bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice
Authors: Wu Min , Jung Lina , Cooper Adrian B. , Fleet Christina , Chen Lihao , Breault Lyne , Clark Kimberly , Cai Zuhua , Vincent Sylvie , Bottega Steve , Shen Qiong , Richardson Andrea , Bosenburg Marcus , Naber Stephen P. , DePinho Ronald A. , Kuperwasser Charlotte , Robinson Murray O.
Published: April 2009

Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.
Oxytocin is an anabolic bone hormone
Authors: Tamma Roberto , Colaianni Graziana , Zhu Ling-ling , DiBenedetto Adriana , Greco Giovanni , Montemurro Gabriella , Patano Nicola , Strippoli Maurizio , Vergari Rosaria , Mancini Lucia , Colucci Silvia , Grano Maria , Faccio Roberta , Liu Xuan , Li Jianhua , Usmani Sabah , Bachar Marilyn , Bab Itai , Nishimori Katsuhiko , Young Larry J. , Buettner Christoph , Iqbal Jameel , Sun Li , Zaidi Mone , Zallone Alberta
Published: April 2009

We report that oxytocin (OT), a primitive neurohypophyseal hormone, hitherto thought solely to modulate lactation and social bonding, is a direct regulator of bone mass. Deletion of OT or the OT receptor (Oxtr) in male or female mice causes osteoporosis resulting from reduced bone formation. Consistent with low bone formation, OT stimulates the differentiation of osteoblasts to a mineralizing phenotype by causing the up-regulation of BMP-2, which in turn controls
Schnurri-2
and
3
,
Osterix
, and
ATF-4
expression. In contrast, OT has dual effects on the osteoclast. It stimulates osteoclast formation both directly, by activating NF-κB and MAP kinase signaling, and indirectly through the up-regulation of RANK-L. On the other hand, OT inhibits bone resorption by mature osteoclasts by triggering cytosolic Ca
2+
release and NO synthesis. Together, the complementary genetic and pharmacologic approaches reveal OT as a novel anabolic regulator of bone mass, with potential implications for osteoporosis therapy.
Francis Whyte Ellis and the Beginning of Comparative Dravidian Linguistics
Authors: Sreekumar P.
Published: April 2009

This article assesses Francis Whyte Ellis’s (1777–1819) “Note to the Introduction” to Alexander Duncan Campbell’s (1789–1857)Grammar of the Teloogoo Language(1816) in the context of the history of comparative linguistics in India. The idea of a ‘South Indian family of languages’, later named ‘Dravidian’ by Robert Caldwell in 1856, was first proposed by Ellis in 1816, and so a case could be made to claim for him the beginnings of a comparative methodology in the study of Dravidian languages. Until now, in the history of comparative Dravidian linguistics Caldwell (1814–1891) has been celebrated as the pioneer in this field. The present study attempts to establish Ellis’s rightful place in this history by critically evaluating his contribution. The careful examination of the data presented by Ellis indeed suggests that he should be regarded as the discoverer of the Dravidian family of languages well before Caldwell.
Sentinel node detection in melanomas using contrast-enhanced ultrasound
Authors: Nielsen K. Rue , Klyver H. , Chakera A. Hougaard , Nedergaard L. , Hesse B. , Nielsen M. Bachmann
Published: April 2009

Background: Sentinel node (SN) biopsy has proven to be a useful clinical method based on the combination of radionuclide tracer principles and the dye technique. Contrast-enhanced ultrasound (CEUS) has been used successfully for detection of SN in animals, but the use of CEUS has not been reported in humans.

Purpose: To investigate the possible use of CEUS in detecting SN in patients with malignant melanomas (MM), and to improve the method by using different concentrations of contrast agent and various positions of the extremity.

Material and Methods: Ten patients with MM on an extremity and one healthy volunteer were included. One milliliter of a contrast agent (Sonovue; Bracco, Milan, Italy) was injected subcutaneously on both sides of the scar from the excised tumor. Contrast-enhanced lymph channels and lymph nodes (LNs) were searched for using low-mechanical-index CEUS and by stimulated acoustic emission. Afterward, lymphoscintigraphy was performed and the patient operated. During surgery, the SNs were located via scintigraphic findings, gamma-probe signals, and blue-dye visualization of lymph channels and LNs. Before the human study, a study of 10 mice was performed to exclude possible tissue damage, as the contrast agent was not registered for subcutaneous administration.

Results: In one patient, two contrast-enhanced inguinal LNs were visualized by CEUS, corresponding to two inguinal SNs found by scintigraphic imaging. No contrast-enhanced lymph channels or LNs were visualized in any other patients or in the volunteer. No tissue damage was observed in the 10 mice.

Conclusion: This study does not support the use of CEUS for detection of SNs in humans. However, the application of CEUS for the investigation of SNs is still not fully explored in humans, and an alternative setup and/or contrast agent might provide better results.
Physiological uptake of 18F-fluorodeoxyglucose in uterine endometrium and myometrium: Correlation with uterine motility evaluated by cine magnetic resonance imaging
Authors: Kido A. , Nakamoto Y. , Nishizawa S. , Yamamoto A. , Fujimoto K. , Okada H. , Togashi K.
Published: April 2009

Background: Accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the uterine endometrium and uterine motility are dependent on menstrual cycle. However, the relationship between them remains unknown.

Purpose: To investigate the relationship between radiometabolic activity of 18F-FDG in the uterus and uterine motility observed by cine magnetic resonance imaging (MRI).

Material and Methods: The study population consisted of 65 healthy, fertile women, selected from 229 women who underwent positron emission tomography (PET), computed tomography (CT), and MRI for cancer screening at our facility. They were divided into three groups according to their menstrual cycle phases: menstrual, follicular-periovulatory, and luteal. Regions of interest (ROIs) were placed over the endometrium and myometrium to calculate the standardized uptake value (SUV). Uterine peristalsis and contraction shown by cine MR imaging were evaluated visually, and the correlation between FDG uptake and uterine movements was assessed.

Results: After excluding nine patients due to inadequate images, 56 patients (19 follicular-periovulatory, 27 luteal, and 10 menstrual) were analyzed. FDG uptake of the endometrium, frequency of peristalsis, and the presence of sustained contraction varied according to the menstruation cycle, with a tendency toward greater uptake in the menstrual phase, but there was little relationship between the frequency of uterine peristalsis and FDG accumulation in the uterus. Significantly higher FDG accumulation in the endometrium was observed in patients with sustained contractions (3.32±1.47) than in those without contractions (2.45±0.66).

Conclusion: Our preliminary data suggest that FDG accumulation in the endometrium tends to be higher in patients with uterine contraction, although there was no significant correlation between uterine peristalsis and FDG uptake in the uterine myometrium or endometrium.
Short article: Action sequences within and across hands: Evidence for hand-related sequence learning
Authors: Berner Michael P. , Hoffmann Joachim
Published: April 2009

Recent research into the acquisition of action sequences involving both hands suggests that the hand-related (sub)sequences are learned at least partly independently of one another. Here we investigated hand-related sequence learning with a novel approach. Eight stimuli were divided into two sets. Participants responded simultaneously to a pair of stimuli (one from each set) with keystrokes of both hands. The stimuli from one set appeared according to a probabilistic structure; no such structure was imposed on the other set of stimuli. The structured stimuli either were assigned to keystrokes of one hand only or were evenly distributed across keystrokes of both hands. Sequence learning was more pronounced under the within-hands assignment than under the across-hands assignment. This finding corroborates hand-related sequence learning and suggests that the executing hand constitutes a dimension that facilitates learning of sequential regularities among elements that pertain to this hand.
Short article: The flexibility of context-specific control: Evidence for context-driven generalization of item-specific control settings
Authors: Crump Matthew J. C. , Milliken Bruce
Published: April 2009

In two experiments we address an ongoing debate concerning the processes driving context-driven modulations to the Stroop effect (Crump, Gong, & Milliken, 2006). In particular, we demonstrate that context-driven processes can modulate the size of the Stroop effect for frequency-unbiased item types. We also clarify the role of item frequency in producing context-driven modulations to the Stroop effect. Taken together, our results provide unambiguous support for the claim that contextual processing can impart fast and flexible control over the operation of selective attention processes during online performance.
Short article: The selective directed forgetting effect: Can people forget only part of a text?
Authors: Delaney Peter F. , Nghiem Khanh N. , Waldum Emily R.
Published: April 2009

Participants studied sentences describing two different characters and then were told to forget the sentences about only one of the characters. A second list contained sentences attributed to a third character. Subsequently, they received a recall test on the sentences about the original two characters. When the sentences could be thematically integrated, participants showed no directed forgetting relative to a control group that was never told to forget. However, with unrelated sentences, participants selectively forgot the target character's sentences without forgetting the other character's sentences. This selective directed forgetting effect is a novel empirical result. We interpret the results as consistent with Radvansky's (1999) ideas about inhibition with textual materials.
Distinctive items are salient during encoding: Delayed judgements of learning predict the isolation effect
Authors: Geraci Lisa , Manzano Isabel
Published: April 2009

Three experiments examined the role of salience in predicting superior memory for incongruent or odd items (the isolation effect). We tested the hypothesis that encoding salience emerges over the course of the encoding episode and predicts the isolation effect. In Experiment 1 participants studied lists of unrelated items and lists of categorized items containing an isolated item (from a different semantic category) that was presented either early or late in the list. Participants made delayed judgements of learning (JOLs) for studied items and were then given a free recall test. Results showed that participants had superior recall for the isolated items regardless of their list position and that delayed JOLs predicted this effect for both early and late isolation conditions. Experiment 2 replicated this delayed JOL effect using a different isolation paradigm that used only a single study list. Experiment 3 examined the specific mechanism by which isolated items become salient over the course of encoding and demonstrated that isolated items become salient as knowledge of the list structure unfolds. Results from these studies suggest that isolated items become salient over the course of the study episode, and that this salience predicts the isolation effect in memory.
Statistical analysis of disruptions in JET
Authors: de Vries P.C. , Johnson M.F. , Segui I.
Published: April 2009

The disruption rate (the percentage of discharges that disrupt) in JET was found to drop steadily over the years. Recent campaigns (2005–2007) show a yearly averaged disruption rate of only 6% while from 1991 to 1995 this was often higher than 20%. Besides the disruption rate, the so-called disruptivity, or the likelihood of a disruption depending on the plasma parameters, has been determined. The disruptivity of plasmas was found to be significantly higher close to the three main operational boundaries for tokamaks; the low-q, high density and β-limit. The frequency at which JET operated close to the density-limit increased six fold over the last decade; however, only a small reduction in disruptivity was found. Similarly the disruptivity close to the low-q and β-limit was found to be unchanged. The most significant reduction in disruptivity was found far from the operational boundaries, leading to the conclusion that the improved disruption rate is due to a better technical capability of operating JET, instead of safer operations close to the physics limits. The statistics showed that a simple protection system was able to mitigate the forces of a large fraction of disruptions, although it has proved to be at present more difficult to ameliorate the heat flux.
Progress in understanding halo current at JET
Authors: Riccardo V. , Arnoux G. , Beaumont P. , Hacquin S. , Hobirk J. , Howell D. , Huber A. , Joffrin E. , Koslowski R. , Lam N. , Leggate H. , Rachlew E. , Sergienko G. , Stephen A. , Todd T. , Zerbini M. , Delogu R. , Grando L. , Marcuzzi D. , Peruzzo S. , Pomaro N. , Sonato P.
Published: April 2009

The poloidal distribution of the halo current density on the top dump plate in JET can now be measured thanks to a new set of Rogowskii coils. These are the first measurements in JET able to offer an insight in the width of the halo current interaction with the wall. Therefore they offer both validation of the assumption made for JET disruption design criteria and one additional point in the extrapolation of the expected halo current width, and hence halo current density (and related local electro-mechanical loads on in-vessel components) for ITER. During upward events, the measured current density is consistent with the measured total poloidal halo current. The halo footprint extends over most of the upper dump plate, converting to a halo current flux tube width of ∼100 mm.

A set of four toridal field pick-up coils installed 90° apart now allows a more accurate measurement of the poloidal halo current, in particular its toroidal peaking factor, and direct comparison between halo and plasma asymmetries.
Whittaker modules for generalized Weyl algebras
Authors: Benkart Georgia , Ondrus Matthew
Published: April 2009

We investigate Whittaker modules for generalized Weyl algebras, a class of associative algebras which includes the quantum plane, Weyl algebras, the universal enveloping algebra of

s
l

2

\mathfrak {sl}_2

and of Heisenberg Lie algebras, Smith’s generalizations of

U
(

s
l

2

)

U(\mathfrak {sl}_2)

, various quantum analogues of these algebras, and many others. We show that the Whittaker modules

V
=
A
w

V = Aw

of the generalized Weyl algebra

A
=
R
(
ϕ
,
t
)

A = R(\phi ,t)

are in bijection with the

ϕ
\phi

-stable left ideals of

R
R

. We determine the annihilator

Ann
A

⁡
(
w
)

\operatorname {Ann}_A(w)

of the cyclic generator

w
w

of

V
V

. We also describe the annihilator ideal

Ann
A

⁡
(
V
)

\operatorname {Ann}_A(V)

under certain assumptions that hold for most of the examples mentioned above. As one special case, we recover Kostant’s well-known results on Whittaker modules and their associated annihilators for

U
(

s
l

2

)

U(\mathfrak {sl}_2)

.
Identification of the Neuroblastoma-amplified Gene Product as a Component of the Syntaxin 18 Complex Implicated in Golgi-to-Endoplasmic Reticulum Retrograde Transport
Authors: Aoki Takehiro , Ichimura Sarah , Itoh Ayano , Kuramoto Mami , Shinkawa Takashi , Isobe Toshiaki , Tagaya Mitsuo
Published: April 2009

Syntaxin 18, a soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) protein implicated in endoplasmic reticulum (ER) membrane fusion, forms a complex with other SNAREs (BNIP1, p31, and Sec22b) and several peripheral membrane components (Sly1, ZW10, and RINT-1). In the present study, we showed that a peripheral membrane protein encoded by the neuroblastoma-amplified gene (NAG) is a subunit of the syntaxin 18 complex. NAG encodes a protein of 2371 amino acids, which exhibits weak similarity to yeast Dsl3p/Sec39p, an 82-kDa component of the complex containing the yeast syntaxin 18 orthologue Ufe1p. Under conditions favoring SNARE complex disassembly, NAG was released from syntaxin 18 but remained in a p31-ZW10-RINT-1 subcomplex. Binding studies showed that the extreme N-terminal region of p31 is responsible for the interaction with NAG and that the N- and the C-terminal regions of NAG interact with p31 and ZW10-RINT-1, respectively. Knockdown of NAG resulted in a reduction in the expression of p31, confirming their intimate relationship. NAG depletion did not substantially affect Golgi morphology and protein export from the ER, but it caused redistribution of Golgi recycling proteins accompanied by a defect in protein glycosylation. These results together suggest that NAG links between p31 and ZW10-RINT-1 and is involved in Golgi-to-ER transport.
Activation of Protein Kinase C α Is Necessary for Sorting the PDGF β-Receptor to Rab4a-dependent Recycling
Authors: Hellberg Carina , Schmees Christian , Karlsson Susann , Åhgren Aive , Heldin Carl-Henrik
Published: April 2009

Previous studies showed that loss of the T-cell protein tyrosine phosphatase (TC-PTP) induces Rab4a-dependent recycling of the platelet-derived growth factor (PDGF) β-receptor in mouse embryonic fibroblasts (MEFs). Here we identify protein kinase C (PKC) α as the critical signaling component that regulates the sorting of the PDGF β-receptor at the early endosomes. Down-regulation of PKC abrogated receptor recycling by preventing the sorting of the activated receptor into EGFP-Rab4a positive domains on the early endosomes. This effect was mimicked by inhibition of PKCα, using myristoylated inhibitory peptides or by knockdown of PKCα with shRNAi. In wt MEFs, short-term preactivation of PKC by PMA caused a ligand-induced PDGF β-receptor recycling that was dependent on Rab4a function. Together, these observations demonstrate that PKC activity is necessary for recycling of ligand-stimulated PDGF β-receptor to occur. The sorting also required Rab4a function as it was prevented by expression of EGFP-Rab4aS22N. Preventing receptor sorting into recycling endosomes increased the rate of receptor degradation, indicating that the sorting of activated receptors at early endosomes directly regulates the duration of receptor signaling. Activation of PKC through the LPA receptor also induced PDGF β-receptor recycling and potentiated the chemotactic response to PDGF-BB. Taken together, our present findings indicate that sorting of PDGF β-receptors on early endosomes is regulated by sequential activation of PKCα and Rab4a and that this sorting step could constitute a point of cross-talk with other receptors.
Microtubule Cytoskeleton Remodeling by Acentriolar Microtubule-organizing Centers at the Entry and Exit from Mitosis inDrosophilaSomatic Cells
Authors: Moutinho-Pereira Sara , Debec Alain , Maiato Helder
Published: April 2009

Cytoskeleton microtubules undergo a reversible metamorphosis as cells enter and exit mitosis to build a transient mitotic spindle required for chromosome segregation. Centrosomes play a dominant but dispensable role in microtubule (MT) organization throughout the animal cell cycle, supporting the existence of concurrent mechanisms that remain unclear. Here we investigated MT organization at the entry and exit from mitosis, after perturbation of centriole function in Drosophila S2 cells. We found that several MTs originate from acentriolar microtubule-organizing centers (aMTOCs) that contain γ-tubulin and require Centrosomin (Cnn) for normal architecture and function. During spindle assembly, aMTOCs associated with peripheral MTs are recruited to acentriolar spindle poles by an Ncd/dynein-dependent clustering mechanism to form rudimentary aster-like structures. At anaphase onset, down-regulation of CDK1 triggers massive formation of cytoplasmic MTs de novo, many of which nucleated directly from aMTOCs. CDK1 down-regulation at anaphase coordinates the activity of Msps/XMAP215 and the kinesin-13 KLP10A to favor net MT growth and stability from aMTOCs. Finally, we show that microtubule nucleation from aMTOCs also occurs in cells containing centrosomes. Our data reveal a new form of cell cycle–regulated MTOCs that contribute for MT cytoskeleton remodeling during mitotic spindle assembly/disassembly in animal somatic cells, independently of centrioles.
LS-SNP/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures
Authors: Ryan Michael , Diekhans Mark , Lien Stephanie , Liu Yun , Karchin Rachel
Published: April 2009

Summary: LS-SNP/PDB is a new WWW resource for genome-wide annotation of human non-synonymous (amino acid changing) SNPs. It serves high-quality protein graphics rendered with UCSF Chimera molecular visualization software. The system is kept up-to-date by an automated, high-throughput build pipeline that systematically maps human nsSNPs onto Protein Data Bank structures and annotates several biologically relevant features.

Availability: LS-SNP/PDB is available at http://ls-snp.icm.jhu.edu/ls-snp-pdb and via links from protein data bank (PDB) biology and chemistry tabs, UCSC Genome Browser Gene Details and SNP Details pages and PharmGKB Gene Variants Downloads/Cross-References pages.

Contact:  karchin@jhu.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Many-core algorithms for statistical phylogenetics
Authors: Suchard Marc A. , Rambaut Andrew
Published: April 2009

Motivation: Statistical phylogenetics is computationally intensive, resulting in considerable attention meted on techniques for parallelization. Codon-based models allow for independent rates of synonymous and replacement substitutions and have the potential to more adequately model the process of protein-coding sequence evolution with a resulting increase in phylogenetic accuracy. Unfortunately, due to the high number of codon states, computational burden has largely thwarted phylogenetic reconstruction under codon models, particularly at the genomic-scale. Here, we describe novel algorithms and methods for evaluating phylogenies under arbitrary molecular evolutionary models on graphics processing units (GPUs), making use of the large number of processing cores to efficiently parallelize calculations even for large state-size models.

Results: We implement the approach in an existing Bayesian framework and apply the algorithms to estimating the phylogeny of 62 complete mitochondrial genomes of carnivores under a 60-state codon model. We see a near 90-fold speed increase over an optimized CPU-based computation and a >140-fold increase over the currently available implementation, making this the first practical use of codon models for phylogenetic inference over whole mitochondrial or microorganism genomes.

Availability and implementation: Source code provided in BEAGLE: Broad-platform Evolutionary Analysis General Likelihood Evaluator, a cross-platform/processor library for phylogenetic likelihood computation (http://beagle-lib.googlecode.com/). We employ a BEAGLE-implementation using the Bayesian phylogenetics framework BEAST (http://beast.bio.ed.ac.uk/).

Contact:  msuchard@ucla.edu; a.rambaut@ed.ac.uk
ViaComplex: software for landscape analysis of gene expression networks in genomic context
Authors: Castro Mauro A. A. , Filho José L. Rybarczyk , Dalmolin Rodrigo J. S. , Sinigaglia Marialva , Moreira José C. F. , Mombach José C. M. , de Almeida Rita M. C.
Published: April 2009

ViaComplex is an open-source application that builds landscape maps of gene expression networks. The motivation for this software comes from two previous publications (Nucleic Acids Res., 35, 1859–1867, 2007; Nucleic Acids Res., 36, 6269–6283, 2008). The first article presents a network-based model of genome stability pathways where we defined a set of genes that characterizes each genetic system. In the second article we analyzed this model by projecting functional information from several experiments onto the gene network topology. In order to systematize the methods developed in these articles, ViaComplex provides tools that may help potential users to assess different high-throughput experiments in the context of six core genome maintenance mechanisms. This model illustrates how different gene networks can be analyzed by the same algorithm.

Availability:  http://lief.if.ufrgs.br/pub/biosoftwares/viacomplex

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact:  mauro@ufrgs.br or rita@if.ufrgs.br
PseudoViewer3: generating planar drawings of large-scale RNA structures with pseudoknots
Authors: Byun Yanga , Han Kyungsook
Published: April 2009

Motivation: Pseudoknots in RNA structures make visualization of RNA structures difficult. Even if a pseudoknot itself is represented without a crossing, visualization of the entire RNA structure with a pseudoknot often results in a drawing with crossings between the pseudoknot and other structural elements, and requires additional intervention by the user to ensure that the structure graph is overlap-free. Many programs such as web services prefer to obtain an overlap-free graph in one-shot rather than get a graph with overlaps to be edited. There are few programs for visualizing RNA pseudoknots, and PseudoViewer has been the almost only program that automatically draws RNA secondary structures with pseudoknots. The previous version of PseudoViewer visualizes all the known types of RNA pseudoknots as planar drawings, but visualizes some hypothetical pseudoknots as non-planar drawings.

Results: We developed a new version of PseudoViewer for efficiently visualizing large RNA structures with any types of pseudoknots, both known and hypothetical, as planar drawings in one-shot. It is about 10 times faster than the previous algorithm, and produces a more compact and aesthetic structure drawing. PseudoViewer3 supports both web services and web applications.

Availability: The new version of PseudoViewer, PseudoViewer3, is available at http://pseudoviewer.inha.ac.kr.

Contact:  khan@inha.ac.kr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fluctuation AnaLysis CalculatOR: a web tool for the determination of mutation rate using Luria–Delbrück fluctuation analysis
Authors: Hall Brandon M. , Ma Chang-Xing , Liang Ping , Singh Keshav K.
Published: April 2009

Summary:The program Fluctuation AnaLysis CalculatOR (FALCOR) is a web tool designed for use with Luria–Delbrück fluctuation analysis to calculate the frequency and rate from various mutation assays in bacteria and yeast. Three calculation methods are available through this program: (i) Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) method, (ii) Lea-Coulson method of the median (LC) and (iii) frequency.

Availability: The FALCOR rate calculator is currently accessible at http://www.mitochondria.org/protocols/FALCOR.html. This program is written as a Java™ Applet, requiring a web browser enabled with Sun MicroSystems' Java Virtual Machine.

Contact:  brandon.hall@roswellpark.org
Metal-MACiE: a database of metals involved in biological catalysis
Authors: Andreini Claudia , Bertini Ivano , Cavallaro Gabriele , Holliday Gemma L. , Thornton Janet M.
Published: April 2009

Summary: Metal-MACiE is a new publicly available web-based database, held in MySQL, which aims to organize the available information on the properties and the roles of metals in the context of the catalytic mechanisms of metalloenzymes. Metal-MACiE, which currently covers 75% of metal-dependent enzyme commission (EC) sub-sub-classes and is continuously growing, exploits the existing MACiE database for the annotation of the reaction mechanisms. The two databases constitute complementary sources of information for enzymology, biochemistry and molecular pharmacology studies.

Availability:  http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html

Contact:  andreini@cerm.unifi.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Towards programming languages for genetic engineering of living cells
Authors: Pedersen Michael , Phillips Andrew
Published: April 2009

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts.
A novel
in vivo
method for quantifying the interfacial biochemical bond strength of bone implants
Authors: Sul Young-Taeg , Johansson Carina , Albrektsson Tomas
Published: April 2009

Quantifying the
in vivo
interfacial biochemical bond strength of bone implants is a biological challenge. We have developed a new and novel
in vivo
method to identify an interfacial biochemical bond in bone implants and to measure its bonding strength. This method, named biochemical bond measurement (BBM), involves a combination of the implant devices to measure true interfacial bond strength and surface property controls, and thus enables the contributions of mechanical interlocking and biochemical bonding to be distinguished from the measured strength values. We applied the BBM method to a rabbit model, and observed great differences in bone integration between the oxygen (control group) and magnesium (test group) plasma immersion ion-implanted titanium implants (0.046 versus 0.086 MPa,
n
=10,
p
=0.005). The biochemical bond in the test implants resulted in superior interfacial behaviour of the implants to bone: (i) close contact to approximately 2 μm thin amorphous interfacial tissue, (ii) pronounced mineralization of the interfacial tissue, (iii) rapid bone healing in contact, and (iv) strong integration to bone. The BBM method can be applied to
in vivo
experimental models not only to validate the presence of a biochemical bond at the bone–implant interface but also to measure the relative quantity of biochemical bond strength. The present study may provide new avenues for better understanding the role of a biochemical bond involved in the integration of bone implants.
Harriot's maps of the Moon: new interpretations
Authors: Pumfrey Stephen
Published: April 2009

July 2009 is the 400th anniversary of the first telescopic observations of the Moon, made by the English scientist Thomas Harriot. Galileo's later drawings were more influential, but some historians now question the traditional view that Harriot's were inferior. Galileo's revealed the mountainous topography of the Moon, but Harriot's arguably had the different, cartographical aim of plotting lunar features precisely. This article suggests that, influenced by the remarkable work of his contemporary William Gilbert, Harriot may have devised or used his splendid Moon map, like Gilbert, to observe the phenomenon of lunar libration decades before Galileo announced its existence.
Oscillating flames: multiple-scale analysis
Authors: Bauwens Luc , Bauwens C. Regis L. , Wierzba Ida
Published: April 2009

A complete multiple-scale solution is constructed for the one-dimensional problem of an oscillating flame in a tube, ignited at a closed end, with the second end open. The flame front moves into the unburnt mixture at a constant burning velocity relative to the mixture ahead, and the heat release is constant. The solution is based upon the assumption that the propagation speed multiplied by the expansion ratio is small compared with the speed of sound. This approximate solution is compared with a numerical solution for the same physical model, assuming a propagation speed of arbitrary magnitude, and the results are close enough to confirm the validity of the approximate solution. Because ignition takes place at the closed end, the effect of thermal expansion is to push the column of fluid in the tube towards the open end. Acoustics set in motion by the impulsive start of the column of fluid play a crucial role in the oscillation. The analytical solution also captures the subsequent interaction between acoustics and the reaction front, the effect of which does not appear to be as significant as that of the impulsive start, however.
An inversion technique for the retrieval of single-point emissions from atmospheric concentration measurements
Authors: Sharan Maithili , Issartel Jean-Pierre , Singh Sarvesh Kumar , Kumar Pramod
Published: April 2009

The aim of the study is to propose a technique for the retrieval of point sources of atmospheric trace species from concentration measurements. The inverse problem of identifying the parameters of a point source is addressed within the assimilative framework of renormalization recently proposed for the identification of distributed emissions. This theory has been extended for the point sources based on the property that these are associated with the maximum of the renormalized estimate computed from the observations. This approach along with an analytic dispersion model is used for point source identification, and the sensitivity of the samplers is described by the same model in backward mode. The proposed technique is illustrated not only with synthetic measurements but also with seven sets of observations, corresponding to convective conditions, taken from the low-wind tracer diffusion experiment conducted at the Indian Institute of Technology Delhi in 1991. The position and intensity of the source are retrieved exactly with the synthetic measurements in all the sets validating the technique. The position of the source is retrieved with an average error of 17 m, mostly along wind; its intensity is estimated within a factor 2 for all the sets of real observations. From a theoretical point of view, the link established between point and distributed sources clarifies new concepts for the exploitation of monitoring networks. In particular, the influence of the noise on the identification of a source is related to the relative visibility of the various regions described with a renormalizing weight function. The geometry of the environment modified according to the weights is interpreted as an apparent geometry. It is analogous to the apparent flatness of the starry sky in eye's view, usually considered an impression rather than a scientific fact.
Signatures of nitrogen limitation in the elemental composition of the proteins involved in the metabolic apparatus
Authors: Acquisti Claudia , Kumar Sudhir , Elser James J.
Published: April 2009

Nitrogen (N) is a fundamental component of nucleotides and amino acids and is often a limiting nutrient in natural ecosystems. Thus, study of the N content of biomolecules may establish important connections between ecology and genomics. However, while significant differences in the elemental composition of whole organisms are well documented, how the flux of nutrients in the cell has shaped the evolution of different cellular processes remains poorly understood. By examining the elemental composition of major functional classes of proteins in four multicellular eukaryotic model organisms, we find that the catabolic machinery shows substantially lower N content than the anabolic machinery and the rest of the proteome. This pattern suggests that ecological selection for N conservation specifically targets cellular components that are highly expressed in response to nutrient limitation. We propose that the RNA component of the anabolic machineries is the mechanistic force driving the elemental imbalance we found, and that RNA functions as an intracellular nutrient reservoir that is degraded and recycled during starvation periods. A comparison of the elemental composition of the anabolic and catabolic machineries in species that have experienced different levels of N limitation in their evolutionary history (animals versus plants) suggests that selection for N conservation has preferentially targeted the catabolic machineries of plants, resulting in a lower N content of the proteins involved in their catabolic processes. These findings link the composition of major cellular components to the environmental factors that trigger the activation of those components, suggesting that resource availability has constrained the atomic composition and the molecular architecture of the biotic processes that enable cells to respond to reduced nutrient availability.
Dietary-dependent trans-generational immune priming in an insect herbivore
Authors: Freitak Dalial , Heckel David G. , Vogel Heiko
Published: April 2009

Trans-generational effects on immunity are well known in vertebrates and are considered in many evolutionary and ecological theories of species interaction. Maternal effects have been identified to be of special importance, and are now recognized as a mechanism for adaptive phenotypic response to environmental heterogeneity. We have previously shown that exposure to dietary non-pathogenic bacteria can induce several aspects of immune response in an insect herbivore, the cabbage semilooper (
Trichoplusia ni
). Here, we test the effects of this exposure on the immune status of the next generation, measuring immune parameters on three different levels—enzyme activities, protein expression and transcript abundance. We also monitored fitness-related traits which are often negatively correlated with increased immunocompetence. We found evidence for trans-generational priming on all these levels, with immune system parameters that are clearly not transmitted in a 1 : 1 ratio from parent to offspring, but rather in a complex manner with a strong but not exclusive maternal component. These findings indicate that trans-generational priming is a complex and multifaceted phenomenon, potentially playing a role as a long-term but non-genetic mode of environmental adaptation.
Evidence from the domestication of apple for the maintenance of autumn colours by coevolution
Authors: Archetti Marco
Published: April 2009

The adaptive value of autumn colours is still a puzzle for evolutionary biology. It has been suggested that autumn colours are a warning signal to insects that use the trees as a host. I show that aphids (
Dysaphis plantaginea
) avoid apple trees (
Malus pumila
) with red leaves in autumn and that their fitness in spring is lower on these trees, which suggests that red leaves are an honest signal of the quality of the tree as a host. Autumn colours are common in wild populations but not among cultivated apple varieties, which are no longer under natural selection against insects. I show that autumn colours remain only in the varieties that are very susceptible to the effects of a common insect-borne disease, fire blight, and therefore are more in need of avoiding insects. Moreover, varieties with red leaves have smaller fruits, which shows that they have been under less effective artificial selection. This suggests a possible trade off between fruit size, leaf colour and resistance to parasites. These results are consistent with the hypothesis that autumn colours are a warning signal to insects, but not with other hypotheses.
Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei
Authors: Siegel T. Nicolai , Hekstra Doeke R. , Kemp Louise E. , Figueiredo Luisa M. , Lowell Joanna E. , Fenyo David , Wang Xuning , Dewell Scott , Cross George A.M.
Published: April 2009

Unusually for a eukaryote, genes transcribed by RNA polymerase II (pol II) in Trypanosoma brucei are arranged in polycistronic transcription units. With one exception, no pol II promoter motifs have been identified, and how transcription is initiated remains an enigma. T. brucei has four histone variants: H2AZ, H2BV, H3V, and H4V. Using chromatin immunoprecipitation (ChIP) and sequencing (ChIP-seq) to examine the genome-wide distribution of chromatin components, we show that histones H4K10ac, H2AZ, H2BV, and the bromodomain factor BDF3 are enriched up to 300-fold at probable pol II transcription start sites (TSSs). We also show that nucleosomes containing H2AZ and H2BV are less stable than canonical nucleosomes. Our analysis also identifies >60 unexpected TSS candidates and reveals the presence of long guanine runs at probable TSSs. Apparently unique to trypanosomes, additional histone variants H3V and H4V are enriched at probable pol II transcription termination sites. Our findings suggest that histone modifications and histone variants play crucial roles in transcription initiation and termination in trypanosomes and that destabilization of nucleosomes by histone variants is an evolutionarily ancient and general mechanism of transcription initiation, demonstrated in an organism in which general pol II transcription factors have been elusive.
Aquaporin-Mediated Reduction in Maize Root Hydraulic Conductivity Impacts Cell Turgor and Leaf Elongation Even without Changing Transpiration
Authors: Ehlert Christina , Maurel Christophe , Tardieu François , Simonneau Thierry
Published: April 2009

Root hydraulic conductivity in plants (Lpr) exhibits large variations in response to abiotic stimuli. In this study, we investigated the impact of dynamic, aquaporin-mediated changes of Lpr on leaf growth, water potential, and water flux throughout the plant. For this, we manipulated Lpr by subjecting roots to four independent treatments, with aquaporin inhibitors applied either to transpiring maize (Zea mays) plants grown in hydroponics or to detopped root systems for estimation of Lpr. The treatments were acid load at pH 6.0 and 5.0 and hydrogen peroxide and anoxia applied for 1 to 2 h and subsequently reversed. First, we established that acid load affected cell hydraulic conductivity in maize root cortex. Lpr was reduced by all treatments by 31% to 63%, with half-times of about 15 min, and partly recovered when treatments were reversed. Cell turgor measured in the elongating zone of leaves decreased synchronously with Lpr, and leaf elongation rate closely followed these changes across all treatments in a dose-dependent manner. Leaf and xylem water potentials also followed changes in Lpr. Stomatal conductance and rates of transpiration and water uptake were not affected by Lpr reduction under low evaporative demand. Increased evaporative demand, when combined with acid load at pH 6.0, induced stomatal closure and amplified all other responses without altering their synchrony. Root pressurization reversed the impact of acid load or anoxia on leaf elongation rate and water potential, further indicating that changes in turgor mediated the response of leaf growth to reductions in Lpr.
Comparison of risk factors and clinical responses to proton pump inhibitors in patients with erosive oesophagitis and non‐erosive reflux disease
Authors: LEE E. S. , KIM N. , LEE S. H. , PARK Y. S. , KIM J. W. , JEONG S. H. , LEE D. H. , JUNG H. C. , SONG I. S.
Published: April 2009

Background  There has been no report on the response to proton pump inhibitor (PPI) therapy and on‐demand or the relapse rate of non‐erosive reflux disease (NERD) and erosive oesophagitis in Korea.

Aim  To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.

Methods  A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On‐demand therapy and the relapse rate of GERD symptoms were investigated during a one‐year follow‐up.

Results  BMI ≥ 25 (OR 3.0, 95% CI 1.1–8.3), alcohol use (OR 2.9, 95% CI 1.0–8.3), hiatal hernia (OR 5.0, 95% CI 1.2–20) and triglyceride ≥150 mg/dL (OR 4.0, 95% CI 1.7–10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra‐oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group (P < 0.001). The PPI response rates at 8 weeks were different (P = 0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on‐demand therapy or the relapse rate.

Conclusion  These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.