bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenyvsreticulation in prehistory
Authors: Bellwood Peter
Published: November 2015

Two pure and opposing models exist to give historical account of the structure in modern cultural patterns. A phylogenetic account explores divergence from some shared commonality (the word ‘phylogenetic’ is from the Greek words for ‘tribal origins’). A reticulate account concentrates on a network of interactions (the word ‘reticulate’ comes via French from the Latin for ‘small net’). It follows that neither model may tell all the story. These continuing issues are explored with particular attention to the relations between histories as they are inferred from archaeological and from linguistic patterns.
The boat models from Eridu: sailing or spinning during the ‘Ubaid period?
Authors: Strasser Thomas F.
Published: November 2015

It has been received wisdom for nearly half a century that 6th-millennium BP models, discovered at Eridu in southern Mesopotamia, are the earliest direct evidence for sailing-boats. Yet certain features of the models, and their contexts, identify them instead as spinning bowls used by weavers.
The origin of the true chariot
Authors: Littauer M. A. , Crouwel J. H.
Published: November 2015

New dates and new finds give cause to look again at that central issue in later European prehistory — the origin of wheeled light vehicles of battle.
Why didn't Westropp's ‘Mesolithic’ catch on in 1872?
Authors: Rowley-Conwy Peter
Published: November 2015

A defined ‘Mesolithic’ era is a fixture in the cultural sequences of European prehistory — though not of other regions of the world. Why and how did the entity come to be invented, and to take just that form?
The plants and the people from Buiston Crannog, Ayrshire, Scotland
Authors: Holden Timothy G.
Published: November 2015

In ANTIQUITY for 1993 Barber & Crone reported their excavations at Buiston, one of the crannogs of southwestern Scotland, whose archaeology was in a remarkable good state despite the draining of its watery site. This further account, in reporting on botanical materials from the site, is able to develop a better knowledge of the plants around the crannog, and of their human uses.
Establishing the Chinese archaeological school: Su Bingqi and contemporary Chinese archaeology
Authors: Tao Wang
Published: November 2015

Most of what is heard in the West of Chinese archaeology is about the physical stuff — the astonishing string of major finds; some, like soldiers from the Terracotta Army of the First Emperor's tumulus, have been exhibited outside China. All archaeological material is excavated, described and explained by reference to some frame of ideas. This essay on the thinking of a leading Chinese archaeologist of our day, Su Bingqi, is accompanied by an article of his in translation.
The Mildenhall Treasure: Roald Dahl's ultimate tale of the unexpected?
Authors: Hobbs Richard
Published: November 2015

Just over 50 years ago, the most magnificent treasure of late Antique silver ever found in Britain was brought out of hiding in a sleepy village in rural Suffolk. The late Roald Dahl, the children's writer, may have held the answer.
Mildenhall: memories of mystery and misgivings
Authors: Ashbee Paul
Published: November 2015

Half a century on, the principals in the Mildenhall affair are deceased. Paul Ashbee, senior prehistorian of East Anglia, has no direct evidence, but material recollections from near to the time. His account, drawing on those memories, notices aspects different to those which are stressed by Richard Hobbs (above), a researcher of a younger generation looking at the written record.
The Neolithic great goddess: a study in modern tradition
Authors: Hutton Ronald
Published: November 2015

Modern belief in the veneration of a single Great Goddess in the European Neolithic is often accompanied by the notion that those cultures of ‘Old Europe’ were woman-centred in society as well as religion. What is the long history which precedes these contemporary notions? What is the complex history of their political development? A chain runs from Classical times to Marija Gimbutas (Meskell 1995) and our own day.
Maximum ages of the Côa valley (Portugal) engravings measured with Chlorine-36
Authors: Phillips Fred M. , Flinsch Montgomery , Elmore David , Sharma Pankaj
Published: November 2015

Panel faces in teh Côa valley, Portugal, were available for engraving during the Upper Palaeolithic, according to 36Cl exposure ages of 16,000 to 136,000 years.
Derivation of ancient Egyptian faience core and glaze materials
Authors: Stocks Denys A.
Published: November 2015

An essential ingredient of the lovely blues in ancient Egyptian materials — faience, glazes, frits — is copper. How did the knowledge of that copper use arise? There is a telling congruence with Egyptian techniques in drilling stone artefacts, and the characteristics of the powder drilled out as waste.
New optical and radiocarbon dates from Ngarrabullgan Cave, a Pleistocene archaeological site in Australia: implications for the comparability of time clocks and for the human colonization of Australia
Authors: David Bruno , Roberts Richard , Tuniz Claudio , Jones Rhys , Head John
Published: November 2015

The human settlement of Australia falls into that period where dating is hard because it is near or beyond the reliable limit of radiocarbon study; instead a range of luminescence methods are being turned to (such as thermoluminescence at Jinmium: December 1996 ANTIQUITY). Ngarrabullgan Cave, a rock-shelter in Queensland, now offers a good suite of radiocarbon determinations which match well a pair of optically stimulated luminescence (OSL) dates — encouraging sign that OSL determinations can be relied on.
Floating obsidian and its implications for the interpretation of Pacific prehistory
Authors: Spennemann Dirk H. R. , Ambrose Wal R.
Published: November 2015

A piece of pumice among drift material on Nadikdik Atoll, Marshall Islands, in far Micronesia had a large chunk of flakeable obsidian attached. As the atoll had been devastated by a typhoon and associated storm surge in 1905, the piece must have arrived by sea within the last 90 years. This and similar incidences of raw materials distributed by ocean drift show how sea-borne dispersal cannot be excluded offhand in the occurrence of obsidian in far-flung places, commonly attributed to human transport.
Emergence of sedentism: new ways of living, new ways of symbolizing
Authors: Haaland Randi
Published: November 2015

What is the role of women in processes leading towards a more sedentary way of life? Pottery plays an important role as a functional factor and in symbolic expressions. With sedentism hearth-centred activities organized around females grew, and the position of the woman as the nurturer. Some of this symbolism, expressed on a multitude of ritual occasions, may be retrievable archaeologically.
A history in paint and stone from Rose Cottage Cave, South Africa
Authors: Ouzman Sven , Wadley Lyn
Published: November 2015

In South Africa, as in so many regions, the world of dirt archaeology in shelter floors and of rock art on shelter walls, have also been rather separate as domains of study. In research at Rose Cottage Cave, bridges are being made to link both strands of evidence of the forager social strategies from which both derive.
On human blood, rock art and calcium oxalate: further studies on organic carbon content and radiocarbon age of materials relating to Australian rock art
Authors: Gillespie Richard
Published: November 2015

Minute biological traces, with their prospect of recovering even ancient DNA, are the most attractive of archaeological materials to work with. This supplementary report on field studies of rock-art first published in ANTIQUITY further explores how these studies may in truth be carried out.
Accelerator radiocarbon dating of Natal Drakensberg paintings: results and implications
Authors: Mazel A. D. , Watchman A. L.
Published: November 2015

As Rosenfeld & Smith report in this number of ANTIQUITY, the reconciliation of conventional chronologies for rock-art with the emergent radiocarbon-based dates is not proving an easy affair. Here are the first steps for the classic area of San hunter-gatherer art, on the South Africa/Lesotho border.
Lapita and the temporal geography of prehistory
Authors: Terrell John Edward , Welsch Robert L.
Published: November 2015

Ambrose (this issue, above) and Sand (this issue, above) reported on Lapita in the specific, without being parochial in their concerns. This paper looks at the largest Lapita picture, but is itself in turn based on new reports in the specific, here from the coast of Papua New Guinea which is key for the relations in space, in time and in cultural affinity of whatever human it is that Lapita is.
Fish trade in Norse Orkney and Caithness: a zooarchaeological approach
Authors: Barrett James H.
Published: November 2015

The trade of dried fish played an important role in the transformation from the Viking Age to the Middle Ages in Scandinavian polities such as Arctic Norway. This paper develops zooarchaeological methods to investigate whether similar processes occurred in the less well documented Norse colonies of northern Scotland — the joint earldoms of Orkney and Caithness.
Human skeletal remains from Tomb 1, Sipán (Lambayeque river valley, Peru); and their social implications
Authors: Verano John W.
Published: November 2015

The Moche tombs at Sipán, on the north Peruvian coast, are a major addition to our knowledge of high-status élite burial rituals. Its Tomb 1 contains the remains of nine individuals — three adult males, one adult female, three adolescent females and one child — besides the principal burial. Who are these people, as their biological remains instruct us?
The site of Saar: Dilmun reconsidered
Authors: Crawford Harriet
Published: November 2015

Recent excavations at the site of Saar, Bahrain, further advance our knowledge of Dilmun, that magical place on the Gulf which was a cross-roads of southwest Asian land and northwest Indian Ocean. Saar is a proto-urban agglomeration with the characteristics of a planned settlement — planned it appears from some other and controlling place.
Charlemagne's black stones: the re-use of Roman columns in early medieval Europe
Authors: Peacock D. P. S.
Published: November 2015

What were the ‘black stones’ about which Charlemagne wrote to King Offa of Mercia just before AD 800? How do these special blocks fit into the broader pattern in re-using Roman columns in early medieval buildings?
Rock-art image in Fern Cave, Lava Beds National Monument, California: not the AD 1054 (Crab Nebula) supernova
Authors: Armitage R. A. , Hyman M. , Southon J. , Barat C. , Rowe M. W.
Published: November 2015

The visual manifestation of the recent Hale-Bopp comet reminds us how telling are those rare objects which suddenly flare in the sky. One can suppose ancient people living by natural light were more compellingly struck by the sight of comets and supernovae, and understandably researchers seek images of them in the shapes of rock-art motifs. An absolute dating contradicts that supposition in respect of a presumed image of the visible supernova of AD 1054.
Towards an absolute chronology for the Iron Age of Inner Asia
Authors: Hall Mark E.
Published: November 2015

For half a century now — ever since radiocarbon dating began — there have been regional reconciliations between relative chronologies and the new absolute dating. Sometimes they have been friendly, some times less so when the two schemes have not matched well. For Inner Asia — centre of the Old World — there is belatedly now the means to resolve some fundamentals.
Images in opposition: polarity, ambivalence and liminality in cult representation
Authors: Green Miranda J.
Published: November 2015

The concept of ‘Celtic’ is fittingly ambiguous, ambivalent and disputed in its archaeological definition: ‘fittingly’ because later prehistoric and Roman iconography in temperate Europe is ambiguous and ambivalent. And ambiguous and ambivalent things are hard to understand unambiguously!
Exploitation of wild plants by the early Neolithic hunter–gatherers of the Western Desert, Egypt: Nabta Playa as a case-study
Authors: Wasylikowa Krystyna , Mitka Józef , Wendorf Fred , Schild Romuald
Published: November 2015

The role of plants in the subsistence economy of pre-agricultural societies of the eastern Sahara is poorly known because vegetal remains, except for wood charcoal, are seldom found in archaeological sites. Site E-75-6 at Nabta Playa, with rich assemblages of charred seeds and fruits, is exceptional. Around 8000 b.p. the inhabitants of this site collected a wide spectrum of wild food plants. Wild sorghum was of special interest and its occasional cultivation cannot be excluded.
New directions in central Mediterranean obsidian studies
Authors: Tykot Robert H. , Ammerman Albert J.
Published: November 2015

Mediterranean obsidian-provenance studies are changing in direction and focus of modern research, with characterization of the Sardinian sources, application of minimally destructive and inexpensive analytical techniques, analysis of complete or large parts of assemblages, and the integration of provenance data with reduction technology and use-wear traces.
A horn worth blowing? A stray find of aurochs from Hungary
Authors: Bartosiewicz László
Published: November 2015

Three aurochs horn cores, unearthed during the construction of the city baths in Vác (Hungary), were purchased from a private collector in 1951. One of these stray finds deserves attention in light of new archaeozoological research, and the relation between mundane horn manufacturing and high-status medieval craft industries.
Misleading images: Stonehenge and Brittany
Authors: Scarre Chris
Published: November 2015

Does a unique eroded prehistoric carving on one of the sarsen uprights at Stonehenge link the most famous of English megalithic monuments to Brittany?
Electronic archives
Authors: Eiteljorg Harrison
Published: November 2015

An archive is a collection of materials intended to be kept safe for the long term. Those materials are gathered by some responsible agency, but they were created originally by others. They were made in the forms and with the methods chosen by their creators. That is, an archive contains materials that have been created by others, that have been formed and informed by the judgements of others and that are intensely idiosyncratic. An archive is not simply a collection of facts or ideas or objects; it is a collection of other peoples’ individual or collected facts and ideas and objects. As a result, the contents of an archive are disparate in the extreme, from books to diaries to maps to photographs. A digital archive is at least as chaotic as any other, probably more so. Its contents may include text files, data-base files, images, CAD files, GIs files and more.
Publishing in the round: a role for CD-ROM in the publication of archaeological field-work results
Authors: Powlesland Dominic
Published: November 2015

Some five months have elapsed since I was invited to write this paper and, as seems always to be the case, the continued rapid change in applied computing and available technology has transformed my view of the potentials offered by CD-ROM (Compact Disk-Read Only Memory) as a publishing medium. The paper I now offer is substantially different in content; the conclusions, however, are the same.
University archaeological education, CD-ROMs and digital media
Authors: Perkins Phil
Published: November 2015

I would like to start with the contentious assertion that there is very little special about CD-ROMs; they are little more than overgrown floppy disks with a long shelf-life, and uncertain sell-by date. A CD-ROM can contain about 650 Mb (Megabytes) of digital information, the equivalent of 450 high-density floppy disks, A CD-ROM is much more durable than a floppy disk, if kept away from small children and dogs, and is certainly more convenient to transport and handle than 450 floppy disks. A floppy disk will fade and its contents will become unreadable after about 4 or 5 years. A shiny CDROM on the other hand will last physically for at least 30 years, we are promised. Unfortunately the CD-ROM is already headed for the scrap heap of our technological past and is set to join the burins and scrapers. Yes, the Digital Versatile Disk (DVD) is coming our way. It can contain up to 17 Gb (Gigabytes) — that’s 17 with nine zeros after it, the equivalent of 11,805 floppy disks full of data. Fifteen years ago, back in 1982, a 10-Mb hard disk was considered an expensive technological marvel with more than enough capacity (equivalent to 25 of the lowercapacity, 400-Kb floppy disks of the ‘80s). Nowadays, the CD-ROM, given away on the front of glossy magazines, and costing Sop to produce, contains 65 times that amount of information. My point is that I don’t think we should become obsessed with the technology and the means of delivery of data on some kind of disk. What is far more important is what is actually on the disk — the message not the messenger.
‘Don't let me go! Hold me down!’: inspiration, voice and image in Kate Bush's ‘Hounds of Love’
Authors: Cawood Ian
Published: November 2015

Although Kate Bush's reputation as a significant musical pioneer has been accepted by most critics and academic commentators since her return to music in 2005, most readings of her work have been highly ahistoric. This paper explores how, with the release of her fifth album, Hounds of Love, in 1985, her popular appeal was widened into a genuine acceptance of her idiom by contemporary cultural commentators. In particular, the paper focuses on the rival inspirations and the shape, form and delivery of the title track, ‘Hounds of Love’ and its ‘alternative’ version, released on a 12” disc. The paper concludes by analysing the visual presentation of the song through the promotional video (directed by Bush herself) and her two mimed performances and offering a contextualised explanation for Bush's perceived ‘authenticity’ as an artist and performer.
Running a record label when records don't sell anymore: empirical evidence from Poland
Authors: Galuszka Patryk , Wyrzykowska Katarzyna M.
Published: November 2015

From an economic point of view, the business of record labels until recently boiled down to managing a portfolio of artists, with successful stars bringing the label enough money to recoup investments in market flops. The decline in record sales has called this model into question and forced labels to look for new sources of revenue. Employing qualitative data gathered in Poland, this paper demonstrates how labels react to adverse market conditions and what determines these reactions. The paper shows that these reactions include the monetisation of the relationship that a label has with artists through signing 360° deals, the commercial exploitation of artists’ brand names, and concentration on niche markets, either foreign or format-based (e.g. the market for vinyl). The paper concludes that record labels, regardless of which approach they choose to deal with the adverse market conditions, still think in terms of managing a portfolio of artists. What is more, there is no universal strategy which can be applied by every label to deal with declining record sales.
Diagnosing dense and magnetized plasmas irradiated by a petawatt laser
Authors: Deutsch C. , Nersisyan H.B. , Bendib A.
Published: November 2015

We survey the present status and potentialities of diagnostics for arbitrary magnetized plasmas of inertial confinement fusion concern. These diagnostics include: Faraday rotation, inverse Faraday effect, Thomson scattering, Stark–Zeeman line broadening as well as proton stopping for any ratio, of the particles plasma frequency to cyclotron frequency. This presentation is timely motivated by recent experiments highlighting laser-produced kilo Teslas and nearly steady magnetic fields in inertial fusion plasmas. Positive synergies due to diagnostics combinations are also addressed.
Die Gründung der Deutschen Gesellschaft für Kinderpsychiatrie und Heilpädagogik
Authors: Schepker Klaus , Fangerau Heiner
Published: November 2015

Zusammenfassung. Der Entstehungsprozess der Fachgesellschaft wird genauer rekonstruiert hinsichtlich der Entwicklungen, die zur formalen Gründung der DGKH (Deutsche Gesellschaft für Kinderpsychiatrie und Heilpädagogik) in der Phase der Patientenmorde beigetragen haben. Methodisch kam eine historische Netzwerkanalyse unter Berücksichtigung der Hauptakteure zur Anwendung. Die Gründung der Fachgesellschaft stellt sich dar als das Resultat eines Zusammenwirkens von a) Reichsgesundheitsamt, dessen Präsidenten Hans Reiter und Fritz Rott als nationalsozialistischen Gesundheitspolitikern, b) der an dieser Politik ausgerichteten wissenschaftlichen Entwicklung einer jungen Disziplin, die ihre Wissensgrundlage und ihren medizinischen ‹Gegenstand› mit etablierten Fächern wie Psychiatrie und Pädiatrie teilte, c) einem postulierten Bedarf nach Charakterkunde, Prognose und Auslese im nationalsozialistischen Alltag, sowie d) den persönlichen sowie professionspolitischen Interessen der Hauptakteure Schröder und Villinger. Einmal mehr zeigt sich, dass Medizin und Politik im Nationalsozialismus nicht nur miteinander verwoben, sondern in bestimmten Bereichen eins waren. Grenzen sind eher zwischen den gesellschaftlichen ‹Ordnungsebenen› zu ziehen, denn die Gründung der DGKH stellt ein weiteres Beispiel für ein «Radikales Ordnungsdenken» nach Raphael dar, das «in den institutionellen Arrangements auf mittlerer Ebene» die «neue nationalsozialistische Ordnung» realisieren sollte ( Raphael, 2001 ).
The epigenomic landscape of African rainforest hunter-gatherers and farmers
Authors: Fagny Maud , Patin Etienne , MacIsaac Julia L. , Rotival Maxime , Flutre Timothée , Jones Meaghan J. , Siddle Katherine J. , Quach Hélène , Harmant Christine , McEwen Lisa M. , Froment Alain , Heyer Evelyne , Gessain Antoine , Betsem Edouard , Mouguiama-Daouda Patrick , Hombert Jean-Marie , Perry George H. , Barreiro Luis B. , Kobor Michael S. , Quintana-Murci Lluis
Published: November 2015

The genetic history of African populations is increasingly well documented, yet their patterns of epigenomic variation remain uncharacterized. Moreover, the relative impacts of DNA sequence variation and temporal changes in lifestyle and habitat on the human epigenome remain unknown. Here we generate genome-wide genotype and DNA methylation profiles for 362 rainforest hunter-gatherers and sedentary farmers. We find that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected strongly differ. Specifically, methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes. Furthermore, methylation variation—particularly that correlated with historical lifestyle—shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Our work provides new insight into the genetic and environmental factors affecting the epigenomic landscape of human populations over time.
p38- and MK2-dependent signalling promotes stress-induced centriolar satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1
Authors: Tollenaere Maxim A. X. , Villumsen Bine H. , Blasius Melanie , Nielsen Julie C. , Wagner Sebastian A. , Bartek Jiri , Beli Petra , Mailand Niels , Bekker-Jensen Simon
Published: November 2015

Centriolar satellites (CS) are small granular structures that cluster in the vicinity of centrosomes. CS are highly susceptible to stress stimuli, triggering abrupt displacement of key CS factors. Here we discover a linear p38-MK2-14-3-3 signalling pathway that specifically targets CEP131 to trigger CS remodelling after cell stress. We identify CEP131 as a substrate of the p38 effector kinase MK2 and pinpoint S47 and S78 as critical MK2 phosphorylation sites in CEP131. Ultraviolet-induced phosphorylation of these residues generates direct binding sites for 14-3-3 proteins, which sequester CEP131 in the cytoplasm to block formation of new CS, thereby leading to rapid depletion of these structures. Mutating S47 and S78 in CEP131 is sufficient to abolish stress-induced CS reorganization, demonstrating that CEP131 is the key regulatory target of MK2 and 14-3-3 in these structures. Our findings reveal the molecular mechanism underlying dynamic CS remodelling to modulate centrosome functions on cell stress.
DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice
Authors: Suberbielle Elsa , Djukic Biljana , Evans Mark , Kim Daniel H. , Taneja Praveen , Wang Xin , Finucane Mariel , Knox Joseph , Ho Kaitlyn , Devidze Nino , Masliah Eliezer , Mucke Lennart
Published: November 2015

Maintaining DNA integrity is vital for all cells and organisms. Defective DNA repair may contribute to neurological disorders, including Alzheimer’s disease (AD). We found reduced levels of BRCA1, but not of other DNA repair factors, in the brains of AD patients and human amyloid precursor protein (hAPP) transgenic mice. Amyloid-β oligomers reduced BRCA1 levels in primary neuronal cultures. In wild-type mice, knocking down neuronal BRCA1 in the dentate gyrus caused increased DNA double-strand breaks, neuronal shrinkage, synaptic plasticity impairments, and learning and memory deficits, but not apoptosis. Low levels of hAPP/Amyloid-β overexpression exacerbated these effects. Physiological neuronal activation increased BRCA1 levels, whereas stimulating predominantly extrasynaptic N-methyl-D-aspartate receptors promoted the proteasomal degradation of BRCA1. We conclude that BRCA1 is regulated by neuronal activity, protects the neuronal genome, and critically supports neuronal integrity and cognitive functions. Pathological accumulation of Aβ depletes neuronal BRCA1, which may contribute to cognitive deficits in AD.
SUMOylation of AMPKα1 by PIAS4 specifically regulates mTORC1 signalling
Authors: Yan Yan , Ollila Saara , Wong Iris P. L. , Vallenius Tea , Palvimo Jorma J. , Vaahtomeri Kari , Mäkelä Tomi P.
Published: November 2015

AMP-activated protein kinase (AMPK) inhibits several anabolic pathways such as fatty acid and protein synthesis, and identification of AMPK substrate specificity would be useful to understand its role in particular cellular processes and develop strategies to modulate AMPK activity in a substrate-specific manner. Here we show that SUMOylation of AMPKα1 attenuates AMPK activation specifically towards mTORC1 signalling. SUMOylation is also important for rapid inactivation of AMPK, to allow prompt restoration of mTORC1 signalling. PIAS4 and its SUMO E3 ligase activity are specifically required for the AMPKα1 SUMOylation and the inhibition of AMPKα1 activity towards mTORC1 signalling. The activity of a SUMOylation-deficient AMPKα1 mutant is higher than the wild type towards mTORC1 signalling when reconstituted in AMPKα-deficient cells. PIAS4 depletion reduced growth of breast cancer cells, specifically when combined with direct AMPK activator A769662, suggesting that inhibiting AMPKα1 SUMOylation can be explored to modulate AMPK activation and thereby suppress cancer cell growth.
A positive feedback loop between Gli1 and tyrosine kinase Hck amplifies shh signaling activities in medulloblastoma
Authors: Shi X , Zhan X , Wu J
Published: November 2015

Sonic hedgehog (Shh) signaling is critical during normal development, and the abnormal activation of the Shh pathway is involved in many human cancers. As a target gene of the Shh pathway and as a transcription activator downstream of Shh signaling, Gli1 autoregulates and increases Shh signaling output. Gli1 is one of the key oncogenic factors in Shh-induced tumors such as medulloblastoma. Gli1 is posttranslationally modified, but the nature of the active form of Gli1 was unclear. Here we identified a Src family kinase Hck as a novel activator of Gli1. In Shh-responsive NIH3T3 cells, Hck interacts with Gli1 and phosphorylates multiple tyrosine residues in Gli1. Gli1-mediated target gene activation was significantly enhanced by Hck with both kinase activity-dependent and -independent mechanisms. We provide evidence showing that Hck disrupts the interaction between Gli1 and its inhibitor Sufu. In both NIH3T3 cells and cerebellum granule neuron precursors, the Hck gene is also a direct target of Gli1. Therefore, Gli1 and Hck form a positive feedback loop that amplifies Shh signaling transcription outcomes. In Shh-induced medulloblastoma, Hck is highly expressed and Gli1 is tyrosine phosphorylated, which may enhance the tumorigenic effects of the Gli1 oncogene. RNAi-mediated inhibition of Hck expression significantly repressed medulloblastoma cell growth. In summary, a novel positive feedback loop contributes to maximal Gli1 oncogenic activities in Shh-induced tumors such as medulloblastoma.
Contrasting diel hysteresis between soil autotrophic and heterotrophic respiration in a desert ecosystem under different rainfall scenarios
Authors: Song Weimin , Chen Shiping , Zhou Yadan , Wu Bo , Zhu Yajuan , Lu Qi , Lin Guanghui
Published: November 2015

Diel hysteresis occurs often between soil CO2 efflux (RS) and temperature, yet, little is known if diel hysteresis occurs in the two components of RS, i.e., autotrophic respiration (RA) and heterotrophic respiration (RH) and how diel hysteresis will respond to future rainfall change. We conducted a field experiment in a desert ecosystem in northern China simulating five different scenarios of future rain regimes. Diel variations of soil CO2 efflux and soil temperature were measured on Day 6 and Day 16 following the rain addition treatments each month during the growing season. We found contrasting responses in the diel hysteresis of RA and RH to soil temperature, with a clockwise hysteresis loop for RH but a counter-clockwise hysteresis loop for RA. Rain addition significantly increased the magnitude of diel hysteresis for both RH and RA on Day 6, but had no influence on either on Day 16 when soil moisture was much lower. These findings underline the different roles of biological (i.e. plant and microbial activities) and physical-chemical (e.g. heat transport and inorganic CO2 exchange) processes in regulating the diel hysteresis of RA and RH, which should be considered when estimating soil CO2 efflux in desert regions under future rainfall regime.
Escherichia coli Nissle 1917 enhances bioavailability of serotonin in gut tissues through modulation of synthesis and clearance
Authors: Nzakizwanayo Jonathan , Dedi Cinzia , Standen Guy , Macfarlane Wendy M. , Patel Bhavik A. , Jones Brian V.
Published: November 2015

Accumulating evidence shows indigenous gut microbes can interact with the human host through modulation of serotonin (5-HT) signaling. Here we investigate the impact of the probiotic Escherichia coli Nissle 1917 (EcN) on 5-HT signalling in gut tissues. Ex-vivo mouse ileal tissue sections were treated with either EcN or the human gut commensal MG1655 and effects on levels of 5-HT, precursors and metabolites, were evaluated using amperometry and high performance liquid chromatography with electrochemical detection (HPLC-EC). Exposure of tissue to EcN cells, but not MG1655 cells, was found to increase levels of extra-cellular 5-HT. These effects were not observed when tissues were treated with cell-free supernatant from bacterial cultures. In contrast, when supernatant recovered from untreated ileal tissue was pre-incubated with EcN, the derivative cell-free supernatant was able to elevate 5-HT overflow when used to treat fresh ileal tissue. Measurement of 5-HT precursors and metabolites indicated EcN also increases intracellular 5-HTP and reduces 5-HIAA. The former pointed to modulation of tryptophan hydroxylase-1 to enhance 5-HT synthesis, while the latter indicates an impact on clearance into enterocytes through SERT. Taken together, these findings show EcN is able to enhance 5-HT bioavailability in ileal tissues through interaction with compounds secreted from host tissues.
Mortality Benefits of Antibiotic Computerised Decision Support System: Modifying Effects of Age
Authors: Chow Angela L. P. , Lye David C. , Arah Onyebuchi A.
Published: November 2015

Antibiotic computerised decision support systems (CDSSs) are shown to improve antibiotic prescribing, but evidence of beneficial patient outcomes is limited. We conducted a prospective cohort study in a 1500-bed tertiary-care hospital in Singapore, to evaluate the effectiveness of the hospital’s antibiotic CDSS on patients’ clinical outcomes and the modification of these effects by patient factors. To account for clustering, we used multilevel logistic regression models. One-quarter of 1886 eligible inpatients received CDSS-recommended antibiotics. Receipt of antibiotics according to CDSS’s recommendations seemed to halve mortality risk of patients (OR 0.54, 95% CI 0.26–1.10, P = 0.09). Patients aged ≤65 years had greater mortality benefit (OR 0.45, 95% CI 0.20–1.00, P = 0.05) than patients that were older than 65 (OR 1.28, 95% CI 0.91–1.82, P = 0.16). No effect was observed on incidence of Clostridium difficile (OR 1.02, 95% CI 0.34–3.01) and multidrug-resistant organism (OR 1.06, 95% CI 0.42–2.71) infections. No increase in infection-related readmission (OR 1.16, 95% CI 0.48–2.79) was found in survivors. Receipt of CDSS-recommended antibiotics reduced mortality risk in patients aged 65 years or younger and did not increase the risk in older patients. Physicians should be informed of the benefits to increase their acceptance of CDSS recommendations.
Peginterferon plus Ribavirin for HIV-infected Patients with Treatment-Naïve Acute or Chronic HCV Infection in Taiwan: A Prospective Cohort Study
Authors: Liu Chen-Hua , Sheng Wang-Hui , Sun Hsin-Yun , Hsieh Szu-Min , Lo Yi-Chun , Liu Chun-Jen , Su Tung-Hung , Yang Hung-Chih , Liu Wen-Chun , Chen Pei-Jer , Chen Ding-Shinn , Hung Chien-Ching , Kao Jia-Horng
Published: November 2015

Data are limited on the effectiveness and safety of peginterferon plus ribavirin in HIV-infected Asian patients with acute or chronic HCV infection. HIV-infected Taiwanese patients with acute HCV infection received peginterferon plus weight-based ribavirin for 24 weeks (n = 24) and those with chronic HCV genotype 1 or 6 (HCV-1/6) and HCV genotype 2 or 3 (HCV-2/3) infection received response-guided therapy for 12–72 and 24–48 weeks, respectively (n = 92). The primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA 24 weeks off-therapy. The SVR rates were 83% and 72% in patients with acute and chronic HCV infection (p = 0.30) and 68% and 72% in patients with chronic HCV-1/6 and HCV-2/3 infection (p = 0.48), respectively. While no factors predicted SVR in acute HCV and chronic HCV-2/3 infection, age (odds ratio [OR] per 1-year increase: 0.88, 95% confidence interval [CI]: 0.78–0.99, p = 0.04), HCV RNA (OR per 1-log10 increase: 0.18, 95% CI: 0.03–0.98, p = 0.03), IL28B genotype (OR: 5.52, 95% CI: 1.55–12.2, p = 0.02) and RVR (OR: 9.62, 95% CI: 3.89–15.3, p = 0.007) predicted SVR in chronic HCV-1/6 infection. In conclusion, the SVR rates of peginterferon plus ribavirin for 24 weeks and for response-guided 12–72 weeks are satisfactory in HIV-infected Taiwanese patients with acute and chronic HCV infection.
NES1/KLK10 gene represses proliferation, enhances apoptosis and down-regulates glucose metabolism of PC3 prostate cancer cells
Authors: Hu Jiajia , Lei Hu , Fei Xiaochun , Liang Sheng , Xu Hanzhang , Qin Dongjun , Wang Yue , Wu Yingli , Li Biao
Published: November 2015

The normal epithelial cell-specific-1 (NES1) gene, also named as KLK10, is recognised as a novel putative tumour suppressor in breast cancer, but few studies have focused on the function of KLK10 in human prostate cancer. Our study confirms that the expression of KLK10 in prostate cancer tissue and cell lines (PC3, DU145 and LNCaP clone FGC) is low. Given that the androgen-independent growth characteristic of the PC3 cell line is more similar to clinical castration-resistant prostate cancer, we studied the role of KLK10 in PC3. In vitro and in vivo assays showed that over-expressing KLK10 in PC3 could decelerate tumour proliferation, which was accompanied with an increase in apoptosis and suppression of glucose metabolism. The related proteins, such as Bcl-2 and HK-2, were down-regulated subsequently. Furthermore, by up-regulating Bcl-2 or HK-2 respectively in the PC3-KLK10 cell line, we observed a subsequent increase of cell proliferation and a synchronous up-regulation of HK-2 and Bcl-2. Besides, KLK10 expression was also increased by Bcl-2 and HK-2, which suggests that there is a negative feedback loop between KLK10 and Bcl-2/HK-2. Thus, our results demonstrated that KLK10 may function as a tumour suppressor by repressing proliferation, enhancing apoptosis and decreasing glucose metabolism in PC3 cells.
In Vivo Linking of Membrane Lipids and the Anion Transporter Band 3 with Thiourea-modified Amphiphilic Lipid Probes
Authors: Moriyama Akihiro , Katagiri Naohiro , Nishimura Shinichi , Takahashi Nobuaki , Kakeya Hideaki
Published: November 2015

Membrane proteins interact with membrane lipids for their structural stability and proper function. However, lipid–protein interactions are poorly understood at a molecular level especially in the live cell membrane, due to current limitations in methodology. Here, we report that amphiphilic lipid probes can be used to link membrane lipids and membrane proteins in vivo. Cholesterol and a phospholipid were both conjugated to a fluorescent tag through a linker containing thiourea. In the erythrocyte, the cholesterol probe fluorescently tagged the anion transporter band 3 via thiourea. Tagging by the cholesterol probe, but not by the phospholipid probe, was competitive with an anion transporter inhibitor, implying the presence of a specific binding pocket for cholesterol in this ~100 kDa protein. This method could prove an effective strategy for analyzing lipid–protein interactions in vivo in the live cell membrane.
Short-term hyperoxia does not exert immunologic effects during experimental murine and human endotoxemia
Authors: Kiers Dorien , Gerretsen Jelle , Janssen Emmy , John Aaron , Groeneveld R. , van der Hoeven Johannes G. , Scheffer Gert-Jan , Pickkers Peter , Kox Matthijs
Published: November 2015

Oxygen therapy to maintain tissue oxygenation is one of the cornerstones of critical care. Therefore, hyperoxia is often encountered in critically ill patients. Epidemiologic studies have demonstrated that hyperoxia may affect outcome, although mechanisms are unclear. Immunologic effects might be involved, as hyperoxia was shown to attenuate inflammation and organ damage in preclinical models. However, it remains unclear whether these observations can be ascribed to direct immunosuppressive effects of hyperoxia or to preserved tissue oxygenation. In contrast to these putative anti-inflammatory effects, hyperoxia may elicit an inflammatory response and organ damage in itself, known as oxygen toxicity. Here, we demonstrate that, in the absence of systemic inflammation, short-term hyperoxia (100% O2 for 2.5 hours in mice and 3.5 hours in humans) does not result in increased levels of inflammatory cytokines in both mice and healthy volunteers. Furthermore, we show that, compared with room air, hyperoxia does not affect the systemic inflammatory response elicited by administration of bacterial endotoxin in mice and man. Finally, neutrophil phagocytosis and ROS generation are unaffected by short-term hyperoxia. Our results indicate that hyperoxia does not exert direct anti-inflammatory effects and temper expectations of using it as an immunomodulatory treatment strategy.
Environmental Surveillance of Genogroup I and II Noroviruses in Shandong Province, China in 2013
Authors: Tao Zexin , Xu Minglei , Lin Xiaojuan , Wang Haiyan , Song Lizhi , Wang Suting , Zhou Nan , Zhang Dongfeng , Xu Aiqiang
Published: November 2015

Noroviruses are the most common cause of epidemic gastroenteritis. However, the case-based surveillance is limited in China. In this study, we analyzed the results of environmental surveillance conducted in two cities of Shandong Province, China from January to December in 2013. Twenty-four sewage samples were collected and concentrated via membrane absorption/elution method. After reverse transcription-PCR, cloning and sequencing on ORF2 region, norovirus nucleic acid was detected in all 24 sewage samples. A total of 403 norovirus sequences of 16 genotypes were detected, among which GII.3 (22.6%), GI.2 (17.1%), GI.5 (13.4%), GI.3 (11.9%), GII.4 (7.7%) and GII.6 (6.7%) were the 6 most common genotypes. Phylogenetic analysis revealed multiple lineages within most common genotypes, especially in GI.3, whereas all GII.4 sequences belonged to Sydney 2012 strain. Recombination events were observed in 5 GI and 4 GII sequences within or near the ORF1/ORF2 overlap. This is the first report on systematic environmental surveillance on norovirus in China. The data presented here reveal co-circulation and high genetic diversity of multiple norovirus genotypes in the two cities and suggest continued environmental surveillance can provide valuable information on norovirus circulation in the population.
Conjunctival fibrosis and the innate barriers to Chlamydia trachomatis intracellular infection: a genome wide association study
Authors: Roberts Chrissy h. , Franklin Christopher S. , Makalo Pateh , Joof Hassan , Sarr Isatou , Mahdi Olaimatu S. , Sillah Ansumana , Bah Momodou , Payne Felicity , Jeffreys Anna E. , Bottomley William , Natividad Angels , Molina-Gonzalez Sandra , Burr Sarah E. , Preston Mark , Kwiatkowski Dominic , Rockett Kirk A. , Clark Taane G. , Burton Matthew J. , Mabey David C. W. , Bailey Robin , Barroso Inês , Holland Martin J.
Published: November 2015

Chlamydia trachomatis causes both trachoma and sexually transmitted infections. These diseases have similar pathology and potentially similar genetic predisposing factors. We aimed to identify polymorphisms and pathways associated with pathological sequelae of ocular Chlamydia trachomatis infections in The Gambia. We report a discovery phase genome-wide association study (GWAS) of scarring trachoma (1090 cases, 1531 controls) that identified 27 SNPs with strong, but not genome-wide significant, association with disease (5 × 10−6 > P > 5 × 10−8). The most strongly associated SNP (rs111513399, P = 5.38 × 10−7) fell within a gene (PREX2) with homology to factors known to facilitate chlamydial entry to the host cell. Pathway analysis of GWAS data was significantly enriched for mitotic cell cycle processes (P = 0.001), the immune response (P = 0.00001) and for multiple cell surface receptor signalling pathways. New analyses of published transcriptome data sets from Gambia, Tanzania and Ethiopia also revealed that the same cell cycle and immune response pathways were enriched at the transcriptional level in various disease states. Although unconfirmed, the data suggest that genetic associations with chlamydial scarring disease may be focussed on processes relating to the immune response, the host cell cycle and cell surface receptor signalling.
Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in InsrP1195L/+ mice fed high-fat-diet
Authors: Lee Eun Young , Sakurai Kenichi , Zhang Xilin , Toda Chitoku , Tanaka Tomoaki , Jiang Meizi , Shirasawa Takuji , Tachibana Kaori , Yokote Koutaro , Vidal-Puig Antonio , Minokoshi Yasuhiko , Miki Takashi
Published: November 2015

High-fat diet (HFD) triggers insulin resistance and diabetes mellitus, but their link remains unclear. Characterization of overt hyperglycemia in insulin receptor mutant (InsrP1195L/+) mice exposed to HFD (InsrP1195L/+/HFD mice) revealed increased glucose-6-phosphatase (G6pc) expression in liver and increased gluconeogenesis from glycerol. Lipolysis in white adipose tissues (WAT) and lipolysis-induced blood glucose rise were increased in InsrP1195L/+/HFD mice, while wild-type WAT transplantation ameliorated the hyperglycemia and the increased G6pc expression. We found that the expressions of genes involved in bile acid (BA) metabolism were altered in InsrP1195L/+/HFD liver. Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in InsrP1195L/+/HFD liver. Reduced Cyp7a1 expression in InsrP1195L/+/HFD liver was rescued by WAT transplantation and the expression of Cyp7a1 was suppressed by glycerol administration in wild-type liver. These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in InsrP1195L/+/HFD liver.
The role of Drosophila mismatch repair in suppressing recombination between diverged sequences
Authors: Do Anthony T. , LaRocque Jeannine R.
Published: November 2015

DNA double-strand breaks (DSBs) must be accurately repaired to maintain genomic integrity. DSBs can be repaired by homologous recombination (HR), which uses an identical sequence as a template to restore the genetic information lost at the break. Suppression of recombination between diverged sequences is essential to the repair of DSBs without aberrant and potentially mutagenic recombination between non-identical sequences, such as Alu repeats in the human genome. The mismatch repair (MMR) machinery has been found to suppress recombination between diverged sequences in murine cells. To test if this phenomenon is conserved in whole organisms, two DSB repair systems were utilized in Drosophila melanogaster. The DR-white and DR-white.mu assays provide a method of measuring DSB repair outcomes between identical and diverged sequences respectively. msh6–/– flies, deficient in MMR, were not capable of suppressing recombination between sequences with 1.4% divergence and the average gene conversion tract length did not differ between msh6–/+ and msh6–/–flies. These findings suggest that MMR has an early role in suppressing recombination between diverged sequences that is conserved in Drosophila.
Synthesis of glycosylphosphatidylinositol (GPI)-anchor glycolipids bearing unsaturated lipids
Authors: Lee B.-Y. , Seeberger P. H. , Varon Silva D.
Published: November 2015

A new strategy involving 2-naphthyl-methyl ethers as permanent protecting groups and their easy removal under acidic conditions is the key to the synthesis of complex glycosylphosphatidylinositol glycolipids containing unsaturated lipids.
Extending human perception of electromagnetic radiation to the UV region through biologically inspired photochromic fuzzy logic (BIPFUL) systems
Authors: Gentili Pier Luigi , Rightler Amanda L. , Heron B. Mark , Gabbutt Christopher D.
Published: November 2015

Biologically inspired fuzzy logic systems allow us to detect and discern UV frequencies.
Mechanistic studies of the reactions of the reduced vitamin B12derivatives with the HNO donor Piloty's acid: further evidence for oxidation of cob(i)alamin by (H)NO
Authors: Subedi Harishchandra , Brasch Nicola E.
Published: November 2015

Kinetic data and product analyses support a mechanism in which cob(II)alamin (Cbl(ii)˙) is reduced by (H)NO to give cob(i)alamin (Cbl(i)−) and ˙NO. Cbl(i)−is subsequently oxidized back to Cbl(ii)˙ by a second (H)NO molecule, and Cbl(ii)˙ reacts rapidly with ˙NO to form nitroxylcobalamin, NOCbl.
Ligand noninnocence in FeNO corroles: insights from β-octabromocorrole complexes
Authors: Norheim Hans-Kristian , Capar Jan , Einrem Rune F. , Gagnon Kevin J. , Beavers Christine M. , Vazquez-Lima Hugo , Ghosh Abhik
Published: November 2015

With a noninnocent {FeNO}7-(corrole˙2−) formulation, the first FeNO octabromocorrole derivatives deepen our appreciation of ligand noninnocence.
Fly ash in landfill top covers – a review
Authors: Brännvall E. , Kumpiene J.
Published: November 2015

Increase of energy recovery from municipal solid waste by incineration results in the increased amounts of incineration residues, such as fly ash, that have to be taken care of.