bluuebunny/crossref_metadata_2025_split huggingface dataset:
The immunological basis of B‐cell therapy in systemic lupus erythematosus
Authors: MOK Mo Yin 
Published: January 2010

AbstractLoss of B‐cell tolerance is a hallmark feature of the pathogenesis in systemic lupus erythematosus (SLE), an autoimmune disease that is characterized by hypergammaglobulinemia and autoantibody production. These autoantibodies lead to formation of immune‐complex deposition in internal organs causing inflammation and damage. Autoreactive B‐cells are believed to be central in the pathophysiology of SLE. Other than its role in the production of antibodies that mediate humoral immune response, B‐cells also function as antigen‐presenting cells and are capable of activating T‐cells. Activated B‐cells may also produce pro‐inflammatory cytokines that aggravate local inflammation. Abnormal B‐cell homeostasis has been described in SLE patients. This may occur as a result of intrinsic B‐cell defect or from aberrant regulation by maturation and survival signals. B‐cell‐based therapy is the current mainstream of research and development of novel therapies in SLE patients with severe and refractory disease. Potential cellular and molecular targets for B‐cell therapies include cell surface molecules such as CD20 (rituximab) and CD22 (epratuzumab); co‐stimulatory molecules involved in B‐cell–T‐cell interaction such as CTLA4 and B7 molecules (abatacept); maturation and growth factors such as B‐cell activating factor and a proliferation‐inducing ligand (belimumab, briobacept, atacicept) and B‐cell tolerogen (abetimus). This article provides an overview on normal B‐cell physiology and abnormal B‐cell biology in SLE that form the immunological basis of B‐cell‐targeted therapy in the treatment of these patients with refractory diseases.
Putative ammonia‐oxidizing bacteria and archaea in an acidic red soil with different land utilization patterns
Authors: Ying Jiao‐Yan , Zhang Li‐Mei , He Ji‐Zheng 
Published: January 2010

SummaryAmmonia‐oxidizers play a key role in nitrification, which is important for nitrogen cycling and soil function. However, little is known about how vegetation successions and agricultural practices caused by human activities impact the ammonia‐oxidizers and nitrification process. Putative ammonia‐oxidizing bacteria (AOB) and archaea (AOA) communities under different land utilization patterns of restoration (forest), degradation (pasture), cropland and pine plantation were analysed in an acidic red soil based on bacterial and archaeal amoA genes together with archaeal 16S rRNA gene. Real‐time PCR, terminal restriction fragment length polymorphism (T‐RFLP) and sequencing of clone libraries were conducted to study their abundance and community structure. Land utilization pattern showed significant effects on the copy numbers of all these genes, but only the bacterial amoA gene correlated significantly with potential nitrification rates (PNR). The cropland plot possessed the highest bacterial amoA gene copies and PNR, while the degradation plot was opposite to that. There were no significant variations in the bacterial amoA gene structure, which was dominated by Clusters 10 and 11 in Nitrosospira. However, archaeal amoA gene structure varied among different land utilization patterns especially for the cropland. The degradation plot was dominated by Crenarchaea 1.1c‐related groups from which the amoA gene could not been amplified in this study, while other plots were dominated by Crenarchaea 1.1a/b group based on archaeal 16S rRNA gene analysis. These results indicated significant effects of land utilization patterns on putative ammonia oxidizers, which were especially obvious in the degradation and cropland plots where frequent human disturbance occurred.
Phylogeny of the coral pathogenVibrio coralliilyticus
Authors: Pollock F. Joseph , Wilson Bryan , Johnson Wesley R. , Morris Pamela J. , Willis Bette L. , Bourne David G. 
Published: January 2010

SummaryA phenotypic and phylogenetic comparison of geographically disparate isolates of the coral pathogenVibrio coralliilyticuswas conducted to determine whether the bacterium exists as a single cosmopolitan clonal population, which might indicate rapid spread of a pandemic strain, or is grouped into endemic and genotypically distinct strains. All strains included in this study displayed similar phenotypic characteristics to those of the typedV. coralliilyticusstrain LMG 20984T. Five phylogenetic marker genes (16S,rpoA,recA,pyrHanddnaJ) frequently used for discriminating closely relatedVibriospecies and a zinc‐metalloprotease gene (vcpA) linked to pathogenicity were sequenced in 13 V. coralliilyticusisolates collected from corals, bivalves, and their surrounding seawater in the Red and Caribbean Seas, and Indian, Pacific and Atlantic Oceans. A high level of genetic polymorphism was observed with all isolates possessing unique genotypes at all six genetic loci examined. No consistent lineage structure was observed within the marker genes and homologous recombination was detected in the16SandvcpAgenes, suggesting thatV. coralliilyticusdoes not possess a highly clonal population structure. Interestingly, two geographically distinct (Caribbean/south‐Atlantic and Indo‐Pacific/north‐Atlantic) and highly divergent clades were detected within the zinc‐metalloprotease gene, but it is not known if these clades correspond to phenotypic differences in virulence. These findings stress the need for a multi‐locus approach for inferringV. coralliilyticusphylogeny and indicate that populations of this bacterium are likely an endemic component of coral reef ecosystems globally.
Inactivation of Murine Norovirus 1 and
Bacteroides fragilis
Phage B40-8 by Mesophilic and Thermophilic Anaerobic Digestion of Pig Slurry
Authors: Baert Leen , De Gusseme Bart , Boon Nico , Verstraete Willy , Debevere Johan , Uyttendaele Mieke 
Published: January 2010

ABSTRACT

Mesophilic (37°C) and thermophilic (52°C) anaerobic digestion of pig slurry induced at least a 4-log decrease in murine norovirus 1, used as a surrogate virus for porcine norovirus, after 13 and 7 days, respectively.
Bacteroides fragilis
phage B40-8, employed as a universal viral model, was lowered by 2.5 log after 7 days. The viral titer declined due to temperature and matrix effects.
Mechanism of
De Novo
Branched-Chain Amino Acid Synthesis as an Alternative Electron Sink in Hypoxic
Aspergillus nidulans
Cells
Authors: Shimizu Motoyuki , Fujii Tatsuya , Masuo Shunsuke , Takaya Naoki 
Published: January 2010

ABSTRACT

Although branched-chain amino acids are synthesized as building blocks of proteins, we found that the fungus
Aspergillus nidulans
excretes them into the culture medium under hypoxia. The transcription of predicted genes for synthesizing branched-chain amino acids was upregulated by hypoxia. A knockout strain of the gene encoding the large subunit of acetohydroxy acid synthase (AHAS), which catalyzes the initial reaction of the synthesis, required branched-chain amino acids for growth and excreted very little of them. Pyruvate, a substrate for AHAS, increased the amount of hypoxic excretion in the wild-type strain. These results indicated that the fungus responds to hypoxia by synthesizing branched-chain amino acids via a
de novo
mechanism. We also found that the small subunit of AHAS regulated hypoxic branched-chain amino acid production as well as cellular AHAS activity. The AHAS knockout resulted in higher ratios of NADH/NAD
+
and NADPH/NADP
+
under hypoxia, indicating that the branched-chain amino acid synthesis contributed to NAD
+
and NADP
+
regeneration. The production of branched-chain amino acids and the hypoxic induction of involved genes were partly repressed in the presence of glucose, where cells produced ethanol and lactate and increased levels of lactate dehydrogenase activity. These indicated that hypoxic branched-chain amino acid synthesis is a unique alternative mechanism that functions in the absence of glucose-to-ethanol/lactate fermentation and oxygen respiration.
Expanding Small-Molecule Functional Metagenomics through Parallel Screening of Broad-Host-Range Cosmid Environmental DNA Libraries in Diverse
Proteobacteria
Authors: Craig Jeffrey W. , Chang Fang-Yuan , Kim Jeffrey H. , Obiajulu Steven C. , Brady Sean F. 
Published: January 2010

ABSTRACT

The small-molecule biosynthetic diversity encoded within the genomes of uncultured bacteria is an attractive target for the discovery of natural products using functional metagenomics. Phenotypes commonly associated with the production of small molecules, such as antibiosis, altered pigmentation, or altered colony morphology, are easily identified from screens of arrayed metagenomic library clones. However, functional metagenomic screening methods are limited by their intrinsic dependence on a heterologous expression host. Toward the goal of increasing the small-molecule biosynthetic diversity found in functional metagenomic studies, we report the phenotypic screening of broad-host-range environmental DNA libraries in six different proteobacteria:
Agrobacterium tumefaciens
,
Burkholderia graminis
,
Caulobacter vibrioides
,
Escherichia coli
,
Pseudomonas putida
, and
Ralstonia metallidurans
. Clone-specific small molecules found in culture broth extracts from pigmented and antibacterially active clones, as well as the genetic elements responsible for the biosynthesis of these metabolites, are described. The host strains used in this investigation provided access to unique sets of clones showing minimal overlap, thus demonstrating the potential advantage conferred on functional metagenomics through the use of multiple diverse host species.
Genotyping of
Giardia duodenalis
Cysts by New Real-Time PCR Assays for Detection of Mixed Infections in Human Samples
Authors: Almeida Andre , Pozio Edoardo , Cacciò Simone M. 
Published: January 2010

ABSTRACT

Of the seven genetic groups, or assemblages, currently recognized in the
Giardia duodenalis
species complex, only assemblages A and B are associated with human infection, but they also infect other mammals. Recent investigations have suggested the occurrence of genetic exchanges among isolates of
G. duodenalis
, and the application of assemblage-specific PCR has shown both assemblages A and B in a significant number of human infections. In this work, three real-time quantitative (qPCR) assays were developed to target the
G. duodenalis
triose phosphate isomerase, glutamate dehydrogenase, and open reading frame C4 sequences. Primers were designed to allow the specific amplification of the DNA of assemblage A or B and to generate products distinguishable by their melting curves or, after qPCR, by their sequences, sizes, or restriction patterns. The assays showed full specificity and detected DNA from a single trophozoite (4 to 8 target copies). We applied these assays, as well as a TaqMan assay that targets the β-
giardin
gene, to genomic DNA extracted from 30 human stools and to
Giardia
cysts purified by immunomagnetic capture from the same samples. Simultaneous detection of both assemblages was observed in a large number of DNAs extracted from stools, and experiments on the cysts purified from the same samples showed that this was essentially attributable to mixed infections, as only one assemblage was detected when dilutions of cysts were tested. In a few cases, detection of both assemblages was observed even when single cysts were tested. This result, which suggests the presence of recombinants, needs to be confirmed using more accurate methods for cyst separation and enumeration. The assays described in this study can be used to detect
Giardia
cysts infectious to humans in samples from animals and in water and food.
Comparison of Two Optical-Density-Based Methods and a Plate Count Method for Estimation of Growth Parameters of
Bacillus cereus
Authors: Biesta-Peters Elisabeth G. , Reij Martine W. , Joosten Han , Gorris Leon G. M. , Zwietering Marcel H. 
Published: January 2010

ABSTRACT

Quantitative microbiological models predicting proliferation of microorganisms relevant for food safety and/or food stability are useful tools to limit the need for generation of biological data through challenge testing and shelf-life testing. The use of these models requires quick and reliable methods for the generation of growth data and estimation of growth parameters. Growth parameter estimation can be achieved using methods based on plate counting and methods based on measuring the optical density. This research compares the plate count method with two optical density methods, namely, the 2-fold dilution (2FD) method and the relative rate to detection (RRD) method. For model organism
Bacillus cereus
F4810/72, the plate count method and both optical density methods gave comparable estimates for key growth parameters. Values for the maximum specific growth rate (
μ
max
) derived by the 2FD method and by the RRD method were of the same order of magnitude, but some marked differences between the two approaches were apparent. Whereas the 2FD method allowed the derivation of values for lag time (λ) from the data, this was not possible with the RRD method. However, the RRD method gave many more data points per experiment and also gave more data points close to the growth boundary. This research shows that all three proposed methods can be used for parameter estimation but that the choice of method depends on the objectives of the research.
Functional Analysis of the Three TATA Binding Protein Homologs in
Methanosarcina acetivorans
Authors: Reichlen Matthew J. , Murakami Katsuhiko S. , Ferry James G. 
Published: January 2010

ABSTRACT

The roles of three TATA binding protein (TBP) homologs (TBP1, TBP2, and TBP3) in the archaeon
Methanosarcina acetivorans
were investigated by using genetic and molecular approaches. Although
tbp2
and
tbp3
deletion mutants were readily obtained, a
tbp1
mutant was not obtained, and the growth of a conditional
tbp1
expression strain was tetracycline dependent, indicating that TBP1 is essential. Transcripts of
tbp1
were 20-fold more abundant than transcripts of
tbp2
and 100- to 200-fold more abundant than transcripts of
tbp3
, suggesting that TBP1 is the primary TBP utilized during growth. Accordingly,
tbp1
is strictly conserved in the genomes of
Methanosarcina
species. Δ
tbp3
and Δ
tbp2
strains exhibited an extended lag phase compared with the wild type, although the lag phase for the Δ
tbp2
strain was less pronounced when this strain was transitioning from growth on methylotrophic substrates to growth on acetate. Acetate-adapted Δ
tbp3
cells exhibited growth rates, final growth yields, and lag times that were significantly reduced compared with those of the wild type when the organisms were cultured with growth-limiting concentrations of acetate, and the acetate-adapted Δ
tbp2
strain exhibited a final growth yield that was reduced compared with that of the wild type when the organisms were cultured with growth-limiting acetate concentrations. DNA microarray analyses identified 92 and 77 genes with altered transcription in the Δ
tbp2
and Δ
tbp3
strains, respectively, which is consistent with a role for TBP2 and TBP3 in optimizing gene expression. Together, the results suggest that TBP2 and TBP3 are required for efficient growth under conditions similar to the conditions in the native environment of
M. acetivorans
.
Heavy Involvement of Stringent Transcription Control Depending on the Adenine or Guanine Species of the Transcription Initiation Site in Glucose and Pyruvate Metabolism inBacillus subtilis
Authors: Tojo Shigeo , Kumamoto Kanako , Hirooka Kazutake , Fujita Yasutaro 
Published: January 2010

ABSTRACTInBacillussubtiliscells, the GTP level decreases and the ATP level increases upon a stringent response. This reciprocal change in the concentrations of the substrates of RNA polymerase affects the rate of transcription initiation of certain stringent genes depending on the purine species at their transcription initiation sites. DNA microarray analysis suggested that not only therrnandilv-leugenes encoding rRNAs and the enzymes for synthesis of branched-chain amino acids, respectively, but also many genes, including genes involved in glucose and pyruvate metabolism, might be subject to this kind of stringent transcription control. Actually, theptsGHIandpdhABCDoperons encoding the glucose-specific phosphoenolpyruvate:sugar phosphotransferase system and the pyruvate dehydrogenase complex were found to be negatively regulated, likerrn, whereas thepycAgene encoding pyruvate carboxylase and thealsSDoperon for synthesis of acetoin from pyruvate were positively regulated, likeilv-leu. Replacement of the guanine at position 1 and/or position 2 ofptsGHIand at position 1 ofpdhABCD(transcription initiation base at position 1) by adenine changed the negative stringent control of these operons in the positive direction. The initiation bases for transcription ofpdhABCDandpycAwere newly determined. Then the promoter sequences of these stringent operons were aligned, and the results suggested that the presence of a guanine(s) and the presence of an adenine(s) at position 1 and/or position 2 might be indispensable for negative and positive stringent control, respectively. Such stringent transcription control that affects the transcription initiation rate through reciprocal changes in the GTP and ATP levels likely occurs for numerous genes ofB. subtilis.
Inactivation of Genes Encoding Plastoglobulin-Like Proteins in
Synechocystis
sp. PCC 6803 Leads to a Light-Sensitive Phenotype
Authors: Cunningham Francis X. , Tice Ashley B. , Pham Christina , Gantt Elisabeth 
Published: January 2010

ABSTRACT

Plastoglobulins (PGL) are the predominant proteins of lipid globules in the plastids of flowering plants. Genes encoding proteins similar to plant PGL are also present in algae and cyanobacteria but in no other organisms, suggesting an important role for these proteins in oxygenic photosynthesis. To gain an understanding of the core and fundamental function of PGL, the two genes that encode PGL-like polypeptides in the cyanobacterium
Synechocystis
sp. PCC 6803 (
pgl1
and
pgl2
) were inactivated individually and in combination. The resulting mutants were able to grow under photoautotrophic conditions, dividing at rates that were comparable to that of the wild-type (WT) under low-light (LL) conditions (10 microeinsteins·m
−2
·s
−1
) but lower than that of the WT under moderately high-irradiance (HL) conditions (150 microeinsteins·m
−2
·s
−1
). Under HL, each Δ
pgl
mutant had less chlorophyll, a lower photosystem I (PSI)/PSII ratio, more carotenoid per unit of chlorophyll, and very much more myxoxanthophyll (a carotenoid symptomatic of high light stress) per unit of chlorophyll than the WT. Large, heterogeneous inclusion bodies were observed in cells of mutants inactivated in
pgl2
or both
pgl2
and
pgl1
under both LL and HL conditions. The mutant inactivated in both
pgl
genes was especially sensitive to the light environment, with alterations in pigmentation, heterogeneous inclusion bodies, and a lower PSI/PSII ratio than the WT even for cultures grown under LL conditions. The WT cultures grown under HL contained 2- to 3-fold more PGL1 and PGL2 per cell than cultures grown under LL conditions. These and other observations led us to conclude that the PGL-like polypeptides of
Synechocystis
play similar but not identical roles in some process relevant to the repair of photooxidative damage.
Binding of Complement Regulators to Invasive Nontypeable
Haemophilus influenzae
Isolates Is Not Increased Compared to Nasopharyngeal Isolates, but Serum Resistance Is Linked to Disease Severity
Authors: Hallström Teresia , Resman Fredrik , Ristovski Mikael , Riesbeck Kristian 
Published: January 2010

ABSTRACT

The aim of the present study was to analyze the importance of nontypeable
Haemophilus influenzae
(NTHi) isolated from patients with sepsis (invasive isolates) compared to nasopharyngeal isolates from patients with upper respiratory tract infection for resistance to complement-mediated attack in human serum and to correlate this result with disease severity. We studied and characterized cases of invasive NTHi disease in detail. All patients with invasive NTHi isolates were adults, and 35% had a clinical presentation of severe sepsis according to the ACCP/SCCM classification of sepsis grading. Moreover, 41% of the patients had evidence of immune deficiency. The different isolates were analyzed for survival in human serum and for binding of
125
I-labeled, purified human complement inhibitors C4b-binding protein (C4BP), factor H, and vitronectin, in addition to binding of regulators directly from serum. No significant differences were found when blood-derived and nasopharyngeal isolates were compared, suggesting that interactions with the complement system are equally important for NTHi strains, irrespective of isolation site. Interestingly, a correlation between serum resistance and invasive disease severity was found. The ability to resist the attack of the complement system seems to be important for NTHi strains infecting the respiratory tract as well as the bloodstream.
Clinical Characteristics, Outcomes, and Microbiologic Features Associated with Methicillin-Resistant
Staphylococcus aureus
Bacteremia in Pediatric Patients Treated with Vancomycin
Authors: Welsh Kerry J. , Abbott April N. , Lewis Evan M. , Gardiner Jeanelle M. , Kruzel Mark C. , Lewis Cole T. , Mohr John F. , Wanger Audrey , Armitige Lisa Y. 
Published: January 2010

ABSTRACT

Vancomycin is the first-line therapy for methicillin-resistant
Staphylococcus aureus
(MRSA) bacteremia, but its efficacy in adult patients has been questioned. Less is known about the outcomes of MRSA bacteremia treated with vancomycin in pediatric patients. This study reviews the outcomes and clinical characteristics of MRSA bacteremia in children treated with vancomycin and characterizes the microbiologic and molecular features of the bloodstream isolates. A retrospective cohort study was conducted among pediatric patients with MRSA bacteremia treated with vancomycin for >5 days from 1 August 2005 to 31 May 2007 in a large tertiary care center. MRSA bloodstream isolates were characterized by antimicrobial susceptibility testing, PCR analysis of virulence genes, and Diversilab typing. Clinical records were reviewed for outcomes and comorbidities. A total of 22 pediatric patients with MRSA bacteremia were identified. Eleven cases (50.0%) were considered vancomycin treatment failures. Features significantly associated with vancomycin treatment failure were prematurity (
P
= 0.02) and isolates positive for Panton-Valentine leukocidin (PVL) (
P
= 0.008). Features typically associated with community-associated MRSA strains were identified in hospital-associated isolates. A dominant clone was not responsible for the high number of treatment failures. Further studies are needed to determine if vancomycin should be the first-line treatment for MRSA bacteremia in premature infants and for PVL-positive isolates.