bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upstream and Downstream Regulation of Asexual Development in
Aspergillus fumigatus
Authors: Mah Jae-Hyung , Yu Jae-Hyuk 
Published: October 2006

ABSTRACT

The opportunistic human pathogen
Aspergillus fumigatus
produces a large quantity of asexual spores (conidia), which are the primary agent causing invasive aspergillosis in immunocompromised patients. We investigated the mechanisms controlling asexual sporulation (conidiation) in
A. fumigatus
via examining functions of four key regulators, GpaA (Gα), AfFlbA (RGS), AfFluG, and AfBrlA, previously studied in
Aspergillus nidulans
. Expression analyses of
gpaA
, Af
flbA
, Af
fluG
, Af
brlA
, and Af
wetA
throughout the life cycle of
A. fumigatus
revealed that, while transcripts of Af
flbA
and Af
fluG
accumulate constantly, the latter two downstream developmental regulators are specifically expressed during conidiation. Both loss-of-function Af
flbA
and dominant activating GpaA
Q204L
mutations resulted in reduced conidiation with increased hyphal proliferation, indicating that GpaA signaling activates vegetative growth while inhibiting conidiation. As GpaA is the primary target of AfFlbA, the dominant interfering GpaA
G203R
mutation suppressed reduced conidiation caused by loss of Af
flbA
function. These results corroborate the hypothesis that functions of G proteins and RGSs are conserved in aspergilli. We then examined functions of the two major developmental activators AfFluG and AfBrlA. While deletion of Af
brlA
eliminated conidiation completely, null mutation of Af
fluG
did not cause severe alterations in
A. fumigatus
sporulation in air-exposed culture, implying that, whereas the two aspergilli may have a common key downstream developmental activator, upstream mechanisms activating
brlA
may be distinct. Finally, both Af
fluG
and Af
flbA
mutants showed reduced conidiation and delayed expression of Af
brlA
in synchronized developmental induction, indicating that these upstream regulators contribute to the proper progression of conidiation.
A Peroxisomal Glutathione Transferase of
Saccharomyces cerevisiae
Is Functionally Related to Sulfur Amino Acid Metabolism
Authors: Barreto Lina , Garcerá Ana , Jansson Kristina , Sunnerhagen Per , Herrero Enrique 
Published: October 2006

ABSTRACT

Saccharomyces cerevisiae
cells contain three omega-class glutathione transferases with glutaredoxin activity (Gto1, Gto2, and Gto3), in addition to two glutathione transferases (Gtt1 and Gtt2) not classifiable into standard classes. Gto1 is located at the peroxisomes, where it is targeted through a PTS1-type sequence, whereas Gto2 and Gto3 are in the cytosol. Among the
GTO
genes,
GTO2
shows the strongest induction of expression by agents such as diamide, 1-chloro-2,4-dinitrobenzene,
tert
-butyl hydroperoxide or cadmium, in a manner that is dependent on transcriptional factors Yap1 and/or Msn2/4. Diamide and 1-chloro-2,4-dinitrobenzene (causing depletion of reduced glutathione) also induce expression of
GTO1
over basal levels. Phenotypic analyses with single and multiple mutants in the
S. cerevisiae
glutathione transferase genes show that, in the absence of Gto1 and the two Gtt proteins, cells display increased sensitivity to cadmium. A
gto1
-null mutant also shows growth defects on oleic acid-based medium, which is indicative of abnormal peroxisomal functions, and altered expression of genes related to sulfur amino acid metabolism. As a consequence, growth of the
gto1
mutant is delayed in growth medium without lysine, serine, or threonine, and the mutant cells have low levels of reduced glutathione. The role of Gto1 at the
S. cerevisiae
peroxisomes could be related to the redox regulation of the Str3 cystathionine β-lyase protein. This protein is also located at the peroxisomes in
S. cerevisiae
, where it is involved in transulfuration of cysteine into homocysteine, and requires a conserved cysteine residue for its biological activity.
RacG Regulates Morphology, Phagocytosis, and Chemotaxis
Authors: Somesh Baggavalli P. , Vlahou Georgia , Iijima Miho , Insall Robert H. , Devreotes Peter , Rivero Francisco 
Published: October 2006

ABSTRACT

RacG
is an unusual member of the complex family of Rho GTPases in
Dictyostelium
. We have generated a knockout (KO) strain, as
well as strains that overexpress wild-type (WT), constitutively active
(V12), or dominant negative (N17) RacG. The protein is targeted to the
plasma membrane, apparently in a nucleotide-dependent manner, and
induces the formation of abundant actin-driven filopods. RacG is
enriched at the rim of the progressing phagocytic cup, and
overexpression of RacG-WT or RacG-V12 induced an increased rate of
particle uptake. The positive effect of RacG on phagocytosis was
abolished in the presence of 50 μM LY294002, a phosphoinositide
3-kinase inhibitor, indicating that generation of phosphatidylinositol
3,4,5-trisphosphate is required for activation of RacG. RacG-KO cells
showed a moderate chemotaxis defect that was stronger in the RacG-V12
and RacG-N17 mutants, in part because of interference with signaling
through Rac1. The in vivo effects of RacG-V12 could not be reproduced
by a mutant lacking the Rho insert region, indicating that this region
is essential for interaction with downstream components. Processes like
growth, pinocytosis, exocytosis, cytokinesis, and development were
unaffected in Rac-KO cells and in the overexpressor mutants. In a
cell-free system, RacG induced actin polymerization upon GTPγS
stimulation, and this response could be blocked by an Arp3 antibody.
While the mild phenotype of RacG-KO cells indicates some overlap with
one or more
Dictyostelium
Rho GTPases, like Rac1 and RacB, the
significant changes found in overexpressors show that RacG plays
important roles. We hypothesize that RacG interacts with a subset of
effectors, in particular those concerned with shape, motility, and
phagocytosis.
TOS9 Regulates White-Opaque Switching in
Candida
albicans
Authors: Srikantha Thyagarajan , Borneman Anthony R. , Daniels Karla J. , Pujol Claude , Wu Wei , Seringhaus Michael R. , Gerstein Mark , Yi Song , Snyder Michael , Soll David R. 
Published: October 2006

ABSTRACT

In
Candida albicans
, the
a
1-α2 complex
represses white-opaque switching, as well as mating. Based upon the
assumption that the
a
1-α2 corepressor complex binds to
the gene that regulates white-opaque switching, a chromatinimmunoprecipitation-microarray analysis strategy was used to identify
52 genes that bound to the complex. One of these genes,
TOS9
,
exhibited an expression pattern consistent with a “master
switch gene.”
TOS9
was only expressed in opaque cells,
and its gene product, Tos9p, localized to the nucleus. Deletion of the
gene blocked cells in the white phase, misexpression in the white phase
caused stable mass conversion of cells to the opaque state, and
misexpression blocked temperature-induced mass conversion from the
opaque state to the white state. A model was developed for the
regulation of spontaneous switching between the opaque state and the
white state that includes stochastic changes of Tos9p levels above and
below a threshold that induce changes in the chromatin state of an
as-yet-unidentified switching locus.
TOS9
has also been
referred to as
EAP2
and
WOR1
.
Paralongidorus sacchari Siddiqi, Hooper & Khan, 1963 and Paraxiphidorus michelluci Coomans & Chaves, 1995 (Nematoda: Longidoridae) from Chile
Authors: Rios Alejandra , Roca Francesco 
Published: October 2006

AbstractSpecimens from soil samples collected at Cocalan, Chile, from the rhizosphere of the Chilean wine palm, Jubaea chilensis, were sent to the Plant Protection Institute, Bari, Italy. The identification revealed the presence of large numbers of Paralongidorus sacchari and a few specimens of Paraxiphidorus michelluci, including several juveniles. Populations were studied morphologically and morphometrically and results are reported herein. Both species represent new records for Chile. Juveniles of Paraxiphidorus michelluci are described for the first time.
Spatial and temporal distribution of Heterorhabditis indica in their natural habitats of Guadeloupe
Authors: Briand Sophie , Denon Dominique , Mauléon Hervé 
Published: October 2006

AbstractThe presence of Heterorhabditis indica in the littoral zone of continental Guadeloupe was assessed by the Galleria trap technique. A total of 309 samples from 192 sampling sites were analysed. Heterorhabditis indica was found in 74 samples from 53 sites (45 beaches and eight limestone cliffs). The ecological characteristics of these places (climate, soil, flora and fauna) were described and the arthropods occupying these locations were tested for their ability to support nematode development. The spatial distribution of H. indica showed that the colonisation of these sites by nematodes is due to a permanent occurrence of patches generally found under the canopy of trees. An annual monitoring (performed in the wet season from 1996-2005) showed that these patches were regularly recovered (10 consecutive years). The population dynamics of H. indica was studied monthly in two sites for 28 months. In both sites, the abundance of nematodes was directly correlated to rainfall. In the dry season, when the soil moisture was lower than 3.5%, nematodes were not detected by the insect traps. The infective juveniles can survive about 6-7 months in such an environment. Field experiments with sterilised soil showed that nematode-free soil is normally recolonised by active migration but recolonisation can also occur when this route is excluded, indicating either infected insects or passive transport (human or animal) as alternative routes.
NSAID injury to the gastrointestinal tract: evidence that NSAIDs interact with phospholipids to weaken the hydrophobic surface barrier and induce the formation of unstable pores in membranes
Authors: Lichtenberger Lenard M , Zhou Yong , Dial Elizabeth J , Raphael Robert M 
Published: October 2006

Abstract
In this review, we have discussed our current understanding of the barrier properties that are in place to protect the upper gastrointestinal mucosa from luminal acid, and the pathogenic mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) induce injury to the gastrointestinal tract. The changes in our view of the importance of NSAID-induced cyclo-oxygenase (COX) inhibition on the pathogenesis and prevention of NSAID-induced gastrointestinal injury is presented. The focus of this paper has been placed on the effects of NSAIDs on the mucosal surface, and specifically the effect of these powerful drugs in inducing changes in the hydrophobicity, fluidity, biomechanical and permeability properties of extracellular and membrane phospholipids. Lastly, recent evidence is presented that salicylic acid and related NSAIDs may alter the stability of membranes, inducing the formation of unstable pores that may lead to back-diffusion of luminal acid and membrane rupture. This understanding of the interaction of NSAIDs with membrane phos-pholipids may prove valuable in the design of novel NSAID formulations with reduced gastrointestinal side-effects.
Intranasal midazolam: a comparison of two delivery devices in human volunteers
Authors: Dale Ola , Nilsen Turid , Loftsson Thorsteinn , Tønnesen Hanne Hjorth , Klepstad Pål , Kaasa Stein , Holand Trond , Djupesland Per G 
Published: October 2006

Abstract
Bidirectional nasal drug delivery is a new administration principle with improved deposition pattern that may increase nasal drug uptake. Twelve healthy subjects were included in this open, non-randomized 3-way crossover study: midazolam (3.4 mg) intravenously (1 mg mL−1), or nasally by bidirectional or traditional spray (2 × 100 μL of a 17 mg mL−1 nasal midazolam formulation). The primary outcome was bioavailability. Blood samples were drawn for 6 h for determination (gas-chromatography-mass-spectrometry) of midazolam and 1-OH-midazolam. Pharmacokinetic calculations were based on non-compartmental modelling, sedation assessed by a subjective 0–10 NRS-scale, and nasal dimensions by non-invasive acoustic rhinometry. Mean bioavailabilities were 0.68-0.71, and Tmax 15 min for the sprays, which also were bioequivalent (ratio geometric means (90%) CI: 97.6% (90% CI 83.5; 113.9)). Sedation after bidirectional spray followed intravenous sedation closely, while sedation after the traditional spray was less pronounced. A negative correlation between Cmax and smallest cross-sectional area was seen. Adverse effects such as local irritation did not differ significantly between the sprays. Apparently bidirectional delivery did not increase systemic bioavailability of midazolam. We cannot disregard that only the traditional spray caused less sedation than intravenous administration. This finding needs to be confirmed in trials designed for this purpose.
Fast-dissolving microparticles fail to show improved oral bioavailability
Authors: Wong S M , Kellaway I W , Murdan S 
Published: October 2006

Abstract
Oral dosage forms are the preferred means of delivering drugs for systemic absorption. However, development problems occur for drugs with poor water solubility and/or gastrointestinal permeability. It is generally believed that the in-vivo bioavailability of poorly water-soluble drugs from Class II of the Biopharmaceutics Classification System can be improved by increasing the dissolution rate. We have attempted to increase the in-vivo oral bioavailability of a model Class II drug (griseofulvin) by preparing rapidly-dissolving particles. The solvent-diffusion method was used to prepare particles with hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies were conducted in rats. The griseofulvin particles produced were bipyramidal in habit with a particle size of 2.18 ± 0.12 mm; they contained crystalline drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The latter and the small particle size ensured rapid particle dispersion and dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the bipyramidal particles had released ∼70% of drug compared with ∼10% from the starting material (particle size 12.61 ± 1.11 μm). However, the rapid and increased drug dissolution in-vitro was not translated to rapid and enhanced absorption in-vivo, and the oral bioavailability of the model drug was found to be the same from the control and from the bipyramidal particles. The poor in-vivo performance of the bipyramidal particles showed that although the dissolution rate of a Class II drug is thought to be a good indicator of its in-vivo bioavailability, this is not always the case.
Decreased B16F10 melanoma growth and impaired tumour vascularization in BDF1 mice with quercetin-cyclodextrin binary system
Authors: Kale Rajendrakumar , Saraf Madhusudan , Juvekar Aarti , Tayade Pralhad 
Published: October 2006

Abstract
The aim of this work was to study the inclusion behaviour of a poorly water-soluble bioflavonoid, quercetin, towards sulfobutyl ether-7β-cyclodextrin. It also involves angiogenesis inhibition in-vivo in addition to in-vitro human cancer cell growth inhibition study of quercetin and its cyclodextrin complex. Drug-cyclodextrin solid inclusion complexes were prepared and characterized in solution and in the solid state. An in-vitro anti-proliferation study using plain drug and its solubilized form was carried out on human cancer cell lines of different origin. Further, an in-vivo tumour growth inhibition study was carried out using a mouse melanoma model. Histological sections of tumours were examined for the evaluation of tumour microvessel density. Significant enhancement of the solubility and dissolution rate of the quercetin, which occurred after complexation, might be attributed to the decrease in crystallinity of drug. SBE7βCD complex of quercetin was more potent for inhibiting cell proliferation in human erythroleukaemia and cervix cancer cells. Decreased tumour microvessel density in mouse melanoma after oral quercetin administration led to diminished tumour cell proliferation. Quercetin-SBE7βCD complex showed significantly improved anti-cancer activity at much lower concentration than the plain drug, providing evidence for dose reduction without affecting therapeutic efficacy when using cyclodextrin carriers.
Protective effect of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins in streptozotocin-induced diabetic rats
Authors: Prince P Stanely Mainzen , Kannan N K 
Published: October 2006

AbstractThe protective role of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins in streptozotocin-induced diabetic rats has been studied. A single intraperitoneal injection of streptozotocin (50 mg kg−1) to rats led to a significant (P &lt; 0.05) increase in the levels of lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in plasma and tissues (liver, kidney, heart and brain). The levels of low density and very low density lipoprotein (LDL and VLDL, respectively) cholesterol were increased, whereas the levels of high density lipoprotein (HDL) cholesterol were decreased significantly (P &lt; 0.05) in plasma. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly (P &lt; 0.05) in liver, kidney and heart, and the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT) decreased significantly (P &lt; 0.05) in the plasma of diabetic rats. Streptozotocin injection also increased the levels of glycoproteins such as hexose, hexosamine, fucose and sialic acid in plasma, liver and kidney. Oral administration of rutin to streptozotocin-induced diabetic rats significantly (P &lt; 0.05) decreased the levels of lipids in plasma and tissues. The levels of plasma HDL-cholesterol increased and the levels of LDL- and VLDL-cholesterol decreased significantly (P &lt; 0.05). The activity of HMG CoA reductase decreased in the tissues and the activity of plasma LPL and LCAT increased significantly (P &lt; 0.05). The levels of glycoproteins were found to be significantly (P &lt; 0.05) decreased in plasma, liver and kidney of rutin-treated diabetic rats. Rutin administration to normal rats did not exhibit any significant (P &lt; 0.05) changes in any of the parameters studied. In conclusion, the beneficial effect of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins could be due to its antioxidant property.
D-chiro-Inositol found in Cucurbita ficifolia (Cucurbitaceae) fruit extracts plays the hypoglycaemic role in streptozocin-diabetic rats
Authors: Xia Tao , Wang Qin 
Published: October 2006

Abstract
Cucurbita ficifolia is commonly used as an antihyperglycaemic agent in Asia. However, the mechanism of its action is unknown. Chemically synthesized D-chiro-inositol (D-CI), a component of an insulin mediator, has been demonstrated to have antihyperglycaemic effects in rats. In this study, we found that C. ficifolia contained fairly high levels of D-CI, thus, C. ficifolia may be a natural source of D-CI for reducing blood glucose concentrations in diabetics. We evaluated C. ficifolia fruit extract, containing D-CI, for its antihyperglycaemic effect in streptozotocin-induced diabetic rats. Oral administration of C. ficifolia fruit extract containing 10 or 20 mg D-CI kg−1 body weight for 30 days resulted in significantly lowered levels of blood glucose, and increased levels of hepatic glycogen, total haemoglobin and plasma insulin. An oral glucose tolerance test was performed in fasted diabetic and normal rats, in which there was a significant improvement in blood glucose tolerance in the diabetic rats treated with C. ficifolia fruit extract. The effects were compared with 20 mg kg−1 body weight chemically synthesized D-CI. Findings from this study demonstrated that C. ficifolia fruit extract was an effective source of D-CI for its hypoglycaemic effects in rats, and therefore may be useful in the treatment of diabetes.
N, N‘ (4,5-Dihydro-1H-imidazol-2-yl)3-aza-1, 10-decane-diamine and N, N’(4,5-dihydro-1H-imidazol-2-yl)3-aza-1, 10-dodecane-diamine antagonize cell proliferation as selective ligands towards topoisomerase II
Authors: Filosa Rosanna , Buonerba Mariafrancesca , Loddo Roberta , Busonera Bernardetta , La Colla Paolo , Saturnino Carmela 
Published: October 2006

Abstract
New alkyl imidazoline derivatives have been synthesized as potential anticancer agents. The anti-4 proliferative activity of these compounds, evaluated against representative human haematological and solid neoplastic cell lines, showed that N, N′-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-decanediamine (8) and N, N′-di (4,5-dihydro-1H-imidazol-2-yl)3-aza-1,10-dodecane-diamine (9) were the most active compounds; in fact, they inhibited the cell proliferation at submicromolar concentrations. In enzyme assays, compound 9 turned out to be an inhibitor of topoisomerase II at concentrations comparable with those of the reference topoisomerase II inhibitor, etoposide.
Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenols
Authors: Zhong Zhi , Connor Henry D , Li Xiangli , Mason Ronald P , Forman Donald T , Lemasters John J , Thurman Ronald G 
Published: October 2006

Abstract
The immunosuppressants ciclosporin (cyclosporin A, CsA) and tacrolimus can cause severe nephrotoxicity. Since CsA increases free radical formation, this study investigated whether an extract from Camellia sinensis, which contains several polyphenolic free radical scavengers, could prevent nephrotoxicity caused by CsA and tacrolimus. Rats were fed powdered diet containing polyphenolic extract (0-0.1%) starting 3 days before CsA or tacrolimus. Free radicals were trapped with α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) and measured using an electron spin resonance spectrometer. Both CsA and tacrolimus decreased glomerular filtration rates (GFR) and caused tubular atrophy, vacuolization and calcification and arteriolar hyalinosis, effects that were blunted by treatment with dietary polyphenols. Moreover, CsA and tacrolimus increased POBN/radical adducts in urine nearly 3.5 fold. Hydroxyl radicals attack dimethyl sulfoxide (DMSO) to produce a methyl radical fragment. Administration of CsA or tacrolimus with 12C-DMSO produced a 6-line spectrum, while CsA or tacrolimus given with 13C-DMSO produced a 12-line ESR spectrum, confirming formation of hydroxyl radicals. 4-Hydroxynonenal (4-HNE), a product of lipid peroxidation, accumulated in proximal and distal tubules after CsA or tacrolimus treatment. ESR changes and 4-HNE formation were largely blocked by polyphenols. Taken together, these results demonstrate that both CsA and tacrolimus stimulate free radical production in the kidney, most likely in tubular cells, and that polyphenols minimize nephrotoxicity by scavenging free radicals.