bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Tanzania, Hemolysis after a Single Dose of Primaquine Coadministered with an Artemisinin Is Not Restricted to Glucose-6-Phosphate Dehydrogenase-Deficient (G6PD A−) Individuals
Authors: Shekalaghe Seif A. , ter Braak Roel , Daou Modibo , Kavishe Reginald , van den Bijllaardt Wouter , van den Bosch Sven , Koenderink Jan B. , Luty Adrian J. F. , Whitty Christopher J. M. , Drakeley Chris , Sauerwein Robert W. , Bousema Teun 
Published: March 2010

ABSTRACT

The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature
P
lasmodium falciparum
gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment. As part of a mass drug intervention, we determined the hemolytic effect of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) plus a single dose of primaquine (PQ; 0.75 mg/kg of body weight) in children aged 1 to 12 years. Children were randomized to receive SP+AS+PQ or placebo; those with a hemoglobin (Hb) level below 8 g/dl were excluded from receiving PQ and received SP+AS. The Hb concentration was significantly reduced 7 days after SP+AS+PQ treatment but not after placebo or SP+AS treatment. This reduction in Hb was most pronounced in G6PD-deficient (G6PD A−) individuals (−2.5 g/dl; 95% confidence interval [95% CI], −1.2 to −3.8 g/dl) but was also observed in heterozygotes (G6PD A) (−1.6 g/dl; 95% CI, −0.9 to −2.2 g/dl) and individuals with the wild-type genotype (G6PD B) (−0.5 g/dl; 95% CI, −0.4 to −0.6 g/dl). Moderate anemia (Hb level of <8 g/dl) was observed in 40% (6/15 individuals) of the G6PD A−, 11.1% (3/27 individuals) of the G6PD A, and 4.5% (18/399 individuals) of the G6PD B individuals; one case of severe anemia (Hb level of <5 g/dl) was observed. PQ may cause moderate anemia when coadministered with artemisinins, and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis.
Expansion and Evolution of the
Streptococcus pneumoniae
Spain
9V
-ST156 Clonal Complex in Poland
Authors: Sadowy Ewa , Kuch Alicja , Gniadkowski Marek , Hryniewicz Waleria 
Published: March 2010

ABSTRACT

In this study, we analyzed 118 penicillin-nonsusceptible
Streptococcus pneumoniae
(PNSP) isolates (MICs, ≥0.12 μg/ml) recovered in Poland in 2003 to 2005 from patients with respiratory tract diseases and invasive infections. Seven different serotypes (14, 9V, 23F, 19F, 6B, 19A, and 6A, in order of descending frequency), seven alleles of the
murM
gene (
murMA
,
murMB6
, and the new
murMB12
to -
16
alleles), and 31 multilocus sequence types (STs) were observed. The vast majority of the PNSP isolates (90.7%) belonged to the international multiresistant clones, and among these, the Spain
9V
-ST156 clonal complex was the most prevalent (56 isolates) and was significantly overrepresented in invasive infections. The clone has been evolving rapidly, as demonstrated by the observed number of STs, the diversity in multiple-locus variable-number-tandem-repeat analysis (MLVA) types, and the polymorphism of
pbp
and
pspA
genes (coding for penicillin-binding proteins and the pneumococcal surface protein A, respectively). The presence and structure of the
rlrA
islet (encoding the pneumococcal pilus) were very well conserved. The Spain
9V
-ST156 clonal complex has been largely responsible for a decreasing susceptibility to penicillin among pneumococci in Poland in recent years, in spite of a relatively moderate antimicrobial use.
Genetic Basis of Multidrug Resistance in
Acinetobacter
Clinical Isolates in Taiwan
Authors: Lin Yu-Chi , Hsia Ko-Chiang , Chen Yee-Chun , Sheng Wang-Huei , Chang Shan-Chwen , Liao Mei-Hui , Li Shu-Ying 
Published: March 2010

ABSTRACT

Multidrug-resistant (MDR)
Acinetobacter
spp. have emerged as a threat to public health. We investigated the various genes involved in resistance to fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems in 75 clinical
Acinetobacter
isolates from a Taiwanese hospital. All isolates were tested for the
gyrA
mutations, the presence of integrons,
bla
AmpC
, and carbapenem resistance genes. The Ser83Leu mutation in GyrA accounted for fluoroquinolone resistance. The presence of integrons containing aminoglycoside-modifying enzymes was associated with resistance to gentamicin and tobramycin but not with resistance to amikacin. The presence of an IS
Aba1
element upstream of
bla
AmpC
was correlated with cephalosporin resistance. Although most
Acinetobacter
baumannii
isolates with IS
Aba1
-
bla
OXA-51-
like
were resistant to carbapenems, several isolates remained susceptible to carbapenems. Transformation by the introduction of IS
Aba1
-
bla
OXA-23
or IS
Aba1
-
bla
OXA-66
into
A. baumannii
ATCC 15151 (CIP 70.10), resulting in the overexpression of OXA-23 or OXA-66, respectively, suggested the role of the IS
Aba1
element as a strong promoter. The two transformants showed significantly increased resistance to piperacillin-tazobactam, imipenem, and meropenem. The cefepime resistance conferred by IS
Aba1
-
bla
OXA-23
and the impact of IS
Aba1
-
bla
OXA-66
on carbapenem resistance in
A. baumannii
are reported here for the first time. Continuous surveillance of antibiotic resistance genes in MDR
Acinetobacter
spp. and elucidation of their antibiotic resistance mechanisms are crucial for the development of therapy regimens and for the prevention of further dissemination of these antibiotic resistance genes.
Identification and Characterization of a Glycosyltransferase Involved in
Acinetobacter baumannii
Lipopolysaccharide Core Biosynthesis
Authors: Luke Nicole R. , Sauberan Shauna L. , Russo Thomas A. , Beanan Janet M. , Olson Ruth , Loehfelm Thomas W. , Cox Andrew D. , St. Michael Frank , Vinogradov Evgeny V. , Campagnari Anthony A. 
Published: March 2010

ABSTRACT

Although
Acinetobacter baumannii
has emerged as a significant cause of nosocomial infections worldwide, there have been few investigations describing the factors important for
A. baumannii
persistence and pathogenesis. This paper describes the first reported identification of a glycosyltransferase, LpsB, involved in lipopolysaccharide (LPS) biosynthesis in
A. baumannii
. Mutational, structural, and complementation analyses indicated that LpsB is a core oligosaccharide glycosyl transferase. Using a genetic approach,
lpsB
was compared with the
lpsB
homologues of several
A. baumannii
strains. These analyses indicated that LpsB is highly conserved among
A. baumannii
isolates. Furthermore, we developed a monoclonal antibody, monoclonal antibody 13C11, which reacts to an LPS core epitope expressed by approximately one-third of the
A. baumannii
clinical isolates evaluated to date. Previous studies describing the heterogeneity of
A. baumannii
LPS were limited primarily to structural analyses; therefore, studies evaluating the correlation between these surface glycolipids and pathogenesis were warranted. Our data from an evaluation of LpsB mutant 307::TN17, which expresses a deeply truncated LPS glycoform consisting of only two 3-deoxy-
d
-manno-octulosonic acid residues and lipid A, suggest that
A. baumannii
LPS is important for resistance to normal human serum and confers a competitive advantage for survival
in vivo
. These results have important implications for the role of LPS in
A. baumannii
infections.
Listeriolysin O-Dependent Bacterial Entry into the Cytoplasm Is Required for Calpain Activation and Interleukin-1α Secretion in Macrophages Infected withListeria monocytogenes
Authors: Dewamitta Sita R. , Nomura Takamasa , Kawamura Ikuo , Hara Hideki , Tsuchiya Kohsuke , Kurenuma Takeshi , Shen Yanna , Daim Sylvia , Yamamoto Takeshi , Qu Huixin , Sakai Shunsuke , Xu Yanting , Mitsuyama Masao 
Published: March 2010

ABSTRACTListeriolysin O (LLO), anhly-encoded cytolysin ofListeria monocytogenes, plays an essential role in the entry ofL. monocytogenesinto the host cell cytoplasm.L. monocytogenes-infected macrophages produce various proinflammatory cytokines, including interleukin-1α (IL-1α), that contribute to the host immune response. In this study, we have examined IL-1α production in macrophages infected with wild-typeL. monocytogenesor a nonescaping mutant strain deficient for LLO (Δhly). Expression of IL-1α mRNA and accumulation of pro-IL-1α in the cytoplasm were induced by both strains. In contrast, the secretion of the mature form of IL-1α from infected macrophages was observed in infection with wild-typeL. monocytogenesbut not with the Δhlymutant. A recovery of the ability to induce IL-1α secretion was shown in a mutant strain complemented with thehlygene. The Toll-like receptor (TLR)/MyD88 signaling pathway was exclusively required for the expression of pro-IL-1α, independently of LLO-mediated cytoplasmic entry ofL. monocytogenes. The LLO-dependent secretion of mature IL-1α was abolished by addition of calcium chelators, and only LLO-producingL. monocytogenesstrains were able to induce elevation of the intracellular calcium level in infected macrophages. A calcium-dependent protease, calpain, was implicated in the maturation and secretion of IL-1α induced by LLO-producingL. monocytogenesstrains based on the effect of calpain inhibitor. Functional activation of calpain was detected in macrophages infected with LLO-producingL. monocytogenesstrains but not with a mutant strain lacking LLO. These results clearly indicated that LLO-mediated cytoplasmic entry of bacteria could induce the activation of intracellular calcium signaling, which is essential for maturation and secretion of IL-1α in macrophages duringL. monocytogenesinfection through activation of a calcium-dependent calpain protease. In addition, recombinant LLO, when added to macrophages infected with the Δhlystrain, could induce calcium influx and IL-1α secretion at doses exhibiting cytolytic activity, suggesting that LLO produced by intracellularL. monocytogenesmay be implicated in induction of calcium influx through pore formation.
The Proline-Rich Region of Pneumococcal Surface Proteins A and C Contains Surface-Accessible Epitopes Common to All Pneumococci and Elicits Antibody-Mediated Protection against Sepsis
Authors: Daniels Calvin C. , Coan Patricia , King Janice , Hale Joanetha , Benton Kimberly A. , Briles David E. , Hollingshead Susan K. 
Published: March 2010

ABSTRACT

Pneumococcal surface protein A (PspA) and PspC of
Streptococcus pneumoniae
are surface virulence proteins that interfere with complement deposition and elicit protective immune responses. The C-terminal halves of PspA and PspC have some structural similarity and contain highly cross-reactive proline-rich (PR) regions. In many PR regions of PspA and PspC, there exists an almost invariant nonproline block (NPB) of about 33 amino acids. Neither the PR regions nor their NPB exhibit the alpha-helical structure characteristic of much of the protection-eliciting N-terminal portions of PspA and PspC. Prior studies of PspA and PspC as immunogens focused primarily on the alpha-helical regions of these molecules that lack the PR and NPB regions. This report shows that immunization with recombinant PR (rPR) molecules and passive immunization with monoclonal antibodies reactive with either NPB or PR epitopes are protective against infection in mice. PR regions of both PspA and PspC were antibody accessible on the pneumococcal surface. Our results indicate that while PspA could serve as a target of these protective antibodies in invasive infections, PspC might not. When antibody responses to rPR immunogens were evaluated by using flow cytometry to measure antibody binding to live pneumococci, it was observed that the mice that survived subsequent challenge produced significantly higher levels of antibodies reactive with exposed PR epitopes than the mice that became moribund. Due to their conservation and cross-reactivity, the PR regions and NPB regions represent potential vaccine targets capable of eliciting cross-protection immunity against pneumococcal infection.
Anthrax Lethal Toxin Impairs CD1d-Mediated Antigen Presentation by Targeting the Extracellular Signal-Related Kinase 1/2 Mitogen-Activated Protein Kinase Pathway
Authors: Khan Masood A. , Gallo Richard M. , Brutkiewicz Randy R. 
Published: March 2010

ABSTRACT

Lethal toxin (LT) is a critical virulence factor of
Bacillus anthracis
and an important means by which this bacterium evades the host's immune system. In this study, we demonstrate that CD1d-expressing cells treated with LT have reduced CD1d-mediated antigen presentation. We earlier showed an important role for the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 (ERK1/2) in the regulation of CD1d-mediated antigen presentation, and we report here that LT impairs antigen presentation by CD1d in an ERK1/2-dependent manner. Similarly, LT and the ERK1/2 pathway-specific inhibitor U0126 caused a decrease in major histocompatibility complex (MHC) class II-mediated antigen presentation. Confocal microscopy analyses revealed altered intracellular distribution of CD1d and LAMP-1 in LT-treated cells, similar to the case for ERK1/2-inhibited cells. These results suggest that
Bacillus anthracis
has the ability to evade the host's innate immune system by reducing CD1d-mediated antigen presentation through targeting the ERK1/2 pathway.
CCR7-Dependent Immunity during Acute
Toxoplasma gondii
Infection
Authors: Noor Shahani , Habashy Andrew S. , Nance J. Philip , Clark Robin T. , Nemati Kiav , Carson Monica J. , Wilson Emma H. 
Published: March 2010

ABSTRACT

The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells and T cells. Interactions with its ligands, CCL19 and CCL21, facilitate priming of immune responses in lymphoid tissue, yet CCR7-independent immune responses can be generated in the presence of sufficient antigen. In these studies, we investigated the role of CCR7 signaling in the generation of protective immune responses to the intracellular protozoan parasite
Toxoplasma gondii
. The results demonstrated a significant increase in the expression of CCL19, CCL21, and CCR7 in peripheral and central nervous system (CNS) tissues over the course of infection. Unexpectedly, despite the presence of abundant antigen, CCR7 was an absolute requirement for protective immunity to
T. gondii
, as CCR7
−/−
mice succumbed to the parasite early in the acute phase of infection. Although serum levels of interleukin 12 (IL-12), IL-6, tumor necrosis factor alpha (TNF-α), and IL-10 remained unchanged, there was a significant decrease in CCL2/monocyte chemoattractant protein 1 (MCP-1) and inflammatory monocyte recruitment to the site of infection. In addition, CCR7
−/−
mice failed to produce sufficient gamma interferon (IFN-γ), a critical Th1-associated effector cytokine required to control parasite replication. As a result, there was increased parasite dissemination and a significant increase in parasite burden in the lungs, livers, and brains of infected mice. Adoptive-transfer experiments revealed that expression of CCR7 on the T-cell compartment alone is sufficient to enable T-cell priming, increase IFN-γ production, and allow the survival of CCR7
−/−
mice. These data demonstrate an absolute requirement for T-cell expression of CCR7 for the generation of protective immune responses to
Toxoplasma
infection.
Minimal Role for the Circumsporozoite Protein in the Induction of Sterile Immunity by Vaccination with Live Rodent Malaria Sporozoites
Authors: Mauduit Marjorie , Tewari Rita , Depinay Nadya , Kayibanda Michèle , Lallemand Eliette , Chavatte Jean-Marc , Snounou Georges , Rénia Laurent , Grüner Anne Charlotte 
Published: March 2010

ABSTRACT

Immunization with live
Plasmodium
sporozoites under chloroquine prophylaxis (Spz plus CQ) induces sterile immunity against sporozoite challenge in rodents and, more importantly, in humans. Full protection is obtained with substantially fewer parasites than with the classic immunization with radiation-attenuated sporozoites. The sterile protection observed comprised a massive reduction in the hepatic parasite load and an additional effect at the blood stage level. Differences in the immune responses induced by the two protocols occur but are as yet little characterized. We have previously demonstrated that in mice immunized with irradiated sporozoites, immune responses against the circumsporozoite protein (CSP), the major component of the sporozoite's surface and the leading malaria vaccine candidate, were not essential for sterile protection. Here, we have employed transgenic
P
lasmodium berghei
parasites in which the endogenous CSP was replaced by that of
P
lasmodium yoelii
, another rodent malaria species, to assess the role of CSP in the sterile protection induced by the Spz-plus-CQ protocol. The data demonstrated that this role was minor because sterile immunity was obtained irrespective of the origin of CSP expressed by the parasites in this model of protection. The immunity was obtained through a single transient exposure of the host to the immunizing parasites (preerythrocytic and erythrocytic), a dose much smaller than that required for immunization with radiation-attenuated sporozoites.
Alkali Metal Cation Transport and Homeostasis in Yeasts
Authors: Ariño Joaquín , Ramos José , Sychrová Hana 
Published: March 2010

SUMMARY

The maintenance of appropriate intracellular concentrations of alkali metal cations, principally K
+
and Na
+
, is of utmost importance for living cells, since they determine cell volume, intracellular pH, and potential across the plasma membrane, among other important cellular parameters. Yeasts have developed a number of strategies to adapt to large variations in the concentrations of these cations in the environment, basically by controlling transport processes. Plasma membrane high-affinity K
+
transporters allow intracellular accumulation of this cation even when it is scarce in the environment. Exposure to high concentrations of Na
+
can be tolerated due to the existence of an Na
+
, K
+
-ATPase and an Na
+
, K
+
/H
+
-antiporter, which contribute to the potassium balance as well. Cations can also be sequestered through various antiporters into intracellular organelles, such as the vacuole. Although some uncertainties still persist, the nature of the major structural components responsible for alkali metal cation fluxes across yeast membranes has been defined within the last 20 years. In contrast, the regulatory components and their interactions are, in many cases, still unclear. Conserved signaling pathways (e.g., calcineurin and HOG) are known to participate in the regulation of influx and efflux processes at the plasma membrane level, even though the molecular details are obscure. Similarly, very little is known about the regulation of organellar transport and homeostasis of alkali metal cations. The aim of this review is to provide a comprehensive and up-to-date vision of the mechanisms responsible for alkali metal cation transport and their regulation in the model yeast Saccharomyces cerevisiae and to establish, when possible, comparisons with other yeasts and higher plants.
Too much programming too soon?
Authors: Guzdial Mark , Robertson Judy 
Published: March 2010

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish excerpts from selected posts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM
Mark Guzdial and Judy Robertson discuss the role of programming in introductory computer science.
Using the forest to see the trees
Authors: Torralba A. , Murphy K. P. , Freeman W. T. 
Published: March 2010

Recognizing objects in images is an active area of research in computer vision. In the last two decades, there has been much progress and there are already object recognition systems operating in commercial products. However, most of the algorithms for detecting objects perform an exhaustive search across all locations and scales in the image comparing local image regions with an object model. That approach ignores the semantic structure of scenes and tries to solve the recognition problem by brute force. In the real world, objects tend to covary with other objects, providing a rich collection of contextual associations. These contextual associations can be used to reduce the search space by looking only in places in which the object is expected to be; this also increases performance, by rejecting patterns that look like the target but appear in unlikely places.
Most modeling attempts so far have defined the context of an object in terms of other previously recognized objects. The drawback of this approach is that inferring the context becomes as difficult as detecting each object. An alternative view of context relies on using the entire scene information holistically. This approach is algorithmically attractive since it dispenses with the need for a prior step of individual object recognition. In this paper, we use a probabilistic framework for encoding the relationships between context and object properties and we show how an integrated system provides improved performance. We view this as a significant step toward general purpose machine vision systems.
Electromigration for microarchitects
Authors: Abella Jaume , Vera Xavier 
Published: March 2010

Degradation of devices has become a major issue for processor design due to continuous device shrinkage and current density increase. Transistors and wires suffer high stress, and failures may appear in the field. In particular, wires degrade mainly due to electromigration when driving current. Techniques to mitigate electromigration to some extent have been proposed from the circuit point of view, but much effort is still required from the microarchitecture side to enable wire scaling in future technologies.
This survey brings to the microarchitecture community a comprehensive study of the causes and implications of electromigration in digital circuits and describes the challenges that must be faced to mitigate electromigration by means of microarchitectural solutions.
AudioNav
Authors: Fallah Navid 
Published: March 2010

This research is to design a novel indoor navigation tool called AudioNav for users with visual impairment. Current navigation systems rely upon expensive physical augmentation of the environment or expensive sensing equipment. The proposed system is infrastructure-free and low cost as it uses only a virtual representation of a building to be navigated.
Our proposed system: 1) extracts a floor-plan and recognizes landmarks in the three-dimensional model of a building, 2) locates and tracks the user inside the building while there is no GPS reception, 3) finds the most suitable path based on the user's special needs, and provides step-by-step direction to the destination using voice, speech, or haptic feedback.