bluuebunny/crossref_metadata_2025_split huggingface dataset:
NB-002, a Novel Nanoemulsion with Broad Antifungal Activity against Dermatophytes, Other Filamentous Fungi, and
Candida albicans
Authors: Pannu J. , McCarthy A. , Martin A. , Hamouda T. , Ciotti S. , Fothergill A. , Sutcliffe J. 
Published: May 2009

ABSTRACT

NB-002 is an oil-in-water emulsion designed for use for the treatment of skin, hair, and nail infections. The activity of NB-002 was compared to the activities of the available antifungal drugs against the major dermatophytes responsible for cutaneous infections,
Trichophyton rubrum
,
Trichophyton mentagrophytes
,
Epidermophyton floccosum
, and
Microsporum
spp., as well as 12 other genera of filamentous fungi. NB-002 consistently displayed fungicidal activity against all dermatophytes. The comparator compounds were either fungistatic or fungicidal, and for some strain-drug combinations, tolerance was observed. Assessment of the development of spontaneous resistance to NB-002 in different dermatophyte species yielded few stably resistant mutants. For filamentous nondermatophyte fungi, the MIC range varied from 0.06 to 0.5 μg/ml for
Alternaria
spp. to 2 to 8 μg/ml for
Paecilomyes
spp. NB-002 had activity against both azole-susceptible and -resistant
Candida albicans
yeast isolates, with MIC
90
s of 2 μg/ml, respectively, and minimum fungicidal concentrations at which 90% of isolates are inhibited of 4 and 8 μg/ml, respectively. The kinetics of the fungicidal activity of NB-002 against
T. rubrum
isolates were compared to those of the other antifungal drugs. NB-002 killed both mycelia and microconidia even when the fungal forms were dormant or not actively growing. Electron micrographs of mycelia and spores treated with NB-002 showed the significant disruption of the fungal structure. The in vitro broad coverage of NB-002 against filamentous fungi, dermatophytes, and
C. albicans
, as well as its rapid fungicidal activity, warrants further investigations to ascertain if NB-002 would be useful for the treatment of cutaneous mycoses.
Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by Gram-Negative Bacteria
Authors: Plachouras D. , Karvanen M. , Friberg L. E. , Papadomichelakis E. , Antoniadou A. , Tsangaris I. , Karaiskos I. , Poulakou G. , Kontopidou F. , Armaganidis A. , Cars O. , Giamarellou H. 
Published: May 2009

ABSTRACT
Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.
Use of
l
-Proline and ATP Production by
Trypanosoma cruzi
Metacyclic Forms as Requirements for Host Cell Invasion
Authors: Martins Rafael Miyazawa , Covarrubias Charles , Rojas Robert Galvez , Silber Ariel Mariano , Yoshida Nobuko 
Published: May 2009

ABSTRACT

The process of host cell invasion by
Trypanosoma cruzi
depends on parasite energy. What source of energy is used for that event is not known. To address this and other questions related to
T. cruzi
energy requirements and cell invasion, we analyzed metacyclic trypomastigote forms of the phylogenetically distant CL and G strains. For both strains, the nutritional stress experienced by cells starved for 24, 36, or 48 h in phosphate-buffered saline reduced the ATP content and the ability of the parasite to invade HeLa cells proportionally to the starvation time. Inhibition of ATP production by treating parasites with rotenone plus antimycin A also diminished the infectivity. Nutrient depletion did not alter the expression of gp82, the surface molecule that mediates CL strain internalization, but increased the expression of gp90, the negative regulator of cell invasion, in the G strain. When
l
-proline was given to metacyclic forms starved for 36 h, the ATP levels were restored to those of nonstarved controls for both strains. Glucose had no such effect, although this carbohydrate and
l
-proline were transported in similar fashions. Recovery of infectivity promoted by
l
-proline treatment of starved parasites was restricted to the CL strain. The profile of restoration of ATP content and gp82-mediated invasion capacity by
l
-proline treatment of starved Y-strain parasites was similar to that of the CL strain, whereas the Dm28 and Dm30 strains, whose infectivity is downregulated by gp90, behaved like the G strain.
l
-Proline was also found to increase the ability of the CL strain to traverse a gastric mucin layer, a property important for the establishment of
T. cruzi
infection by the oral route. Efficient translocation of parasites through gastric mucin toward the target epithelial cells in the stomach mucosa is an essential requirement for subsequent cell invasion. By relying on these closely associated ATP-driven processes, the metacyclic trypomastigotes effectively accomplish their internalization.
Overexpression of the Natural Inhibitor of Cysteine Peptidases inLeishmania mexicanaLeads to Reduced Virulence and a Th1 Response
Authors: Bryson Karen , Besteiro Sébastien , McGachy H. Adrienne , Coombs Graham H. , Mottram Jeremy C. , Alexander James 
Published: May 2009

ABSTRACTLeishmania mexicanacysteine peptidases (CPs) have been identified as important parasite virulence factors. More recently, a natural inhibitor of CPs (ICP) fromL. mexicanahas been characterized, and ICP mutants have been created. Infection of BALB/c mice with ICP null mutants or ICP reexpressing mutants resulted in nonhealing, progressively growing lesions albeit slightly attenuated compared with the growth of lesions produced by wild-type parasites. In contrast, BALB/c mice infected with mutants overexpressing ICP were able to significantly control lesion growth or heal. While BALB/c mice infected with wild-type parasites, ICP null mutants, or ICP reexpressing mutants produced significant antibody responses, including immunoglobulin E (IgE), no Th1 response, as indicated by antigen-induced splenocyte gamma interferon (IFN-γ) production, could be demonstrated. In contrast, BALB/c mice infected with mutants overexpressing ICP produced significantly less antibody, particularly IgE, as well as significantly reduced splenocyte interleukin-4 and enhanced IFN-γ production. BALB/c mice were able to resolve infection following infection with one ICP overexpressing clone, which was subsequently used for vaccination studies with BALB/c mice. However, no protection was afforded these mice when they were challenged with wild-type parasites. Nevertheless, two other mouse strains susceptible toL. mexicana, C3H and C57BL/6, vaccinated with overexpressing ICP mutants were able to control challenge infection associated with an enhanced Th1 response. This study confirms thatL. mexicanaCPs are virulence factors and that ICPs have therapeutic potential.
Role of Teichoic Acid Choline Moieties in the Virulence of
Streptococcus pneumoniae
Authors: Gehre Florian , Spisek Radek , Kharat Arun S. , Matthews Phillip , Kukreja Anjli , Anthony Robert M. , Dhodapkar Madhav V. , Vollmer Waldemar , Tomasz Alexander 
Published: May 2009

ABSTRACT

In recent reports it was shown that genetically modified choline-free strains of
Streptococcus pneumoniae
(D39Cho
−
licA64 and D39ChiplicB31) expressing the type II capsular polysaccharide were virtually avirulent in the murine sepsis model, in sharp contrast to the isogenic and highly virulent strains D39Cho
−
and D39Chip, which have retained the choline residues at their surface. We now demonstrate that this choline-associated virulence is independent of Toll-like receptor 2 recognition. Also, despite the lack of virulence, choline-free strains of
S. pneumoniae
were able to activate splenic dendritic cells, induce secretion of proinflammatory cytokines, and produce specific protective immunity against subsequent challenge. However, after this transient engagement of the immune system the choline-free bacteria were rapidly cleared from the blood, while the isogenic virulent strain D39Cho
−
continued to grow, accompanied by prolonged expression of cytokines, eventually killing the experimental animals. The critical contribution of choline residues to the virulence potential of pneumococci appears to be the role that these amino alcohol residues play in a pneumococcal immune evasion strategy, the mechanism of which is unknown at the present time.
Sortase A Confers Protection against
Streptococcus pneumoniae
in Mice
Authors: Gianfaldoni Claudia , Maccari Silvia , Pancotto Laura , Rossi Giacomo , Hilleringmann Markus , Pansegrau Werner , Sinisi Antonia , Moschioni Monica , Masignani Vega , Rappuoli Rino , Del Giudice Giuseppe , Ruggiero Paolo 
Published: May 2009

ABSTRACT

Streptococcus pneumoniae
sortase A (SrtA) is a transpeptidase that is highly conserved among pneumococcal strains, whose involvement in adhesion/colonization has been reported. We found that intraperitoneal immunization with recombinant SrtA conferred to mice protection against
S. pneumoniae
intraperitoneal challenge and that the passive transfer of immune serum before intraperitoneal challenge was also protective. Moreover, by using the intranasal challenge model, we observed a significant reduction of bacteremia when mice were intraperitoneally immunized with SrtA, while a moderate decrease of lung infection was achieved by intranasal immunization, even though no influence on nasopharynx colonization was seen. Taken together, our results suggest that SrtA is a good candidate for inclusion in a multicomponent, protein-based, pneumococcal vaccine.
Perturbation of the Small Intestine Microbial Ecology by Streptomycin Alters Pathology in a
Salmonella enterica
Serovar Typhimurium Murine Model of Infection
Authors: Garner Cherilyn D. , Antonopoulos Dionysios A. , Wagner Bettina , Duhamel Gerald E. , Keresztes Ivan , Ross Deborah A. , Young Vincent B. , Altier Craig 
Published: May 2009

ABSTRACT

The small intestine is an important site of infection for many enteric bacterial pathogens, and murine models, including the streptomycin-treated mouse model of infection, are frequently used to study these infections. The environment of the mouse small intestine and the microbiota with which enteric pathogens are likely to interact, however, have not been well described. Therefore, we compared the microbiota and the concentrations of short-chain fatty acids (SCFAs) present in the ileum and cecum of streptomycin-treated mice and untreated controls. We found that the microbiota in the ileum of untreated mice differed greatly from that of the cecum of the same mice, primarily among families of the phylum
Firmicutes
. Upon treatment with streptomycin, substantial changes in the microbial composition occurred, with a marked loss of population complexity. Characterization of the metabolic products of the microbiota, the SCFAs, showed that formate was present in the ileum but low or not detectable in the cecum while butyrate was present in the cecum but not the ileum. Treatment with streptomycin altered the SCFAs in the cecum, significantly decreasing the concentration of acetate, propionate, and butyrate. In this work, we also characterized the pathology of
Salmonella
infection in the ileum. Infection of streptomycin-treated mice with
Salmonella
was characterized by a significant increase in the relative and absolute levels of the pathogen and was associated with more severe ileal inflammation and pathology. Together these results provide a better understanding of the ileal environment in the mouse and the changes that occur upon streptomycin treatment.
Anomalous Quantitation Standard Growth Curves in a Laboratory-Developed Hepatitis C Virus (HCV) RNA Quantification Assay Using the TaqMan HCV Analyte-Specific Reagent
Authors: Germer Jeffrey J. , Kathrotiya Jemee D. , Bouse Carrie F. , Mitchell P. Shawn , Yao Joseph D. C. 
Published: May 2009

ABSTRACT
A retrospective examination of quantitation standard growth curves associated with 1,000 unique clinical serum specimens tested by a laboratory-developed TaqMan hepatitis C virus analyte-specific reagent-based assay revealed anomalous growth curves associated with 0.40% (95% confidence interval, 0.11% to 1.00%) of these specimens.
Delivery of Human Immunodeficiency Virus Vaccine Vectors to the Intestine Induces Enhanced Mucosal Cellular Immunity
Authors: Wang Lingshu , Cheng Cheng , Ko Sung-Youl , Kong Wing-Pui , Kanekiyo Masaru , Einfeld David , Schwartz Richard M. , King C. Richter , Gall Jason G. D. , Nabel Gary J. 
Published: May 2009

ABSTRACTEffective vaccines for human immunodeficiency virus type 1 (HIV-1) will likely need to stimulate protective immunity in the intestinal mucosa, where HIV-1 infection causes severe CD4+T-cell depletion. While replication-competent recombinant adenovirus (rAd) vectors can stimulate adenovirus-specific mucosal immunity after replication, oral delivery of replication-defective rAd vectors encoding specific immunogens has proven challenging. In this study, we have systematically identified barriers to effective gut delivery of rAd vectors and identified sites and strategies to induce potent cellular and humoral immunity. Vector-mediated gene transfer by rAd5 was susceptible to low-pH buffer, gastric and pancreatic proteases, and extracellular mucins. Using ex vivo organ explants, we found that transduction with rAd5 was highest in the ileum and colon among all intestinal segments. Transgene expression was 100-fold higher after direct surgical introduction into the ileum than after oral gavage, with rAd5 showing greater potency than the rAd35 or the rAd41 vector. A single immunization of rAd5 encoding HIV-1 gp140B to the ileum stimulated potent CD8+T-cell responses in the intestinal and systemic compartments, and these responses were further enhanced by intramuscular rAd5 boosting. These studies suggest that induction of primary immune responses by rAd5 gut immunization and subsequent systemic boosting elicits potent antigen-specific gut mucosal responses.
On the role of photosynthesis in the nitrate-dependent induction of the alternative oxidase inChlamydomonas reinhardtii
Authors: Pakkiriswami Shanmugasundaram , Beall Benjamin F.N. , Maxwell Denis P. 
Published: May 2009

In the green alga Chlamydomonas reinhardtii Dangeard a shift in nitrogen source from ammonium to nitrate results in the rapid induction of the mitochondrial alternative oxidase (AOX). It has been hypothesized that this induction compensates for the increased generation of ATP in the chloroplast. Based upon light response curves of oxygen evolution, a shift from ammonium to nitrate resulted in a significant increase in both apparent quantum yield of oxygen evolution and photosynthetic capacity. Changes in chlorophyll a fluorescence including a decrease in both excitation pressure and nonphotochemical quenching were also observed over a 12 h nitrate shift. To investigate whether changes in chloroplast ATP generation were behind the nitrate-dependent induction of AOX, transcript and protein accumulation were monitored in cells grown under high, moderate and low irradiances. No major differences in Aox1 gene expression or AOX accumulation were found among the different light regimes. These data do not support the hypothesis that an increase in AOX within the mitochondrion in response to nitrate is tied to changes in photosynthesis occurring within the chloroplast.
Latitudinal decrease in acorn size in bur oak (Quercus macrocarpa) is due to environmental constraints, not avian dispersal
Authors: Koenig Walter D. , Knops Johannes M. H. , Dickinson Janis L. , Zuckerberg Benjamin 
Published: May 2009

The size of acorns produced by several species of eastern North American oaks decreases with latitude. We investigated three hypotheses for this pattern in the bur oak ( Quercus macrocarpa Michx.) using samples collected over 2 years throughout the species’ range. We found strong support for the hypothesis that abiotic factors, including both temperature and rainfall, constrain acorn size. There was also a smaller but important difference in acorn size related to whether sites were glaciated or not, providing support for the hypothesis that some factor associated with the history of glaciation affects acorn mass. In contrast, although blue jays ( Cyanocitta cristata L.) prefer smaller acorns and are an important dispersal agent, the latitudinal patterns of acorn size and variability were not consistent with predictions of the hypothesis that they are the product of blue jay dispersal during bur oak’s postglacial Holocene expansion. Assuming that there is a lower limit to the size that acorns can be and still be successful, the strong role of environmental constraints on acorn size may be important in explaining the apparently contradictory interspecific pattern that North American oaks successfully colonizing areas further north during the Holocene are those that produce relatively larger acorns.
Climatic determinants of berry crops in the boreal forest of the southwestern Yukon
Authors: Krebs C. J. , Boonstra R. , Cowcill K. , Kenney A. J. 
Published: May 2009

Berry crops in the southwestern Yukon were quantified from 1997 to 2008 at 10 locations along 210 km of the Alaska and Haines highways. We tested the hypothesis that the size of berry crops could be predicted from spring and summer temperature and rainfall of years t, t–1 (1 year prior), and t–2 (2 years prior). Six common species were studied in the boreal forest of the Kluane region: Arctostaphylos rubra (Rehd. & Wils.) Fern., Arctostaphylos uva-ursi (L.) Spreng. s.l., Empetrum nigrum L., Vaccinium vitis-idaea L., Geocaulon lividum (Richards) Fern, and Shepherdia canadensis (L.) Nutt.. For the first five species we counted berries on fixed 40 cm × 40 cm quadrats to obtain an index of berry production for the Kluane region for each of the 12 years, and for S. canadensis we counted berries on two tagged branches of 10 bushes at each location. Stepwise multiple regressions were utilized to predict the size of berry crops for each species. For all species, predictive equations could explain statistically 80%–96% of the variation in berry crops. Different weather variables characterized each plant species, and there was no common weather regression that could explain the variation in berry crops in all species. Rainfall and temperature from years t–1 and t–2 were typically the significant predictors. There was no indication of a periodicity in berry production, and 43%–60% of the quadrats counted had large berry crops at one year intervals, while other quadrats never had a high crop during the study interval.
Calculated and observed behaviour of clayey soil under cyclic loading beneath preloading embankments for oil tanks
Authors: Gajo A. , Colleselli F. 
Published: May 2009

Two accurately monitored preloading embankments built to reduce the settlement of two oil tanks for a thermoelectric power plant near Mantova, Italy, were analysed using the finite element method and different constitutive assumptions. The most prominent feature of the proposed case study is that it involved two major loading cycles (preloading embankment construction–removal and oil tank filling–emptying) of different amplitudes (embankment heights of 8.60 and 12.50 m and a tank level of 14.00 m). Further minor loading cycles were also applied due to changes (of up to 6–7 m) in the hydrometric levels of the Po River. Because of the cyclic nature of the loading and the detailed measurements (of pore pressures and horizontal and vertical movements on the ground surface and in depth), this case study proves very useful for validating advanced features of modern constitutive models. The effects of elastic anisotropy, plastic anisotropy, and destructuration are considered in two different bounding-surface, kinematic-hardening plasticity models specific to clays and sands. The effects of permeability and Poisson’s ratio are also analysed. The conclusions have a general applicability and are not specific to the selected constitutive models.
An early 'ostrich dinosaur' (Theropoda: Ornithomimosauria) from the Early Cretaceous Sao Khua Formation of NE Thailand
Authors: Buffetaut Eric , Suteethorn Varavudh , Tong Haiyan 
Published: May 2009

Abstract

Postcranial remains of a small theropod dinosaur, including vertebrae, incomplete pubes, tibiae, an incomplete fibula, metatarsals and phalanges, from the Early Cretaceous Sao Khua Formation of Phu Wiang, Khon Kaen Province, NE Thailand, are described as a new taxon of ornithomimosaur,
Kinnareemimus khonkaenensis
, gen. et sp. nov. This early ‘ostrich dinosaur’ is characterized by a fairly advanced metatarsus, in which metatarsal III, although still visible proximally between metatarsals II and IV in cranial view, is markedly ‘pinched’ more distally and becomes triangular in cross-section. The condition of its metatarsus shows that
Kinnareemimus khonkaenensis
is more derived than the geologically younger primitive ornithomimosaurs
Harpymimus
and
Garudimimus
, but less derived than
Archaeornithomimus
. Its occurrence in the Early Cretaceous of Thailand suggests that advanced ornithomimosaurs may have originated in Asia.
Mesozoic vertebrate footprints of Thailand and Laos
Authors: Le Loeuff Jean , Saenyamoon Tida , Souillat Christel , Suteethorn Varavudh , Buffetaut Eric 
Published: May 2009

Abstract

Vertebrate footprints have been discovered in recent years from seven Mesozoic formations of Thailand and Laos dating from the Late Triassic (Kuchinari Group) and the Early Cretaceous (Khorat Group). The sites are reviewed here in chronological order. The ichnological record reflects fairly well the broad picture of the evolution of continental vertebrates in Asia known from the skeletal record. Norian basal archosaurs are replaced by Rhaetian dinosaurs although both footprint morphotypes look different from the contemporaneous European and North American forms. Two successive ornithopod radiations can be observed in the Early Cretaceous, with primitive small tetradactyl
Hypsilophodon
-like dinosaurs in the Earliest Cretaceous followed by advanced iguanodontoids with tridactyl fleshy footprints in the Aptian. Late Early Cretaceous dinosaur footprints from NE Thailand, however, do not validate previous hypotheses on the geographical distribution of Cretaceous ornithopod tracks in Asia. The ichnological record also reveals a hitherto unsuspected high diversity of theropods in the early Cretaceous with many different morphotypes.