bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Changes in Patch Characteristics and Plant Communities in the Jalca Grasslands of the Peruvian Andes
Authors: Tovar Carolina , Duivenvoorden Joost F. , Sánchez‐Vega Isidoro , Seijmonsbergen Arie C. 
Published: November 2011

AbstractHabitat loss and fragmentation are considered major threats to biodiversity, especially in tropical mountain ecosystems. Most studies focus on the relationships between biodiversity and patch characteristics such as patch size, connectivity or degree of contrast with the surrounding matrix, but leave the rate of change within these variables little explored. We analyzed the importance of changes in patch characteristics over time on species diversity and species composition in the paramo of northern Peru, a tropical grassland ecosystem, locally known as jalca. We obtained land use/cover maps for 1987 and 2007 spanning an area of 6300 km2, and quantified land use change, jalca patch characteristics and their proportional changes over 20 yr. In 2009, 371 vascular plant species were recorded in 92 plots, each plot representative of single patches. Between 1987 and 2007, jalca cover decreased from 47 to 35 percent due to encroaching agriculture. This activity showed an upward shift probably favored by climate change. The number of jalca patches increased, mean patch size decreased, and the patches showed a higher contrast with the surrounding matrix. Multiple linear regression failed to show that species diversity relates to changes in patch characteristics. Canonical correspondence analysis indicated that species composition relates to the degree of contrast between the patch and its surrounding matrix and its changes through time. We concluded that changes in patch characteristics are important only for species composition. This study highlights the importance of considering matrix management with a long term perspective for conservation efforts.
The use of ice‐lollies for pain relief post‐paediatric tonsillectomy. A single‐blinded, randomised, controlled trial
Authors: Sylvester D.C. , Rafferty A. , Bew S. , Knight L.C. 
Published: November 2011

Clin. Otolaryngol. 2011, 36, 566–570Objectives:  To assess whether the use of ice‐lollies after tonsillectomy with or without adenoidectomy in children aged 2–12 reduces pain in the immediate postoperative period.Design:  A prospective, randomised, single‐blinded study design consisting of two groups with an intention to treat analysis.Setting:  Tertiary referral centre.Participants:  Children aged 2–12 undergoing tonsillectomy with or without adenoidectomy.Main outcome measures:  Pain assessment by nursing staff in the form of the validated modified Children’s Hospital of Eastern Ontario Pain Scale at 15, 30 and 60 min and 4 h.Results:  Ninety‐two patients were recruited into the study with 46 allocated to receive an ice‐lolly and 41 not to receive an ice‐lolly after exclusion of those with incomplete data. The two groups were comparable for number, age, sex and diagnosis. The pain score at every time interval was lower in the group that had received the ice‐lolly compared with the group that had not. This was statistically significant at 30 (P = 0.008) and 60 min (P = 0.049).Conclusion:  Our data suggest that ice‐lollies are a cheap, effective and safe method of reducing postoperative pain up to one hour following paediatric tonsillectomy.
3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins: a new class of P-glycoprotein modulators
Authors: Shen Xiaoling , Chen Guangying , Zhu Guoyuan , Cai Jiazhong , Wang Lu , Hu Yingjie , Fong Wang-Fun 
Published: November 2011

Abstract

Objectives
P-glycoprotein (Pgp) overexpression in tumour cells leads to multidrug resistance (MDR) and causes failure in cancer chemotherapy. We have previously identified (±)-praeruptorin A (PA) as a potential lead compound for Pgp modulators. In this study we investigated the MDR-reversing activities of PA derivatives.

Methods
Series 7,8-pyranocoumarins with various C-3′ and C-4′ side chains had been semi-synthesized and their MDR-reversing activity was investigated in Pgp-overexpressing MDR tumour cell line HepG2/Dox and in a KB V1 xenograft animal model.

Key findings
All 7,8-pyranocoumarins exhibited equal or higher activity in modulating Pgp. DCK (12), DMDCK (15), 16, 21, 23 and 24 at 4 µm achieved 91%∼99% decrease in IC50 value (concentration inhibiting cell growth by 50%) of anticancer agents vinblastine, doxorubicin, puromycin and paclitaxel, and were more active than others. DMDCK also remarkably enhanced the growth inhibitory effect of paclitaxel on KB V1 xenografts (P &lt; 0.05), showing a potency required for clinical usage. Mechanistic studies suggested that these 7,8-pyranocoumarins might reverse Pgp-MDR through directly binding to substrate binding site(s) or allosteric site(s) on Pgp therefore impairing Pgp-mediated drug transport.

Conclusions
Results from the study suggested that 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins could serve as a new class of Pgp modulator. Acyls play an important role in maintaining and enhancing the Pgp-modulating ability of pyranocoumarins. 3,4-Dimethoxyl substituted aromatic acyls, bearing a methoxy that might interact with Pgp as hydrogen bond accepter, were shown to be the most potent for reversing MDR.
Contribution of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 to hepatic uptake of nateglinide, and the prediction of drug–drug interactions via these transporters
Authors: Takanohashi Toshiyuki , Kubo Satoru , Arisaka Harumi , Shinkai Kenji , Ubukata Kazuyuki 
Published: November 2011

Abstract

Objectives
We have investigated the contributions of organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 to the hepatic uptake of nateglinide, and the possibility of drug–drug interactions via these transporters.

Methods
Uptake studies using transporter-expressing HEK293 cells and cryopreserved human hepatocytes were performed to examine the contributions of each transporter. Inhibition studies using cryopreserved human hepatocytes were performed to examine the possibility of drug–drug interactions.

Key findings
The rate of saturable hepatic uptake of nateglinide using human hepatocytes was 47.6%. A certain increase in uptake was observed in the examination using transporter-expressing HEK293 cells, indicating contributions of OATP1B1 and OATP1B3 to hepatic nateglinide uptake. The 50% inhibitory concentration (IC50) values of nateglinide using cryopreserved human hepatocytes for uptake of estrone 3-sulfate (substrate of OATP1B1), and cholecystokinin octapeptide (substrate of OATP1B3) were 168 and 17.4 µmol/l, respectively. Moreover, ciclosporin inhibited saturable hepatic uptake of nateglinide with an IC50 value of 6.05 µmol/l. The calculated 1 + Iin,max,u/IC50 values for inhibition of OATP1B1 and OATP1B3 by nateglinide, and the inhibition of saturable uptake of nateglinide by ciclosporin, were all close to 1, indicating a low clinical risk of drug–drug interaction with nateglinide taken up via OATP1B1 and OATP1B3.

Conclusions
OATP1B1 and OATP1B3 may have contributed to the hepatic uptake of nateglinide, but the possibility of drug–drug interactions appeared to be low.
Everted gut sac model as a tool in pharmaceutical research: limitations and applications
Authors: Alam Mohd Aftab , Al-Jenoobi Fahad Ibrahim , Al-mohizea Abdullah M 
Published: November 2011

Abstract

Objectives
This review discusses the limitations and applications of the everted gut sac model in studying drug absorption, metabolism, and interaction.

Key findings
The mechanism of drug absorption, interaction and the effect of factors such as age, sex, species, chronic therapy, and disease state on drug absorption have been summarized. The experimental conditions and their effects on the outcomes of trials have been discussed also.

Summary
The everted sac model is an efficient tool for studying in-vitro drug absorption mechanisms, intestinal metabolism of drugs, role of transporter in drug absorption, and for investigating the role of intestinal enzymes during drug transport through the intestine.
Transient receptor potential vanilloid-1 participates in the inhibitory effect of ginsenoside Rg1 on capsaicin-induced interleukin-8 and prostaglandin E2 production in HaCaT cells
Authors: Huang Jin , Ding Li , Shi Duo , Hu Jin-hong , Zhu Quan-gang , Gao Shen , Qiu Lei 
Published: November 2011

Abstract

Objectives
Ginsenoside Rg1 (GRg1), one of the major active constituents of Panax notoginseng, has shown anti-inflammatory and antinocioceptic activity, but its role in keratinocytes needs further study. We have examined the inhibitory effect of GRg1 on transient receptor potential vanilloid-1 (TRPV1) activation in keratinocyte HaCaT cells and explored its involved mechanism.

Methods
HEK 293T cells over-expressing exogenous TRPV1 were constructed and named HEK 293T-TRPV1 cells. The effects of GRg1 on production of interleukin-8 (IL-8) and prostaglandin E2 (PGE2), calcium influx, the expression of cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) transcriptional activity in HEK 293T-TRPV1 and HaCaT cells were examined by ELISA, Fluo 3-AM fluorescence probe, Western blot and Dual-Luciferase Reporter Assay, respectively.

Key findings
The results showed that GRg1 blocked intracellular calcium by both capsaicin and proton activation in a TRPV1-dependent manner. Furthermore, GRg1 inhibited the expression of COX-2 and NF-κB transcriptional activity induced by capsaicin in keratinocytes. The inhibitory effect of GRg1 was similar to capsazepine, an antagonist of TRPV1. More importantly, GRg1 dose-dependently inhibited capsaicin-induced PGE2 and IL-8 secretion in HaCaT cells and HEK 293T-TRPV1 cells.

Conclusions
These data showed that GRg1 could inhibit TRPV1 mediated responses in HaCaT cells, indicating that GRg1 acted as a TRPV1 antagonist.
Factors Influencing the Microbial Composition of Metalworking Fluids and Potential Implications for Machine Operator's Lung
Authors: Murat Jean-Benjamin , Grenouillet Frédéric , Reboux Gabriel , Penven Emmanuelle , Batchili Adam , Dalphin Jean-Charles , Thaon Isabelle , Millon Laurence 
Published: November 2011

ABSTRACT

Hypersensitivity pneumonitis, also known as “machine operator's lung” (MOL), has been related to microorganisms growing in metalworking fluids (MWFs), especially
Mycobacterium immunogenum
. We aimed to (i) describe the microbiological contamination of MWFs and (ii) look for chemical, physical, and environmental parameters associated with variations in microbiological profiles. We microbiologically analyzed 180 MWF samples from nonautomotive plants (e.g., screw-machining or metal-cutting plants) in the Franche-Comté region in eastern France and 165 samples from three French automotive plants in which cases of MOL had been proven. Our results revealed two types of microbial biomes: the first was from the nonautomotive industry, showed predominantly Gram-negative rods (GNR), and was associated with a low risk of MOL, and the second came from the automotive industry that was affected by cases of MOL and showed predominantly Gram-positive rods (GPR). Traces of
M. immunogenum
were sporadically detected in the first type, while it was highly prevalent in the automotive sector, with up to 38% of samples testing positive. The use of chromium, nickel, or iron was associated with growth of Gram-negative rods; conversely, growth of Gram-positive rods was associated with the absence of these metals. Synthetic MWFs were more frequently sterile than emulsions. Vegetable oil-based emulsions were associated with GNR, while mineral ones were associated with GPR. Our results suggest that metal types and the nature of MWF play a part in MWF contamination, and this work shall be followed by further
in vitro
simulation experiments on the kinetics of microbial populations, focusing on the phenomena of inhibition and synergy.
Vanillin Catabolism in Rhodococcus jostii RHA1
Authors: Chen Hao-Ping , Chow Mindy , Liu Chi-Chun , Lau Alice , Liu Jie , Eltis Lindsay D. 
Published: November 2011

ABSTRACT

Genes encoding vanillin dehydrogenase (
vdh
) and vanillate
O
-demethylase (
vanAB
) were identified in
Rhodococcus jostii
RHA1 using gene disruption and enzyme activities. During growth on vanillin or vanillate,
vanA
was highly upregulated while
vdh
was not. This study contributes to our understanding of lignin degradation by RHA1 and other actinomycetes.
α1,3 Glucans Are Dispensable in Aspergillus fumigatus
Authors: Henry Christine , Latgé Jean-Paul , Beauvais Anne 
Published: November 2011

ABSTRACT

A triple α1,3 glucan synthase mutant of
Aspergillus fumigatus
obtained by successive deletions of the three α1,3 glucan synthase genes (
AGS1
,
AGS2
, and
AGS3
) has a cell wall devoid of α1,3 glucans. The lack of α1,3 glucans affects neither conidial germination nor mycelial vegetative growth and is compensated by an increase in β1,3 glucan and/or chitin content.
Activation of the Cryptic PhnE Permease Promotes Rapid Adaptive Evolution in a Population of Escherichia coli K-12 Starved for Phosphate
Authors: Guillemet Mélanie L. , Moreau Patrice L. 
Published: November 2011

ABSTRACT

Escherichia coli
K-12 suffers acetic acid stress during prolonged incubation in glucose minimal medium containing a limiting concentration of inorganic phosphate (0.1 mM P
i
), which decreases the number of viable cells from 6 × 10
8
to ≤10 CFU/ml between days 6 and 14 of incubation. Here we show that following two serial transfers into P
i
-limiting medium, evolved mutants survived prolonged incubation (≈10
7
CFU/ml on day 14 of incubation). The evolved strains that overtook the populations were generally PhnE
+
, whereas the ancestral K-12 strain carries an inactive
phnE
allele, which prevents the transport of phosphonates. The switching in
phnE
occurred with a high frequency as a result of the deletion of an 8-bp repeated sequence. In a mixed culture starved for P
i
that contained the K-12 ancestral strain in majority, evolved strains grew through PhnE-dependent scavenging of probably organic phosphate esters (not phosphonates or P
i
) released by
E. coli
K-12 between days 1 and 3, before acetic acid excreted by
E. coli
K-12 reached toxic levels. The growth yield of
phnE
+
strains in mixed culture was dramatically enhanced by mutations that affect glucose metabolism, such as an
rpoS
mutation inactivating the alternative sigma factor RpoS. The long-term viability of evolved populations was generally higher when the ancestral strain carried an inactive rather than an active
phnE
allele, which indicates that cross-feeding of phosphorylated products as a result of the
phnE
polymorphism may be essential for the spread of mutants which eventually help populations to survive under P
i
starvation conditions.
Characterization of the Escherichia coli SecA Signal Peptide-Binding Site
Authors: Grady Lorry M. , Michtavy Jennifer , Oliver Donald B. 
Published: November 2011

ABSTRACT

SecA signal peptide interaction is critical for initiating protein translocation in the bacterial Sec-dependent pathway. Here, we have utilized the recent nuclear magnetic resonance (NMR) and Förster resonance energy transfer studies that mapped the location of the SecA signal peptide-binding site to design and isolate signal peptide-binding-defective
secA
mutants. Biochemical characterization of the mutant SecA proteins showed that Ser226, Val310, Ile789, Glu806, and Phe808 are important for signal peptide binding. A genetic system utilizing alkaline phosphatase secretion driven by different signal peptides was employed to demonstrate that both the PhoA and LamB signal peptides appear to recognize a common set of residues at the SecA signal peptide-binding site. A similar system containing either SecA-dependent or signal recognition particle (SRP)-dependent signal peptides along with the
prlA
suppressor mutation that is defective in signal peptide proofreading activity were employed to distinguish between SecA residues that are utilized more exclusively for signal peptide recognition or those that also participate in the proofreading and translocation functions of SecA. Collectively, our data allowed us to propose a model for the location of the SecA signal peptide-binding site that is more consistent with recent structural insights into this protein translocation system.
Escape from a Dominant HLA-B*15-Restricted CD8
+
T Cell Response against Hepatitis C Virus Requires Compensatory Mutations outside the Epitope
Authors: Ruhl Marianne , Chhatwal Patrick , Strathmann Heiko , Kuntzen Thomas , Bankwitz Dorothea , Skibbe Kathrin , Walker Andreas , Heinemann Falko M. , Horn Peter A. , Allen Todd M. , Hoffmann Daniel , Pietschmann Thomas , Timm Jörg 
Published: November 2011

ABSTRACT

Antiviral CD8
+
T cells are a key component of the adaptive immune system against hepatitis C virus (HCV). For the development of immune therapies, it is essential to understand how CD8
+
T cells contribute to clearance of infection and why they fail so often. A mechanism for secondary failure is mutational escape of the virus. However, some substitutions in viral epitopes are associated with fitness costs and often require compensatory mutations. We hypothesized that compensatory mutations may point toward epitopes under particularly strong selection pressure that may be beneficial for vaccine design because of a higher genetic barrier to escape. We previously identified two HLA-B*15-restricted CD8
+
epitopes in NS5B (LLRHHNMVY
2450-2458
and SQRQKKVTF
2466-2474
), based on sequence analysis of a large HCV genotype 1b outbreak. Both epitopes are targeted in about 70% of HLA-B*15-positive individuals exposed to HCV. Reproducible selection of escape mutations was confirmed in an independent multicenter cohort in the present study. Interestingly, mutations were also selected in the epitope flanking region, suggesting that compensatory evolution may play a role. Covariation analysis of sequences from the database confirmed a significant association between escape mutations inside one of the epitopes (H2454R and M2456L) and substitutions in the epitope flanking region (S2439T and K2440Q). Functional analysis with the subgenomic replicon Con1 confirmed that the primary escape mutations impaired viral replication, while fitness was restored by the additional substitutions in the epitope flanking region. We concluded that selection of escape mutations inside an HLA-B*15 epitope requires secondary substitutions in the epitope flanking region that compensate for fitness costs.
Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease
Authors: Frieman Matthew , Yount Boyd , Agnihothram Sudhakar , Page Carly , Donaldson Eric , Roberts Anjeanette , Vogel Leatrice , Woodruff Becky , Scorpio Diana , Subbarao Kanta , Baric Ralph S. 
Published: November 2011

ABSTRACT
SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease.
Cross-Species Transmission of Simian Foamy Virus to Humans in Rural Gabon, Central Africa
Authors: Mouinga-Ondémé Augustin , Caron Mélanie , Nkoghé Dieudonné , Telfer Paul , Marx Preston , Saïb Ali , Leroy Eric , Gonzalez Jean-Paul , Gessain Antoine , Kazanji Mirdad 
Published: November 2011

ABSTRACT

In order to characterize simian foamy retroviruses (SFVs) in wild-born nonhuman primates (NHPs) in Gabon and to investigate cross-species transmission to humans, we obtained 497 NHP samples, composed of 286 blood and 211 tissue (bush meat) samples. Anti-SFV antibodies were found in 31 of 286 plasma samples (10.5%). The integrase gene sequence was found in 38/497 samples, including both blood and tissue samples, with novel SFVs in several
Cercopithecus
species. Of the 78 humans, mostly hunters, who had been bitten or scratched by NHPs, 19 were SFV seropositive, with 15 cases confirmed by PCR. All but one were infected with ape SFV. We thus found novel SFV strains in NHPs in Gabon and high cross-species transmission of SFVs from gorilla bites.
A pH-Sensitive Heparin-Binding Sequence from Baculovirus gp64 Protein Is Important for Binding to Mammalian Cells but Not to Sf9 Insect Cells
Authors: Wu Chunxiao , Wang Shu 
Published: November 2011

ABSTRACT
Binding to heparan sulfate is essential for baculovirus transduction of mammalian cells. Our previous study shows that gp64, the major glycoprotein on the virus surface, binds to heparin in a pH-dependent way, with a stronger binding at pH 6.2 than at 7.4. Using fluorescently labeled peptides, we mapped the pH-dependent heparin-binding sequence of gp64 to a 22-amino-acid region between residues 271 and 292. Binding of this region to the cell surface was also pH dependent, and peptides containing this sequence could efficiently inhibit baculovirus transduction of mammalian cells at pH 6.2. When the heparin-binding peptide was immobilized onto the bead surface to mimic the high local concentration of gp64 on the virus surface, the peptide-coated magnetic beads could efficiently pull down cells expressing heparan sulfate but not cells pretreated with heparinase or cells not expressing heparan sulfate. Interestingly, although this heparin-binding function is essential for baculovirus transduction of mammalian cells, it is dispensable for infection of Sf9 insect cells. Virus infectivity on Sf9 cells was not reduced by the presence of heparin or the identified heparin-binding peptide, even though the peptide could bind to Sf9 cell surface and be efficiently internalized. Thus, our data suggest that, depending on the availability of the target molecules on the cell surface, baculoviruses can use two different methods, electrostatic interaction with heparan sulfate and more specific receptor binding, for cell attachment.