bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia
Authors: Germeshausen Manuela , Welte Karl , Ballmaier Matthias 
Published: November 2008

Abstract
Severe congenital neutropenia (CN) is a rare bone marrow failure syndrome with a high incidence of acute leukemia. In previous studies, we could show that point mutations in the gene for the granulocyte colony-stimulating factor (G-CSF) receptor CSF3R are a highly predictive marker for leukemic development in CN patients. To find out at which stage of hematopoietic development these mutations emerge and how they are propagated during hematopoietic differentiation, we analyzed single cells of different hematopoietic subpopulations from CN patients with CSF3R mutations. We found that CSF3R mutations are not restricted to the myeloid compartment but are also detectable in lymphoid cells, although at a much lower percentage. From our observations, we conclude that CSF3R mutations are acquired in multipotent hematopoietic progenitor cells in CN patients and that they are clonally expanded in myeloid cells expressing the G-CSF receptor due to the growth advantage mediated by the CSF3R mutation.
Prosecutor: parameter-free inference of gene function for prokaryotes using DNA microarray data, genomic context and multiple gene annotation sources
Authors: Blom Evert Jan , Breitling Rainer , Hofstede Klaas Jan , Roerdink Jos BTM , van Hijum Sacha AFT , Kuipers Oscar P 
Published: November 2008

Abstract

Background
Despite a plethora of functional genomic efforts, the function of many genes in sequenced genomes remains unknown. The increasing amount of microarray data for many species allows employing the guilt-by-association principle to predict function on a large scale: genes exhibiting similar expression patterns are more likely to participate in shared biological processes.

Results
We developed Prosecutor, an application that enables researchers to rapidly infer gene function based on available gene expression data and functional annotations. Our parameter-free functional prediction method uses a sensitive algorithm to achieve a high association rate of linking genes with unknown function to annotated genes. Furthermore, Prosecutor utilizes additional biological information such as genomic context and known regulatory mechanisms that are specific for prokaryotes. We analyzed publicly available transcriptome data sets and used literature sources to validate putative functions suggested by Prosecutor. We supply the complete results of our analysis for 11 prokaryotic organisms on a dedicated website.

Conclusion
The Prosecutor software and supplementary datasets available at http://www.prosecutor.nl allow researchers working on any of the analyzed organisms to quickly identify the putative functions of their genes of interest. A de novo analysis allows new organisms to be studied.
A genome survey of Moniliophthora perniciosa gives new insights into Witches' Broom Disease of cacao
Authors: Mondego Jorge MC , Carazzolle Marcelo F , Costa Gustavo GL , Formighieri Eduardo F , Parizzi Lucas P , Rincones Johana , Cotomacci Carolina , Carraro Dirce M , Cunha Anderson F , Carrer Helaine , Vidal Ramon O , Estrela Raíssa C , García Odalys , Thomazella Daniela PT , de Oliveira Bruno V , Pires Acássia BL , Rio Maria Carolina S , Araújo Marcos Renato R , de Moraes Marcos H , Castro Luis AB , Gramacho Karina P , Gonçalves Marilda S , Neto José P Moura , Neto Aristóteles Góes , Barbosa Luciana V , Guiltinan Mark J , Bailey Bryan A , Meinhardt Lyndel W , Cascardo Julio CM , Pereira Gonçalo AG 
Published: November 2008

Abstract

Background
The basidiomycete fungus Moniliophthora perniciosa is the causal agent of Witches' Broom Disease (WBD) in cacao (Theobroma cacao). It is a hemibiotrophic pathogen that colonizes the apoplast of cacao's meristematic tissues as a biotrophic pathogen, switching to a saprotrophic lifestyle during later stages of infection. M. perniciosa, together with the related species M. roreri, are pathogens of aerial parts of the plant, an uncommon characteristic in the order Agaricales. A genome survey (1.9× coverage) of M. perniciosa was analyzed to evaluate the overall gene content of this phytopathogen.

Results
Genes encoding proteins involved in retrotransposition, reactive oxygen species (ROS) resistance, drug efflux transport and cell wall degradation were identified. The great number of genes encoding cytochrome P450 monooxygenases (1.15% of gene models) indicates that M. perniciosa has a great potential for detoxification, production of toxins and hormones; which may confer a high adaptive ability to the fungus. We have also discovered new genes encoding putative secreted polypeptides rich in cysteine, as well as genes related to methylotrophy and plant hormone biosynthesis (gibberellin and auxin). Analysis of gene families indicated that M. perniciosa have similar amounts of carboxylesterases and repertoires of plant cell wall degrading enzymes as other hemibiotrophic fungi. In addition, an approach for normalization of gene family data using incomplete genome data was developed and applied in M. perniciosa genome survey.

Conclusion
This genome survey gives an overview of the M. perniciosa genome, and reveals that a significant portion is involved in stress adaptation and plant necrosis, two necessary characteristics for a hemibiotrophic fungus to fulfill its infection cycle. Our analysis provides new evidence revealing potential adaptive traits that may play major roles in the mechanisms of pathogenicity in the M. perniciosa/cacao pathosystem.
Immunological evaluation of Lactobacillus casei Zhang: a newly isolated strain from koumiss in Inner Mongolia, China
Authors: Ya Tuo , Zhang Qijin , Chu Fuliang , Merritt Justin , Bilige Menhe , Sun Tiansong , Du Ruiting , Zhang Heping 
Published: November 2008

Abstract

Background
There is increasing evidence to suggest an immunomodulation function both within the intestines and systemically upon consuming probiotic species. We recently isolated a novel LAB, Lactobacillus casei Zhang (LcZhang) from koumiss. LcZhang exhibited favorable probiotic properties, such as acid resistance, bile resistance, gastrointestinal (GI) colonization ability, etc. In order to examine the immunomodulatory qualities of LcZhang, we administered LcZhang to healthy mice with varying doses of either live or heat-killed LcZhang and measured various parameters of the host immune response.

Results
The study was performed in four separate experiments via oral administration of live and heat-killed LcZhang to BALB/c mice for several consecutive days. We investigated the immunomodulating capacity of LcZhang in vivo by analyzing the profile of cytokines, T cell subpopulations, and immunoglobulin concentrations induced in blood serum and intestinal fluid in BALB/c mice. Only live bacteria elicited a wide range of immune responses, which include the increased production of interferon-γ (IFN-γ), and depression of tumor necrosis factor-α (TNF-α) levels. In addition, interleukin-2 (IL-2) and IL-2 receptor gene transcription increased significantly, but the proportion of T cell subsets appeared to be unaffected. We also observed that LcZhang was capable of inducing gut mucosal responses by enhancing the production of secretory Immunoglobulin A (sIgA) as well influencing the systemic immunity via the cytokines released to the circulating blood.

Conclusion
The present work shows that the dose-dependent administration of LcZhang is capable of influencing immune responses, implying that it may be a valuable strain for probiotic use in humans.
Characterization of Mce4A protein of Mycobacterium tuberculosis: role in invasion and survival
Authors: Saini Neeraj Kumar , Sharma Monika , Chandolia Amita , Pasricha Rashmi , Brahmachari Vani , Bose Mridula 
Published: November 2008

Abstract

Background
The mce4 operon is one of the four homologues of mammalian cell entry (mce) operons of Mycobacterium tuberculosis. The mce4A (Rv3499c) gene within this operon is homologous to mce1A (Rv0169), that has a role in host cell invasion by M. tuberculosis. Our earlier reports show that mce4 operon is expressed during the stationary phase of growth of the bacillus in culture and during the course of infection in mammalian hosts. M. tuberculosis carrying mutation in mce4 operon shows growth defect and reduced survival in infected mice. However, the intracellular localization of Mce4A protein and its direct role in cell entry or survival of the bacillus has not been demonstrated so far.

Results
By transmission electron microscopy we have demonstrated that recombinant Mce4A protein facilitates the invasion of non-pathogenic strain of E. coli into non-phagocytic HeLa cells. We observe that mce4A gene has a role comparable to mce1A in the survival of recombinant E. coli in human macrophages. Using antibodies raised against Mce4A protein, we show that the protein is localized in the cell wall fraction of M. tuberculosis H37Rv stationary phase culture only.

Conclusion
Mce4A protein is expressed during the stationary phase of broth culture and localizes in the cell wall fraction of M. tuberculosis. Mce4A protein expressed in non-pathogenic E. coli enables it to enter and survive within HeLa cells and the macrophages. As Mce4A protein is expressed during later phase of mycobacterial growth, our results raise the possibility of it playing a role in maintenance of persistent tubercular infection.
Expression of the pstS gene of Streptomyces lividansis regulated by the carbon source and is partially independent of the PhoP regulator
Authors: Esteban Ana , Díaz Margarita , Yepes Ana , Santamaría Ramón I 
Published: November 2008

Abstract

Background
PstS is a phosphate-binding lipoprotein that is part of the high-affinity phosphate transport system. Streptomyces lividans accumulates high amounts of the PstS protein in the supernatant of liquid cultures grown in the presence of different carbon sources, such as fructose or mannose, but not in the presence of glucose or in basal complex medium.

Results
Functionality experiments revealed that this extracellular PstS protein does not have the capacity to capture phosphate and transfer it to the cell. Regulation of the pstS promoter was studied with Northern blot experiments, and protein levels were detected by Western blot analysis. We observed that the pstS gene was expressed in cultures containing glucose or fructose, but not in complex basal medium. Northern blot analyses revealed that the pst operon (pstSCAB) was transcribed as a whole, although higher transcript levels of pstS relative to those of the other genes of the operon (pstC, pstA and pstB) were observed. Deletion of the -329/-144 fragment of the pstS promoter, including eight degenerated repeats of a sequence of 12 nucleotides, resulted in a two-fold increase in the expression of this promoter, suggesting a regulatory role for this region. Additionally, deletion of the fragment corresponding to the Pho boxes recognized by the PhoP regulator (from nucleotide -141 to -113) resulted in constitutive pstS expression that was independent of this regulator. Thus, the PhoP-independent expression of the pstS gene makes this system different from all those studied previously.

Conclusion
1.- In S. lividans, only the PstS protein bound to the cell has the capacity to bind phosphate and transfer it there, whereas the PstS form accumulated in the supernatant lacks this capacity. 2.- The stretch of eight degenerated repeats present in the pstS promoter may act as a binding site for a repressor. 3.- There is a basal expression of the pstS gene that is not controlled by the main regulator: PhoP.
Preparation of alginate coated chitosan microparticles for vaccine delivery
Authors: Li XingYi , Kong XiangYe , Shi Shuai , Zheng XiuLing , Guo Gang , Wei YuQuan , Qian ZhiYong 
Published: November 2008

AbstractBackgroundAbsorption of antigens onto chitosan microparticles via electrostatic interaction is a common and relatively mild process suitable for mucosal vaccine. In order to increase the stability of antigens and prevent an immediate desorption of antigens from chitosan carriers in gastrointestinal tract, coating onto BSA loaded chitosan microparticles with sodium alginate was performed by layer-by-layer technology to meet the requirement of mucosal vaccine.ResultsThe prepared alginate coated BSA loaded chitosan microparticles had loading efficiency (LE) of 60% and loading capacity (LC) of 6% with mean diameter of about 1 μm. When the weight ratio of alginate/chitosan microparticles was greater than 2, the stable system could be obtained. The rapid charge inversion of BSA loaded chitosan microparticles (from +27 mv to -27.8 mv) was observed during the coating procedure which indicated the presence of alginate layer on the chitosan microparticles surfaces. According to the results obtained by scanning electron microscopy (SEM), the core-shell structure of BSA loaded chitosan microparticles was observed. Meanwhile,in vitrorelease study indicated that the initial burst release of BSA from alginate coated chitosan microparticles was lower than that observed from uncoated chitosan microparticles (40% in 8 h vs. about 84% in 0.5 h). SDS-polyacrylamide gel electrophoresis (SDS-PAGE) assay showed that alginate coating onto chitosan microparticles could effectively protect the BSA from degradation or hydrolysis in acidic condition for at least 2 h. The structural integrity of alginate modified chitosan microparticles incubated in PBS for 24 h was investigated by FTIR.ConclusionThe prepared alginate coated chitosan microparticles, with mean diameter of about 1 μm, was suitable for oral mucosal vaccine. Moreover, alginate coating onto the surface of chitosan microparticles could modulate the release behavior of BSA from alginate coated chitosan microparticles and could effectively protect model protein (BSA) from degradation in acidic mediumin vitrofor at least 2 h. In all, the prepared alginate coated chitosan microparticles might be an effective vehicle for oral administration of antigens.
Ligand-induced conformational changes in a thermophilic ribose-binding protein
Authors: Cuneo Matthew J , Beese Lorena S , Hellinga Homme W 
Published: November 2008

Abstract

Background
Members of the periplasmic binding protein (PBP) superfamily are involved in transport and signaling processes in both prokaryotes and eukaryotes. Biological responses are typically mediated by ligand-induced conformational changes in which the binding event is coupled to a hinge-bending motion that brings together two domains in a closed form. In all PBP-mediated biological processes, downstream partners recognize the closed form of the protein. This motion has also been exploited in protein engineering experiments to construct biosensors that transduce ligand binding to a variety of physical signals. Understanding the mechanistic details of PBP conformational changes, both global (hinge bending, twisting, shear movements) and local (rotamer changes, backbone motion), therefore is not only important for understanding their biological function but also for protein engineering experiments.

Results
Here we present biochemical characterization and crystal structure determination of the periplasmic ribose-binding protein (RBP) from the hyperthermophile Thermotoga maritima in its ribose-bound and unliganded state. The T. maritima RBP (tmRBP) has 39% sequence identity and is considerably more resistant to thermal denaturation (
app

T

m
value is 108°C) than the mesophilic Escherichia coli homolog (ecRBP) (
app

T

m
value is 56°C). Polar ligand interactions and ligand-induced global conformational changes are conserved among ecRBP and tmRBP; however local structural rearrangements involving side-chain motions in the ligand-binding site are not conserved.

Conclusion
Although the large-scale ligand-induced changes are mediated through similar regions, and are produced by similar backbone movements in tmRBP and ecRBP, the small-scale ligand-induced structural rearrangements differentiate the mesophile and thermophile. This suggests there are mechanistic differences in the manner by which these two proteins bind their ligands and are an example of how two structurally similar proteins utilize different mechanisms to form a ligand-bound state.
Alterations on peripheral B cell subsets following an acute uncomplicated clinical malaria infection in children
Authors: Asito Amolo S , Moormann Ann M , Kiprotich Chelimo , Ng'ang'a Zipporah W , Ploutz-Snyder Robert , Rochford Rosemary 
Published: November 2008

AbstractBackgroundThe effects ofPlasmodium falciparumon B-cell homeostasis have not been well characterized. This study investigated whether an episode of acute malaria in young children results in changes in the peripheral B cell phenotype.MethodsUsing flow-cytofluorimetric analysis, the B cell phenotypes found in the peripheral blood of children aged 2–5 years were characterized during an episode of acute uncomplicated clinical malaria and four weeks post-recovery and in healthy age-matched controls.ResultsThere was a significant decrease in CD19+B lymphocytes during acute malaria. Characterization of the CD19+B cell subsets in the peripheral blood based on expression of IgD and CD38 revealed a significant decrease in the numbers of naive 1 CD38-IgD+B cells while there was an increase in CD38+IgD-memory 3 B cells during acute malaria. Further analysis of the peripheral B cell phenotype also identified an expansion of transitional CD10+CD19+B cells in children following an episode of acute malaria with up to 25% of total CD19+B cell pool residing in this subset.ConclusionChildren experiencing an episode of acute uncomplicated clinical malaria experienced profound disturbances in B cell homeostasis.
Vitamin E supplementation and pneumonia risk in males who initiated smoking at an early age: effect modification by body weight and dietary vitamin C
Authors: Hemilä Harri , Kaprio Jaakko 
Published: November 2008

Abstract
Background
We had found a 14% higher incidence of pneumonia with vitamin E supplementation in a subgroup of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Study cohort: participants who had initiated smoking by the age of 20 years. In this study, we explored the modification of vitamin E effect by body weight, because the same dose could lead to a greater effect in participants with low body weight.

Methods
The ATBC Study recruited males aged 50–69 years who smoked at least 5 cigarettes per day at the baseline; it was conducted in southwestern Finland in 1985–1993. The current study was restricted to 21,657 ATBC Study participants who initiated smoking by the age of 20 years; the median follow-up time was 6.0 years. The hospital-diagnosed pneumonia cases were retrieved from the national hospital discharge register (701 cases).

Results
Vitamin E supplementation had no effect on the risk of pneumonia in participants with body weight in a range from 70 to 89 kg (n = 12,495), risk ratio (RR) = 0.99 (95% CI: 0.81 to 1.22). Vitamin E increased the risk of pneumonia in participants with body weight less than 60 kg (n = 1054), RR = 1.61 (1.03 to 2.53), and in participants with body weight over 100 kg (n = 1328), RR = 2.34 (1.07 to 5.08). The harm of vitamin E supplementation was restricted to participants with dietary vitamin C intake above the median.

Conclusion
Vitamin E supplementation may cause harmful effects on health in certain groups of male smokers. The dose of vitamin E used in the ATBC Study, 50 mg/day, is substantially smaller than conventional vitamin E doses that are considered safe. Our findings should increase caution towards taking vitamin E supplements.

Trial registration
ClinicalTrials.gov NCT00342992.
Circulating IGF-binding protein 7 (IGFBP7) levels are elevated in patients with endometriosis or undergoing diabetic hemodialysis
Authors: Kutsukake Masahiko , Ishihara Ryosuke , Momose Katsutoshi , Isaka Keiichi , Itokazu Osamu , Higuma Chinatsu , Matsutani Takeshi , Matsuda Akihisa , Sasajima Koji , Hara Takahiko , Tamura Kazuhiro 
Published: November 2008

Abstract

Background
Insulin-like growth factor-binding protein-7 (IGFBP7) is a secretory protein with a molecular mass of approximately 30 kDa. It is abundantly expressed in the uterine endometrium during the secretory phase of the menstrual cycle. Decreased IGFBP7 expression has been observed in some cancers and leiomyomata.

Methods
To determine whether serum IGFBP7 levels reflect changes in uterine IGFBP7 expression in humans during the menstrual cycle, and to examine whether serum IGFBP7 levels are altered in patients with various disorders, we developed a novel, dual-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Firstly, concentrations of IGFBP7 released into the medium were determined in cultured endometrial stromal and glandular cells. Blood samples were collected from women who had normal menstrual cycles and who had been diagnosed with endometriosis. Serum from hemodialysis patients and gastrointestinal cancers was also used to determine the IGFBP7 levels.

Results
Using this new ELISA, we demonstrated that cultured uterine cells secrete IGFBP7 into the medium. Patients with endometriosis and those with type II diabetes mellitus undergoing hemodialysis had significantly higher serum concentrations of IGFBP7 than the relevant control subjects. There were no differences in serum IGFBP7 levels in women at different stages of the menstrual cycle. Furthermore, serum IGFBP7 levels in patients with colorectal, esophageal, or endometrial cancer were not different than normal healthy subjects.

Conclusion
Our observations suggest that IGFBP7 is associated with the pathophysiology of endometriosis and diabetes mellitus, and that serum IGFBP7 levels do not reflect enhanced uterine expression of IGFBP7 mRNA during the menstrual cycle.
Impaired urge-to-cough in elderly patients with aspiration pneumonia
Authors: Yamanda Shinsuke , Ebihara Satoru , Ebihara Takae , Yamasaki Miyako , Asamura Takaaki , Asada Masanori , Une Kaori , Arai Hiroyuki 
Published: November 2008

Abstract

Background
The down-regulation of the cough reflex in patients with aspiration pneumonia can involve both cortical facilitatory pathways for cough and medullary reflex pathways. In order to study the possible involvement of the supramedullary system in the down-regulation of cough reflex, we evaluated the urge-to-cough in patients with aspiration pneumonia.

Methods
Cough reflex sensitivity and the urge-to-cough to inhaled citric acid were evaluated in patients with at least a history of aspiration pneumonia and age-matched healthy elderly people. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough scores at the concentration of C2 and C5, and at the concentration of two times dilution of C2 (C2/2) and C5 (C5/2) were estimated for each subject.

Results
Both C2 and C5 in the control subjects were significantly greater than those for patients with aspiration pneumonia. There were no significant differences in the urge-to-cough at C2 and C5 between control subjects and patients with aspiration pneumonia. However, the urge-to-cough scores at both C2/2 and C5/2 in patients with aspiration pneumonia were significantly lower than those in control subjects. The number of coughs at C5/2 was significantly greater in the control subjects than those in the patients with aspiration pneumonia whereas the number of coughs at C2/2 did not show a significant difference between the control subjects and the patients with aspiration pneumonia.

Conclusion
The study suggests the involvement of supramedullary dysfunction in the etiology of aspiration pneumonia in the elderly. Therefore, restoration of the cough motivation system could be a new strategy to prevent aspiration pneumonia in the elderly.