafficking were investigated towards a better apprehension and fine control of the piggyBac transposase bioavailability.

Results
The mRNA prototype designed in this study provides a very narrow expression window of transposase, which allows high efficiency transposition with no cytotoxicity. Our data reveal that exogenous transposase mRNA enters cells by clathrin and caveolae-mediated endocytosis, before finishing in late endosomes 3 h after transfection. At this point, the mRNA is dissociated from its carrier and localized in stress granules, but not in cytoplasmic processing bodies. Some weaker signals have been observed in stress granules at 18 h and 48 h without causing prolonged production of the transposase. So, we designed an mRNA that is efficiently translated with a peak of transposase production 18 h post-transfection without additional release of the molecule. This confines the integration of the transgene in a very small time window.

Conclusion
Our results shed light on processes of exogenous mRNA trafficking, which are crucial to estimate the mRNA bioavailability, and increase the biosafety of transgene integration mediated by transposition. This approach provides a new way for limiting the transgene copy in the genome and their remobilization by mRNA engineering and trafficking.
Hypnotics and mortality in an elderly general population: a 12-year prospective study
Authors: Jaussent Isabelle , Ancelin Marie-Laure , Berr Claudine , Pérès Karine , Scali Jacqueline , Besset Alain , Ritchie Karen , Dauvilliers Yves 
Published: September 2013

Abstract

Background
Hypnotics are widely used by the elderly, and their impact on mortality remains controversial. The inconsistent findings could be due to methodological limitations, notably the lack of control for underlying sleep symptoms or illness associated with hypnotic use, for example, insomnia symptoms and excessive daytime sleepiness, depression and anxiety. Our objective was to examine the association between the use of hypnotics and mortality risk in a large cohort of community-dwelling elderly, taking into account a wide range of potential competing risks including sociodemographic characteristics, lifestyle, and chronic disorders as well as underlying psychiatric disorders and sleep complaints.

Methods
Analyses were carried out on 6,696 participants aged 65 years or older randomly recruited from three French cities and free of dementia at baseline. Adjusted Cox proportional hazards models with delayed entry, and age of the participants as the time scale, were used to determine the association between hypnotic use and 12-year survival.

Results
At baseline, 21.7% of the participants regularly used at least one hypnotic. During follow-up, 1,307 persons died, 480 from cancer and 344 from cardiovascular disease. Analyses adjusted for study center, age and gender showed a significantly greater risk of all-cause and cardiovascular-related mortality with hypnotics, particularly benzodiazepines, and this increased with the number of hypnotics used. None of these associations were significant in models adjusting for sociodemographic and lifestyle characteristics, chronic disorders including cardiovascular pathologies, sleep and psychiatric disorders. Results remained unchanged when duration of past hypnotic intake or persistent versus intermittent use during follow-up were taken into account.

Conclusions
When controlling for a large range of potential confounders, the risk of mortality was not significantly associated with hypnotic use regardless of the type and duration. Underlying psychiatric disorders appear to be the principal confounders of the observed association.
Novel protein isoforms of carcinoembryonic antigen are secreted from pancreatic, gastric and colorectal cancer cells
Authors: Hatakeyama Keiichi , Wakabayashi-Nakao Kanako , Ohshima Keiichi , Sakura Naoki , Yamaguchi Ken , Mochizuki Tohru 
Published: September 2013

Abstract

Background
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is an oncofetal cell surface glycoprotein. Because of its high expression in cancer cells and secretion into serum, CEA has been widely used as a serum tumor marker. Although other members of CEACAM family were investigated for splice variants/variants-derived protein isoforms, few studies about the variants of CEACAM5 have been reported. In this study, we demonstrated the existence of novel CEACAM5 splice variants and splice variant-derived protein isoforms in gastrointestinal cancer cell lines.

Results
We identified two novel CEACAM5 splice variants in gastrointestinal (pancreatic, gastric, and colorectal) cancer cell lines. One of the variants possessed an alternative minor splice site that allowed generation of GC-AG intron. Furthermore, CEA protein isoforms derived from the novel splice variants were expressed in cancer cell lines and those protein isoforms were secreted into the culture medium. Although CEA protein isoforms always co-existed with the full-length protein, the secretion patterns of these isoforms did not correlate with the expression patterns.

Conclusions
This is the first study to identify the expression of CEA isoforms derived from the novel splice variants processed on the unique splice site. In addition, we also revealed the secretion of those isoforms from gastrointestinal cancer cell lines. Our findings suggested that discrimination between the full-length and identified protein isoforms may improve the clinical utility of CEA as a tumor marker.
Comparison of BEAM vs. LEAM regimen in autologous transplant for lymphoma at AIIMS
Authors: Sharma Atul , Kayal Smita , Iqbal Sobuhi , Malik Prabhat Singh , Raina Vinod 
Published: September 2013

Abstract
BEAM (BCNU, etoposide, cytarabine, melphalan) is the most widely used high dose chemotherapy regimen for autologous transplant in lymphoid malignancies. We report our early experience with an alternative regimen LEAM where BCNU was replaced with the oral analogue CCNU (lomustine) to tide over the non-availability of BCNU. Fifty one patients of relapsed or refractory lymphoma who received BEAM (n= 34) and LEAM (n= 17) from September 2001 to February 2012 were analyzed. From October 2009 onwards LEAM was used as the conditioning regimen instead of conventional BEAM. Patients in the LEAM group had more chemorefractory disease (35% vs 9%, p = 0.045) and high risk comorbidity score (24% vs 0%, p = 0.019). Grade 3 and 4 oral mucositis (67.6% vs. 64.7%, p = 0.834) and diarrhea (47% vs. 41.1%, p = 0.691) were similar. No difference was noted between the two groups in terms of engraftment, documented infections, antibiotic use, cumulative toxicity risk, length of hospital stay and 100 day transplant related mortality. The estimated 2 year overall survival (61.7% vs. 62.7%, p = 0.928) and event free survival (44.6% vs. 41.1%, p = 0.510) of the regimens BEAM and LEAM respectively were comparable. Thus LEAM appeared equivalent to BEAM in terms of toxicity and efficacy and can be used as an alternative to BEAM.
Th17 and Th22 cells in psoriatic arthritis and psoriasis
Authors: Benham Helen , Norris Paul , Goodall Jane , Wechalekar Mihir D , FitzGerald Oliver , Szentpetery Agnes , Smith Malcolm , Thomas Ranjeny , Gaston Hill 
Published: September 2013

Abstract
Introduction
The aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA).

Methods
Flow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22.

Results
Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent.

Conclusions
Elevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.
Genome sequencing reveals fine scale diversification and reticulation history during speciation in Sus
Authors: Frantz Laurent AF , Schraiber Joshua G , Madsen Ole , Megens Hendrik-Jan , Bosse Mirte , Paudel Yogesh , Semiadi Gono , Meijaard Erik , Li Ning , Crooijmans Richard PMA , Archibald Alan L , Slatkin Montgomery , Schook Lawrence B , Larson Greger , Groenen Martien AM 
Published: September 2013

Abstract
Background
Elucidating the process of speciation requires an in-depth understanding of the evolutionary history of the species in question. Studies that rely upon a limited number of genetic loci do not always reveal actual evolutionary history, and often confuse inferences related to phylogeny and speciation. Whole-genome data, however, can overcome this issue by providing a nearly unbiased window into the patterns and processes of speciation. In order to reveal the complexity of the speciation process, we sequenced and analyzed the genomes of 10 wild pigs, representing morphologically or geographically well-defined species and subspecies of the genus Sus from insular and mainland Southeast Asia, and one African common warthog.

Results
Our data highlight the importance of past cyclical climatic fluctuations in facilitating the dispersal and isolation of populations, thus leading to the diversification of suids in one of the most species-rich regions of the world. Moreover, admixture analyses revealed extensive, intra- and inter-specific gene-flow that explains previous conflicting results obtained from a limited number of loci. We show that these multiple episodes of gene-flow resulted from both natural and human-mediated dispersal.

Conclusions
Our results demonstrate the importance of past climatic fluctuations and human mediated translocations in driving and complicating the process of speciation in island Southeast Asia. This case study demonstrates that genomics is a powerful tool to decipher the evolutionary history of a genus, and reveals the complexity of the process of speciation.
The unfolded protein response has a protective role in yeast models of classic galactosemia
Authors: De-Souza Evandro A. , Pimentel Felipe S. A. , Machado Caio M. , Martins Larissa S. , da-Silva Wagner S. , Montero-Lomelí Mónica , Masuda Claudio A. 
Published: September 2013

Summary
Classic galactosemia is a human autosomal recessive disorder caused by mutations in the GALT gene (GAL7 in yeast) which encodes the enzyme galactose-1-phosphate uridyltransferase. Here we show that the unfolded protein response pathway is triggered by galactose in two yeast models of galactosemia: lithium-treated cells and the gal7Δ mutant. The synthesis of galactose-1-phosphate is essential to trigger the unfolded protein response under these conditions because the deletion of the galactokinase-encoding gene GAL1 completely abolishes unfolded protein response activation and galactose toxicity. Impairment of the unfolded protein response in both yeast models makes cells even more sensitive to galactose, unmasking its cytotoxic effect. These results indicate that endoplasmic reticulum stress is induced under galactosemic conditions and underscores the importance of the unfolded protein response pathway to the cellular adaptation in these models of classic galactosemia.
Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice
Authors: Lapinski Philip E. , Meyer Melissa F. , Feng Gen-Sheng , Kamiya Nobuhiro , King Philip D. 
Published: September 2013

SummaryIn mice, induced global disruption of the Ptpn11 gene, which encodes the SHP-2 tyrosine phosphatase, results in severe skeletal abnormalities. To understand the extent to which skeletal abnormalities can be attributed to perturbation of SHP-2 function in bone-forming osteoblasts and chondrocytes, we generated mice in which disruption of Ptpn11 is restricted to mesenchymal stem cells (MSCs) and their progeny, which include both cell types. MSC-lineage-specific SHP-2 knockout (MSC SHP-2 KO) mice exhibited postnatal growth retardation, limb and chest deformity, and calvarial defects. These skeletal abnormalities were associated with an absence of mature osteoblasts and massive chondrodysplasia with a vast increase in the number of terminally differentiated hypertrophic chondrocytes in affected bones. Activation of mitogen activated protein kinases (MAPKs) and protein kinase B (PKB; also known as AKT) was impaired in bone-forming cells of MSC SHP-2 KO mice, which provides an explanation for the skeletal defects that developed. These findings reveal a cell-autonomous role for SHP-2 in bone-forming cells in mice in the regulation of skeletal development. The results add to our understanding of the pathophysiology of skeletal abnormalities observed in humans with germline mutations in the PTPN11 gene (e.g. Noonan syndrome and LEOPARD syndrome).
Towards a Comparative Approach to Demonology in Antiquity: The Case of Ancient Egypt and Mesopotamia
Authors: Lucarelli Rita 
Published: September 2013

Abstract This essay provides a general introduction to demonology in antiquity as well as a focus on ancient Egypt and Mesopotamia. It is also meant as an introduction to those papers which were originally presented at the international conference titled “Evil Spirits, Monsters and Benevolent Protectors: Demonology in Ancient Egypt and Mesopotamia,” held on April 23, 2012 at the Institute for the Study of the Ancient World of New York University, contained in the first section of this volume. Questions of the definition and function of demons in ancient Egyptian and Mesopotamian civilizations are raised and discussed in light of a comparative approach to the study of ancient religions.
Divine Taxonomy in the Underworld Books
Authors: Manassa Colleen 
Published: September 2013

Abstract The Underworld Books provide a unique perspective on divine taxonomy, juxtaposing gods with large, formal cults with gods whose existence is predicated on their membership within constellations of other netherworldly divinities. Examination of the ontological status of deities within the “Catalog” of the Book of Amduat and the Great Litany of the Book of Adoring Re in the West (a.k.a. The Litany of Re), including their use in non-funerary contexts, reveals a new definition for daimones within Egyptian theology.
Mesopotamian Conceptions of the Supernatural: A Taxonomy of Zwischenwesen
Authors: Sonik Karen 
Published: September 2013

Abstract The monsters and daimons (demons) of Mesopotamia belonged to a constellation of Zwischenwesen - interstitial beings with supernatural qualities or capacities - that occupied the space between humans and their gods. As the “Other,” if not always the enemy, their alterity was not only inscribed in their bodies but also reflected in their social alienation and geographical isolation. Strikingly imagined, where depicted or described, as morphologically anomalous or miscegenated (Mischwesen), the monsters and daimons lacked the kinship affiliations of both citydwelling humans and their gods and properly dwelt at the wild and inhospitable margins of the known world. This study explores their definition, functioning, and classification in a cosmos in which the overarching conflict was between order and chaos rather than good and evil, in which divinely organized and guarded civilization was ever threatened by the pressing and savage forces gathered in the wilderness beyond the city walls.
The Head of Humbaba
Authors: Graff Sarah B. 
Published: September 2013

Abstract A large corpus of terracotta plaques bearing the image of the demon Humbaba/ Huwawa, a major character in the Gilgamesh epic, have been excavated from late third and early second millennium BCE contexts at numerous sites in Mesopotamia. This essay explores the motif of Humbaba’s severed head within its ancient Near Eastern context in order to demonstrate that the head differs from other images of decapitation, as a representation whose supernatural power is unaffected by death. It concludes that the terracotta plaques were interpreted in sophisticated and multivalent ways by ancient audiences: as visual narratives representing a key moment in the epic; as apotropaic images displayed to guard transitions; and as important omens recorded in the past, which had the potential to reappear in the present.
The Corpse Daemon Antinoos
Authors: Németh György 
Published: September 2013

Abstract On the basis of the preserved evidence, corpse daemons were practically employed in two specific fields: in love magic and in chariot racing. In this respect, the material of our sources seems significant: in Egyptian papyri the daemons are primarily used in erotic magic, whereas in lead tablets they are meant to manipulate chariot races. The study examines all known occurrences of nekydaimones, analyzing their functions and names, whenever referred to in the sources.
Bodiless Docetists and the Daimonic Jesus: Daimonological Discourse and Anti-Docetic Polemic in Ignatius’ Letter to the Smyrnaeans
Authors: Proctor Travis W. 
Published: September 2013

Abstract In his Letter to the Smyrnaeans, Ignatius of Antioch condemns his opponents to a “bodiless” and “daimonic” afterlife, and also quotes an apocryphal resurrection tradition wherein the risen Jesus eschews the label “bodiless daimon.” Ignatius, therefore, defines both Jesus’ and his opponents’ physiology in terms of the ‘daimonic’; but what would such an existence have entailed in antiquity? In what follows, I explore the rhetorical functions of Ignatius’ daimonic terminology by situating it within larger discourses surrounding daimonic physiologies. I contend that Ignatius’ daimonological terminology not only caricatures the docetic belief in a bodiless risen Jesus, but also condemns Ignatius’ opponents to a morose afterlife that runs directly counter to their anticipations. When contextualized within his letters more generally, Ignatius’ derisive rhetoric solidifies his construction of ‘docetic’ Christians: they are evil, sub-human, and daimonic, the epitome of the ‘other,’ doomed to inhabit the cosmic and societal margins, and unworthy of interaction with Ignatius’ fellow ‘orthodox’ Christians.
Sampling and storage conditions influencing the measurement of parathyroid hormone in blood samples: a systematic review
Authors: Hanon Elodie A. , Sturgeon Catharine M. , Lamb Edmund J. 
Published: September 2013

Abstract
Parathyroid hormone (PTH) is relatively unstable: optimisation of pre-analytical conditions, including specimen type, sampling time and storage conditions, is essential. We have undertaken a systematic review of these pre-analytical conditions. An electronic search of the PubMed, Embase, Cochrane, Centre for Research and Dissemination and Bandolier databases was undertaken. Of 5511 papers identified, 96 underwent full text review, of which 83 were finally included. At room temperature PTH was stable in ethylenediaminetetraacetic acid (EDTA) preserved whole blood for at least 24 h and in EDTA plasma for at least 48 h after venepuncture. Losses were observed in clotted blood samples after 3 h and in serum after 2 h. At 4°C PTH was more stable in EDTA plasma (at least 72 h) than serum (at least 24 h). Central venous PTH concentrations were higher than peripheral venous concentrations. In the northern hemisphere, PTH concentrations were higher in winter than summer. PTH has a circadian rhythm characterised by a nocturnal acrophase and mid-morning nadir. Data related to frozen storage of PTH (−20°C and −80°C) were limited and contradictory. We recommend that blood samples for PTH measurement should be taken into tubes containing EDTA, ideally between 10:00 and 16:00, and plasma separated within 24 h of venepuncture. Plasma samples should be stored at 4°C and analysed within 72 h of venepuncture. Particular regard must be paid to the venepuncture site when interpreting PTH concentration. Further research is required to clarify the suitability of freezing samples prior to PTH measurement.