bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of evidence‐based medicine on the treatment of patients with unresectable hepatocellular carcinoma
Authors: GIANNINI E. G. , BODINI G. , CORBO M. , SAVARINO V. , RISSO D. , DI NOLFO M. A. , DEL POGGIO P. , BENVEGNÙ L. , FARINATI F. , ZOLI M. , BORZIO F. , CATURELLI E. , CHIARAMONTE M. , TREVISANI F. ,   FOR THE ITALIAN LIVER CANCER (ITA.LI.CA.) GROUP
Published: November 2009

Aliment Pharmacol Ther 31, 493–501SummaryBackground  A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well‐selected patients with unresectable hepatocellular carcinoma (HCC).Aim  To access whether this information has modified the use of TACE in clinical practice.Methods  From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4‐year periods (1999–2002, n = 161 and 2003–2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival.Results  Patients undergoing TACE increased in the 2003–2006 period (from 62% to 73%, P = 0.035), with an increase in of Child‐Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999–2002 period, there was no significant difference in survival between TACE‐treated and untreated patients, while in the 2003–2006 period, TACE‐treated patients survived longer (P < 0.0001).Conclusions  Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well‐compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage.
Degradation of cytokinins by maize cytokinin dehydrogenase is mediated by free radicals generated by enzymatic oxidation of natural benzoxazinones
Authors: Frébortová Jitka , Novák Ondřej , Frébort Ivo , Jorda Radek 
Published: November 2009

SummaryHydroxamic acid 2,4‐dihydroxy‐7‐methoxy‐1,4‐benzoxazin‐one (DIMBOA) was isolated from maize phloem sap as a compound enhancing the degradation of isopentenyl adenine by maize cytokinin dehydrogenase (CKX), after oxidative conversion by either laccase or peroxidase. Laccase and peroxidase catalyze oxidative cleavage of DIMBOA to 4‐nitrosoresorcinol‐1‐monomethyl ether (coniferron), which serves as a weak electron acceptor of CKX. The oxidation of DIMBOA and coniferron generates transitional free radicals that are used by CKX as effective electron acceptors. The function of free radicals in the CKX‐catalyzed reaction was also verified with a stable free radical of 2,2′‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulfonic acid. Application of exogenous cytokinin to maize seedlings resulted in an enhanced benzoxazinoid content in maize phloem sap. The results indicate a new function for DIMBOA in the metabolism of the cytokinin group of plant hormones.
Medicago truncatula Vapyrin is a novel protein required for arbuscular mycorrhizal symbiosis
Authors: Pumplin Nathan , Mondo Stephen J. , Topp Stephanie , Starker Colby G. , Gantt J. Stephen , Harrison Maria J. 
Published: November 2009

SummaryArbuscular mycorrhizal (AM) symbiosis is a widespread mutualism formed between vascular plants and fungi of the Glomeromycota. In this endosymbiosis, fungal hyphae enter the roots, growing through epidermal cells to the cortex where they establish differentiated hyphae called arbuscules in the cortical cells. Reprogramming of the plant epidermal and cortical cells occurs to enable intracellular growth of the fungal symbiont; however, the plant genes underlying this process are largely unknown. Here, through the use of RNAi, we demonstrate that the expression of a Medicago truncatula gene named Vapyrin is essential for arbuscule formation, and also for efficient epidermal penetration by AM fungi. Vapyrin is induced transiently in the epidermis coincident with hyphal penetration, and then in the cortex during arbuscule formation. The Vapyrin protein is cytoplasmic, and in cells containing AM fungal hyphae, the protein accumulates in small puncta that move through the cytoplasm. Vapyrin is a novel protein composed of two domains that mediate protein–protein interactions: an N‐terminal VAMP‐associated protein (VAP)/major sperm protein (MSP) domain and a C‐terminal ankyrin‐repeat domain. Putative Vapyrin orthologs exist widely in the plant kingdom, but not in Arabidopsis, or in non‐plant species. The data suggest a role for Vapyrin in cellular remodeling to support the intracellular development of fungal hyphae during AM symbiosis.
The Chloroplast Function Database: a large‐scale collection of Arabidopsis Ds/Spm‐ or T‐DNA‐tagged homozygous lines for nuclear‐encoded chloroplast proteins, and their systematic phenotype analysis
Authors: Myouga Fumiyoshi , Akiyama Kenji , Motohashi Reiko , Kuromori Takashi , Ito Takuya , Iizumi Haruko , Ryusui Rie , Sakurai Tetsuya , Shinozaki Kazuo 
Published: November 2009

SummaryA majority of the proteins of the chloroplast are encoded by the nuclear genome, and are post‐translationally targeted to the chloroplast. From databases of tagged insertion lines at international seed stock centers and our own stock, we selected 3246 Ds/Spm (dissociator/suppressor–mutator) transposon‐ or T‐DNA‐tagged Arabidopsis lines for genes encoding 1369 chloroplast proteins (about 66% of the 2090 predicted chloroplast proteins) in which insertions disrupt the protein‐coding regions. We systematically observed 3‐week‐old seedlings grown on agar plates, identified mutants with abnormal phenotypes and collected homozygous lines with wild‐type phenotypes. We also identified insertion lines for which no homozygous plants were obtained. To date, we have identified 111 lines with reproducible seedling phenotypes, 122 lines for which we could not obtain homozygotes and 1290 homozygous lines without a visible phenotype. The Chloroplast Function Database presents the molecular and phenotypic information obtained from this resource. The database provides tools for searching for mutant lines using Arabidopsis Genome Initiative (AGI) locus numbers, tagged line numbers and phenotypes, and provides rapid access to detailed information on the tagged line resources. Moreover, our collection of insertion homozygotes provides a powerful tool to accelerate the functional analysis of nuclear‐encoded chloroplast proteins in Arabidopsis. The Chloroplast Function Database is freely available at http://rarge.psc.riken.jp/chloroplast/. The homozygous lines generated in this project are also available from the various Arabidopsis stock centers. We have donated the insertion homozygotes to their originating seed stock centers.
Regional differences in local recurrence rates after rectal cancer surgery
Authors: Kodeda K. , Holmberg E. , Steineck G. , Nordgren S. 
Published: November 2009

AbstractAim  To analyse a substantial regional difference in local failure rate after rectal cancer surgery focusing on management.Method  National, population‐based, prospective registry data were used, including comprehensive 5‐year follow up of 3783 patients operated on in the period 1998–2000. Local recurrence rates were compared using crude rate, Kaplan–Meier estimates and competing risk methodology. Resected patients (651 regional and 3132 national) were analysed and subgroup comparisons of management were performed.Results  The crude local recurrence rate was 13.7% in the regional cohort and 7.1% in the national cohort. The absolute difference of 6.6% may partly be explained by systematic errors of underreporting (≤ 1.4%), differences in patient populations and indications for surgery. A significant difference in the use of neoadjuvant radiotherapy (explaining ≤ 1.0%) and some aspects of surgical strategy were also observed.Conclusions  We conclude that some of the difference in the registered incidence of local recurrence between the regional and the national cohorts remains unexplained and may depend on surgical technique in terms of lack of radicality in removing tumour tissue.
A randomized, prospective, double‐blind, placebo‐controlled trial of the effect of topical diltiazem on posthaemorrhoidectomy pain
Authors: Amoli H. A. , Notash A. Y. , Shahandashti F. J. , Kenari A. Y. , Ashraf H. 
Published: November 2009

AbstractAim  Spasm of the internal anal sphincter plays a role in haemorrhoidal disease and may be a source of anal pain after haemorrhoid surgery. In this study, we investigated the effect of topical diltiazem (DTZ) on postoperative pain following Milligan–Morgan haemorrhoidectomy.Method  After haemorrhoidectomy, 33 patients were randomly assigned to receive DTZ ointment (2%; n = 16) or a placebo ointment (n = 17). Ointments were applied to the perianal region three times daily for 7 days. A Visual Analogue Scale was used to assess postoperative pain. The primary end‐point was reduction in postoperative pain.Results  Patients using the DTZ cream had significantly less pain and greater benefit than those in the placebo group throughout the first postoperative week, and total and daily narcotic analgesic use was higher in the placebo group. There were no differences in morbidity between the two groups.Conclusion  Perianal application of DTZ cream after haemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial, with no increase in associated morbidity.
Nanosized Iron Oxide Colloids Strongly Enhance Microbial Iron Reduction
Authors: Bosch Julian , Heister Katja , Hofmann Thilo , Meckenstock Rainer U. 
Published: November 2009

ABSTRACT

Microbial iron reduction is considered to be a significant subsurface process. The rate-limiting bioavailability of the insoluble iron oxyhydroxides, however, is a topic for debate. Surface area and mineral structure are recognized as crucial parameters for microbial reduction rates of bulk, macroaggregate iron minerals. However, a significant fraction of iron oxide minerals in the subsurface is supposed to be present as nanosized colloids. We therefore studied the role of colloidal iron oxides in microbial iron reduction. In batch growth experiments with
Geobacter sulfurreducens
, colloids of ferrihydrite (hydrodynamic diameter, 336 nm), hematite (123 nm), goethite (157 nm), and akaganeite (64 nm) were added as electron acceptors. The colloidal iron oxides were reduced up to 2 orders of magnitude more rapidly (up to 1,255 pmol h
−
1
cell
−
1
) than bulk macroaggregates of the same iron phases (6 to 70 pmol h
−
1
cell
−
1
). The increased reactivity was not only due to the large surface areas of the colloidal aggregates but also was due to a higher reactivity per unit surface. We hypothesize that this can be attributed to the high bioavailability of the nanosized aggregates and their colloidal suspension. Furthermore, a strong enhancement of reduction rates of bulk ferrihydrite was observed when nanosized ferrihydrite aggregates were added.
Emergence of a Cell Wall Protease in the
Streptococcus thermophilus
Population
Authors: Delorme Christine , Bartholini Claire , Bolotine Alexander , Ehrlich S. Dusko , Renault Pierre 
Published: November 2009

ABSTRACT

Streptococcus thermophilus
is perceived as a recently emerged food bacterium that evolved from a commensal ancestor by loss and gain of functions. Here, we provide data allowing a better understanding of this evolutionary scheme. A multilocus sequence typing approach that we developed showed that
S. thermophilus
diverges significantly from its potential ancestors of the salivarius group and displays a low level of allelic variability, confirming its likely recent emergence. An analysis of the origin and dissemination of the
prtS
gene was carried out within this evolutionary scheme. This gene encodes a protease that allows better growth in milk by facilitating casein breakdown to supply amino acids. The
S. thermophilus
protease exhibits 95% identity to the animal
Streptococcus suis
protein PrtS. Genomic analysis showed that
prtS
is part of an island flanked by two tandem insertion sequence elements and containing three other genes which present the best identities and synteny with the
S. suis
genome. These data indicate a potential origin for this “ecological” island in a species closely related to
S. suis
. The analysis of the distribution of the
prtS
gene in
S. thermophilus
showed that the gene is infrequent in historical collections but frequent in recent industrial ones. Moreover, this “ecological” island conferring an important metabolic trait for milk adaptation appears to have disseminated by lateral transfer in the
S. thermophilus
population. Taken together, these data support an evolutionary scheme of
S. thermophilus
where gene acquisition and selection by food producers are determining factors. The source and impact of genes acquired by horizontal gene transfer on the physiology and safety of strains should be addressed.
Involvement of Vacuolar Sequestration and Active Transport in Tolerance of
Saccharomyces
cerevisiae
to Hop Iso-α-Acids
Authors: Hazelwood Lucie A. , Walsh Michael C. , Pronk Jack T. , Daran Jean-Marc 
Published: November 2009

ABSTRACT

The hop plant,
Humulus
lupulus
L., has an exceptionally high content of secondary metabolites, the hop α-acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso-α-acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso-α-acid resistance in the model eukaryote
Saccharomyces
cerevisiae
. Growth inhibition occurred at concentrations of hop iso-α-acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the
S
.
cerevisiae
haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso-α-acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso-α-acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso-α-acids and alteration of cell wall structure and, to a lesser extent, active export of iso-α-acids across the plasma membrane. Furthermore, iso-α-acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.
Probabilistic Model of Microbial Cell Growth, Division, and Mortality
Authors: Horowitz Joseph , Normand Mark D. , Corradini Maria G. , Peleg Micha 
Published: November 2009

ABSTRACT

After a short time interval of length δ
t
during microbial growth, an individual cell can be found to be divided with probability

P
d

(
t
)δ
t
, dead with probability

P
m

(
t
)δ
t
, or alive but undivided with the probability 1 − [

P
d

(
t
)

+ P
m

(
t
)]δ
t
, where
t
is time,

P
d

(
t
) expresses the probability of division for an individual cell per unit of time, and

P
m

(
t
) expresses the probability of mortality per unit of time. These probabilities may change with the state of the population and the habitat's properties and are therefore functions of time. This scenario translates into a model that is presented in stochastic and deterministic versions. The first, a stochastic process model, monitors the fates of individual cells and determines cell numbers. It is particularly suitable for small populations such as those that may exist in the case of casual contamination of a food by a pathogen. The second, which can be regarded as a large-population limit of the stochastic model, is a continuous mathematical expression that describes the population's size as a function of time. It is suitable for large microbial populations such as those present in unprocessed foods. Exponential or logistic growth with or without lag, inactivation with or without a “shoulder,” and transitions between growth and inactivation are all manifestations of the underlying probability structure of the model. With temperature-dependent parameters, the model can be used to simulate nonisothermal growth and inactivation patterns. The same concept applies to other factors that promote or inhibit microorganisms, such as pH and the presence of antimicrobials, etc. With

P
d

(
t
) and

P
m

(
t
) in the form of logistic functions, the model can simulate all commonly observed growth/mortality patterns. Estimates of the changing probability parameters can be obtained with both the stochastic and deterministic versions of the model, as demonstrated with simulated data.
Integrated Bioprocessing for the pH-Dependent Production of 4-Valerolactone from Levulinate in
Pseudomonas putida
KT2440
Authors: Martin Collin H. , Wu Danyi , Prather Kristala L. Jones 
Published: November 2009

ABSTRACT

Enzymes are powerful biocatalysts capable of performing specific chemical transformations under mild conditions, yet as catalysts they remain subject to the laws of thermodynamics, namely, that they cannot catalyze chemical reactions beyond equilibrium. Here we report the phenomenon and application of using extracytosolic enzymes and medium conditions, such as pH, to catalyze metabolic pathways beyond their intracellular catalytic limitations. This methodology, termed “integrated bioprocessing” because it integrates intracellular and extracytosolic catalysis, was applied to a lactonization reaction in
Pseudomonas putida
for the economical and high-titer biosynthesis of 4-valerolactone from the inexpensive and renewable source levulinic acid. Mutant paraoxonase I (PON1) was expressed in
P. putida
, shown to export from the cytosol in
Escherichia coli
and
P. putida
using an N-terminal sequence, and demonstrated to catalyze the extracytosolic and pH-dependent lactonization of 4-hydroxyvalerate to 4-valerolactone. With this production system, the titer of 4-valerolactone was enhanced substantially in acidic medium using extracytosolically expressed lactonase versus an intracellular lactonase: from <0.2 g liter
−1
to 2.1 ± 0.4 g liter
−1
at the shake flask scale. Based on these results, the production of 4-hydroxyvalerate and 4-valerolactone was examined in a 2-liter bioreactor, and titers of 27.1 g liter
−1
and 8.2 g liter
−1
for the two respective compounds were achieved. These results illustrate the utility of integrated bioprocessing as a strategy for enabling production from novel metabolic pathways and enhancing product titers.
Elimination of Glycerol Production in Anaerobic Cultures of a
Saccharomyces cerevisiae
Strain Engineered To Use Acetic Acid as an Electron Acceptor
Authors: Medina Víctor Guadalupe , Almering Marinka J. H. , van Maris Antonius J. A. , Pronk Jack T. 
Published: November 2009

ABSTRACT

In anaerobic cultures of wild-type
Saccharomyces cerevisiae
, glycerol production is essential to reoxidize NADH produced in biosynthetic processes. Consequently, glycerol is a major by-product during anaerobic production of ethanol by
S. cerevisiae
, the single largest fermentation process in industrial biotechnology. The present study investigates the possibility of completely eliminating glycerol production by engineering
S. cerevisiae
such that it can reoxidize NADH by the reduction of acetic acid to ethanol via NADH-dependent reactions. Acetic acid is available at significant amounts in lignocellulosic hydrolysates of agricultural residues. Consistent with earlier studies, deletion of the two genes encoding NAD-dependent glycerol-3-phosphate dehydrogenase (
GPD1
and
GPD2
) led to elimination of glycerol production and an inability to grow anaerobically. However, when the
E. coli mhpF
gene, encoding the acetylating NAD-dependent acetaldehyde dehydrogenase (EC 1.2.1.10; acetaldehyde + NAD
+
+ coenzyme A ↔ acetyl coenzyme A + NADH + H
+
), was expressed in the
gpd1
Δ
gpd2
Δ strain, anaerobic growth was restored by supplementation with 2.0 g liter
−1
acetic acid. The stoichiometry of acetate consumption and growth was consistent with the complete replacement of glycerol formation by acetate reduction to ethanol as the mechanism for NADH reoxidation. This study provides a proof of principle for the potential of this metabolic engineering strategy to improve ethanol yields, eliminate glycerol production, and partially convert acetate, which is a well-known inhibitor of yeast performance in lignocellulosic hydrolysates, to ethanol. Further research should address the kinetic aspects of acetate reduction and the effect of the elimination of glycerol production on cellular robustness (e.g., osmotolerance).
Expression of the
Clostridium botulinum
A2 Neurotoxin Gene Cluster Proteins and Characterization of the A2 Complex
Authors: Lin Guangyun , Tepp William H. , Pier Christina L. , Jacobson Mark J. , Johnson Eric A. 
Published: November 2009

ABSTRACT

Clostridium botulinum
subtype A2 possesses a botulinum neurotoxin type A (BoNT/A) gene cluster consisting of an
orfX
cluster containing open reading frames (ORFs) of unknown functions. To better understand the association between the BoNT/A2 complex proteins, first, the
orfX
cluster proteins (ORFX1, ORFX3, P47, and the middle part of NTNH) from
C. botulinum
A2 strain Kyoto F and NTNH of A1 strain ATCC 3502 were expressed by using either an
Escherichia coli
or a
C. botulinum
expression system. Polyclonal antibodies against individual
orfX
cluster proteins were prepared by immunizing a rabbit and mice against the expressed proteins. Antibodies were then utilized as probes to determine which of the A2
orfX
cluster genes were expressed in the native A2 culture. N-terminal protein sequencing was also employed to specifically detect ORFX2. Results showed that all of the neurotoxin cluster proteins, except ORFX1, were expressed in the A2 culture. A BoNT/A2 toxin complex (TC) was purified which showed that
C. botulinum
A2 formed a medium-size (300-kDa) TC composed of BoNT/A2 and NTNH without any of the other OrfX cluster proteins. NTNH subtype-specific immunoreactivity was also discovered, allowing for the differentiation of subtypes based on cluster proteins associated with BoNT.
Role of Extracellular Polymeric Substances in the Surface Chemical Reactivity of
Hymenobacter aerophilus
, a Psychrotolerant Bacterium
Authors: Baker M. G. , Lalonde S. V. , Konhauser K. O. , Foght J. M. 
Published: November 2009

ABSTRACT

Bacterial surface layers, such as extracellular polymeric substances (EPS), are known to play an important role in metal sorption and biomineralization; however, there have been very few studies investigating how environmentally induced changes in EPS production affect the cell's surface chemistry and reactivity. Acid-base titrations, cadmium adsorption assays, and Fourier transform infrared spectroscopy (FT-IR) were used to characterize the surface reactivities of
Hymenobacter aerophilus
cells with intact EPS (WC) or stripped of EPS (SC) and purified EPS alone. Linear programming modeling of titration data showed SC to possess functional groups corresponding to phosphoryl (pK
a
∼6.5), phosphoryl/amine (pK
a
∼7.9), and amine/hydroxyl (pK
a
∼9.9). EPS and WC both possess carboxyl groups (pK
a
∼5.1 to 5.8) in addition to phosphoryl and amine groups. FT-IR confirmed the presence of polysaccharides and protein in purified EPS that can account for the additional carboxyl groups. An increased ligand density was observed for WC relative to that for SC, leading to an increase in the amount of Cd adsorbed (0.53 to 1.73 mmol/liter per g [dry weight] and 0.53 to 0.59 mmol/liter per g [dry weight], respectively). Overall, the presence of EPS corresponds to an increase in the number and type of functional groups on the surface of
H. aerophilus
that is reflected by increased metal adsorption relative to that for EPS-free cells.