bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Characterization of a Novel
N
-Acetylneuraminate Lyase from
Lactobacillus plantarum
WCFS1
Authors: Sánchez-Carrón Guiomar , García-García María Inmaculada , López-Rodríguez Ana Belén , Jiménez-García Sofía , Sola-Carvajal Agustín , García-Carmona Francisco , Sánchez-Ferrer Álvaro
Published: February 2011

N
-Acetylneuraminate lyases (NALs) or sialic acid aldolases catalyze the reversible aldol cleavage of
N
-acetylneuraminic acid (Neu5Ac) to form pyruvate and
N
-acetyl-
d
-mannosamine (ManNAc). In nature,
N
-acetylneuraminate lyase occurs mainly in pathogens. However, this paper describes how an
N
-acetylneuraminate lyase was cloned from the human gut commensal
Lactobacillus plantarum
WCFS1 (LpNAL), overexpressed, purified, and characterized for the first time. This novel enzyme, which reaches a high expression level (215 mg liter
−1
culture), shows similar catalytic efficiency to the best NALs previously described. This homotetrameric enzyme (132 kDa) also shows high stability and activity at alkaline pH (pH > 9) and good temperature stability (60 to 70°C), this last feature being further improved by the presence of stabilizing additives. These characteristics make LpNAL a promising biocatalyst. When its sequence was compared with that of other, related (real and putative) NALs described in the databases, it was seen that NAL enzymes could be divided into four structural groups and three subgroups. The relation of these subgroups with human and other mammalian NALs is also discussed.
Mitosis in the Human Malaria Parasite Plasmodium falciparum
Authors: Gerald Noel , Mahajan Babita , Kumar Sanjai
Published: February 2011

Malaria is caused by intraerythrocytic protozoan parasites belonging to
Plasmodium
spp. (phylum
Apicomplexa
) that produce significant morbidity and mortality, mostly in developing countries.
Plasmodium
parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for
Plasmodium
reproduction; however, some aspects of
Plasmodium
mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in
Plasmodium falciparum
and related parasites and compare them with the traditional mitotic events described for other eukaryotes.
Plasmodium falciparum var Gene Silencing Is Determined bycisDNA Elements That Form Stable and Heritable Interactions
Authors: Swamy Lakshmi , Amulic Borko , Deitsch Kirk W.
Published: February 2011

Antigenic variation in the human malaria parasitePlasmodium falciparumdepends on the transcriptional regulation of thevargene family. In each individual parasite, mRNA is expressed exclusively from 1vargene out of ∼60, while the rest of the genes are transcriptionally silenced. Both modifications to chromatin structure and DNA regulatory elements associated with eachvargene have been implicated in the organization and maintenance of the silent state. Whether silencing is established at the level of entire chromosomal regions via heterochromatin spreading or at the level of individualvarpromoters through the action of a silencing element within eachvarintron has been debated. Here, we consider both possibilities, using clonal parasite lines carrying chromosomally integrated transgenes. We confirm a previous finding that the loss of an adjacentvarintron results invarpromoter activation and further show that transcriptional activation of avarpromoter within a cluster does not affect the transcriptional activity of neighboringvarpromoters. Our results provide more evidence for the hypothesis thatvargenes are primarily silenced at the level of an individual gene, rather than by heterochromatin spreading. We also tested the intrinsic directionality of an intron's silencing effect on upstream or downstreamvarpromoters. We found that an intron is capable of silencing in either direction and that, once established, avarpromoter-intron pair is stably maintained through many generations, suggesting a possible role in epigenetic memory. This study provides insights into the regulation of endogenousvargene clusters.
An Enterotoxin-Bearing Pathogenicity Island in Staphylococcus epidermidis
Authors: Madhusoodanan Jyoti , Seo Keun Seok , Remortel Brian , Park Joo Youn , Hwang Sun Young , Fox Lawrence K. , Park Yong Ho , Deobald Claudia F. , Wang Dan , Liu Song , Daugherty Sean C. , Gill Ann Lindley , Bohach Gregory A. , Gill Steven R.
Published: February 2011

Cocolonization of human mucosal surfaces causes frequent encounters between various staphylococcal species, creating opportunities for the horizontal acquisition of mobile genetic elements. The majority of
Staphylococcus aureus
toxins and virulence factors are encoded on
S. aureus
pathogenicity islands (SaPIs). Horizontal movement of SaPIs between
S. aureus
strains plays a role in the evolution of virulent clinical isolates. Although there have been reports of the production of toxic shock syndrome toxin 1 (TSST-1), enterotoxin, and other superantigens by coagulase-negative staphylococci, no associated pathogenicity islands have been found in the genome of
Staphylococcus epidermidis
, a generally less virulent relative of
S. aureus
. We show here the first evidence of a composite

S

.

e

pidermidis
p
athogenicity
i
sland (SePI), the product of multiple insertions in the genome of a clinical isolate. The taxonomic placement of
S. epidermidis
strain FRI909 was confirmed by a number of biochemical tests and multilocus sequence typing. The genome sequence of this strain was analyzed for other unique gene clusters and their locations. This pathogenicity island encodes and expresses staphylococcal enterotoxin C3 (SEC3) and staphylococcal enterotoxin-like toxin L (SElL), as confirmed by quantitative reverse transcription-PCR (qRT-PCR) and immunoblotting. We present here an initial characterization of this novel pathogenicity island, and we establish that it is stable, expresses enterotoxins, and is not obviously transmissible by phage transduction. We also describe the genome sequence, excision, replication, and packaging of a novel bacteriophage in
S. epidermidis
FRI909, as well as attempts to mobilize the SePI element by this phage.
Fatty Acid-Related Phylogeny of Myxobacteria as an Approach to Discover Polyunsaturated Omega-3/6 Fatty Acids
Authors: Garcia Ronald , Pistorius Dominik , Stadler Marc , Müller Rolf
Published: February 2011

In an analysis of 47 aerobic myxobacterial strains, representing 19 genera in suborders
Cystobacterineae
,
Nannocystineae
,
Sorangiineae
, and a novel isolate, “
Aetherobacter
” SBSr008, an enormously diverse array of fatty acids (FAs) was found. The distribution of straight-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) supports the reported clustering of strains in the phylogenetic tree based on 16S rRNA genes. This finding additionally allows the prediction and assignment of the novel isolate SBSr008 into its corresponding taxon.
Sorangiineae
predominantly contains larger amounts of SCFA (57 to 84%) than BCFA. On the other hand,
Cystobacterineae
exhibit significant BCFA content (53 to 90%), with the exception of the genus
Stigmatella
. In
Nannocystineae
, the ratio of BCFA and SCFA seems dependent on the taxonomic clade. Myxobacteria could also be identified and classified by using their specific and predominant FAs as biomarkers.
Nannocystineae
is remarkably unique among the suborders for its absence of hydroxy FAs. After the identification of arachidonic (AA) FA in
Phaselicystidaceae
, eight additional polyunsaturated fatty acids (PUFAs) belonging to the omega-6 and omega-3 families were discovered. Here we present a comprehensive report of FAs found in aerobic myxobacteria. Gliding bacteria belonging to
Flexibacter
and
Herpetosiphon
were chosen for comparative analysis to determine their FA profiles in relation to the myxobacteria.
Lactococcus lactis ZitR Is a Zinc-Responsive Repressor Active in the Presence of Low, Nontoxic Zinc Concentrations In Vivo
Authors: Llull Daniel , Son Olivier , Blanié Sandrine , Briffotaux Julien , Morello Eric , Rogniaux Hélène , Danot Olivier , Poquet Isabelle
Published: February 2011

In the family
Streptococcaceae
, the genes encoding zinc ABC uptake systems (called
zit
or
adc
) are regulated by a coencoded MarR family member (i.e., ZitR or AdcR), whereas in the great majority of bacteria, these genes are regulated by Zur, the Fur-like zinc-responsive repressor. We studied the
zit
operon from
Lactococcus lactis
and its regulation in response to Zn(II)
in vivo. zit
transcription is repressed by Zn(II) in a wide concentration range starting from nontoxic micromolar levels and is derepressed at nanomolar concentrations. The level of
zit
promoter downregulation by environmental Zn(II) is correlated with the intracellular zinc content. The helix-turn-helix domain of ZitR is required for downregulation.
In vitro
, the purified protein is a dimer that complexes up to two zinc ligands per monomer and specifically binds two intact palindromic operator sites overlapping the −35 and −10 boxes of the
zit
promoter. DNA binding is abolished by the chelator EDTA or TPEN and fully restored by Zn(II) addition, indicating that the active repressor complexes Zn(II) with high affinity. These results suggest that derepression under starvation conditions could be an essential emergency mechanism for preserving Zn(II) homeostasis by uptake; under Zn(II)-replete conditions, the function of ZitR repression could be to help save energy rather than to avoid Zn(II) toxicity. The characterization of a MarR family zinc-responsive repressor in this report gives insight into the way
Streptococcaceae
efficiently adapt to Zn(II) fluctuations in their diverse ecological niches.
The Interplay of ClpXP with the Cell Division Machinery in Escherichia coli
Authors: Camberg Jodi L. , Hoskins Joel R. , Wickner Sue
Published: February 2011

ClpXP is a two-component protease composed of ClpX, an ATP-dependent chaperone that recognizes and unfolds specific substrates, and ClpP, a serine protease. One ClpXP substrate in
Escherichia coli
is FtsZ, which is essential for cell division. FtsZ polymerizes and forms the FtsZ ring at midcell, where division occurs. To investigate the role of ClpXP in cell division, we examined the effects of
clpX
and
clpP
deletions in several strains that are defective for cell division. Together, our results suggested that ClpXP modulates cell division through degradation of FtsZ and possibly other cell division components that function downstream of FtsZ ring assembly. In the
ftsZ84
strain, which is temperature sensitive for filamentation due to a mutation in
ftsZ
, we observed that deletion of
clpX
or
clpP
suppresses filamentation and reduces FtsZ84 degradation. These results are consistent with ClpXP playing a role in cell division by modulating the level of FtsZ through degradation. In another division-defective strain, Δ
minC
, the additional deletion of
clpX
or
clpP
delays cell division and exacerbates filamentation. Our results demonstrate that ClpXP modulates division in cells lacking MinC by a mechanism that requires ATP-dependent degradation. However, antibiotic chase experiments
in vivo
indicate that FtsZ degradation is slower in the Δ
minC
strain than in the wild type, suggesting there may be another cell division component degraded by ClpXP. Taken together these studies suggest that ClpXP may degrade multiple cell division proteins, thereby modulating the precise balance of the components required for division.
A Glutathione Redox Effect on Photosynthetic Membrane Expression in Rhodospirillum rubrum
Authors: Carius Anke Berit , Henkel Marius , Grammel Hartmut
Published: February 2011

The formation of intracytoplasmic photosynthetic membranes by facultative anoxygenic photosynthetic bacteria has become a prime example for exploring redox control of gene expression in response to oxygen and light. Although a number of redox-responsive sensor proteins and transcription factors have been characterized in several species during the last several years in some detail, the overall understanding of the metabolic events that determine the cellular redox environment and initiate redox signaling is still poor. In the present study we demonstrate that inRhodospirillum rubrum, the amount of photosynthetic membranes can be drastically elevated by external supplementation of the growth medium with the low-molecular-weight thiol glutathione. Neither the widely used reductant dithiothreitol nor oxidized glutathione caused the same response, suggesting that the effect was specific for reduced glutathione. By determination of the extracellular and intracellular glutathione levels, we correlate the GSH/GSSG redox potential to the expression level of photosynthetic membranes. Possible regulatory interactions with periplasmic, membrane, and cytosolic proteins are discussed. Furthermore, we found thatR. rubrumcultures excrete substantial amounts of glutathione to the environment.
Expanding the Definition of Class 3 Inteins and Their Proposed Phage Origin
Authors: Tori Kazuo , Perler Francine B.
Published: February 2011

Inteins are the protein equivalent of introns. Their protein splicing activity is essential for the host protein's maturation and function. Inteins are grouped into three classes based on sequence signature and splicing mechanism. The sequence signature of the recently characterized class 3 inteins is a noncontiguous Trp-Cys-Thr (WCT) motif and the absence of the standard class 1 Cys
1
or Ser
1
N-terminal nucleophile. The intein N-terminal Cys
1
or Ser
1
residue is essential for splicing in class 1 inteins. The mycobacteriophage Catera Gp206,
Nocardioides
sp. strain JS614 TOPRIM, and
Thermobifida fusca
YX Tfu2914 inteins have a mixture of class 1 and class 3 motifs. They carry the class 3 Trp-Cys-Thr motif and have the standard class 1 N-terminal Ser
1
or Cys
1
. This study determined which class the mycobacteriophage Catera Gp206 and
Nocardioides
sp. JS614 TOPRIM inteins belong to based on catalytic mechanism. The mycobacteriophage Catera Gp206 intein (starting with Ser
1
) is a class 3 intein, and its Ser
1
residue is not required for splicing. Based on phylogenetic analysis, we propose that class 3 inteins arose from a single mutated intein that was spread by phage into predominantly helicase genes in various phages and their hosts.
Anomalous Spatial Redistribution of Competing Bacteria under Starvation Conditions
Authors: Lambert Guillaume , Liao David , Vyawahare Saurabh , Austin Robert H.
Published: February 2011

Bacterial cells evolved under prolonged stress often have a growth advantage in stationary phase (GASP); we expect GASP cells to maintain a proliferative state and dominate wild-type cells during starvation, especially when nutrients are limited and the medium has been conditioned. However, when we compete GASP mutants against wild-type cells in a chain of microfluidic microhabitat patches (MHPs) with alternating nutrient-rich and nutrient-limited regions, we observe the reverse effect: wild-type cells achieve maximum relative density under nutrient-limited conditions, while GASP cells dominate nutrient-rich regions. We explain this surprising observation in terms of ideal free distributions, where we show that wild-type cells maximize their fitness at high cell density by redistributing themselves to sparsely populated MHPs. At the microscopic level, we describe how biofilm formation also contributes to the population redistribution. We conclude by discussing the implications of these results for social interactions of more complex organisms.
The
sigE
Gene Is Required for Normal Expression of Heterocyst-Specific Genes in Anabaena sp. Strain PCC 7120
Authors: Mella-Herrera Rodrigo A. , Neunuebel M. Ramona , Kumar Krithika , Saha Sushanta K. , Golden James W.
Published: February 2011

The filamentous cyanobacterium
Anabaena
(
Nostoc
) sp. strain PCC 7120 produces specialized cells for nitrogen fixation called heterocysts. Previous work showed that the group 2 sigma factor
sigE
(alr4249; previously called
sigF
) is upregulated in differentiating heterocysts 16 h after nitrogen step-down. We now show that the
sigE
gene is required for normal heterocyst development and normal expression levels of several heterocyst-specific genes. Mobility shift assays showed that the transcription factor NtcA binds to sites in the upstream region of
sigE
and that this binding is enhanced by 2-oxoglutarate (2-OG). Deletions of the region containing the NtcA binding sites in P

sigE
-gfp

reporter plasmids showed that the sites contribute to normal developmental regulation but are not essential for upregulation in heterocysts. Northern RNA blot analysis of
nifH
mRNA revealed delayed and reduced transcript levels during heterocyst differentiation in a
sigE
mutant background. Quantitative reverse transcription-PCR (qRT-PCR) analyses of the
sigE
mutant showed lower levels of transcripts for
nifH
,
fdxH
, and
hglE2
but normal levels for
hupL
. We developed a P

nifHD
-gfp

reporter construct that showed strong heterocyst-specific expression. Time-lapse microscopy of the P

nifHD
-gfp

reporter in a
sigE
mutant background showed delayed development and undetectable green fluorescent protein (GFP) fluorescence. Overexpression of
sigE
caused accelerated heterocyst development, an increased heterocyst frequency, and premature expression of GFP fluorescence from the P

nifHD
-gfp

reporter.
Successful treatment of equine sarcoids by topical aciclovir application
Authors: Stadler S. , Kainzbauer C. , Haralambus R. , Brehm W. , Hainisch E. , Brandt S.
Published: February 2011

Based on the anecdotally reported eradication of a sarcoid using aciclovir cream, the curative potential of this ointment was investigated in 22 sarcoid‐affected horses referred to the Equine Clinic Tillysburg, Austria, between 2006 and 2009. Sarcoid disease was diagnosed by clinical examination and bovine papillomavirus types 1 and 2 from intact skin and tumour tissue. As nine horses had more than one lesion, a total of 47 sarcoids were treated by daily topical application of aciclovir 5 per cent cream for a period of two to six months; in four horses, surgical tumour ablation was performed before treatment. Disease parameters, including the tumour type, number, location and size, were recorded before and after aciclovir therapy. All 47 (100 per cent) of the sarcoids responded to treatment, with complete tumour regression observed for 32 (68 per cent) lesions and no recurrences reported thus far. Incomplete resolution was observed for 15 (32 per cent) lesions, probably due to their thickness. Aciclovir is proposed to be routinely used for the treatment of mild‐type sarcoids and as an adjuvant therapeutic agent in combination with surgery.
Myogenic mRNA markers in young and old human skeletal muscle prior to and following sequential exercise bouts
Authors: Roberts Michael D. , Dalbo Vincent J. , Sunderland Kyle , Poole Chris , Hassell Scott E. , Kerksick Chad M.
Published: February 2011

This study examined how multiple bouts of conventional resistance training affected the mRNA expression of transcripts and a protein associated with satellite cell activity in human skeletal muscle. Ten younger men (means ± SE; age, 21.0 ± 0.5 years; body mass, 82.3 ± 4.2 kg; height, 178.4 ± 2.2 cm; percent body fat, 15.4% ± 2.9%) and 10 older men (age, 66.4 ± 1.6 years; body mass, 94.2 ± 3.7 kg; height, 180.9 ± 2.2 cm; percent body fat, 27.4% ± 1.8%) completed 3 lower-body workouts (Monday, Wednesday, Friday; 9 sets of 10 repetitions at 80% 1 repetition maximum). Vastus lateralis muscle biopsies were collected prior to intervention (T1), 48 h following workout 1 (T2), 48 h following workout 2 (T3), and 24 h following workout 3 (T4). Real-time reverse transcription–polymerase chain reaction was performed to assess genes of interest, and muscle proliferating cell nuclear antigen (PCNA) was assessed using Western blotting. The CYCLIN D1 gene was expressed more highly in the older vs. younger men (p < 0.05), whereas the expression of all other genes and muscle PCNA were similar between age groups. MYOD mRNA expression increased at T2 (p < 0.05) and MHCEMB gene expression modestly increased (p < 0.05) at T4 relative to baseline expression values in the younger men. Baseline elevations in CYCLIN D1 mRNA expression in older persons may indicate that a compensatory expression of this transcript is occurring in an attempt to retain the muscle’s proliferative potential. Increases in MYOD and MHCEMB indicate that 1 week of conventional resistance exercise may i\ncrease myogenic activity, including satellite cell proliferation and differentiation, respectively, in younger men.
Regional and relative adiposity patterns in relation to carbohydrate and lipid metabolism in men with spinal cord injury
Authors: Gorgey Ashraf S. , Gater David R.
Published: February 2011

This study examined the relationship among regional and relative adipose tissue distribution, glucose, and lipid metabolism in men with spinal cord injury (SCI). After overnight fasting, 32 individuals with motor complete tetraplegia (Tetra) (n = 7) and paraplegia (Para) (n = 25) underwent resting energy expenditure and measurement of serum lipid profile, followed by an oral glucose tolerance test to measure plasma glucose and plasma insulin concentrations. Regional fat mass (FM) and fat-free mass were quantified using dual-energy X-ray absorptiometry. Relative adipose tissue was calculated as the ratio of leg FM/trunk FM, leg FM/whole-body FM, and trunk FM/whole-body FM. Individuals with Tetra have greater leg FM/trunk FM (45%) and leg FM/body FM (26%) and lower trunk FM/body FM (29%) ratios than individuals with Para (p < 0.05). Glucose area under the curve (AUC) was positively related to leg FM (r = 0.34, p = 0.05) but not to trunk or body FM. Strong negative relationships were noted between the ratio of trunk FM to body FM and glucose AUC (r = –0.38, p = 0.03) and low-density lipoprotein cholesterol (LDL-C) (r = –0.45, p = 0.001). Whole-body FM was negatively related to high-density lipoprotein cholesterol (r = –0.49, p = 0.007) after controlling for percentage of trunk FM. Both leg and trunk FM may play a pivotal role in determining the metabolic profile in individuals with SCI. Relative to whole-body FM and leg FM, trunk FM may induce a protective effect on glucose homeostasis and the LDL-C profile.
Canadian Sedentary Behaviour Guidelines for Children and Youth
Authors: Tremblay Mark S. , LeBlanc Allana G. , Janssen Ian , Kho Michelle E. , Hicks Audrey , Murumets Kelly , Colley Rachel C. , Duggan Mary
Published: February 2011

The Canadian Society for Exercise Physiology (CSEP), in partnership with the Healthy Active Living and Obesity Research Group (HALO) at the Children’s Hospital of Eastern Ontario Research Institute, and in collaboration with ParticipACTION, and others, has developed the Canadian Sedentary Behaviour Guidelines for Children (aged 5–11 years) and Youth (aged 12–17 years). The guidelines include a preamble to provide context, followed by the specific recommendations for sedentary behaviour. The entire development process was guided by the Appraisal of Guidelines for Research Evaluation (AGREE) II instrument, which is the international standard for clinical practice guideline development. Thus, the guidelines have gone through a rigorous and transparent developmental process and the recommendations are based on evidence from a systematic review and interpretation of the research evidence. The final guidelines benefitted from an extensive online consultation process with 230 domestic and international stakeholders and key informants. The final guideline recommendations state that for health benefits, children (aged 5–11 years) and youth (aged 12–17 years) should minimize the time that they spend being sedentary each day. This may be achieved by (i) limiting recreational screen time to no more than 2 h per day — lower levels are associated with additional health benefits; and (ii) limiting sedentary (motorized) transport, extended sitting time, and time spent indoors throughout the day. These are the first evidence-based Canadian Sedentary Behaviour Guidelines for Children and Youth and provide important and timely recommendations for the advancement of public health based on a systematic synthesis, interpretation, and application of the current scientific evidence.
Production control in precast fabrication: considering demand variability in production schedules
Authors: Ko Chien-Ho
Published: February 2011

On-time delivery is a key factor in the business success of precast fabricators. The greatest obstacle to achieving this goal is demand variability. The objective of this research is to develop a plan that continuously improves production control systems for precast fabrication. This plan involves a lead time estimation model (LTEM) and schedule adjustment principles. The LTEM is established to estimate the impact of demand variability. In the model, previous jobs are analyzed as indicators of customer behavior. Using the captured behavior, fabrication lead time can be estimated for forthcoming projects. Two principles are proposed to adjust the production schedule according to the estimated lead times. Two adjustment principles are designed to reduce the impact of demand variability: (1) start fabrication later relative to the required delivery dates and (2) shift production milestones backward to the end of the production process. The effectiveness of the developed improvement plan including LTEM and the adjustment principles were validated using a real precast fabricator. The proposed approach is one of the first studies to use historical data to estimate the impacts of demand variability based on customer behavior.
Capturing variability in pavement performance models from sufficient time-series predictors: a case study of the New Brunswick road network
Authors: Amador-Jiménez Luis Esteban , Mrawira Donath
Published: February 2011

This paper proposes the use of multi-level Bayesian modeling for calibrating mechanistic model parameters from historical data while capturing reliability by estimating a desired confidence interval of the predictions. The model is capable of estimating the parameters from the observed data and expert criteria even in cases of missing data points. This approach allows rapid generation of several deterioration models without the need to partition the data into pavement families. It estimates posterior distributions for model coefficients and predicts values of the response for unobserved levels of the causal factors. A case study from the New Brunswick Department of Transportation is used to calibrate a simplified mechanistic pavement roughness progression model based on 6-year international roughness index (IRI) observations. The model incorporates the effects of pavement structural capacity in terms of deflection basin parameter (AREA) in place of the modified structural number, traffic loading (ESAL) and environmental factors. The results of the model showed that, as expected, chipseal roads have higher as built roughness and deteriorate faster than asphalt roads. Sensitivity analysis of the deterministic (the mean predictions) part of the model showed that in New Brunswick where traffic is relatively low the environment is the most important factor.
Nucleosome distribution and linker DNA: connecting nuclear function to dynamic chromatin structureThis paper is one of a selection of papers published in a Special Issue entitled 31st Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.
Authors: Szerlong Heather J. , Hansen Jeffrey C.
Published: February 2011

Genetic information in eukaryotes is managed by strategic hierarchical organization of chromatin structure. Primary chromatin structure describes an unfolded nucleosomal array, often referred to as “beads on a string”. Chromatin is compacted by the nonlinear rearrangement of nucleosomes to form stable secondary chromatin structures. Chromatin conformational transitions between primary and secondary structures are mediated by both nucleosome-stacking interactions and the intervening linker DNA. Chromatin model system studies find that the topography of secondary structures is sensitive to the spacing of nucleosomes within an array. Understanding the relationship between nucleosome spacing and higher order chromatin structure will likely yield important insights into the dynamic nature of secondary chromatin structure as it occurs in vivo. Genome-wide nucleosome mapping studies find the distance between nucleosomes varies, and regions of uniformly spaced nucleosomes are often interrupted by regions of nonuniform spacing. This type of organization is found at a subset of actively transcribed genes in which a nucleosome-depleted region near the transcription start site is directly adjacent to uniformly spaced nucleosomes in the coding region. Here, we evaluate secondary chromatin structure and discuss the structural and functional implications of variable nucleosome distributions in different organisms and at gene regulatory junctions.
Application of anifHmicroarray to assess the impact of environmental factors on free-living diazotrophs in a glacier forefield
Authors: Duc Laurence , Neuenschwander Stefan , Rehrauer Hubert , Zeyer Josef
Published: February 2011

Glacier forefield environments are exposed to extreme and fluctuating climatic and nutritional conditions. The high diversity of free-living diazotrophic communities found in these environments indicates that nitrogen fixers are able to efficiently cope with such conditions. In this study, a nifH microarray was used to monitor changes in diazotrophic populations in the field over a season, in the presence or absence of plants and in 2 glacier forefields characterized by a different bedrock type (siliceous or calcareous), as well as at different temperatures (10 °C, 15 °C) and under different nitrogen fertilization regimes (0, 10, 40 kg N·ha–1·year–1) in laboratory systems. Population structures responded highly dynamically to environmental changes. Plant presence had the strongest impact, which decreased toward the end of the season and with high amounts of nitrogen fertilization. Temperature and nitrogen fertilization increases indirectly affected diazotrophic communities through their positive impact on plant growth. These results indicate strong carbon limitation in young glacier forefield soils. Phylotypes related to the genus Methylocystis strongly responded to environmental variations. These methanotrophic microorganisms, which are able to retrieve nitrogen and carbon from the atmospheric pool, are particularly adapted to the extreme nutritional conditions found in glacier forefields.
HIGH-RESOLUTION HYPERNUCLEAR SPECTROSCOPY ELECTRON SCATTERING AT JLab, HALL A
Authors:   For the Hall A Collaboration, Garibaldi F. , Cisbani E. , Cusanno F. , Frullani S. , Iodice M. , Urciuoli G. M. , De Leo R. , Lagamba L. , Marrone S. , LeRose John J. , de Jager C. W. , Feuerbach R. J. , Higinbotham D. W. , Reitz B. , Acha A. , Markowitz P. , Bydžovský P. , Sotona M. , Chang C. C. , Millener J.
Published: February 2011

The characteristics of the Jefferson LAB electron beam, together with those of the experimental equipments, offer a unique opportunity to study hypernuclear spectroscopy via electromagnetic induced reactions. Experiment 94-107 started a systematic study on 1p-shell targets, 12 C , 9 Be and 16 O . We present the results from 12 C , 16 O and very preliminary results from 9 Be . For 12 C for the first time measurable strength in the core-excited part of the spectrum between the ground state and the pΛ state was shown in [Formula: see text] for the first time. A high-quality 16Λ N spectrum was produced for the first time with sub-MeV Energy resolution. A very precise B Λ value for 16Λ N , calibrated against the elementary ( e , e ′ K +) reaction on hydrogen, has also been obtained. Final data on 9 Be will be available soon. The missing energy resolution is the best ever obtained in hypernuclear production experiments.
RECENT RESULTS ON MESONIC WEAK DECAY OF Λ-HYPERNUCLEI
Authors:   For the FINUDA Collaboration, Botta E. , Bressani T. , De Mori F. , Marcello S. , Bufalino S. , Calvo D. , Feliciello A. , Filippi A. , Wheadon R. , Busso L. , Morra O. , Agnello M. , Benussi L. , Bertani M. , Fabbri F. L. , Gianotti P. , Hartmann O. , Lucherini V. , Pace E. , Pompili F. , Andronenkov A. , Palomba M. , Pantaleo A. , Paticchio V. , Dalena B. , D'Erasmo G. , Fiore E. M. , Simonetti G. , Lenti V. , Bonomi G. , Zenoni A. , Fontana A. , Genova P. , Panzarasa A. , Montagna P. , Bregant M. , Camerini P. , Rui R. , Grion N. , Piano S. , Fujioka H. , Nagae T. , Outa H. , Sekimoto M. , Toyoda A. , Maruta T. , Bhang H. C. , Kang B. , Nakajima D. , Mirfakhrai N. , Beer G. , Lorente A. Sanchez
Published: February 2011

The FINUDA experiment has performed a systematic study of mesonic weak decay of p-shell Λ-hypernuclei. Recent results on the mesonic decay spectra and ratios are illustrated and discussed.
STATUS OF STRANGENESS ELECTRO-PRODUCTION AT MAMI
Authors:   For the A1 Collaboration, Achenbach P. , Achenbach P. , Gayoso C. Ayerbe , Bernauer J. C. , Böhm R. , Bösz M. , Bosnar D. , Debenjak L. , Esser A. , Distler M. O. , Rodríguez M. Gómez , Grießinger K. , Jennewein P. , Makek M. , Merkel H. , Müller U. , Nungesser L. , Pochodzalla J. , Potokar M. , Majos S. Sánchez , Schlimme B. S. , Širca S. , Walcher Th. , Weinriefer M. , Yoon C. J.
Published: February 2011

At the Institut für Kernphysik in Mainz, Germany, the microtron MAMI has been upgraded to 1.5 GeV electron beam energy and can now be used to study strange hadronic systems. The magnetic spectrometer KAOS from GSI was dismantled and re-installed in the spectrometer facility operated by the A1 collaboration. The spectrometer's primary purpose is to study strangeness electro-production. Its compact design and its capability to detect negative and positive charged particles simultaneously under forward scattering angles complements the existing spectrometers.

In 2008, an important milestone has been reached by the successful measurement of kaon production off a liquid hydrogen target. The identification of Λ and Σ0 hyperons in the missing mass spectra has demonstrated the capability of the extended facility to perform strangeness electro-production spectroscopy.

To operate KAOS as a double-arm spectrometer under zero degree scattering angle major modifications are needed. A new vacuum chamber was constructed and installed, a new coordinate detector with many thousands of channels was built and tested, a new trigger system for the high rate environment was developed, and a magnetic chicane for the primary electron beam is under construction.
Modeling and simulation of SIP tandem server with finite buffer
Authors: Hong Yang , Huang Changcheng , Yan James
Published: February 2011

Recent collapses of SIP servers (e.g., Skype outage) indicate that the built-in SIP overload control mechanism cannot mitigate overload effectively. We introduce our analytical approach by investigating an overloaded tandem server scenario. Our analytical model: (1) considers a general case that both arrival rate and service rate for signaling messages are generic random processes; (2) makes a detailed analysis of departure processes; (3) allows us to run fluid-based simulations to observe and analyze SIP system performance under some specific scenarios. This approach is much faster than event-driven simulation which needs to track thousands of retransmission timers for outstanding messages and may crash a simulator due to limited computing resources. Our numerical results help us reach a counterintuitive conclusion: A SIP system with a large buffer size may continuously exhibit overload and long queuing delay after experiencing a short period of demand burst or a temporary server slowdown. Small buffer size, on the other hand, can mitigate overload quickly by rejecting a large portion of the requests from a demand burst, and then resume normal operation after a short period of time. Furthermore, numerical results demonstrate that overload at a downstream server may propagate or migrate to its upstream servers and therefore cause widespread server crashes in a real SIP network.
Efficient extraction and analysis of preprocessor-based variability
Authors: Sincero Julio , Tartler Reinhard , Lohmann Daniel , Schröder-Preikschat Wolfgang
Published: February 2011

The C Preprocessor (CPP) is the tool of choice for the implementation of variability in many large-scale configurable software projects. Linux, probably the most-configurable piece of software ever, employs more than 10,000 preprocessor variables for this purpose. However, this de-facto variability tends to be "hidden in the code"; which on the long term leads to variability defects, such as dead code or inconsistencies with respect to the intended (modeled) variability of the software. This calls for tool support for the efficient extraction of (and reasoning over) CPP-based variability.

We suggest a novel approach to extract CPP-based variability. Our tool transforms CPP-based variability in O(n) complexity into a propositional formula that "mimics" all valid effects of conditional compilation and can be analyzed with standard SAT or BDD packages.

Our evaluation results demonstrate the scalability and practicability of the approach. A dead-block-analysis on the complete Linux source tree takes less than 30 minutes; we thereby have revealed 60 dead blocks, 2 of which meanwhile have been confirmed as new (and long-lasting) bugs; the rest is still under investigation.
Iterative type inference with attribute grammars
Authors: Middelkoop Arie , Dijkstra Atze , Swierstra S. Doaitse
Published: February 2011

Type inference is the process of constructing a typing derivation while gradually discovering type information. During this process, inference algorithms typically make subtle decisions based on the derivation constructed so far.

Because a typing derivation is a decorated tree we aim to use attribute grammars as the main implementation tool. Unfortunately, we can neither express iteration, nor express decisions based on intermediate derivations in such grammars.

We present the language ruler-front, a conservative extension to ordered attribute grammars, that deals with the aforementioned problems. We show why this extension is suitable for the description of constraint-based inference algorithms.
Modular domain-specific language components in scala
Authors: Hofer Christian , Ostermann Klaus
Published: February 2011

Programs in domain-­specific embedded languages (DSELs) can be represented in the host language in different ways, for instance implicitly as libraries, or explicitly in the form of abstract syntax trees. Each of these representations has its own strengths and weaknesses. The implicit approach has good composability properties, whereas the explicit approach allows more freedom in making syntactic program transformations.

Traditional designs for DSELs fix the form of representation, which means that it is not possible to choose the best representation for a particular interpretation or transformation. We propose a new design for implementing DSELs in Scala which makes it easy to use different program representations at the same time. It enables the DSL implementor to define modular language components and to compose transformations and interpretations for them.
What Makes a Good Learning Game?
Authors: Egenfeldt-Nielsen Simon
Published: February 2011

Presented herein is a simple and pragmatic framework for primarily analyzing and evaluating the design quality of a learning game. The framework focuses on the characteristics of learning games compared to computer games, in general, to find the key parameters to analyze. The key variables in the framework are integration, focus and motivation.
Exercise limits the production of endothelin in the coronary vasculature
Authors: de Beer Vincent J. , Bender Shawn B. , Taverne Yannick J. , Gao Fen , Duncker Dirk J. , Laughlin M. Harold , Merkus Daphne
Published: February 2011

We previously demonstrated that endothelin (ET)-mediated coronary vasoconstriction wanes with increasing exercise intensity via a nitric oxide- and prostacyclin-dependent mechanism (Ref. 23). Therefore, we hypothesized that the waning of ET coronary vasoconstriction during exercise is the result of decreased production of ET and/or decreased ET receptor sensitivity. We investigated coronary ET receptor sensitivity using intravenous infusion of ET and coronary ET production using intravenous infusion of the ET precursor Big ET, at rest and during continuous treadmill exercise at 3 km/h in 16 chronically instrumented swine. In the systemic vasculature, Big ET and ET induced similar changes in hemodynamic parameters at rest and during continuous exercise at 3 km/h, indicating that exercise does not alter ET production or receptor sensitivity in the systemic vasculature. In the coronary vasculature, infusion of ET resulted in similar dose-dependent decreases in coronary blood flow and coronary venous oxygen tension and saturation at rest and during exercise. In contrast, administration of Big ET resulted in dose-dependent decreases in coronary blood flow, as well as coronary venous oxygen tension and saturation at rest. These effects of Big ET were significantly reduced during exercise. Altogether, our data indicate that continuous exercise at 3 km/h attenuates ET-mediated coronary vasoconstriction through reduced production of ET from Big ET rather than through reduced ET sensitivity of the coronary vasculature. The decreased ET production during exercise likely contributes to metabolic coronary vasodilation.
Ventilatory baroreflex sensitivity in humans is not modulated by chemoreflex activation
Authors: Stewart Julian M. , Rivera Eileen , Clarke Debbie A. , Baugham Ila L. , Ocon Anthony J. , Taneja Indu , Terilli Courtney , Medow Marvin S.
Published: February 2011

Increasing arterial blood pressure (AP) decreases ventilation, whereas decreasing AP increases ventilation in experimental animals. To determine whether a “ventilatory baroreflex” exists in humans, we studied 12 healthy subjects aged 18–26 yr. Subjects underwent baroreflex unloading and reloading using intravenous bolus sodium nitroprusside (SNP) followed by phenylephrine (“Oxford maneuver”) during the following “gas conditions:” room air, hypoxia (10% oxygen)-eucapnia, and 30% oxygen-hypercapnia to 55–60 Torr. Mean AP (MAP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), expiratory minute ventilation (VE), respiratory rate (RR), and tidal volume were measured. After achieving a stable baseline for gas conditions, we performed the Oxford maneuver. VE increased from 8.8 ± 1.3 l/min in room air to 14.6 ± 0.8 l/min during hypoxia and to 20.1 ± 2.4 l/min during hypercapnia, primarily by increasing tidal volume. VE doubled during SNP. CO increased from 4.9 ± .3 l/min in room air to 6.1 ± .6 l/min during hypoxia and 6.4 ± .4 l/min during hypercapnia with decreased TPR. HR increased for hypoxia and hypercapnia. Sigmoidal ventilatory baroreflex curves of VE versus MAP were prepared for each subject and each gas condition. Averaged curves for a given gas condition were obtained by averaging fits over all subjects. There were no significant differences in the average fitted slopes for different gas conditions, although the operating point varied with gas conditions. We conclude that rapid baroreflex unloading during the Oxford maneuver is a potent ventilatory stimulus in healthy volunteers. Tidal volume is primarily increased. Ventilatory baroreflex sensitivity is unaffected by chemoreflex activation, although the operating point is shifted with hypoxia and hypercapnia.
Atorvastatin suppresses LPS-induced rapid upregulation of Toll-like receptor 4 and its signaling pathway in endothelial cells
Authors: Wang Ying , Zhang Ming Xiang , Meng Xiao , Liu Fu Qiang , Yu Guang Sheng , Zhang Cheng , Sun Tao , Wang Xu Ping , Li Li , Wang Yuan Yuan , Ding Shi Fang , Yang Jian Min , Zhang Yun
Published: February 2011

In the present study, we tested our hypothesis that atorvastatin exerts its anti-inflammation effect via suppressing LPS-induced rapid upregulation of Toll-like receptor 4 (TLR4) mRNA and its downstream p38, ERK, and NF-κB signaling pathways in human umbilical-vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs). TLR4 mRNA expression and its downstream kinase activities induced by LPS alone or atorvastatin + LPS in endothelial cells were quantified using quantitative real-time PCR and enzyme-linked immunosorbent assay. Preincubation of LPS-stimulated endothelial cells with TLR4 siRNA was conducted to identify the target of the anti-inflammatory effects of atorvastatin. Atorvastatin incubation resulted in the reduction of LPS-induced TLR4 mRNA expression, ERK1/2 and P38 MAPK phosphorylation, and NF-κB binding activity. Pretreatment with MEK/ERK1/2 inhibitor PD98059 attenuated atorvastatin + LPS-induced NF-κB activity but had no effect on P38 MAPK phosphorylation. In contrast, pretreatment with P38 MAPK inhibitor SB203580 resulted in upregulation of atorvastatin + LPS-induced ERK1/2 phosphorylation but had no significant effects on NF-κB activity. On the other hand, blocking NF-κB with SN50 produced no effects on atorvastatin + LPS-induced ERK1/2 and P38 MAPK phosphorylation. Moreover, TLR4 gene silencing produced the same effects as the atorvastatin treatment. In conclusion, atorvastatin downregulated TLR4 mRNA expression by two distinct signaling pathways. First, atorvastatin stabilized Iκ-Bα, which directly inhibited NF-κB activation. Second, atorvastatin inactivated ERK phosphorylation, which indirectly inhibited NF-κB activation. Suppression of p38 MAPK by atorvastatin upregulates ERK but exerts no effect on NF-κB.
Stability, Bifurcation, and Chaos in N‐Firm Nonlinear Cournot Games
Authors: Matsumoto Akio , Szidarovszky Ferenc
Published: February 2011

An N‐firm production game known as oligopoly will be examined with isoelastic price function and linear cost under al Cournot competition. After the best responses of the firms are determined, a dynamic system with adaptive expectations is introduced. It is first shown that the local asymptotic behavior of the system is identical with that of the adaptive adjustment process in which the firms cautiously determine their outputs. Dynamic analysis is confined to two special cases, one in which
N is divided into two groups and the other in which
N is divided into three groups. Then stability conditions will be derived and the global behavior of the equilibria will be illustrated including chaos control. Lastly the two‐ and three‐group models are compared with two‐firm (duopoly) and three‐firm (triopoly) models to shed light on roles of the number of the firms.
Genetics, Cytogenetics, and Epigenetics of Colorectal Cancer
Authors: Migliore Lucia , Migheli Francesca , Spisni Roberto , Coppedè Fabio
Published: February 2011

Most of the colorectal cancer (CRC) cases are sporadic, only 25% of the patients have a family history of the disease, and major genes causing syndromes predisposing to CRC only account for 5‐6% of the total cases. The following subtypes can be recognized: MIN (microsatellite instability), CIN (chromosomal instability), and CIMP (CpG island methylator phenotype). CIN occurs in 80–85% of CRC. Chromosomal instability proceeds through two major mechanisms, missegregation that results in aneuploidy through the gain or loss of whole chromosomes, and unbalanced structural rearrangements that lead to the loss and/or gain of chromosomal regions. The loss of heterozygosity that occur in the first phases of the CRC cancerogenesis (in particular for the genes on 18q) as well as the alteration of methylation pattern of multiple key genes can drive the development of colorectal cancer by facilitating the acquisition of multiple tumor‐associated mutations and the instability phenotype.