bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumour and free radical scavenging effects of γ-mangostin isolated from Garcinia mangostana pericarps against hepatocellular carcinoma cell
Authors: Chang Hui-Fang , Wu Chih-Hsiung , Yang Ling-Ling 
Published: July 2013

Abstract

Objectives
Liver cancer is one of the highest rate diseases in southeastern Asia. Recently, many of functional foods and alternative medicines are very popularly utilized to prevent chronic diseases and cancer in Taiwan. In this study, we wanted to select and develop some of novel effectual agents or phytochemicals of γ-mangostin for clinical management or prevent hepatocellular carcinoma cell (HCC).

Methods
Lipid peroxidation (LPO) is an autocatalytic mechanism which induced tissue injure and carcinogenesis. In this study, the inhibitory activity of γ-mangostin on oxidative damage induced rat mitochondria LPO, the free radical scavenging of γ-mangostin and the apoptotic effects of γ-mangostin on HepG2 cells were investigated.

Key findings
γ-Mangostin processed activity to inhibit LPO and scavenge 2,2-diphenyl-1-picrylhydrazyl. γ-Mangostin showed antiproliferative activity and induced nuclear condensation and apoptotic bodies appearance under Giemsa staining by microscopic observation. In addition, γ-mangostin showed increases of hypodiploid cells via propidium iodide, 2′7′-dichlorofluorescein diacetate, and 3,3′-dihexyloxacarbocyanine iodide staining by flow cytometry analysis in HepG2 cells.

Conclusions
γ-Mangostin has demonstrated free radical scavenging activity, and antiproliferative and apoptotic activity in HepG2 cells. The proof suggests that γ-mangostin is a lead compound candidate for clinical management or prevent HCC.
Are relatively rare antelope narrowly selective feeders? A sable antelope and zebra comparison
Authors: Owen‐Smith N. , Le Roux E. , Macandza V. 
Published: July 2013

AbstractAnimals that are relatively rare in local species assemblages are commonly assumed to be narrowly selective in their habitat or dietary requirements, with the latter generally assessed in terms of the range of food types consumed. We investigated whether a narrow dietary range might help explain the restricted distribution and low local densities attained by sable antelope Hippotragus niger compared with other grazing ungulates. Selection by sable antelope for grass species, its relation to species availability and the resulting evenness of the diet were compared with these measures for zebra Equus quagga, which are assumed to be generalist feeders owing to their hindgut fermentation system, under dry season conditions when food was most limiting. Both grazers exhibited a clear distinction between highly favoured and infrequently accepted or rejected grass species in the same region, and both favoured mostly the same common grass species, but sable showed greater acceptance of several less common grass species than did zebra. Distinctions were evident among individual sable herds in favoured grass species, dependent on local availability. Dietary evenness was similar for sable and zebra herds overall, although seasonal trends differed depending on whether animals concentrated their diet more narrowly on a few grass species or broadened it during more extremely dry conditions. Hence, although sable were more narrowly selective for green leaf content than zebra, the dietary acceptance range of these two grazers at grass species level did not differ fundamentally. In particular, sable readily consumed tall grass species rated as having low to moderate forage value. This dietary tolerance enables sable antelope to occupy savannah woodlands associated with relatively infertile soils where the risk of predation is reduced due to the relatively low abundance of other prey. Accordingly, the causes of local rarity may lie in the restricted availability of food in the places to which these species are restricted by other factors.
FtsEX is required for CwlO peptidoglycan hydrolase activity during cell wall elongation in Bacillus subtilis
Authors: Meisner Jeffrey , Montero Llopis Paula , Sham Lok‐To , Garner Ethan , Bernhardt Thomas G. , Rudner David Z. 
Published: July 2013

SummaryThe peptidoglycan (PG) sacculus, a meshwork of polysaccharide strands cross‐linked by short peptides, protects bacterial cells against osmotic lysis. To enlarge this covalently closed macromolecule, PG hydrolases must break peptide cross‐links in the meshwork to allow insertion of new glycan strands between the existing ones. In the rod‐shaped bacterium Bacillus subtilis, cell wall elongation requires two redundant endopeptidases, CwlO and LytE. However, it is not known how these potentially autolytic enzymes are regulated to prevent lethal breaches in the cell wall. Here, we show that the ATP‐binding cassette transporter‐like FtsEX complex is required for CwlO activity. In Escherichia coli, FtsEX is thought to harness ATP hydrolysis to activate unrelated PG hydrolases during cell division. Consistent with this regulatory scheme, B. subtilis FtsE mutants that are unable to bind or hydrolyse ATP cannot activate CwlO. Finally, we show that in cells depleted of both CwlO and LytE, the PG synthetic machinery continues moving circumferentially until cell lysis, suggesting that cross‐link cleavage is not required for glycan strand polymerization. Overall, our data support a model in which the FtsEX complex is a remarkably flexible regulatory module capable of controlling a diverse set of PG hydrolases during growth and division in different organisms.
Proteomic identification of potential target proteins regulated by the SCFFbp1‐mediated proteolysis pathway in Fusarium oxysporum
Authors: Miguel‐Rojas Cristina , Hera Concepcion 
Published: July 2013

SummaryF‐box proteins function in the recruitment of proteins for SCF ubiquitination and proteasome degradation. Here, we studied the role of Fbp1, a nonessential F‐box protein of the tomato pathogen Fusarium oxysporum f. sp. lycopersici. The Δfbp1 mutant showed a significant delay in the production of wilt symptoms on tomato plants and was impaired in invasive growth on cellophane membranes and on living plant tissue. To search for target proteins recruited by Fbp1, a combination of sodium dodecylsulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and matrix‐assisted laser desorption/ionization time‐of‐flight/time‐of‐flight (MALDI‐TOF/TOF) was used to compare proteins in mycelia of the wild‐type and Δfbp1 mutant. The proteomic approach identified 41 proteins differing significantly in abundance between the two strains, 17 of which were more abundant in the Δfbp1 mutant, suggesting a possible regulation by proteasome degradation. Interestingly, several of the identified proteins were related to vesicle trafficking. Microscopic analysis revealed an impairment of the Δfbp1 strain in directional growth and in the structure of the Spitzenkörper, suggesting a role of Fbp1 in hyphal orientation. Our results indicate that Fbp1 regulates protein turnover and pathogenicity in F. oxysporum.
Effectiveness of an electronic inpatient medication record in reducing medication errors in Singapore
Authors: Choo Janet , Johnston Linda , Manias Elizabeth 
Published: July 2013

AbstractThis study examined the effectiveness of an inpatient electronic medication record system in reducing medication errors in Singaporean hospitals. This pre‐ and post‐intervention study involving a control group was undertaken in two Singaporean acute care hospitals. In one hospital the inpatient electronic medication record system was implemented while in another hospital the paper‐based medication record system was used. The mean incidence difference in medication errors of 0.06 between pre‐intervention (0.72 per 1000 patient days) and post‐intervention (0.78 per 1000 patient days) for the two hospitals was not statistically significant (95%, CI: [0.26, 0.20]). The mean incidence differences in medication errors relating to prescription, dispensing, and administration were also not statistically different. Common system failures involved a lack of medication knowledge by health professionals and a lack of a systematic approach in identifying correct dosages. There was no difference in the incidence of medication errors following the introduction of the electronic medication record system. More work is needed on how this system can reduce medication error rates and improve medication safety.
Auswirkungen der Hartz-Reformen auf den Arbeitsmarkt und auf die Bundesagentur für Arbeit
Authors: Weise Frank-J. 
Published: July 2013

Abstract
Starting in 2003, the labour market in Germany underwent major reforms. They introduced new types of employment, reshaped the benefit system, and remodelled active labour market policies. Over the 10 following years, unemployment fell dramatically and participation hit record levels, while rising non-standard employment and wage inequality became causes for concern. The Bundesagentur für Arbeit has developed into a modern service provider whose programmes are scientifically evaluated. Anticipating future trends on the labour market, the Bundesagentur has recently devised a strategy to cope with them. Overall, the German experience with labour market reforms points to the benefits of evidence-based policies.
ATP release and Ca2+ signalling by human bronchial epithelial cells following Alternaria aeroallergen exposure
Authors: O'Grady Scott M. , Patil Nandadavi , Melkamu Tamene , Maniak Peter J. , Lancto Cheryl , Kita Hirohito 
Published: July 2013

Key points
Exposure of human bronchial epithelial (HBE) cells to fungal aeroallergens derived from Alternaria alternata stimulates Ca2+‐dependent and Ca2+‐independent ATP release across the apical membrane.
The Ca2+‐dependent component was blocked by inhibitors of both ATP uptake and transport of exocytotic vesicles to the plasma membrane.
Treatment with inhibitors that target cysteine proteases significantly blocked Ca2+‐dependent ATP release evoked by Alternaria in normal HBE cells, but not in cells derived from asthmatic patients.
The magnitude of ATP release and associated intracellular Ca2+ mobilization was significantly greater in bronchial epithelial cells obtained from patients with asthma.
These findings establish a novel role for ATP release as a mechanism underlying Alternaria aeroallergen activation of airway mucosal immunity and that cells derived from patients with asthma exhibit greater responsiveness to these allergens.
Abstract  Exposure of human bronchial epithelial (HBE) cells from normal and asthmatic subjects to extracts from Alternaria alternata evoked a rapid and sustained release of ATP with greater efficacy observed in epithelial cells from asthmatic patients. Previously, Alternaria allergens were shown to produce a sustained increase in intracellular Ca2+ concentration ([Ca2+]i) that was dependent on the coordinated activation of specific purinergic receptor (P2Y2 and P2X7) subtypes. In the present study, pretreatment with a cell‐permeable Ca2+‐chelating compound (BAPTA‐AM) significantly inhibited ATP release, indicating dependency on [Ca2+]i. Alternaria‐evoked ATP release exhibited a greater peak response and a slightly lower EC50 value in cells obtained from asthmatic donors compared to normal control cells. Furthermore, the maximum increase in [Ca2+]i resulting from Alternaria treatment was greater in cells from asthmatic patients compared to normal subjects. The vesicle transport inhibitor brefeldin A and BAPTA‐AM significantly blocked Alternaria‐stimulated incorporation of fluorescent lipid (FM1‐43)‐labelled vesicles into the plasma membrane and ATP release. In addition, inhibiting uptake of ATP into exocytotic vesicles with bafilomycin also reduced ATP release comparable to the effects of brefeldin A and BAPTA‐AM. These results indicate that an important mechanism for Alternaria‐induced ATP release is Ca2+ dependent and involves exocytosis of ATP. Serine and cysteine protease inhibitors also reduced Alternaria‐induced ATP release; however, the sustained increase in [Ca2+]i typically observed following Alternaria exposure appeared to be independent of protease‐activated receptor (PAR2) stimulation.
Biomechanical Analysis of Glenohumeral Internal Rotation Deficit in a Cadaveric Model
Authors: Gupta Akash , Gates Jeffrey , McGarry Michelle H. , Tibone James E. , Lee Thay Q. 
Published: July 2013

Overhead throwing athletes have been shown to develop adaptive changes in humeral rotation to allow for higher throwing velocities. This manifests as an increase in humeral external rotation and a decrease in internal rotation, which is called glenohumeral internal rotation deficit (GIRD). The percentage of GIRD that significantly affects glenohumeral joint kinematics is not known. The objective of the study was to create a throwers shoulder model with fixed percentages of GIRD to determine at which point kinematic changes start occurring.
The results showed that there was a significant decrease in posterior translation starting at 10% GIRD. With inferior translational loads, significantly less inferior translation starts occurring at 20% GIRD. The humeral head apex position at maximum external rotation moves superiorly, posteriorly and laterally, with significant changes in the superior direction occurring with 10% GIRD onwards. Overall, significant kinematic changes begin at 10% GIRD and this should be taken into account for clinical decision-making as to when intervention is necessary.
Improved Efficacy of Fosmidomycin against Plasmodium and Mycobacterium Species by Combination with the Cell-Penetrating Peptide Octaarginine
Authors: Sparr Christof , Purkayastha Nirupam , Kolesinska Beata , Gengenbacher Martin , Amulic Borko , Matuschewski Kai , Seebach Dieter , Kamena Faustin 
Published: July 2013

ABSTRACT

Cellular drug delivery can improve efficacy and render intracellular pathogens susceptible to compounds that cannot permeate cells. The transport of physiologically active compounds across membranes into target cells can be facilitated by cell-penetrating peptides (CPPs), such as oligoarginines. Here, we investigated whether intracellular delivery of the drug fosmidomycin can be improved by combination with the CPP octaarginine. Fosmidomycin is an antibiotic that inhibits the second reaction in the nonmevalonate pathway of isoprenoid biosynthesis, an essential pathway for many obligate intracellular pathogens, including mycobacteria and apicomplexan parasites. We observed a strict correlation between octaarginine host cell permeability and its ability to improve the efficacy of fosmidomycin.
Plasmodium berghei
liver-stage parasites were only partially susceptible to an octaarginine-fosmidomycin complex. Similarly,
Toxoplasma gondii
was only susceptible during the brief extracellular stages. In marked contrast, a salt complex of octaarginine and fosmidomycin greatly enhanced efficacy against blood-stage
Plasmodium falciparum
. This complex and a covalently linked conjugate of octaarginine and fosmidomycin also reverted resistance of
Mycobacteria
to fosmidomycin. These findings provide chemical genetic evidence for vital roles of the nonmevalonate pathway of isoprenoid biosynthesis in a number of medically relevant pathogens. Our results warrant further investigation of octaarginine as a delivery vehicle and alternative fosmidomycin formulations for malaria and tuberculosis drug development.
Characterization of Binding of Raltegravir to Plasma Proteins
Authors: Barau Caroline , Furlan Valérie , Yazdanpanah Yazdan , Fagard Catherine , Molina Jean-Michel , Taburet Anne-Marie , Barrail-Tran Aurélie 
Published: July 2013

ABSTRACT

The objective of this study was to characterize raltegravir (RAL) binding to albumin and alpha-1-acid glycoprotein (AAG). Unbound and bound RAL were separated by ultrafiltration. The association constant (

K
a

) was estimated by a graphical method. In HIV-infected patients, the average plasma protein binding is 76%. RAL did not bind to AAG but bound to nonsaturable, low-affinity albumin sites with an
n
(number of sites) ·

K
a

product of 9.8 × 10
2
liters/mol. A pH increase of 0.2 U led to a 2% increase in the bound fraction.
Association of Fluoroquinolone Resistance, Virulence Genes, and IncF Plasmids with Extended-Spectrum-β-Lactamase-Producing Escherichia coli Sequence Type 131 (ST131) and ST405 Clonal Groups
Authors: Matsumura Yasufumi , Yamamoto Masaki , Nagao Miki , Ito Yutaka , Takakura Shunji , Ichiyama Satoshi 
Published: July 2013

ABSTRACT

The global increase of extended-spectrum-β-lactamase (ESBL)-producing
Escherichia coli
is associated with the specific clonal group sequence type 131 (ST131). In order to understand the successful spread of ESBL-producing
E. coli
clonal groups, we characterized fluoroquinolone resistance determinants, virulence genotypes, and plasmid replicons of ST131 and another global clonal group, ST405. We investigated 41 ST131-O25b, 26 ST131-O16, 41 ST405, and 41 other ST (OST) ESBL-producing isolates, which were collected at seven acute care hospitals in Japan. The detection of ESBL types, fluoroquinolone resistance-associated mutations (including quinolone resistance-determining regions [QRDRs]), virulence genotypes, plasmid replicon types, and IncF replicon sequence types was performed using PCR and sequencing.
bla
CTX-M
, specifically
bla
CTX-M-14
, was the most common ESBL gene type among the four groups. Ciprofloxacin resistance was found in 90% of ST131-O25b, 19% of ST131-O16, 100% of ST405, and 54% of OST isolates. Multidrug resistance was more common in the ST405 group than in the ST131-O25 group (56% versus 32%;
P
= 0.045). All ST131-O25b isolates except one had four characteristic mutations in QRDRs, but most of the isolates from the other three groups had three mutations in common. The ST131-O25b and ST405 groups had larger numbers of virulence genes than the OST group. All of the ST131-O25b and ST405 isolates and most of the ST131-O16 and OST isolates carried IncF replicons. The most prevalent IncF replicon sequence types differed between the four clonal groups. Both the ST131-O25b and ST405 clonal groups had a fluoroquinolone resistance mechanism in QRDRs, multidrug resistance, high virulence, and IncF plasmids, suggesting the potential for further global expansion and a need for measures against these clonal groups.
Echocardiogram Study To Evaluate the Effect of the Novel Hepatitis C Virus NS5A Inhibitor GSK2336805 on Cardiac Contractility in Healthy Subjects
Authors: Wilfret D. A. , Adkison K. K. , Jones L. A. , Lou Y. , Gan J. , Spreen W. 
Published: July 2013

ABSTRACT
GSK2336805 is a hepatitis C virus NS5A inhibitor in clinical development for the treatment of chronic hepatitis C virus infection. This was a single-center, randomized, double-blind, placebo-controlled, two-period crossover study in healthy adults to evaluate the effects of a single 150-mg dose of GSK2336805 on echocardiographic measures of contractility. GSK2336805 had no effect on ejection fraction, and there was no significant correlation between GSK2336805 plasma concentration and ejection fraction. (This study has been registered at Clinicaltrials.gov under registration no. NCT01424540.)
Characterization of Ribosomal Binding and Antibacterial Activities Using Two Orthogonal High-Throughput Screens
Authors: King Ada , Watkins Derrick , Kumar Sunil , Ranjan Nihar , Gong Changjun , Whitlock Jarred , Arya Dev P. 
Published: July 2013

ABSTRACT
We report here the affinity and antibacterial activity of a structurally similar class of neomycin dimers. The affinity of the dimer library for rRNA was established by using a screen that measures the displacement of fluorescein-neomycin (F-neo) probe from RNA. A rapid growth inhibition assay using a single drug concentration was used to examine the antibacterial activity. The structure-activity relationship data were then rapidly analyzed using a two-dimensional ribosomal binding-bacterial inhibition plot analysis.
Antiviral Efficacy of Favipiravir against Two Prominent Etiological Agents of Hantavirus Pulmonary Syndrome
Authors: Safronetz David , Falzarano Darryl , Scott Dana P. , Furuta Yousuke , Feldmann Heinz , Gowen Brian B. 
Published: July 2013

ABSTRACTHantavirus pulmonary syndrome (HPS) is caused by infection with severalSigmodontinae- andNeotominae-borne hantaviruses and has a case fatality rate of 30 to 50%. Humans often become infected by inhalation of materials contaminated with virus-laden rodent urine or saliva, although human-to-human transmission has also been documented for Andes virus (ANDV). The ability to transmit via aerosolization, coupled with the high mortality rates and lack of therapeutic options, makes the development of medical countermeasures against HPS imperative. In the present study, we evaluated the efficacy of the broad-spectrum antiviral agent favipiravir (T-705) against Sin Nombre virus (SNV) and ANDV, the predominant causes of HPS in North and South America, respectively.In vitro, T-705 potently inhibited SNV and ANDV, as evidenced by decreased detection of viral RNA and reduced infectious titers. For both viruses, the 90% effective concentration was estimated at ≤5 μg/ml (≤31.8 μM). In the lethal ANDV hamster model, daily administration of oral T-705 at 50 or 100 mg/kg of body weight diminished the detection of viral RNA and antigen in tissue specimens and significantly improved survival rates. Oral T-705 therapy remained protective against HPS when treatment was initiated prior to the onset of viremia. No disease model for SNV exists; however, using a hamster-adapted SNV, we found that daily administration of oral T-705 significantly reduced the detection of SNV RNA and antigen in tissue specimens, suggesting that the compound would also be effective against HPS in North America. Combined, these results suggest that T-705 treatment is beneficial for postexposure prophylaxis against HPS-causing viruses and should be considered for probable exposures.
Pharmacokinetic and
In Vivo
Efficacy Studies of the Mycobactin Biosynthesis Inhibitor Salicyl-AMS in Mice
Authors: Lun Shichun , Guo Haidan , Adamson John , Cisar Justin S. , Davis Tony D. , Chavadi Sivagami Sundaram , Warren J. David , Quadri Luis E. N. , Tan Derek S. , Bishai William R. 
Published: July 2013

ABSTRACT

Mycobactin biosynthesis in
Mycobacterium tuberculosis
facilitates iron acquisition, which is required for growth and virulence. The mycobactin biosynthesis inhibitor salicyl-AMS [5′-
O
-(
N
-salicylsulfamoyl)adenosine] inhibits
M. tuberculosis
growth
in vitro
under iron-limited conditions. Here, we conducted a single-dose pharmacokinetic study and a monotherapy study of salicyl-AMS with mice. Intraperitoneal injection yielded much better pharmacokinetic parameter values than oral administration did. Monotherapy of salicyl-AMS at 5.6 or 16.7 mg/kg significantly inhibited
M. tuberculosis
growth in the mouse lung, providing the first
in vivo
proof of concept for this novel antibacterial strategy.