bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational design of synthetic gene circuits with composable parts
Authors: Marchisio M.A. , Stelling J. 
Published: June 2008

Abstract
Motivation: In principle, novel genetic circuits can be engineered using standard parts with well-understood functionalities. However, no model based on the simple composition of these parts has become a standard, mainly because it is difficult to define signal exchanges between biological units as unambiguously as in electrical engineering. Corresponding concepts and computational tools for easy circuit design in biology are missing.
Results: Taking inspiration from (and slightly modifying) ideas in the ‘MIT Registry of Standard Biological Parts’, we developed a method for the design of genetic circuits with composable parts. Gene expression requires four kinds of signal carriers: RNA polymerases, ribosomes, transcription factors and environmental ‘messages’ (inducers or corepressors). The flux of each of these types of molecules is a quantifiable biological signal exchanged between parts. Here, each part is modeled independently by the ordinary differential equations (ODE) formalism and integrated into the software ProMoT (Process Modeling Tool). In this way, we realized a ‘drag and drop’ tool, where genetic circuits are built just by placing biological parts on a canvas and by connecting them through ‘wires’ that enable flow of signal carriers, as it happens in electrical engineering. Our simulations of well-known synthetic circuits agree well with published computational and experimental results.
Availability: The code is available on request from the authors.
Contact: mario.marchisio@bsse.ethz.ch
Supplementary information: Supplementary data are available at Bioinformatics online.
CellML and associated tools and techniques
Authors: Garny Alan , Nickerson David P , Cooper Jonathan , Santos Rodrigo Weber dos , Miller Andrew K , McKeever Steve , Nielsen Poul M.F , Hunter Peter J 
Published: June 2008

We have, in the last few years, witnessed the development and availability of an ever increasing number of computer models that describe complex biological structures and processes. The multi-scale and multi-physics nature of these models makes their development particularly challenging, not only from a biological or biophysical viewpoint but also from a mathematical and computational perspective. In addition, the issue of sharing and reusing such models has proved to be particularly problematic, with the published models often lacking information that is required to accurately reproduce the published results.
The International Union of Physiological Sciences Physiome Project was launched in 1997 with the aim of tackling the aforementioned issues by providing a framework for the modelling of the human body. As part of this initiative, the specifications of the CellML mark-up language were released in 2001.
Now, more than 7 years later, the time has come to assess the situation, in particular with regard to the tools and techniques that are now available to the modelling community. Thus, after introducing CellML, we review and discuss existing editors, validators, online repository, code generators and simulation environments, as well as the CellML Application Program Interface. We also address possible future directions including the need for additional mark-up languages.
Influence of Host Interleukin-10 Polymorphisms on Development of Traveler's Diarrhea Due to Heat-Labile Enterotoxin-ProducingEscherichia coliin Travelers from the United States Who Are Visiting Mexico
Authors: Flores Jose , DuPont Herbert L. , Lee Stephanie A. , Belkind-Gerson Jaime , Paredes Mercedes , Mohamed Jamal A. , Armitige Lisa Y. , Guo Dong-Chuan , Okhuysen Pablo C. 
Published: June 2008

ABSTRACTUp to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenicEscherichia coli(ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position −1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position −819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position −592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%;P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.
Effects of Multispecies Probiotic Combination on
Helicobacter pylori
Infection In Vitro
Authors: Myllyluoma E. , Ahonen A.-M. , Korpela R. , Vapaatalo H. , Kankuri E. 
Published: June 2008

ABSTRACT

Probiotic bacteria alleviate many gastrointestinal symptoms, but the current trend of combining bacteria for additional benefit may make their effects more complex. We characterize four probiotics and their combination in terms of pathogen adhesion, barrier function, cell death, and inflammatory response in
Helicobacter pylori
-infected epithelial cells.
H. pylori
-infected Caco-2 cells were pretreated with
Lactobacillus rhamnosus
GG,
Lactobacillus rhamnosus
Lc705,
Propionibacterium freudenreichii
subsp.
shermanii
Js,
Bifidobacterium breve
Bb99, or all four organisms in combination. We evaluated the adhesion of
H. pylori
by in situ immunofluorescence; epithelial barrier function by measurement of transepithelial resistance; apoptosis by measurement of caspase 3 activation; cell membrane leakage by measurement of lactate dehydrogenase release; and inflammation by measurement of interleukin-8 (IL-8), IL-10, prostaglandin E
2
(PGE
2
), and leukotriene B
4
(LTB
4
) release. All probiotics inhibited
H. pylori
adhesion.
L. rhamnosus
GG,
L. rhamnosus
Lc705,
P. freudenreichii
subsp.
shermanii
Js, and the combination inhibited
H. pylori
-induced cell membrane leakage.
L. rhamnosus
GG,
L. rhamnosus
Lc705, and the combination initially improved epithelial barrier function but increased the
H. pylori
-induced barrier deterioration after incubation for 24 to 42 h.
L. rhamnosus
GG,
L. rhamnosus
Lc705, and
P. freudenreichii
subsp.
shermanii
Js inhibited
H. pylori
-induced IL-8 release, whereas
L. rhamnosus
GG,
L. rhamnosus
Lc705, and
B. breve
Bb99 suppressed PGE
2
release. None of these anti-inflammatory effects persisted when the probiotics were used in combination. The combination thus increased the levels of IL-8, PGE
2
, and LTB
4
released from
H. pylori
-infected epithelial cells. The proinflammatory actions of the individual components dominated the anti-inflammatory effects when the probiotic bacteria were used in combination. Our results stress that the therapeutic response can be optimized if probiotic strains are characterized before they are used in combination.
Differential Expression of Interleukin-4 (IL-4) and IL-4δ2 mRNA, but Not Transforming Growth Factor Beta (TGF-β), TGF-βRII, Foxp3, Gamma Interferon, T-bet, or GATA-3 mRNA, in Patients with Fast and Slow Responses to Antituberculosis Treatment
Authors: Djoba Siawaya Joel Fleury , Bapela Nchinya Bennedict , Ronacher Katharina , Beyers Nulda , van Helden Paul , Walzl Gerhard 
Published: June 2008

ABSTRACTThis study investigated interleukin-4 (IL-4), IL-4δ2, transforming growth factor beta (TGF-β), TGF-βRII, Foxp3, GATA-3, T-bet, and gamma interferon (IFN-γ) transcription in peripheral blood samples of adult pulmonary tuberculosis patients prior to and after 1 week of therapy. Twenty patients with positive results for sputum culture forMycobacterium tuberculosiswere enrolled and treated with directly observed short-course antituberculosis chemotherapy. Early treatment response was assessed. At the end of the intensive phase of treatment (month 2), 12 patients remained sputum culture positive (slow responders) and 8 converted to a negative culture (fast responders). Only the expression levels of IL-4 (4-fold decrease) and IL-4δ2 (32-fold increase) changed significantly during the first week of therapy in the 20 patients. No baseline differences were present between the responder groups, but fast responders had significantly higher IL-4 transcripts than slow responders at week 1. Fast responders showed a 19-fold upregulation and slow responders a 47-fold upregulation of IL-4δ2 at week 1. Only slow responders also showed a significant decrease in IL-4 expression at week 1. There were no significant differences in expression of TGF-β, TGF-βRII, Foxp3, IFN-γ, and GATA-3 between the groups. These data show that differential IL-4-related gene expression in the early stage of antituberculosis treatment accompanies differential treatment responses and may hold promise as a marker for treatment effect.
Interleukin-23 Is Required for Development of Arthritis in Mice Vaccinated and Challenged withBorreliaSpecies
Authors: Kotloski Nicholas J. , Nardelli Dean T. , Peterson Sara Heil , Torrealba Jose R. , Warner Thomas F. , Callister Steven M. , Schell Ronald F. 
Published: June 2008

ABSTRACTWe recently hypothesized that T helper 17 (Th17) cells and their associated cytokines are involved in the development of arthritis following infection withBorrelia burgdorferi. Here, we show that interleukin-23 (IL-23), a survival factor for Th17 cells, is required for the induction of arthritis in mice vaccinated withB. burgdorferistrain 297 and challenged with “Borrelia bissettii.” WhenBorrelia-vaccinated and -challenged mice were given antibodies to the p19 subunit of IL-23, they failed to develop the histopathological changes observed in untreated vaccinated and challenged mice. In addition, viableB. bissettiiorganisms stimulated the secretion of IL-17 fromBorrelia-immune lymph node cells during in vitro culture. When anti-IL-23 p19 antibody was included in cultures ofB. bissettiiorganisms andBorrelia-immune lymph node cells, the production of IL-17 was reduced to levels observed in cultures containing immune cells alone. Taken together, these results support the hypothesis that Th17 cell-associated cytokines are involved in the development ofBorrelia-mediated arthritis. These findings provide insight into previously overlooked immune mechanisms responsible for the development of Lyme arthritis.
Novel Protective Antigens Expressed by
Trypanosoma cruzi
Amastigotes Provide Immunity to Mice Highly Susceptible to Chagas' Disease
Authors: Silveira Eduardo L. V. , Claser Carla , Haolla Filipe A. B. , Zanella Luiz G. , Rodrigues Mauricio M. 
Published: June 2008

ABSTRACT

Earlier studies have demonstrated in A/Sn mice highly susceptible to Chagas' disease protective immunity against lethal
Trypanosoma cruzi
infection elicited by vaccination with an open reading frame (ORF) expressed by amastigotes. In our experiments, we used this mouse model to search for other amastigote-expressed ORFs with a similar property. Fourteen ORFs previously determined to be expressed in this developmental stage were individually inserted into a eukaryotic expression vector containing a nucleotide sequence that encoded a mammalian secretory signal peptide. Immunization with 13 of the 14 ORFs induced specific antibodies which recognized the amastigotes. Three of those immune sera also reacted with trypomastigotes and epimastigotes. After a lethal challenge with Y strain trypomastigotes, the vast majority of plasmid-injected mice succumbed to infection. In some cases, a significant delay in mortality was observed. Only two of these ORFs provided protective immunity against the otherwise lethal infection caused by trypomastigotes of the Y or Colombia strain. These ORFs encode members of the
trans
-sialidase family of surface antigens related to the previously described protective antigen amastigote surface protein 2 (ASP-2). Nevertheless, at the level of antibody recognition, no cross-reactivity was observed between the ORFs and the previously described ASP-2 from the Y strain. In immunofluorescence analyses, we observed the presence of epitopes related to both proteins expressed by amastigotes of seven different strains. In conclusion, our approach allowed us to successfully identify two novel protective ORFs which we consider interesting for future studies on the immune response to Chagas' disease.
Quantitative Survival of Aerobic and Anaerobic Microorganisms in Port-A-Cul and Copan Transport Systems
Authors: Stoner Kevin A. , Rabe Lorna K. , Austin Michele N. , Meyn Leslie A. , Hillier Sharon L. 
Published: June 2008

ABSTRACT

Transport media should preserve the viability and stability of microorganisms in clinical specimens. In this study, the Port-A-Cul transport system and the Copan transport system without charcoal, both designed to preserve anaerobes, were evaluated. Dacron swabs were inoculated with two combinations of facultative and anaerobic organisms typically found in vaginal swab samples. Combination I contained
Candida albicans
,
Escherichia coli
,
Enterococcus
spp., group B streptococci,
Lactobacillus crispatus
, and
Staphylococcus aureus
. Combination II contained
Lactobacillus iners
,
Peptoniphilus asaccharolyticus
,
Mycoplasma hominis
,
Prevotella bivia
,
Prevotella corporis
,
Porphyromonas asaccharolytica
,
Mobiluncus curtisii
,
Peptostreptococcus anaerobius
, and
Gardnerella vaginalis
. Duplicate swabs were placed into the two transporters and held for 24, 48, 72, and 96 h at 4 and 24°C. Both transporters maintained the viability of organisms better at 4°C than at 24°C.
Prevotella bivia
and
Prevotella corporis
had a loss of viability in both transporters at both temperatures. However, at 24°C, there was a significantly greater loss of viability for
Mycoplasma hominis
,
Prevotella bivia
,
Prevotella corporis
, and
Peptoniphilus asaccharolyticus
when the organisms were stored in Copan transport medium than when they were stored in Port-A-Cul transport medium for 96 h (
P
< 0.002). Some organisms proliferated in the transport media, but when transporters were held at 24°C for 96 h, a significantly greater increase in the concentrations of group B streptococci and
Candida albicans
,
Escherichia coli
, and
Enterococcus
spp. organisms in Copan medium than in Port-A-Cul medium was observed (
P
< 0.002). At room temperature, the Port-A-Cul system is superior to the Copan system with respect to the preservation of fastidious microorganisms and the prevention of the proliferation of facultative organisms.
Characterization of Small-Colony Variants ofEnterococcus faecalisIsolated from Chickens with Amyloid Arthropathy
Authors: Petersen Andreas , Chadfield Mark S. , Christensen Jens P. , Christensen Henrik , Bisgaard Magne 
Published: June 2008

ABSTRACTIn this study we report the isolation and characterization of normal-sized and small-colony variants ofEnterococcus faecalisfrom outbreaks of amyloid arthropathy in chickens. Postmortem examinations of 59 chickens revealed orange deposits in the knee joints, typical for amyloid arthropathy. Bacterial cultures from 102 joints and 43 spleens exhibited pure (n= 88) and mixed (n= 11) cultures of normal (n= 60) and pinpoint (n= 28) colonies ofE.faecalis. Pulsed-field gel electrophoresis of 62 isolates demonstrated seven different band patterns with at most two band size variations, and multilocus sequence typing demonstrated two different sequence types, sharing six out of seven alleles, suggesting a close evolutionary relationship between isolates obtained from four outbreaks. In addition, all isolates were clonally related to an amyloid arthropathy reference strain from The Netherlands, previously shown to be globally dispersed. Initial investigation of the isolated small-colony variant phenotype revealed no difference in whole-cell protein profiling between normal and pinpoint colonies. However, the pinpoint colony isolates appeared to be more virulent in an in vivo challenge model in chickens than their normal-sized-colony counterparts. In addition, pinpoint morphology and associated slow growth were expressed without reversion after in vitro and in vivo passage, suggesting a genuine altered phenotype, and in some instances normal colonies converted to pinpoint morphology postinfection. In conclusion, small-colony variants ofE. faecalisare described for the first time from veterinary clinical sources and in relation to amyloid arthropathy in chickens.
Anomalies in the Influenza Virus Genome Database: New Biology or Laboratory Errors?
Authors: Krasnitz Michael , Levine Arnold J. , Rabadan Raul 
Published: June 2008

ABSTRACT
A search of the influenza virus genome database reveals anomalies associated with a nonnegligible number of submitted sequences. There are many pairs of viral segments that are very close to each other in nucleotide sequence but relatively far apart in reported time of isolation, resulting in an abnormally low evolutionary rate. Also, some sequences show clear evidence of apparent homologous recombination, a process normally assumed to be extremely rare or nonexistent in this virus. These findings may point to surprising new biology but are perhaps more readily explained by stock contamination or other errors in the sequencing laboratories.
Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells Express the Serotonin Receptor and Are Susceptible to JC Virus Infection
Authors: Schaumburg C. , O'Hara B. A. , Lane T. E. , Atwood W. J. 
Published: June 2008

ABSTRACT

We studied the susceptibility of human embryonic stem cell-derived oligodendrocyte progenitor cells to infection with JC virus, the causative agent of progressive multifocal leukoencephalopathy (PML). A human embryonic stem cell line, H7, was used to derive an enriched population of cells expressing the oligodendrocyte progenitor cell-specific marker NG2. These cells expressed the 5HT
2a
receptor (5HT
2a
R) for JC virus and were highly susceptible to infection. Infection was reduced by treatment with anti-5HT
2a
R antibodies and by the 5HT
2a
R antagonists ritanserin and ketanserin. This is the first demonstration that human embryonic stem cell-derived oligodendrocyte progenitor cells are susceptible to JC virus infection and indicates that cells poised to replenish mature oligodendrocytes in PML lesions may also be a target of viral infection.
STAT-1- and IRF-3-Dependent Pathways Are Not Essential for Repression of ICP0-Null Mutant Herpes Simplex Virus Type 1 in Human Fibroblasts
Authors: Everett Roger D. , Young Dan F. , Randall Rick E. , Orr Anne 
Published: June 2008

ABSTRACT
Efficient herpes simplex virus type 1 (HSV-1) infection of human fibroblasts (HFs) is highly dependent on the viral immediate-early regulatory protein ICP0 unless the infection is conducted at a high multiplicity. ICP0-null mutant HSV-1 exhibits a plaque-forming defect of up to 3 orders of magnitude in HFs, whereas in many other cell types, this defect varies between 10- and 30-fold. The reasons for the high ICP0 requirement for HSV-1 infection in HFs have not been established definitively. Previous studies using other cell types suggested that ICP0-null mutant HSV-1 is hypersensitive to interferon and that this sensitivity is dependent on the cellular promyelocytic leukemia (PML) protein. To investigate the roles of two important aspects of interferon signaling in the phenotype of ICP0-null mutant HSV-1, we isolated HFs depleted of STAT-1 or interferon regulatory factor 3 (IRF-3). Surprisingly, plaque formation by the mutant virus was not improved in either cell type. We found that the sensitivity to interferon pretreatment of both ICP0-null mutant and wild-type (wt) HSV-1 was highly dependent on the multiplicity of infection. At a low multiplicity in virus yield experiments, both viruses were extremely susceptible to interferon pretreatment of HFs, but the sensitivity of the wild type but not the mutant could be overcome at higher multiplicities. We found that both wt and ICP0-null mutant HSV-1 remained sensitive to interferon in PML-depleted HFs albeit to an apparently lesser extent than in control cells. The data imply that the substantial reduction in ICP0-null HSV-1 infectivity at a low multiplicity in HFs does not occur through the activities of STAT-1- and IRF-3-dependent pathways and cannot be explained solely by enhanced sensitivity to interferon. We suggest that antiviral activities induced by interferon may be separable from and additive to those resulting from PML-related intrinsic resistance mechanisms.
Linker Histones Are Mobilized during Infection with Herpes Simplex Virus Type 1
Authors: Conn Kristen L. , Hendzel Michael J. , Schang Luis M. 
Published: June 2008

ABSTRACT
Histones interact with herpes simplex virus type 1 (HSV-1) genomes and localize to replication compartments early during infections. However, HSV-1 genomes do not interact with histones in virions and are deposited in nuclear domains devoid of histones. Moreover, late viral replication compartments are also devoid of histones. The processes whereby histones come to interact with HSV-1 genomes, to be later displaced, remain unknown. However, they would involve the early movement of histones to the domains containing HSV-1 genomes and the later movement away from them. Histones unbind from chromatin, diffuse through the nucleoplasm, and rebind at different sites. Such mobility is upregulated by, for example, phosphorylation or acetylation. We evaluated whether HSV-1 infection modulates histone mobility, using fluorescence recovery after photobleaching. All somatic H1 variants were mobilized to different degrees. H1.2, the most mobilized, was mobilized at 4 h and further so at 7 h after infection, resulting in increases in its “free” pools. H1.2 was mobilized to a “basal” degree under conditions of little to no HSV-1 protein expression. This basal mobilization required nuclear native HSV-1 genomes but was independent of HSV-1 proteins and most likely due to cellular responses. Mobilization above this basal degree, and increases in H1.2 free pools, however, depended on immediate-early or early HSV-1 proteins, but not on HSV-1 genome replication or late proteins. Linker histone mobilization is a novel consequence of cell-virus interactions, which is consistent with the dynamic interactions between histones and HSV-1 genomes during lytic infection; it may also participate in the regulation of viral gene expression.