bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multivalent chimeric vaccine composed of Schistosoma mansoni SmTSP‐2 and Sm29 was able to induce protection against infection in mice
Authors: Pinheiro C. S. , Ribeiro A. P. D. , Cardoso F. C. , Martins V. P. , Figueiredo B. C. P. , Assis N. R. G. , Morais S. B. , Caliari M. V. , Loukas A. , Oliveira S. C. 
Published: April 2014

SummarySchistosoma mansoni is a blood fluke parasite responsible for schistosomiasis. The best long‐term strategy to control schistosomiasis is through immunization combined with drug treatment. In this study, we cloned, expressed and purified SmTSP‐2 fused to the N‐ and C‐terminal halves of Sm29 and tested these chimeras as vaccine candidates using an adjuvant approved to be used in humans. The results demonstrated that vaccination with SmTSP‐2 fused to N‐ or C‐terminus of Sm29‐induced reduction in worm burden and liver pathology when compared to control animals. Additionally, we detected high levels of mouse‐specific IgG, IgG1 and IgG2a against both chimeras and significant amounts of IFN‐γ and TNF‐α and no IL‐4. Finally, studies with sera from patients resistant to infection and living in schistosomiasis endemic areas revealed high levels of specific IgG to both chimeras when compared to healthy individuals. In conclusion, SmTSP‐2/Sm29 chimeras tested here induced partial protection against infection and might be a potential vaccine candidate.
Effect of salt‐tolerant plant growth‐promoting rhizobacteria on wheat plants and soil health in a saline environment
Authors: Upadhyay S. K. , Singh D. P. 
Published: April 2014

AbstractSalt‐tolerant plant growth‐promoting rhizobacteria (ST‐PGPR) significantly influence the growth and yield of wheat crops in saline soil. Wheat growth improved in pots with inoculation of all nine ST‐PGPR (ECe = 4.3 dS·m−1; greenhouse experiment), while maximum growth and dry biomass was observed in isolate SU18 Arthrobacter sp.; simultaneously, all ST‐PGPR improved soil health in treated pot soil over controls. In the field experiment, maximum wheat root dry weight and shoot biomass was observed after inoculation with SU44 B. aquimaris, and SU8 B. aquimaris, respectively, after 60 and 90 days. Isolate SU8 B. aquimaris, induced significantly higher proline and total soluble sugar accumulation in wheat, while isolate SU44 B. aquimaris, resulted in higher accumulation of reducing sugars after 60 days. Percentage nitrogen (N), potassium (K) and phosphorus (P) in leaves of wheat increased significantly after inoculation with ST‐PGPR, as compared to un‐inoculated plants. Isolate SU47 B. subtilis showed maximum reduction of sodium (Na) content in wheat leaves of about 23% at both 60 and 90 days after sowing, and produced the best yield of around 17.8% more than the control.
Dissecting the mechanism of Solanum lycopersicum and Solanum chilense flower colour formation
Authors: Gao M. , Qu H. , Gao L. , Chen L. , Sebastian R. S. J. , Zhao L. 
Published: April 2014

AbstractFlowers are the defining feature of angiosperms, and function as indispensable organs for sexual reproduction. Flower colour typically plays an important role in attracting pollinators, and can show considerable variation, even between closely related species. For example, domesticated tomato (S. lycopersicum) has orange/yellow flowers, while the wild relative S. chilense (accession LA2405) has bright yellow flowers. In this study, the mechanism of flower colour formation in these two species was compared by evaluating the accumulation of carotenoids, assessing the expression genes related to carotenoid biosynthetic pathways and observing chromoplast ultrastructure. In S. chilense petals, genes associated with the lutein branch of the carotenoid biosynthetic pathway, phytoene desaturase (PDS), ζ‐carotene desaturase (ZDS), lycopene β‐cyclase (LCY‐B), β‐ring hydroxylase (CRTR‐B) and ε‐ring hydroxylase (CRTR‐E), were highly expressed, and this was correlated with high levels of lutein accumulation. In contrast, PDS, ZDS and CYC‐B from the neoxanthin biosynthetic branch were highly expressed in S. lycopersicum anthers, leading to increased β‐carotene accumulation and hence an orange/yellow colour. Changes in the size, amount and electron density of plastoglobules in chromoplasts provided further evidence of carotenoid accumulation and flower colour formation. Taken together, these results reveal the biochemical basis of differences in carotenoid pigment accumulation and colour between petals and anthers in tomato.
Metapeyssonnelia tangerina (Peyssonneliaceae, Rhodophyta), a new species associated with coral reef habitats in Puerto Rico, Caribbean Sea
Authors: Ballantine David L. , Lozada‐Troche Chad , Ruiz Hector 
Published: April 2014

SummaryA new Metapeyssonnelia species that comprises up to 7% bottom cover at shallow‐water reef habitats in southwest Puerto Rico is described herein. It forms conspicuous orange encrustations on hard substrata and does not grow on living coral as does its two Caribbean congeners. The new species possesses conspicuous, to 30 cm in extent, tightly adherent crusts up to 950 μm thick, only hypobasal calcification, hypothallial cells arranged in broad flabellules and superficial (raised) tetrasporangial and carposporangial nemathecia. Tetrasporangia are pedicellate, borne laterally from cup‐like cells that are derived from basal paraphysal cells. Tetrasporangia measure up to 120 μm long and individual carposporangia to 80 μm long. The new species differs from other Metapeyssonnelia species developmentally in that perithallial cells at mid thallus height will divide laterally to form a new hypothallium. Small subunit gene sequences relate the new species to the two Metapeyssonnelia species that are previously known from Puerto Rico.
Measuring Multi‐Membership in Economic Integration and Its Trade Impact: A Comparative Study of ECOWAS and SADC
Authors: Afesorgbor Sylvanus Kwaku , van Bergeijk Peter A. G. 
Published: April 2014

AbstractOne of the intriguing aspects of African regional trade agreements (RTAs) is the extent of multi‐membership, where many African countries are members of more than one RTA. Using a gravity model for 25 countries and the years 1980‐2006, we measure the extent of multi‐membership and compare its impact in two major African regional blocs, Economic Community of West Africa States (ECOWAS) and Southern Africa Development Community (SADC). We find that the impact of multi‐membership critically depends on the characteristics of the multi‐membership of regional integration initiatives. We find a positive impact if an additional membership complements the integration process of the original regional integration initiative: overlapping memberships had a much stronger and significant positive effect on bilateral trade within ECOWAS compare with an insignificant impact within the SADC.
A Reference Architecture for Mobile SOA
Authors: Sefid‐Dashti Behrouz , Habibi Jafar 
Published: April 2014

ABSTRACTIntegration of mobile devices into a service‐oriented system involves the consideration of architectural design principles and trade‐offs among interdependent design decisions to cope with limitations of mobile devices in terms of resources available within a device and aspects of network connectivity. Mobile devices consume some services and provide others. A reference architecture (RA) that provides solutions, baseline and future insights is the priority in designing efficient mobile service oriented architecture (SOA). This paper discusses nuances of the concept of RA. The paper presents a survey of 26 mobile SOA patterns and proposes mobile SOA RA that extends Open Group SOA RA based on the catalogue of mobile SOA patterns proposed in this paper. Evaluations are made and discussed for both RA and its possible instantiation.
A Conserved Hydrogen-Bonding Network of P2
bis
-Tetrahydrofuran-Containing HIV-1 Protease Inhibitors (PIs) with a Protease Active-Site Amino Acid Backbone Aids in Their Activity against PI-Resistant HIV
Authors: Yedidi Ravikiran S. , Garimella Harisha , Aoki Manabu , Aoki-Ogata Hiromi , Desai Darshan V. , Chang Simon B. , Davis David A. , Fyvie W. Sean , Kaufman Joshua D. , Smith David W. , Das Debananda , Wingfield Paul T. , Maeda Kenji , Ghosh Arun K. , Mitsuya Hiroaki 
Published: April 2014

ABSTRACT

In the present study, GRL008, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), and darunavir (DRV), both of which contain a P2-
bis
-tetrahydrofuranyl urethane (
bis
-THF) moiety, were found to exert potent antiviral activity (50% effective concentrations [EC
50
s], 0.029 and 0.002 μM, respectively) against a multidrug-resistant clinical isolate of HIV-1 (HIV
A02
) compared to ritonavir (RTV; EC
50
, >1.0 μM) and tipranavir (TPV; EC
50
, 0.364 μM). Additionally, GRL008 showed potent antiviral activity against an HIV-1 variant selected in the presence of DRV over 20 passages (HIV
DRV
R
P20
), with a 2.6-fold increase in its EC
50
(0.097 μM) compared to its corresponding EC
50
(0.038 μM) against wild-type HIV-1
NL4-3
(HIV
WT
). Based on X-ray crystallographic analysis, both GRL008 and DRV showed strong hydrogen bonds (H-bonds) with the backbone-amide nitrogen/carbonyl oxygen atoms of conserved active-site amino acids G27, D29, D30, and D30′ of HIV
A02
protease (PR
A02
) and wild-type PR in their corresponding crystal structures, while TPV lacked H-bonds with G27 and D30′ due to an absence of polar groups. The P2′ thiazolyl moiety of RTV showed two conformations in the crystal structure of the PR
A02
-RTV complex, one of which showed loss of contacts in the S2′ binding pocket of PR
A02
, supporting RTV's compromised antiviral activity (EC
50
, >1 μM). Thus, the conserved H-bonding network of P2-
bis
-THF-containing GRL008 with the backbone of G27, D29, D30, and D30′ most likely contributes to its persistently greater antiviral activity against HIV
WT
, HIV
A02
, and HIV
DRV
R
P20
.
Population Pharmacokinetic Analysis of Piperacillin in Burn Patients
Authors: Jeon Sangil , Han Seunghoon , Lee Jongtae , Hong Taegon , Paek Jeongki , Woo Heungjeong , Yim Dong-Seok 
Published: April 2014

ABSTRACT

Piperacillin in combination with tazobactam, a β-lactamase inhibitor, is a commonly used intravenous antibiotic for the empirical treatment of infection in intensive care patients, including burn patients. The purpose of this study was to develop a population pharmacokinetic (PK) model for piperacillin in burn patients and to predict the probability of target attainment (PTA) using MICs and concentrations simulated from the PK model. Fifty burn patients treated with piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered via infusion for approximately 30 min at a dose of 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 h. Blood samples were collected just prior to and at 1, 2, 3, 4, and 6 h after the end of the infusion at steady state. The population PK model of piperacillin was developed using NONMEM. A two-compartment first-order elimination PK model was finally chosen. The covariates included were creatinine clearance (CL
CR
), day after burn injury (DAI), and sepsis. The final PK parameters were clearance (liters/h) (equal to 16.6 × [CL
CR
/132] + DAI × [−0.0874]), central volume (liters) (equal to 25.3 + 14.8 × sepsis [0 for the absence or 1 for the presence of sepsis]), peripheral volume (liters) (equal to 16.1), and intercompartmental clearance (liters/h) (equal to 0.636). The clearance and volume of piperacillin were higher than those reported in patients without burns, and the terminal half-life and PTA decreased with the increased CL
CR
. Our PK model suggests that higher daily doses or longer durations of infusion of piperacillin should be considered, especially for burn patients with a CL
CR
of ≥160 ml/min.
Copper Complexation Screen Reveals Compounds with Potent Antibiotic Properties against Methicillin-Resistant Staphylococcus aureus
Authors: Haeili Mehri , Moore Casey , Davis Christopher J. C. , Cochran James B. , Shah Santosh , Shrestha Tej B. , Zhang Yaofang , Bossmann Stefan H. , Benjamin William H. , Kutsch Olaf , Wolschendorf Frank 
Published: April 2014

ABSTRACT

Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant
Staphylococcus aureus
(MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface.
In Vitro
and
In Vivo
Biological Effects of Novel Arylimidamide Derivatives against Trypanosoma cruzi
Authors: Timm Bruno Lisboa , da Silva Patrícia Bernadino , Batista Marcos Meuser , da Silva Francisca Hildemagna Guedes , da Silva Cristiane França , Tidwell Richard R. , Patrick Donald A. , Jones Susan Kilgore , Bakunov Stanislav A. , Bakunova Svetlana M. , Soeiro Maria de Nazaré C. 
Published: April 2014

ABSTRACT

Chagas disease (CD), a neglected tropical disease caused by
Trypanosoma cruzi
, remains a serious public health problem in several Latin American countries. The available chemotherapies for CD have limited efficacy and exhibit undesirable side effects. Aromatic diamidines and arylimidamides (AIAs) have shown broad-spectrum activity against intracellular parasites, including
T. cruzi
. Therefore, our aim was to evaluate the biological activity of eight novel AIAs (16DAP002, 16SAB079, 18SAB075, 23SMB022, 23SMB026, 23SMB054, 26SMB070, and 27SMB009) against experimental models of
T. cruzi
infection
in vitro
and
in vivo
. Our data show that none of the compounds induced a loss of cellular viability up to 32 μM. Two AIAs, 18SAB075 and 16DAP002, exhibited good
in vitro
activity against different parasite strains (Y and Tulahuen) and against the two relevant forms of the parasite for mammalian hosts. Due to the excellent selective indexes of 18SAB075, this AIA was moved to
in vivo
tests for acute toxicity and parasite efficacy; nontoxic doses (no-observed-adverse-effect level [NOAEL], 50 mg/kg) were employed in the tests for parasite efficacy. In experimental models of acute
T. cruzi
infection, 18SAB075 reduced parasitemia levels only up to 50% and led to 40% protection against mortality (at 5 mg/kg of body weight), being less effective than the reference drug, benznidazole.
Plasmid Carriage of
bla
NDM-1
in Clinical Acinetobacter baumannii Isolates from India
Authors: Jones Lim S. , Toleman Mark A. , Weeks Janis L. , Howe Robin A. , Walsh Timothy R. , Kumarasamy Karthikeyan K. 
Published: April 2014

ABSTRACT

NDM-1 probably emerged in
Acinetobacter
species prior to its dissemination among
Enterobacteriaceae
, and NDM-1-like enzymes are increasingly reported in
Acinetobacter
species. Here, we report on the genetic context of
bla
NDM-1
in the earliest known NDM-1-producing organisms, clinical isolates of
Acinetobacter
from India in 2005. These strains harbor
bla
NDM-1
plasmids of different sizes. The gene is associated with the remnants of the Tn
125
transposon normally associated with
bla
NDM-1
in
Acinetobacter
spp. The transposon has been disrupted by the IS
26
insertion and subsequent movement events.
Relationship between Time to Clinical Response and Outcomes among Pneumonia Outcomes Research Team (PORT) Risk Class III and IV Hospitalized Patients with Community-Acquired Pneumonia Who Received Ceftriaxone and Azithromycin
Authors: Zasowski Evan , Butterfield Jill M. , McNutt Louise-Ann , Cohen Jason , Cosler Leon , Pai Manjunath P. , Gottwald Joseph , Chen Wen Zhen , Lodise Thomas P. 
Published: April 2014

ABSTRACT

Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, it is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable real-world outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than those who responded by day 5 (22.4% versus 6.9%,
P
= 0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indictor of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin.
Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis
Authors: Ryan Lisa K. , Freeman Katie B. , Masso-Silva Jorge A. , Falkovsky Klaudia , Aloyouny Ashwag , Markowitz Kenneth , Hise Amy G. , Fatahzadeh Mahnaz , Scott Richard W. , Diamond Gill 
Published: April 2014

ABSTRACT

There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of
Candida
, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against
C. albicans
and other species of
Candida
, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for
Candida
over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total
Candida
burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.
IS
1R
-Mediated Plasticity of IncL/M Plasmids Leads to the Insertion of
bla
OXA-48
into the Escherichia coli Chromosome
Authors: Beyrouthy R. , Robin F. , Delmas J. , Gibold L. , Dalmasso G. , Dabboussi F. , Hamzé M. , Bonnet R. 
Published: April 2014

ABSTRACT

The OXA-48 carbapenemase is mainly encoded by ∼62-kb IncL/M plasmids. However, chromosome-mediated genes have been observed in
Escherichia coli
isolates. In this work, we investigated the genetic environment of OXA-48 in members of the family
Enterobacteriaceae
(
n
= 22) to understand how the OXA-48-encoding gene is transferred into the
E. coli
chromosome. The OXA-48-encoding gene was located within intact Tn
1999.2
transposons in the ∼62-kb plasmids or within a truncated variant of Tn
1999.2
for the OXA-48-encoding genes located in the chromosomes of
E. coli
bacteria. The analysis of the Tn
1999.2
genetic environment revealed an inverted orientation of the transposon in five ∼62-kb plasmids (5/14 [35%]) and in all chromosome inserts (
n
= 8). The sequencing of pRA35 plasmid showed that this orientation of Tn
1999.2
and the acquisition of an IS
1R
insertion sequence generated a 21.9-kb IS
1R
-based composite transposon encoding OXA-48 and designated Tn
6237
. The sequencing of a chromosomal insert encoding OXA-48 also revealed this new transposon in the
E. coli
chromosome. PCR mapping showed the presence of this element in all strains harboring an OXA-48-encoding chromosomal insert. However, different insertion sites of this transposon were observed in the
E. coli
chromosome. Overall, these findings indicate a plasticity of the OXA-48 genetic environment mediated by IS
1R
insertion sequences. The insertion sequences can induce the transfer of the OXA-encoding gene into
E. coli
chromosomes and thereby promote its persistence and expression at low levels.
Emergence of Clinical Salmonella enterica Serovar Typhimurium Isolates with Concurrent Resistance to Ciprofloxacin, Ceftriaxone, and Azithromycin
Authors: Wong Marcus Ho Yin , Yan Meiying , Chan Edward Wai Chi , Biao Kan , Chen Sheng 
Published: April 2014

ABSTRACT

Salmonella
infection is an important public health issue for which the needs of antimicrobial treatment are increasing. A total of 546 human clinical
S. enterica
serovar Typhimurium isolates were recovered from patients in hospitals in China during the period of 2005 to ∼2011. Twenty percent of the isolates exhibited resistance to ciprofloxacin, and 4% were resistant to ceftriaxone. Importantly, for the first time, 12 (2%)
S
. Typhimurium isolates resistant to both ciprofloxacin and ceftriaxone were recovered; among these 12 isolates, two were also resistant to azithromycin, and one was resistant to all other drugs tested. The combined effects of various transferrable extended-spectrum β-lactamase determinants and a novel efflux-based ciprofloxacin resistance mechanism encoded by the mobile efflux gene
oqxAB
were responsible for the emergence of these extremely (highly) drug-resistant (XDR)
S
. Typhimurium isolates. The dissemination of resistance genes, such as those encoding ESBLs and the OqxAB pump, among
Salmonella
organisms will speed up the selection of XDR
Salmonella
, posing a huge threat to public health and
Salmonella
infection control.