bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes Susceptibility in the Canadian Oji-Cree Population Is Moderated by Abnormal mRNA Processing of HNF1A G319S Transcripts
Authors: Harries Lorna W. , Sloman Melissa J. , Sellers Elizabeth A.C. , Hattersley Andrew T. , Ellard Sian
Published: April 2008

OBJECTIVE—The G319S HNF1A variant is associated with an increased risk of type 2 diabetes in the Canadian Oji-Cree population. We hypothesized that the variant site at the 3′ end of exon 4 might influence splicing and characterized mRNA transcripts to investigate the mutational mechanism underlying this susceptibility to diabetes.

RESEARCH DESIGN AND METHODS—We established lymphoblastoid cell lines from a G319S homozygote and controls. HNF1A transcripts were characterized in the cell lines and pancreatic tissue by sequence analysis of RT-PCR products and quantification using real-time PCR. Susceptibility to mRNA surveillance was investigated using cycloheximide.

RESULTS—Full-length G319S mRNA accounted for 24% of mRNA transcripts in the homozygous G319S cell line. A novel isoform lacking the terminal 12 bases of exon 4 was upregulated (55% of mRNA transcripts) compared with control cell lines (33%) and human pancreatic tissue (17%). Two abnormal transcripts present only in the G319S cell line included premature termination codons as a result of the inclusion of seven nucleotides from intron 4 or the deletion of exon 8. Cycloheximide treatment increased the levels of both transcripts.

CONCLUSIONS—The G319S variant results in the production of two abnormal transcripts and an alteration in the relative balance of normal splicing products. This is predicted to lead to a reduction in total HNF1A transcript levels, but residual hepatocyte nuclear factor-1α protein activity in G319S homozygotes may still reach up to 66% of normal levels. A combination of abnormal splicing and reduced activity of the G319S protein may explain the diabetes susceptibility.
Ferrite transformation from oxide–steel interface in HAZ-simulated C–Mn steel
Authors: Koseki Toshihiko , Kato Hiroki , Tsutsumi Masanori , Kasai Keiichiro , Inoue Junya
Published: April 2008

In steel weld metals and their heat affected zones, acicular ferrite or intragranular ferrite developed on selected oxide inclusions within prior austenite is a key to refining the microstructure and hence improving the toughness. In this study, to obtain a better understanding of the mechanism of the intragranular ferrite formation, different oxides were deposited onto C – Mn steel by a physical vapor deposition process, and ferrite formation was examined at the different oxide – steel interfaces after an HAZ-simulated thermal cycle. TiO, MgO, CaO and Al2O3 were deposited on C – Mn steel containing 0.16% C and 1.4% Mn and then they were heated up to 1623 K and cooled down at a cooling rate of 20 K s−1. Allotriomorphic ferrite was found to develop from TiO and MgO, while no allotriomorphic ferrite but Widmanstätten ferrite formed from CaO and Al2O3. Electron backscatter diffraction pattern analysis indicates that the allotriomorphic ferrite growing from the oxide has a specific orientation relationship either with the oxide or with prior-austenite. In the former case, the ferrite seems to be aligned so as to minimize the misfit against the oxide, implying that the likelihood of ferrite formation can be increased by the oxides having a good lattice match with ferrite. Manganese depletion was identified in the vicinity of TiO, but it is concluded that, although it encourages ferrite formation from the oxide, it is not a critical factor for the ferrite formation because of the fact that the ferrite formation was even found from TiO in manganese-free steel. First principles calculation indicates that the interfacial energy between oxide and steel is reduced when the magnesium in MgO is replaced by titanium, which suggests that the ferrite formation from TiO is also affected by the chemical effect of titanium.
Influence of metastable tetragonal ZrO2-reinforcements on the properties of MoSi2-composites
Authors: Bauer Johannes T. , Scholz Alfred , Berger Christina , Weiler Ludwig , Achtermann Matthias
Published: April 2008

In this work, MoSi2 – ZrO2-composites with different volume fractions (15-, 25-, 35 vol.% ZrO2) were examined. Zirconium oxide was successfully tetragonal stabilised (metastable state) through a high temperature isostatic pressure process, where the tetragonal – monoclinic phase transformation is inhibited by the pressure of the MoSi2-matrix. Stabilisers, e. g. Y2O3 were not used. Increasing ZrO2 content enhances strength and fracture toughness at room temperature. For temperatures above 900°C up to 1500°C no influence of the volume fraction of ZrO2 was observed with respect to the compression tests. Wear of pre-oxidised samples (20 min at 1000°C) is higher for the 25 and 35 vol.% than non-oxidised material. Oxidation resistance is observed to be poor and decreases with increasing ZrO2 content in the composite. Early crack initiation leads to poor creep behaviour and thermo-shock behaviour. This is probably due to the oxygen diffusing through the ZrO2-particles. Consequently no continuous protective SiO2-layer can be built as known from pure MoSi2-materials. In general the investigated material is not suitable for high temperature applications because of the poor oxidation behaviour.
Precipitation behaviour of an Fe–Co–Mo-alloy during non-isothermal ageing
Authors: Leitner H. , Schober M. , Clemens H. , Caliskanoglu D. , Danoix F.
Published: April 2008

Fe – Co – Mo alloys show hardening behaviour comparable to that of precipitation hardened Al-alloys, which is characterised by a low hardness after solution annealing and a significant increase in the hardness during subsequent ageing at higher temperatures. In this study, the precipitation behaviour of Fe-25% Co-15% Mo (wt.%) has been studied applying non-isothermal ageing. High sensitivity differential scanning calorimetry and atom probe tomography have been used to characterise the precipitation sequence. Three overlapping exothermic reactions, which are related to precipitation reactions, are observed in the temperature range of 400 to 700°C. The investigations have shown that precipitation starts with diffusion of Mo, followed by the formation of the intermetallic μ-phase which reaches its equilibrium composition at a temperature of about 615°C.
Effect of boron on creep deformation behavior and microstructure evolution in 9% Cr steel at 650°C
Authors: Abe Fujio
Published: April 2008

The effect of boron on creep deformation behavior and microstructure evolution during creep has been investigated for a tempered martensitic 9Cr-3W-3Co-VNb steel containing boron up to 140 ppm at 650°C (923 K) with the emphasis on long term behavior. Creep tests were carried out at 650°C for up to about 70 000 h. The base steel without boron exhibits degradation in creep rupture strength after times above about 1000 h. The addition of boron retards the onset of tertiary or acceleration creep, where the creep rate increases with time after reaching a minimum creep rate, at low stresses and long times. This effectively decreases the minimum creep rate and increases the time to rupture. The addition of boron reduces the coarsening rate of Ostwald ripening of M23C6 carbides near prior austenite grain boundaries during creep, which retards the onset of acceleration creep. It is considered that boron atoms occupy vacancies in the vicinity of growing carbide interfaces near prior austenite grain boundaries, which makes it difficult to accommodate local volume change around growing carbides and hence causes the reduction in coarsening rate.
The L2 norm of the deviation between the measured and computed transient displacement field in a test weld
Authors: Goldak John , Johnsson Eric , El-Zein Mohamad , Zhou Jianguo , Tchernov Stanislav , Downey Dan , Wang Shaodong , Coulombe Mark
Published: April 2008

The transient displacement field caused by an arc weld was measured experimentally with an Aramis stereo-camera. The transient displacement field was also predicted using a computational weld mechanics program called VrWeld for ten different sets of model parameters. The objective was to identify the effect of model parameters on the deviation between experimental data and the data computed by computational weld mechanics. For each set of model parameters, the L2 norm of the difference between the experimental and computed displacement fields was computed for each of the 800 time steps. The structure being welded was a mm stringer fillet welded to a mm low alloy steel plate. The displacement field was measured on the ‘back’ surface of the plate. A robot made the metal-inert-gas weld. The parameters varied in the ten models included welding current, width of the power density distribution, convection coefficient and yield stress of austenite at high temperatures.
Bench‐scale evaluation of nonvolatilealpha‐branched chain fatty esters as potential lubricants
Authors: Ault Waldo C. , Parker Winfred E. , Eisner Abner , Koos R. E. , Knight H. B.
Published: April 2008

Several nonvolatile esters of α‐branched fatty acids have been prepared in a highly purified state and examined by bench‐scale tests of the sort usually used in the preliminary evaluation of lubricants. Viscosity characteristics and Shell‐Boerlage wear‐test results for these compounds are comparable with those of compounds used in the manufacture of modern synthetic lubricants. These esters are substantially superior to one such compound in thermal stability and resistance to acid hydrolysis.
Cyanoethylation of hydroxy derivatives of fats
Authors: Maerker G. , Kenney H. E. , Donahue E. T.
Published: April 2008

Mono‐, di‐, and trihydroxy derivatives of fats have been cyanoethylated in high yields by use of excess acrylonitrile as solvent and aqueous benzyltrimethylammonium hydroxide as catalyst. Reaction variables of the cyanoethylation in excess acrylonitrile have been examined with methyl 12‐hydroxystearate as the model compound. At moderate reaction temperatures the cyanoethylation reaction is 93% complete before the competing polymerization of the acrylonitrile consumes the catalyst.
Urethane foams from animal fats. IV. Rigid foams from epoxidized glycerides
Authors: Scholnick F. , Saggese E. J. , Wrigley A. N. , Ault W. C. , Monroe H. A. , Zubillaga M.
Published: April 2008

Liquid polyols have been prepared from epoxidized glyceryl trioleate, glyceryl monooleate, lard oil, neatsfoot oil, and soybean oil by hydration with 24% fluoboric acid. Upon adjustment of the equivalent weight to 100 with triisopropanolamine, the polyols were foamed by reaction with a prepolymer made from oxypropylated sorbitol and tolylene diisocyanate. The resulting rigid foams had densities between 1.66 and 2.34 lbs/ft3 and compressive strengths ranging from 23 to 39 psi (10% compression).

The same polyols were used in one‐step systems with PAPI as the isocyanate. In general, foam properties were comparable with those obtained from the prepolymer systems.
The action of various lime soap dispersants
Authors: Schönfeldt N.
Published: April 2008

The course of the lime soap‐dispersing action of various surfactants has been examined by use of a titrimetric method. Two types of dispersants can be distinguished. With the addition of a surfactant of the first type, the concentration of the dispersed fatty acid increases gradually. If a surfactant of the second type is used, a definite increase of the fatty acid concentration first occurs after the addition of considerable amounts of the dispersant.

Ethylene oxide adducts and sodium triethylene glycol monolauryl ether sulfate behave like dispersants of the first type whereas sodium dodecylbenzenesulphonate and sodium lauryl sulfate belong to those of the second type. The dispersing action of both types of surfactants is discussed.
Comparison of soil‐deposition and redeposition tests in evaluating drycleaning detergents
Authors: Smith William H. , Wentz Manfred , Martin Albert R.
Published: April 2008

A method for testing drycleaning detergents for their ability to inhibit soil redeposition is described. It involves the measurement of soil transfer from a soiled to a clean fabric. The customary practice of using suspensions of a model soil in a detergent solution is a soil‐deposition test and does not give results comparable with the soil‐redeposition test.

The major argument against redeposition tests in the past has been that they do not permit two detergents to be compared at the same soil concentration in the suspension. It is therefore argued that redeposition tests “stack the cards” against better detergents because soil must be removed before it can be redeposited. Present results refute this argument and show that detergents exhibiting low soil‐removal generally show high graying and vice versa. These two qualities either correlate or they are two aspects of the same quality.

A possible explanation for the difference between the two test procedures is that the degree of dispersion of soil is much greater in the redeposition test.
Rapeseed oil in a two‐component margarine base stock
Authors: Zalewski Stanislaw , Kummerow F. A.
Published: April 2008

A two‐component margarine base stock with liquid oil as one component allowed for a lowertransfatty acid content and at the same time provided for a higher essential fatty acid level than a one‐component base stock. Transesterification softened a two‐component margarine base stock and resulted in a steeper solid fat index curve, but did allow for a lowertransfatty acid level in a margarine base stock. The high content of erucic acid in rapeseed oil did not change the physical properties of a margarine base stock and provided a good hardstock when this oil was hydrogenated. The use of a hydrogenated rapeseed oil ensured interchangeability of liquid oils in blends and rearranged blends, also seemed superior to soybean hardstocks in this respect.
Color problems in oils from experimental safflower varieties
Authors: Burkhardt H. J.
Published: April 2008

The dark color found in extracted oils from two new thin‐hull safflower varieties is formed from a colorless precursor or precursors, which for convenience will be considered a single precursor. This precursor is extracted into the oil from the kernel portion of the seed with hot hexane. It condenses to a dark pigment, if heated for prolonged times in excess of 100C, and was found in varying amounts in hot extracted oils of pigmentless, brown‐striped, and commercially grown Gila varieties. The color precursor can be removed from the oil by extraction with water or by alkali‐refining. The dark pigment can be removed by treatment with dilute alkaline peroxide. Oil, free of pigment and pigment precursor, can be obtained if the press‐cake or whole cracked seeds are extracted with hexane at room temperature.
Reconceptualizing the effects of lean on production costs with evidence from the F‐22 program
Authors: Browning Tyson R. , Heath Ralph D.
Published: April 2008

A central tenet in the theory of lean production is that the implementation of lean practices will reduce waste and thereby decrease costs. However, not all lean implementations have produced such results. Apparently, this effect is moderated by several factors, potentially even to the point of reversal. It is important to increase our understanding of how this might occur. In this paper, we explore how novelty, complexity, instability, and buffering affect the relationship between lean implementation and production costs. An interest in these factors drew us to study the case of Lockheed Martin's production system for the F‐22, an extremely complex and innovative product. To build theory, we synthesize our empirical data from the case with other existing theory, such as theories of learning and complexity. Through this analysis, we develop a revised framework that reconceptualizes the effect of lean on production costs and use it to develop 11 propositions to direct further research. Included among these are propositions about how the timing, scale, and extent of lean implementation can regulate the benefits of lean. Furthermore, when the objective of lean is construed as the provision of value, we propose that this value is an emergent property of a complex process, different from the mere sum of the values provided by its constituent tasks. Therefore, the elimination of tasks will not guarantee cost reduction, and lean may provide even greater value by incorporating some aspects of agile manufacturing. Overall, we develop a fuller range of the effects of lean practices on production costs and illuminate how operations managers might control key variables to draw greater benefits from lean implementation.
Gelb oder kein Gelb?
Authors: Memmert Daniel , Unkelbach Christian , Ertmer Julia , Rechner Michael
Published: April 2008

Zusammenfassung. In einer Datenbankanalyse wird gezeigt, dass in der ersten Viertelstunde eines Fußballspiels signifikant weniger persönliche Verwarnungen (“gelbe Karten”) ausgesprochen werden als im Rest des Spiels. Neben pragmatischen Gründen (z. B. keine Wiederholungsfouls zu Beginn) erklären wir diesen Effekt als Resultat einer notwendigen Kalibrierung der Schiedsrichter. Nach dem Konsistenzmodell ( Haubensak, 1992a ) für solche Urteile entwickeln Menschen (Schiedsrichterinnen und Schiedsrichter) zu Beginn einer Stimulusserie (des Spiels) eine Urteilsskala und verwenden diese konsistent (über die gesamte Spielzeit). Diese Urteilsskala muss zunächst kalibriert werden: würden leichte Vergehen zu Beginn als “gelbe Karte” klassifiziert, müssten alle nachfolgenden Vergehen gleicher oder größerer Schwere ebenfalls zu gelben Karten führen. Da aber eine Norm herrscht, persönliche Verwarnungen sparsam einzusetzen, können zu Beginn des Spiels nur wenige gelbe Karten vergeben werden; d. h. objektiv sollte für ein Vergehen zu Beginn mit höherer Wahrscheinlichkeit eine gelbe Karte gegeben werden als dies realiter der Fall ist. Diese Vorhersage wurde in einem Experiment getestet und die Implikationen für die Urteilssituation von Schiedsrichterinnen und Schiedsrichtern werden diskutiert.
Fairness im Fußball
Authors: Herrmann Mario , Dalbert Claudia , Stoll Oliver
Published: April 2008

Zusammenfassung. In einer Fragebogenstudie an 117 Fußballspielern aus 14 Fußballvereinen wurden individuelle Unterschiede in der Fairness im Fußball untersucht und die Hypothese getestet, dass Fairness im Fußball sowohl auf intuitiver als auch auf kontrollierter Ebene durch das Streben nach Gerechtigkeit (Gerechtigkeitsmotiv) erklärt werden kann. Hierbei wurde zwischen der Bereitschaft zu taktischen Regelverstößen (zu formeller Unfairness) sowie zu informeller Fairness unterschieden. Beide Dispositionen konnten durch das Gerechtigkeitsmotiv sowie durch Gerechtigkeitserfahrungen mit Schiedsrichtern erklärt werden und das Gerechtigkeitsmotiv hing positiv mit Gerechtigkeitskognitionen bezüglich Schiedsrichtern, Trainern und Mannschaftskameraden zusammen. Regelverstöße wurden jedoch ausschließlich durch Gerechtigkeitserfahrungen mit Schiedsrichtern aufgeklärt. Leistungsmotiv und Tabellenposition sowie Gerechtigkeitserfahrungen mit Trainer und Mannschaftskameraden konnten wenig zur Erklärung beitragen. Die Ergebnisse werden vor dem Hintergrund der Gerechtigkeitsmotivtheorie und Überlegungen zur Bedeutung des Exklusionsempfindens diskutiert.
Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane
Authors: Engel Maarten F. M. , Khemtémourian Lucie , Kleijer Cécile C. , Meeldijk Hans J. D. , Jacobs Jet , Verkleij Arie J. , de Kruijff Ben , Killian J. Antoinette , Höppener Jo W. M.
Published: April 2008

Fibrillar protein deposits (amyloid) in the pancreatic islets of Langerhans are thought to be involved in death of the insulin-producing islet β cells in type 2 diabetes mellitus. It has been suggested that the mechanism of this β cell death involves membrane disruption by human islet amyloid polypeptide (hIAPP), the major constituent of islet amyloid. However, the molecular mechanism of hIAPP-induced membrane disruption is not known. Here, we propose a hypothesis that growth of hIAPP fibrils at the membrane causes membrane damage. We studied the kinetics of hIAPP-induced membrane damage in relation to hIAPP fibril growth and found that the kinetic profile of hIAPP-induced membrane damage is characterized by a lag phase and a sigmoidal transition, which matches the kinetic profile of hIAPP fibril growth. The observation that seeding accelerates membrane damage supports the hypothesis. In addition, variables that are well known to affect hIAPP fibril formation, i.e., the presence of a fibril formation inhibitor, hIAPP concentration, and lipid composition, were found to have the same effect on hIAPP-induced membrane damage. Furthermore, electron microscopy analysis showed that hIAPP fibrils line the surface of distorted phospholipid vesicles, in agreement with the notion that hIAPP fibril growth at the membrane and membrane damage are physically connected. Together, these observations point toward a mechanism in which growth of hIAPP fibrils, rather than a particular hIAPP species, is responsible for the observed membrane damage. This hypothesis provides an additional mechanism next to the previously proposed role of oligomers as the main cytotoxic species of amyloidogenic proteins.
Cassandraretrotransposons carry independently transcribed 5S RNA
Authors: Kalendar Ruslan , Tanskanen Jaakko , Chang Wei , Antonius Kristiina , Sela Hanan , Peleg Ofer , Schulman Alan H.
Published: April 2008

We report a group of TRIMs (terminal-repeat retrotransposons in miniature), which are small nonautonomous retrotransposons. These elements, namedCassandra, universally carry conserved 5S RNA sequences and associated RNA polymerase (pol) III promoters and terminators in their long terminal repeats (LTRs). They were found in all vascular plants investigated. Uniquely for LTR retrotransposons,Cassandraproduces noncapped, polyadenylated transcripts from the 5S pol III promoter. Capped, read-through transcripts containingCassandrasequences can also be detected in RNA and in EST databases. The predictedCassandraRNA 5S secondary structures resemble those for cellular 5S rRNA, with high information content specifically in the pol III promoter region. Genic integration sites are common forCassandra, an unusual feature for abundant retrotransposons. The 5S in each LTR produces a tandem 5S arrangement with an inter-5S spacing resembling that of cellular 5S. The distribution of 5S genes is very variable in flowering plants and may be partially explained byCassandraactivity. Cassandra thus appears both to have adapted a ubiquitous cellular gene for ribosomal RNA for use as a promoter and to parasitize an as-yet-unidentified group of retrotransposons for the proteins needed in its lifecycle.
Proton order in the ice crystal surface
Authors: Buch V. , Groenzin H. , Li I. , Shultz M. J. , Tosatti E.
Published: April 2008

The physics of the ice crystal surface and its interaction with adsorbates are not only of fundamental interest but also of considerable importance to terrestrial and planetary chemistry. Yet the atomic-level structure of even the pristine ice surface at low temperature is still far from well understood. This computational study focuses on the pattern of dangling H and dangling O (lone pairs) atoms at the basal ice surface. Dangling atoms serve as binding sites for adsorbates capable of hydrogen- and electrostatic bonding. Extension of the well known orientational disorder (“proton disorder”) of bulk crystal ice to the surface would naturally suggest a disordered dangling atom pattern; however, extensive computer simulations employing two different empirical potentials indicate significant free energy preference for a striped phase with alternating rows of dangling H and dangling O atoms, as suggested long ago by Fletcher [Fletcher NH (1992)
Philos Mag
66:109–115]. The presence of striped phase domains within the basal surface is consistent with the hitherto unexplained minor fractional peaks in the helium diffraction pattern observed 10 years ago. Compared with the disordered model, the striped model yields improved agreement between computations and experimental
ppp
-polarized sum frequency generation spectra.
Nonuniform distribution of glucosinolates in
Arabidopsis thaliana
leaves has important consequences for plant defense
Authors: Shroff Rohit , Vergara Fredd , Muck Alexander , Svatoš Aleš , Gershenzon Jonathan
Published: April 2008

The spatial distribution of plant defenses within a leaf may be critical in explaining patterns of herbivory. The generalist lepidopteran larvae,
Helicoverpa armigera
(the cotton bollworm), avoided the midvein and periphery of
Arabidopsis thaliana
rosette leaves and fed almost exclusively on the inner lamina. This feeding pattern was attributed to glucosinolates because it was not evident in a myrosinase mutant that lacks the ability to activate glucosinolate defenses by hydrolysis. To measure the spatial distribution of glucosinolates in
A. thaliana
leaves at a fine scale, we constructed ion intensity maps from MALDI-TOF (matrix assisted laser desorption/ionization-time of flight) mass spectra. The major glucosinolates were found to be more abundant in tissues of the midvein and the periphery of the leaf than the inner lamina, patterns that were validated by HPLC analyses of dissected leaves. In addition, there were differences in the proportions of the three major glucosinolates in different leaf regions. Hence, the distribution of glucosinolates within the leaf appears to control the feeding preference of
H. armigera
larvae. The preferential allocation of glucosinolates to the periphery may play a key role in the defense of leaves by creating a barrier to the feeding of chewing herbivores that frequently approach leaves from the edge.
An essential sensor histidine kinase controlled by transmembrane helix interactions with its auxiliary proteins
Authors: Szurmant Hendrik , Bu Lintao , Brooks Charles L. , Hoch James A.
Published: April 2008

Two-component signal transduction systems with membrane-embedded sensor histidine kinases are believed to recognize environmental signals and transduce this information over the cellular membrane to influence the activity of a transcription factor to which they are mated. The YycG sensor kinase of
Bacillus subtilis
, containing two transmembrane helices, is subject to a complicated activity-control circuit involving two other proteins with N-terminal transmembrane helices, YycH and YycI. Truncation studies of YycH and YycI demonstrated that the individual transmembrane helices of these proteins are sufficient to adjust YycG activity, indicating that this control is achieved at the membrane level. A replica exchange molecular dynamics computational approach generated
in silico
structural models of the transmembrane helix complex that informed mutagenesis studies of the YycI transmembrane helix supporting the accuracy of the
in silico
model. The results predict that signal recognition by any of the extracellular domains of the sensor histidine kinase YycG or the associated proteins YycH and YycI is transmitted across the cellular membrane by subtle alterations in the positions of the helices within the transmembrane complex of the three proteins.
An overlapping essential gene in the Potyviridae
Authors: Chung Betty Y.-W. , Miller W. Allen , Atkins John F. , Firth Andrew E.
Published: April 2008

The family
Potyviridae
includes >30% of known plant virus species, many of which are of great agricultural significance. These viruses have a positive sense RNA genome that is ≈10 kb long and contains a single long ORF. The ORF is translated into a large polyprotein, which is cleaved into ≈10 mature proteins. We report the discovery of a short ORF embedded within the P3 cistron of the polyprotein but translated in the +2 reading-frame. The ORF, termed
pipo
, is conserved and has a strong bioinformatic coding signature throughout the large and diverse
Potyviridae
family. Mutations that knock out expression of the PIPO protein in Turnip mosaic potyvirus but leave the polyprotein amino acid sequence unaltered are lethal to the virus. Immunoblotting with antisera raised against two nonoverlapping 14-aa antigens, derived from the PIPO amino acid sequence, reveals the expression of an ≈25-kDa PIPO fusion product
in planta
. This is consistent with expression of PIPO as a P3-PIPO fusion product via ribosomal frameshifting or transcriptional slippage at a highly conserved G
1-2
A
6-7
motif at the 5′ end of
pipo
. This discovery suggests that other short overlapping genes may remain hidden even in well studied virus genomes (as well as cellular organisms) and demonstrates the utility of the software package MLOGD as a tool for identifying such genes.
The genome of
Bacillus coahuilensis
reveals adaptations essential for survival in the relic of an ancient marine environment
Authors: Alcaraz Luis David , Olmedo Gabriela , Bonilla Germán , Cerritos René , Hernández Gustavo , Cruz Alfredo , Ramírez Enrique , Putonti Catherine , Jiménez Beatriz , Martínez Eva , López Varinia , Arvizu Jacqueline L. , Ayala Francisco , Razo Francisco , Caballero Juan , Siefert Janet , Eguiarte Luis , Vielle Jean-Philippe , Martínez Octavio , Souza Valeria , Herrera-Estrella Alfredo , Herrera-Estrella Luis
Published: April 2008

The Cuatro Ciénegas Basin (CCB) in the central part of the Chihuahan desert (Coahuila, Mexico) hosts a wide diversity of microorganisms contained within springs thought to be geomorphological relics of an ancient sea. A major question remaining to be answered is whether bacteria from CCB are ancient marine bacteria that adapted to an oligotrophic system poor in NaCl, rich in sulfates, and with extremely low phosphorus levels (<0.3 μM). Here, we report the complete genome sequence of
Bacillus coahuilensis
, a sporulating bacterium isolated from the water column of a desiccation lagoon in CCB. At 3.35 Megabases this is the smallest genome sequenced to date of a
Bacillus
species and provides insights into the origin, evolution, and adaptation of
B. coahuilensis
to the CCB environment. We propose that the size and complexity of the
B. coahuilensis
genome reflects the adaptation of an ancient marine bacterium to a novel environment, providing support to a “marine isolation origin hypothesis” that is consistent with the geology of CCB. This genomic adaptation includes the acquisition through horizontal gene transfer of genes involved in phosphorous utilization efficiency and adaptation to high-light environments. The
B. coahuilensis
genome sequence also revealed important ecological features of the bacterial community in CCB and offers opportunities for a unique glimpse of a microbe-dominated world last seen in the Precambrian.
Activity-dependent repression of muscle genes by NFAT
Authors: Rana Zaheer A. , Gundersen Kristian , Buonanno Andres
Published: April 2008

Adult skeletal muscles retain an adaptive capacity to switch between slow- and fast-twitch properties that largely depend on motoneuron activity. The NFAT (nuclear factor of activated T cells) family of calcium-dependent transcription factors has been implicated in the up-regulation of genes encoding slow contractile proteins in response to slow-patterned motoneuron depolarization. Here, we demonstrate an unexpected, novel function of NFATc1 in slow-twitch muscles. Using the troponin I fast (TnIf) intronic regulatory element (FIRE), we identified sequences that down-regulate its function selectively in response to patterns of electrical activity that mimic slow motoneuron firing. A bona fide NFAT binding site in the TnIf FIRE was identified by site-directed mutations and by electrophoretic mobility and supershift assays. The activity-dependent transcriptional repression of FIRE is mediated through this NFAT site and, importantly, its mutation did not alter the up-regulation of TnIf transcription by fast-patterned activity. siRNA-mediated knockdown of NFATc1 in adult muscles resulted in ectopic activation of the FIRE in the slow soleus, without affecting enhancer activity in the fast extensor digitorum longus muscle. These findings demonstrate that NFAT can function as a repressor of fast contractile genes in slow muscles and they exemplify how an activity pattern can increase or decrease the expression of distinct contractile genes in a use-dependent manner as to enhance phenotypic differences among fiber types or induce adaptive changes in adult muscles.
Parallel striatal and hippocampal systems for landmarks and boundaries in spatial memory
Authors: Doeller Christian F. , King John A. , Burgess Neil
Published: April 2008

How the memory systems centered on the hippocampus and dorsal striatum interact to support behavior remains controversial. We used functional MRI while people learned the locations of objects by collecting and replacing them over multiple trials within a virtual environment comprising a landmark, a circular boundary, and distant cues for orientation. The relative location of landmark and boundary was occasionally changed, with specific objects paired with one or other cue, allowing dissociation of learning and performance relative to either cue. Right posterior hippocampal activation reflected learning and remembering of boundary-related locations, whereas right dorsal striatal activation reflected learning and remembering of landmark-related locations. Within the right hippocampus, anterior processing of environmental change (spatial novelty) was dissociated from posterior processing of location. Behavioral studies show that landmark-related learning obeys associative reinforcement, whereas boundary-related learning is incidental [Doeller CF, Burgess N (2008)
Proc Natl Acad Sci USA
105:5909–5914]. The distinct incidental hippocampal processing of boundaries is suggestive of a “geometric module” or “cognitive map” and may explain the hippocampal support of incidental/observational learning in “declarative” or “episodic” memory versus the striatal support of trial-and-error learning in “procedural” memory. Finally, the hippocampal and striatal systems appear to combine “bottom-up,” simply influencing behavior proportional to their activations, without direct interaction, with “top-down” ventromedial prefrontal involvement when both are similarly active.
Conservation analysis predicts
in vivo
occupancy of glucocorticoid receptor-binding sequences at glucocorticoid-induced genes
Authors: So Alex Yick-Lun , Cooper Samantha B. , Feldman Brian J. , Manuchehri Mitra , Yamamoto Keith R.
Published: April 2008

The glucocorticoid receptor (GR) interacts with specific GR-binding sequences (GBSs) at glucocorticoid response elements (GREs) to orchestrate transcriptional networks. Although the sequences of the GBSs are highly variable among different GREs, the precise sequence within an individual GRE is highly conserved. In this study, we examined whether sequence conservation of sites resembling GBSs is sufficient to predict GR occupancy of GREs at genes responsive to glucocorticoids. Indeed, we found that the level of conservation of these sites at genes up-regulated by glucocorticoids in mouse C3H10T1/2 mesenchymal stem-like cells correlated directly with the extent of occupancy by GR. In striking contrast, we failed to observe GR occupancy of GBSs at genes repressed by glucocorticoids, despite the occurrence of these sites at a frequency similar to that of the induced genes. Thus, GR occupancy of the GBS motif correlates with induction but not repression, and GBS conservation alone is sufficient to predict GR occupancy and GRE function at induced genes.
Mitochondrial heteroplasmy and the evolution of insecticide resistance: Non-Mendelian inheritance in action
Authors: Van Leeuwen Thomas , Vanholme Bartel , Van Pottelberge Steven , Van Nieuwenhuyse Pieter , Nauen Ralf , Tirry Luc , Denholm Ian
Published: April 2008

Genes encoded by mitochondrial DNA (mtDNA) exist in large numbers per cell but can be selected very rapidly as a result of unequal partitioning of mtDNA between germ cells during embryogenesis. However, empirical studies of this “bottlenecking” effect are rare because of the apparent scarcity of heteroplasmic individuals possessing more than one mtDNA haplotype. Here, we report an example of insecticide resistance in an arthropod pest (
Tetranychus urticae
) being controlled by mtDNA and on its inheritance in a heteroplasmic mite strain. Resistance to the insecticide bifenazate is highly correlated with remarkable mutations in cytochrome
b
, a mitochondrially encoded protein in the respiratory pathway. Four sites in the Q
o
site that are absolutely conserved across fungi, protozoa, plants, and animals are mutated in resistant mite strains. Despite the unusual nature of these mutations, resistant mites showed no fitness costs in the absence of insecticide. Partially resistant strains, consisting of heteroplasmic individuals, transmit their resistant and susceptible haplotypes to progeny in highly variable ratios consistent with a sampling bottleneck of ≈180 copies. Insecticide selection on heteroplasmic individuals favors those carrying resistant haplotypes at a frequency of 60% or more. This combination of factors enables very rapid evolution and accounts for mutations being fixed in most field-collected resistant strains. The results provide a rare insight into non-Mendelian mechanisms of mitochondrial inheritance and evolution, relevant to anticipating and understanding the development of other mitochondrially encoded adaptations in arthropods. They also provide strong evidence of cytochrome
b
being the target site for bifenazate in spider mites.
Universality of random energy model-like ageing in mean field spin glasses
Authors: Ben Arous Gérard , Bovier Anton , Černý Jiří
Published: April 2008

Ageing has become the paradigm for describing dynamical behavior of glassy systems, and
in particular spin glasses. Trap models have been introduced as simple caricatures of the
effective dynamics of such systems. In this Letter we show that in a wide class of mean field
models and on a wide range of time scales, ageing occurs precisely as predicted by the
random energy model-like trap model of Bouchaud and Dean. This is the first rigorous
result concerning ageing in mean field models other than the random energy model and the
spherical model.
Divisive Correlation Clustering Algorithm (DCCA) for grouping of genes: detecting varying patterns in expression profiles
Authors: Bhattacharya Anindya , De Rajat K.
Published: April 2008

Motivation: Cluster analysis (of gene-expression data) is a useful tool for identifying biologically relevant groups of genes that show similar expression patterns under multiple experimental conditions. Various methods have been proposed for clustering gene-expression data. However most of these algorithms have several shortcomings for gene-expression data clustering. In the present article, we focus on several shortcomings of conventional clustering algorithms and propose a new one that is able to produce better clustering solution than that produced by some others.

Results: We present the Divisive Correlation Clustering Algorithm (DCCA) that is suitable for finding a group of genes having similar pattern of variation in their expression values. To detect clusters with high correlation and biological significance, we use the correlation clustering concept introduced by Bansal et al. Our proposed algorithm DCCA produces a clustering solution without taking number of clusters to be created as an input. DCCA uses the correlation matrix in such a way that all genes in a cluster have highest average correlation with genes in that cluster. To test the performance of the DCCA, we have applied DCCA and some well-known conventional methods to an artificial dataset, and nine gene-expression datasets, and compared the performance of the algorithms. The clustering results of the DCCA are found to be more significantly relevant to the biological annotations than those of the other methods. All these facts show the superiority of the DCCA over some others for the clustering of gene-expression data.

Availability: The software has been developed using C and Visual Basic languages, and can be executed on the Microsoft Windows platforms. The software may be downloaded as a zip file from http://www.isical.ac.in/~rajat. Then it needs to be installed. Two word files (included in the zip file) need to be consulted before installation and execution of the software.

Contact:  rajat@isical.ac.in

Supplementary information:  Supplementary data are available at Bioinformatics online.
Individual Patient Data Meta‐Analysis of Survival and Psychosomatic Self‐Regulation from Published Prospective Controlled Cohort Studies for Long‐Term Therapy of Breast Cancer Patients with a Mistletoe Preparation (Iscador)
Authors: Ziegler R. , Grossarth-Maticek Ronald
Published: April 2008

Mistletoe preparations such as Iscador are in common use as complementary/anthroposophic medications for many cancer indications, particularly for solid cancers. The efficacy is still discussed controversially. This paper presents an individual patient data meta‐analysis of all published prospective matched‐pair studies with breast cancer patients concerned with long‐term application of a complementary/anthroposophic therapy with the mistletoe preparation Iscador. Six sets of data were available for individual patient meta‐analysis of breast cancer patients, matched according to prognostic factors into pairs with and without mistletoe (Iscador) therapy. The main outcome measures were overall survival and psychosomatic self‐regulation. Overall survival was almost significant in favor of the Iscador group in the combined data set of the randomized studies: estimate of the hazard ratio with 95% confidence interval 0.59 (0.34, 1.02). Overall survival was highly significant in the combined data set of the non‐randomized studies: 0.43 (0.34, 0.56). In the combined analysis of the randomized studies, improvement of psychosomatic self‐regulation, as a measure of autonomous coping with the disease, was highly significant in favor of the Iscador group: estimate of the median difference 0.45 (0.15, 0.80), P = 0.0051. The analyzed studies show that therapy with Iscador might prolong overall survival and improve psychosomatic self‐regulation of breast cancer patients.
Anaplastic, T-Cell, Non-Hodgkin's Lymphoma Presenting with Haematuria
Authors: Blick C. , Abdelhadi S. , Bailey D. , Muneer A.
Published: April 2008

Non-Hodgkin's lymphoma (NHL) represents about 3% of new cancer cases[1]. Bladder involvement has been found in approximately 3-13% of NHL patients when studied at postmortem[2]. Although accounting for only 0.2% of all primary bladder tumours, the majority of bladder lymphomas are B-cell lymphomas. T-cell lymphoma of the bladder is incredibly rare. We describe a case of anaplastic, T-cell lymphoma presenting with haematuria and loin pain, with unilateral upper tract obstruction.
Mutations inString/CDC25inhibit cell cycle re-entry and neurodegeneration in aDrosophilamodel of Ataxia telangiectasia
Authors: Rimkus Stacey A. , Katzenberger Rebeccah J. , Trinh Anthony T. , Dodson Gerald E. , Tibbetts Randal S. , Wassarman David A.
Published: April 2008

Mutations inATM(Ataxia telangiectasia mutated) result in Ataxia telangiectasia (A-T), a disorder characterized by progressive neurodegeneration. Despite advances in understanding how ATM signals cell cycle arrest, DNA repair, and apoptosis in response to DNA damage, it remains unclear why loss of ATM causes degeneration of post-mitotic neurons and why the neurological phenotype of ATM-null individuals varies in severity. To address these issues, we generated aDrosophilamodel of A-T. RNAi knockdown ofATMin the eye caused progressive degeneration of adult neurons in the absence of exogenously induced DNA damage. Heterozygous mutations in select genes modified the neurodegeneration phenotype, suggesting that genetic background underlies variable neurodegeneration in A-T. The neuroprotective activity of ATM may be negatively regulated by deacetylation since mutations in a protein deacetylase gene,RPD3, suppressed neurodegeneration, and a human homolog of RPD3, histone deacetylase 2, bound ATM and abrogated ATM activation in cell culture. Moreover, knockdown ofATMin post-mitotic neurons caused cell cycle re-entry, and heterozygous mutations in the cell cycle activator geneString/CDC25inhibited cell cycle re-entry and neurodegeneration. Thus, we hypothesize that ATM performs a cell cycle checkpoint function to protect post-mitotic neurons from degeneration and that cell cycle re-entry causes neurodegeneration in A-T.
Regulation of Dormancy in Barley by Blue Light and After-Ripening: Effects on Abscisic Acid and Gibberellin Metabolism
Authors: Gubler Frank , Hughes Trijntje , Waterhouse Peter , Jacobsen John
Published: April 2008

White light strongly promotes dormancy in freshly harvested cereal grains, whereas dark and after-ripening have the opposite effect. We have analyzed the interaction of light and after-ripening on abscisic acid (ABA) and gibberellin (GA) metabolism genes and dormancy in barley (Hordeum vulgare ‘Betzes’). Analysis of gene expression in imbibed barley grains shows that different ABA metabolism genes are targeted by white light and after-ripening. Of the genes examined, white light promotes the expression of an ABA biosynthetic gene, HvNCED1, in embryos. Consistent with this result, enzyme-linked immunosorbent assays show that dormant grains imbibed under white light have higher embryo ABA content than grains imbibed in the dark. After-ripening has no effect on expression of ABA biosynthesis genes, but promotes expression of an ABA catabolism gene (HvABA8′OH1), a GA biosynthetic gene (HvGA3ox2), and a GA catabolic gene (HvGA2ox3) following imbibition. Blue light mimics the effects of white light on germination, ABA levels, and expression of GA and ABA metabolism genes. Red and far-red light have no effect on germination, ABA levels, or HvNCED1. RNA interference experiments in transgenic barley plants support a role of HvABA8′OH1 in dormancy release. Reduced HvABA8′OH1 expression in transgenic HvABA8′OH1 RNAi grains results in higher levels of ABA and increased dormancy compared to nontransgenic grains.