bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Diversity of the Syndinean Genus Euduboscquella Based on Single-Cell PCR Analysis
Authors: Bachvaroff Tsvetan R. , Kim Sunju , Guillou Laure , Delwiche Charles F. , Coats D. Wayne 
Published: November 2011

ABSTRACT

The genus
Euduboscquella
is one of a few described genera within the syndinean dinoflagellates, an enigmatic lineage with abundant diversity in marine environmental clone libraries based on small subunit (SSU) rRNA. The region composed of the SSU through to the partial large subunit (LSU) rRNA was determined from 40 individual tintinnid ciliate loricae infected with
Euduboscquella
sampled from eight surface water sites in the Northern Hemisphere, producing seven distinct SSU sequences. The corresponding host SSU rRNA region was also amplified from eight host species. The SSU tree of
Euduboscquella
and syndinean group I sequences from environmental clones had seven well-supported clades and one poorly supported clade across data sets from 57 to 692 total sequences. The genus
Euduboscquella
consistently formed a supported monophyletic clade within a single subclade of group I sequences. For most parasites with identical SSU sequences, the more variable internal transcribed spacer (ITS) to LSU rRNA regions were polymorphic at 3 to 10 sites. However, in
E. cachoni
there was variation between ITS to LSU copies at up to 20 sites within an individual, while in a parasite of
Tintinnopsis
spp., variation between different individuals ranged up to 19 polymorphic sites. However, applying the compensatory base change model to the ITS2 sequences suggested no compensatory changes within or between individuals with the same SSU sequence, while one to four compensatory changes between individuals with similar but not identical SSU sequences were found. Comparisons between host and parasite phylogenies do not suggest a simple pattern of host or parasite specificity.
A Flucytosine-Responsive Mbp1/Swi4-Like Protein, Mbs1, Plays Pleiotropic Roles in Antifungal Drug Resistance, Stress Response, and Virulence of Cryptococcus neoformans
Authors: Song Min-Hee , Lee Jang-Won , Kim Min Su , Yoon Ja-Kyung , White Theodore C. , Floyd Anna , Heitman Joseph , Strain Anna K. , Nielsen Judith N. , Nielsen Kirsten , Bahn Yong-Sun 
Published: November 2011

ABSTRACT

Cryptococcosis, caused by the basidiomycetous fungus
Cryptococcus neoformans
, is responsible for more than 600,000 deaths annually in AIDS patients. Flucytosine is one of the most commonly used antifungal drugs for its treatment, but its resistance and regulatory mechanisms have never been investigated at the genome scale in
C. neoformans
. In the present study, we performed comparative transcriptome analysis by employing two-component system mutants (
tco1
Δ and
tco2
Δ) exhibiting opposing flucytosine susceptibility. As a result, a total of 177 flucytosine-responsive genes were identified, and many of them were found to be regulated by Tco1 or Tco2. Among these, we discovered an APSES-like transcription factor, Mbs1 (
Mb
p1- and
S
wi4-like protein 1). Expression analysis revealed that
MBS1
was regulated in response to flucytosine in a Tco2/Hog1-dependent manner. Supporting this,
C. neoformans
with the deletion of
MBS1
exhibited increased susceptibility to flucytosine. Intriguingly, Mbs1 played pleiotropic roles in diverse cellular processes of
C. neoformans
. Mbs1 positively regulated ergosterol biosynthesis and thereby affected polyene and azole drug susceptibility. Mbs1 was also involved in genotoxic and oxidative stress responses. Furthermore, Mbs1 promoted production of melanin and capsule and thereby was required for full virulence of
C. neoformans
. In conclusion, Mbs1 is considered to be a novel antifungal therapeutic target for treatment of cryptococcosis.
Neddylation and CAND1 Independently Stimulate SCF Ubiquitin Ligase Activity in Candida albicans
Authors: Sela Nadine , Atir-Lande Avigail , Kornitzer Daniel 
Published: November 2011

ABSTRACT

SCF (Skp1–cullin/Cdc53–F-box protein) ubiquitin ligases bind substrates via the variable F-box protein and, in conjunction with the RING domain protein Rbx1 and the ubiquitin-conjugating enzyme Ubc3/Cdc34, catalyze substrate ubiquitination. The cullin subunit can be modified covalently by conjugation of the ubiquitin-like protein Rub1/NEDD8 (neddylation) or bound noncovalently by the protein CAND1 (cullin-associated, neddylation-dissociated). Expression of the
Candida albicans
CAND1 gene homolog Ca
TIP120
in
Saccharomyces cerevisiae
is toxic only in the presence of CaCdc53, consistent with a specific interaction between CaTip120 and CaCdc53. To genetically analyze this system in
C. albicans
, we deleted the homologs of
RUB1
/NEDD8,
TIP120
/CAND1, and the deneddylase gene
JAB1
, and we also generated a temperature-sensitive allele of the essential Ca
CDC53
gene by knock-in site-directed mutagenesis. Deletion of Ca
RUB1
and Ca
TIP120
caused morphological, growth, and protein degradation phenotypes consistent with a reduction in SCF ubiquitin ligase activity. Furthermore, the double Ca
rub1
−/−
Ca
tip120
−/−
mutant was more defective in SCF activity than either individual deletion mutant. These results indicate that CAND1 stimulates SCF ubiquitin ligase activity and that it does so independently of neddylation. Our data do not support a role for CAND1 in the protection of either the F-box protein or cullin from degradation but are consistent with the suggested role of CAND1 in SCF complex remodeling.
Benzoate Mediates Repression of C
4
-Dicarboxylate Utilization in “Aromatoleum aromaticum” EbN1
Authors: Trautwein Kathleen , Grundmann Olav , Wöhlbrand Lars , Eberlein Christian , Boll Matthias , Rabus Ralf 
Published: November 2011

ABSTRACT

Diauxic growth was observed in anaerobic C
4
-dicarboxylate-adapted cells of “
Aromatoleum aromaticum
” EbN1 due to preferred benzoate utilization from a substrate mixture of a C
4
-dicarboxylate (succinate, fumarate, or malate) and benzoate. Differential protein profiles (two-dimensional difference gel electrophoresis [2D DIGE]) revealed dynamic changes in abundance for proteins involved in anaerobic benzoate catabolism and C
4
-dicarboxylate uptake. In the first active growth phase, benzoate utilization was paralleled by maximal abundance of proteins involved in anaerobic benzoate degradation (e.g., benzoyl-coenzyme A [CoA] reductase) and minimal abundance of DctP (EbA4158), the periplasmic binding protein of a predicted C
4
-dicarboxylate tripartite ATP-independent periplasmic (TRAP) transporter (DctPQM). The opposite was observed during subsequent succinate utilization in the second active growth phase. The increased
dctP
(respectively,
dctPQM
) transcript and DctP protein abundance following benzoate depletion suggests that repression of C
4
-dicarboxylate uptake seems to be a main determinant for the observed diauxie.
Perturbation of FliL Interferes with Proteus mirabilis Swarmer Cell Gene Expression and Differentiation
Authors: Cusick Kathleen , Lee Yi-Ying , Youchak Brian , Belas Robert 
Published: November 2011

ABSTRACT

Proteus mirabilis
is a dimorphic, motile bacterium often associated with urinary tract infections. Colonization of urinary tract surfaces is aided by swarmer cell differentiation, which is initiated by inhibition of flagellar rotation when the bacteria first contact a surface. Mutations in
fliL
, encoding a flagellar structural protein with an enigmatic function, result in the inappropriate production of differentiated swarmer cells, called pseudoswarmer cells, under noninducing conditions, indicating involvement of FliL in the surface sensing pathway. In the present study, we compared the
fliL
transcriptome with that of wild-type swarmer cells and showed that nearly all genes associated with motility (flagellar class II and III genes) and chemotaxis are repressed. In contrast, spontaneous motile revertants of
fliL
cells that regained motility yet produced differentiated swarmer cells under noninducing conditions transcribed flagellar class II promoters at consistent levels. Expression of
umoA
(a known regulator of swarmer cells),
flgF
, and
flgI
increased significantly in both swarmer and pseudoswarmer cells, as did genes in a degenerate prophage region situated immediately adjacent to the Rcs phosphorelay system. Unlike swarmer cells, pseudoswarmers displayed increased activity, rather than transcription, of the flagellar master regulatory protein, FlhD
4
C
2
, and analyses of the
fliL
parent strain and its motile revertants showed that they result from mutations altering the C-terminal 14 amino acids of FliL. Collectively, the data suggest a functional role for the C terminus of FliL in surface sensing and implicate UmoA as part of the signal relay leading to the master flagellar regulator FlhD
4
C
2
, which ultimately controls swarmer cell differentiation.
Thiosulfate Reduction in Salmonella enterica Is Driven by the Proton Motive Force
Authors: Stoffels Laura , Krehenbrink Martin , Berks Ben C. , Unden Gottfried 
Published: November 2011

ABSTRACT

Thiosulfate respiration in
Salmonella enterica
serovar Typhimurium is catalyzed by the membrane-bound enzyme thiosulfate reductase. Experiments with quinone biosynthesis mutants show that menaquinol is the sole electron donor to thiosulfate reductase. However, the reduction of thiosulfate by menaquinol is highly endergonic under standard conditions (Δ
E
°′ = −328 mV). Thiosulfate reductase activity was found to depend on the proton motive force (PMF) across the cytoplasmic membrane. A structural model for thiosulfate reductase suggests that the PMF drives endergonic electron flow within the enzyme by a reverse loop mechanism. Thiosulfate reductase was able to catalyze the combined oxidation of sulfide and sulfite to thiosulfate in a reverse of the physiological reaction. In contrast to the forward reaction the exergonic thiosulfate-forming reaction was PMF independent. Electron transfer from formate to thiosulfate in whole cells occurs predominantly by intraspecies hydrogen transfer.
A-Type Carrier Protein ErpA Is Essential for Formation of an Active Formate-Nitrate Respiratory Pathway in Escherichia coli K-12
Authors: Pinske Constanze , Sawers R. Gary 
Published: November 2011

ABSTRACT

A-type carrier (ATC) proteins of the Isc (
i
ron-
s
ulfur
c
luster) and Suf (
su
l
f
ur mobilization) iron-sulfur ([Fe-S]) cluster biogenesis pathways are proposed to traffic preformed [Fe-S] clusters to apoprotein targets. In this study, we analyzed the roles of the ATC proteins ErpA, IscA, and SufA in the maturation of the nitrate-inducible, multisubunit anaerobic respiratory enzymes formate dehydrogenase N (Fdh-N) and nitrate reductase (Nar). Mutants lacking SufA had enhanced activities of both enzymes. While both Fdh-N and Nar activities were strongly reduced in an
iscA
mutant, both enzymes were inactive in an
erpA
mutant and in a mutant unable to synthesize the [Fe-S] cluster scaffold protein IscU. It could be shown for both Fdh-N and Nar that loss of enzyme activity correlated with absence of the [Fe-S] cluster-containing small subunit. Moreover, a slowly migrating form of the catalytic subunit FdnG of Fdh-N was observed, consistent with impeded twin arginine translocation (TAT)-dependent transport. The highly related Fdh-O enzyme was also inactive in the
erpA
mutant. Although the Nar enzyme has its catalytic subunit NarG localized in the cytoplasm, it also exhibited aberrant migration in an
erpA iscA
mutant, suggesting that these modular enzymes lack catalytic integrity due to impaired cofactor biosynthesis. Cross-complementation experiments demonstrated that multicopy IscA could partially compensate for lack of ErpA with respect to Fdh-N activity but not Nar activity. These findings suggest that ErpA and IscA have overlapping roles in assembly of these anaerobic respiratory enzymes but demonstrate that ErpA is essential for the production of active enzymes.
Genome Sequences and Phylogenetic Analysis of K88- and F18-Positive Porcine Enterotoxigenic Escherichia coli
Authors: Shepard Sara M. , Danzeisen Jessica L. , Isaacson Richard E. , Seemann Torsten , Achtman Mark , Johnson Timothy J. 
Published: November 2011

ABSTRACT

Porcine enterotoxigenic
Escherichia coli
(ETEC) continues to result in major morbidity and mortality in the swine industry via postweaning diarrhea. The key virulence factors of ETEC strains, their serotypes, and their fimbrial components have been well studied. However, most studies to date have focused on plasmid-encoded traits related to colonization and toxin production, and the chromosomal backgrounds of these strains have been largely understudied. Here, we generated the genomic sequences of K88-positive and F18-positive porcine ETEC strains and examined the phylogenetic distribution of clinical porcine ETEC strains and their plasmid-associated genetic content. The genomes of porcine ETEC strains UMNK88 and UMNF18 were both found to contain remarkable plasmid complements containing known virulence factors, potential novel virulence factors, and antimicrobial resistance-associated elements. The chromosomes of these strains also possessed several unique genomic islands containing hypothetical genes with similarity to classical virulence factors, although phage-associated genomic islands dominated the accessory genomes of these strains. Phylogenetic analysis of 78 clinical isolates associated with neonatal and porcine diarrhea revealed that a limited subset of porcine ETEC lineages exist that generally contain common toxin and fimbrial profiles, with many of the isolates belonging to the ST10, ST23, and ST169 multilocus sequencing types. These lineages were generally distinct from existing human ETEC database isolates. Overall, most porcine ETEC strains appear to have emerged from a limited subset of
E. coli
lineages that either have an increased propensity to carry plasmid-encoded virulence factors or have the appropriate ETEC core genome required for virulence.
Hepatology training in the UK
Authors: Patanwala Imran , Hudson Mark 
Published: November 2011

ObjectivesTo establish the perceived adequacy of the hepatology training component of the unified gastroenterology and hepatology training programme in the UK by assessing the attitudes and experiences of trainees in the programme.Design and interventionOnline cross-sectional questionnaire survey linked to the annual British Society of Gastroenterology/Trainee in Gastroenterology survey in 2010.Setting and participantsNational survey of all specialist gastroenterology trainees in the UK.Results283/489 (58%) trainees responded, 68% were male. 54% of all trainees wanted to deliver liver services as consultants. 25% of trainees complete training without exposure to a liver unit providing comprehensive specialist hepatology services. Median time spent in such a unit for the others was 8 months (IQR 6). Significantly fewer trainees lacked confidence in managing liver-related conditions if they had spent time training in a specialist liver unit and with increasing years in training. One in three trainees is dissuaded from a career in hepatology. One in five trainees wished to work part time as consultants—an option preferred significantly more by women.ConclusionsHepatology training in the UK is perceived by trainees as being suboptimal. A national strategy aimed at improving and standardising hepatology training and making specialist liver unit experience available for every trainee is required.
Cumulative exposure to poor housing affordability and its association with mental health in men and women
Authors: Bentley Rebecca , Baker Emma , Mason Kate 
Published: November 2011

BackgroundPoor housing affordability affects around 10% of the Australian population and is increasingly prevalent. The authors tested two hypotheses: that cumulative exposure to housing affordability stress (HAS) is associated with poorer mental health and that effects vary by gender.MethodsThe authors estimated the relationship between cumulative exposure to HAS and mental health among 15 478 participants in an Australian longitudinal survey between 2001 and 2009. Individuals were classified as being in HAS if household income was in the lowest 40% of the national distribution and housing costs exceeded 30% of income. Exposure to HAS ranged from 1 to 8 annual waves. Mental health was measured using the Short Form 36 Mental Component Summary (MCS) score. To test the extent to which any observed associations were explained by compositional factors, random- and fixed-effects models were estimated.ResultsIn the random-effects models, mental health scores decreased with increasing cumulative exposure to HAS (up until 4+ years). This relationship differed by gender, with a stronger dose-response observed among men. The mean MCS score of men experiencing four to eight waves of housing stress was 2.02 points lower than men not in HAS (95% CI −3.89 to −0.16). In the fixed-effects models, there was no evidence of acumulativeeffect of HAS on mental health; however, lower MCS was observed after a single year in HAS (β=−0.70, 95% CI −1.02 to −0.37).ConclusionsWhile average mental health was lower for individuals with longer exposure to HAS, the mental health effect appears to be due to compositional factors. Furthermore, men and women appear to experience cumulative HAS differently.
Contrasting Behavior of the p18INK4c and p16INK4a Tumor Suppressors in Both Replicative and Oncogene-Induced Senescence
Authors: Gagrica Sladjana , Brookes Sharon , Anderton Emma , Rowe Janice , Peters Gordon 
Published: November 2011

Abstract
The cyclin-dependent kinase (CDK) inhibitors, p18INK4c and p16INK4a, both have the credentials of tumor suppressors in human cancers and mouse models. For p16INK4a, the underlying rationale is its role in senescence, but the selective force for inactivation of p18INK4c in incipient cancer cells is less clear. Here, we show that in human fibroblasts undergoing replicative or oncogene-induced senescence, there is a marked decline in the levels of p18INK4c protein and RNA, which mirrors the accumulation of p16INK4a. Downregulation of INK4c is not dependent on p16INK4a, and RAS can promote the loss of INK4c without cell-cycle arrest. Downregulation of p18INK4c correlates with reduced expression of menin and E2F1 but is unaffected by acute cell-cycle arrest or inactivation of the retinoblastoma protein (pRb). Collectively, our data question the idea that p18INK4c acts as a backup for loss of p16INK4a and suggest that the apparent activation of p18INK4c in some settings represents delayed senescence rather than increased expression. We propose that the contrasting behavior of the two very similar INK4 proteins could reflect their respective roles in senescence versus differentiation. Cancer Res; 72(1); 165–75. ©2011 AACR.
A Phase I Weekly Dosing Study of Brentuximab Vedotin in Patients with Relapsed/Refractory CD30-Positive Hematologic Malignancies
Authors: Fanale Michelle A. , Forero-Torres Andres , Rosenblatt Joseph D. , Advani Ranjana H. , Franklin Anna R. , Kennedy Dana A. , Han Tae H. , Sievers Eric L. , Bartlett Nancy L. 
Published: November 2011

Abstract
Purpose: The antibody–drug conjugate (ADC) brentuximab vedotin comprises a CD30-directed antibody covalently attached to the potent antimicrotubule agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. This study explored the safety, maximum-tolerated dose (MTD), and activity of weekly dosing of brentuximab vedotin in patients with relapsed or refractory CD30-positive hematologic malignancies.
Experimental Design: In this phase I dose-escalation study, brentuximab vedotin was administered intravenously on Days 1, 8, and 15, of each 28-day cycle at doses ranging from 0.4 to 1.4 mg/kg. Forty-four patients were enrolled: 38 with Hodgkin lymphoma, five with systemic anaplastic large cell lymphoma, and one with peripheral T-cell lymphoma not otherwise specified. Doses were escalated in increments of 0.2 mg/kg until dose-limiting toxicity (DLT) was observed. Patients were monitored for antitherapeutic antibodies and pharmacokinetic parameters. Antitumor assessments were carried out every two cycles.
Results: The MTD was 1.2 mg/kg. The most common adverse events were peripheral sensory neuropathy, fatigue, nausea, diarrhea, arthralgia, and pyrexia; and the majority of events were mild to moderate in severity. Tumor regression occurred in 85% of patients and the overall objective response rate was 59% (n = 24), with 34% (n = 14) complete remissions. The median duration of response was not reached at a median follow-up of 45 weeks on study.
Conclusions: Weekly administration of brentuximab vedotin resulted in tumor regression and durable remissions in patients with CD30-positive malignancies. This ADC was associated with manageable toxicity, including peripheral neuropathy. Further study in CD30-positive malignancies is warranted. Clin Cancer Res; 18(1); 248–55. ©2011 AACR.
Reliability and validity of the five-repetition sit-to-stand test for children with cerebral palsy
Authors: Wang Tze-Hsuan , Liao Hua-Fang , Peng Yi-Chun 
Published: November 2011

Objective To investigate the psychometric properties of the five-repetition sit-to-stand test, a functional strength test, in children with spastic diplegia. Design: Methodology study. Settings: Hospital, laboratory or home. Participants: In total, 108 children with spastic diplegia and 62 with typical development aged from five to 12 years were tested. For test-retest reliability, 22 children with spastic diplegia were tested twice within one week. Interventions: Not applicable. Main measures: The five-repetition sit-to-stand test measures time needed to complete five consecutive sit-to-stand cycles as quickly as possible. The higher the rate of five-repetition sit-to-stand (repetitions per second), the more strength a person has. Results: The intraclass correlation coefficients of intra-session reliability and test-retest reliability were 0.95 and 0.99 respectively. The minimal detectable difference was 0.06 rep/sec. The convergent validity of the five-repetition sit-to-stand test was supported by significant correlation with one-repetition maximum of the loaded sit-to-stand test, isometric muscle strength, scores of Gross Motor Function Measure, and gait function ( r or rho = 0.40–0.78). For known group validity, children with typical development and children classified as Gross Motor Function Classification System level I performed higher rates of five-repetition sit-to-stand than children classified as level II, and children classified as level II performed higher rates than level III. Conclusion: The five-repetition sit-to-stand test was a reliable and valid test to measure functional muscle strength in children with spastic diplegia in clinics.
Reduction of ostazine dyes’ photodynamic effect by Fenton reaction
Authors: Mackuľak Tomáš , Smolinská Miroslava , Olejníková Petra , Prousek Josef , Takáčová Alžbeta 
Published: November 2011

AbstractThe aim of this work was to evaluate the influence of ostazine dyes on the microbial population in environment. These dyes act as photosensitizers after irradiation by visible light. The photodynamic effect was induced in this way. The effect of irradiated water solutions of ostazine green, ostazine yellow, and ostazine blue on the Escherichia coli growth was tested. Furthermore, the effect of these dyes (at c = 3.5 μg mL−1) on bacterial growth was evaluated after their pretreatment by the Fenton reaction. Dramatic changes in dyes’ toxicity were observed after coloured solutions were pretreated by the Fenton reaction.