bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward the Rational Design of a Malaria Vaccine Construct Using the MSP3 Family as an Example: Contribution of Immunogenicity Studies in Models
Authors: Daher Lena-Juliette , Demanga Corine G. , Prieur Eric , Pérignon Jean-Louis , Bouharoun-Tayoun Hasnaa , Druilhe Pierre 
Published: July 2009

ABSTRACT

Plasmodium falciparum
merozoite surface protein 3 (MSP3), the target of antibodies that mediate parasite killing in cooperation with blood monocytes and are associated with protection in exposed populations, is a vaccine candidate under development. It belongs to a family of six structurally related genes. To optimize immunogenicity, we attempted to improve its design based on knowledge of antigenicity of various regions from the conserved C terminus of the six proteins and an analysis of the immunogenicity of “tailored” constructs. The immunogenicity studies were conducted in BALB/c and C57BL/6J mice, using MSP3 (referred to here as MSP3-1) as a model. Four constructs were designed in order to assess the effect of sequences flanking the 69-amino-acid region of MSP3-1 previously shown to be the target of biologically active antibodies. The results indicate major beneficial effects of removing (i) the subregion downstream from the 69-amino-acid sequence, since antibody titers increased by 2 orders of magnitude, and (ii) the upstream subregion which, although it defines a T-helper cell epitope, is not the target of antibodies. The construct, excluding both flanking sequences, was able to induce Th1-like responses, with a dominance of cytophilic antibodies. This led to design a multigenic construct based on these results, combining the six members of the MSP3 family. This new construction was immunogenic in mice, induced antibodies that recognized the parasite native proteins, and inhibited parasite growth in the functional antibody-dependent cellular inhibition assay, thus satisfying the preclinical criteria for a valuable vaccine candidate.
Structure of Compositionally Simple Lipopolysaccharide from Marine
Synechococcus
Authors: Snyder D. Scott , Brahamsha Bianca , Azadi Parastoo , Palenik Brian 
Published: July 2009

ABSTRACT

Lipopolysaccharide (LPS) is the first defense against changing environmental factors for many bacteria. Here, we report the first structure of the LPS from cyanobacteria based on two strains of marine
Synechococcus
, WH8102 and CC9311. While enteric LPS contains some of the most complex carbohydrate residues in nature, the full-length versions of these cyanobacterial LPSs have neither heptose nor 3-deoxy-
d
-
manno
-octulosonic acid (Kdo) but instead 4-linked glucose as their main saccharide component, with low levels of glucosamine and galacturonic acid also present. Matrix-assisted laser desorption ionization mass spectrometry of the intact minimal core LPS reveals triacylated and tetraacylated structures having a heterogeneous mix of both hydroxylated and nonhydroxylated fatty acids connected to the diglucosamine backbone and a predominantly glucose outer core-like region for both strains. WH8102 incorporated rhamnose in this region as well, contributing to differences in sugar composition and possibly nutritional differences between the strains. In contrast to enteric lipid A, which can be liberated from LPS by mild acid hydrolysis, lipid A from these organisms could be produced by only two novel procedures: triethylamine-assisted periodate oxidation and acetolysis. The lipid A contains odd-chain hydroxylated fatty acids, lacks phosphate, and contains a single galacturonic acid. The LPS lacks any limulus amoebocyte lysate gelation activity. The highly simplified nature of LPSs from these organisms leads us to believe that they may represent either a primordial structure or an adaptation to the relatively higher salt and potentially growth-limiting phosphate levels in marine environments.
The Autolysin LytA Contributes to Efficient Bacteriophage Progeny Release in
Streptococcus pneumoniae
Authors: Frias Maria João , Melo-Cristino José , Ramirez Mário 
Published: July 2009

ABSTRACT

Most bacteriophages (phages) release their progeny through the action of holins that form lesions in the cytoplasmic membrane and lysins that degrade the bacterial peptidoglycan. Although the function of each protein is well established in phages infecting
Streptococcus pneumoniae
, the role—if any—of the powerful bacterial autolysin LytA in virion release is currently unknown. In this study, deletions of the bacterial and phage lysins were done in lysogenic
S. pneumoniae
strains, allowing the evaluation of the contribution of each lytic enzyme to phage release through the monitoring of bacterial-culture lysis and phage plaque assays. In addition, we assessed membrane integrity during phage-mediated lysis using flow cytometry to evaluate the regulatory role of holins over the lytic activities. Our data show that LytA is activated at the end of the lytic cycle and that its triggering results from holin-induced membrane permeabilization. In the absence of phage lysin, LytA is able to mediate bacterial lysis and phage release, although exclusive dependence on the autolysin results in reduced virion egress and altered kinetics that may impair phage fitness. Under normal conditions, activation of bacterial LytA, together with the phage lysin, leads to greater phage progeny release. Our findings demonstrate that
S. pneumoniae
phages use the ubiquitous host autolysin to accomplish an optimal phage exiting strategy.
In Situ Characterization of Differences in the Viscoelastic Response of Individual Gram-Negative and Gram-Positive Bacterial Cells
Authors: Vadillo-Rodriguez Virginia , Schooling Sarah R. , Dutcher John R. 
Published: July 2009

ABSTRACT

We used a novel atomic force microscopy (AFM)-based technique to compare the local viscoelastic properties of individual gram-negative (
Escherichia coli
) and gram-positive (
Bacillus subtilis
) bacterial cells. We found that the viscoelastic properties of the bacterial cells are well described by a three-component mechanical model that combines an instantaneous elastic response and a delayed elastic response. These experiments have allowed us to investigate the relationship between the viscoelastic properties and the structure and composition of the cell envelope. In addition, this is the first report in which the mechanical role of Lpp, the major peptidoglycan-associated lipoprotein and one of the most abundant outer membrane proteins in
E. coli
cells, has been quantified. We expect that our findings will be helpful in increasing the understanding of the structure-property relationships of bacterial cell envelopes.
Staphylococcus aureus
YoeB Homologues Inhibit Translation Initiation
Authors: Yoshizumi Satoshi , Zhang Yonglong , Yamaguchi Yoshihiro , Chen Liang , Kreiswirth Barry N. , Inouye Masayori 
Published: July 2009

ABSTRACT

YoeB is a bacterial toxin encoded by the
yefM-yoeB
toxin-antitoxin system found in various bacterial genomes. Here, we show that
Staphylococcus aureus
contains two YoeB homologues, both of which function as ribosome-dependent mRNA interferases to inhibit translation initiation in a manner identical to that of YoeB-ec from
Escherichia coli
.
Characterization of the Dicarboxylate Transporter DctA in
Corynebacterium glutamicum
Authors: Youn Jung-Won , Jolkver Elena , Krämer Reinhard , Marin Kay , Wendisch Volker F. 
Published: July 2009

ABSTRACT

Transporters of the dicarboxylate amino acid-cation symporter family often mediate uptake of C
4
-dicarboxylates, such as succinate or
l
-malate, in bacteria. A member of this family, dicarboxylate transporter A (DctA) from
Corynebacterium glutamicum
, was characterized to catalyze uptake of the C
4
-dicarboxylates succinate, fumarate, and
l
-malate, which was inhibited by oxaloacetate, 2-oxoglutarate, and glyoxylate. DctA activity was not affected by sodium availability but was dependent on the electrochemical proton potential. Efficient growth of
C. glutamicum
in minimal medium with succinate, fumarate, or
l
-malate as the sole carbon source required high
dctA
expression levels due either to a promoter-up mutation identified in a spontaneous mutant or to ectopic overexpression. Mutant analysis indicated that DctA and DccT, a C
4
-dicarboxylate divalent anion/sodium symporter-type transporter, are the only transporters for succinate, fumarate, and
l
-malate in
C. glutamicum
.
Pneumococcal LytR, a Protein from the LytR-CpsA-Psr Family, Is Essential for Normal Septum Formation in
Streptococcus pneumoniae
Authors: Johnsborg Ola , Håvarstein Leiv Sigve 
Published: July 2009

ABSTRACT

Proliferation of the human-pathogenic bacterium
Streptococcus pneumoniae
is fundamentally linked to the bacterial proteins that function in cell division. Here, we show that LytR, a pneumococcal protein from the LytR-CpsA-Psr family, is essential to this process.
α-Keto Acid Metabolites of Naturally Occurring Organoselenium Compounds as Inhibitors of Histone Deacetylase in Human Prostate Cancer Cells
Authors: Lee Jeong-In , Nian Hui , Cooper Arthur J.L. , Sinha Raghu , Dai Jenny , Bisson William H. , Dashwood Roderick H. , Pinto John T. 
Published: July 2009

AbstractHistone deacetylase (HDAC) inhibitors are gaining interest as cancer therapeutic agents. We tested the hypothesis that natural organoselenium compounds might be metabolized to HDAC inhibitors in human prostate cancer cells. Se-Methyl-l-selenocysteine (MSC) and selenomethionine are amino acid components of selenium-enriched yeast. In a cell-free system, glutamine transaminase K (GTK) and l-amino acid oxidase convert MSC to the corresponding α-keto acid, β-methylselenopyruvate (MSP), and l-amino acid oxidase converts selenomethionine to its corresponding α-keto acid, α-keto-γ-methylselenobutyrate (KMSB). Although methionine (sulfur analogue of selenomethionine) is an excellent substrate for GTK, selenomethionine is poorly metabolized. Structurally, MSP and KMSB resemble the known HDAC inhibitor butyrate. We examined androgen-responsive LNCaP cells and androgen-independent LNCaP C4-2, PC-3, and DU145 cells and found that these human prostate cancer cells exhibit endogenous GTK activities. In the corresponding cytosolic extracts, the metabolism of MSC was accompanied by the concomitant formation of MSP. In MSP-treated and KMSB-treated prostate cancer cell lines, acetylated histone 3 levels increased within 5 hours, and returned to essentially baseline levels by 24 hours, suggesting a rapid, transient induction of histone acetylation. In an in vitro HDAC activity assay, the selenoamino acids, MSC and selenomethionine, had no effect at concentrations up to 2.5 mmol/L, whereas MSP and KMSB both inhibited HDAC activity. We conclude that, in addition to targeting redox-sensitive signaling proteins and transcription factors, α-keto acid metabolites of MSC and selenomethionine can alter HDAC activity and histone acetylation status. These findings provide a potential new paradigm by which naturally occurring organoselenium might prevent the progression of human prostate cancer.
Cortical Projection Topography of the Human Splenium: Hemispheric Asymmetry and Individual Differences
Authors: Putnam Mary Colvin , Steven Megan S. , Doron Karl W. , Riggall Adam C. , Gazzaniga Michael S. 
Published: July 2009

AbstractThe corpus callosum is the largest white matter pathway in the human brain. The most posterior portion, known as the splenium, is critical for interhemispheric communication between visual areas. The current study employed diffusion tensor imaging to delineate the complete cortical projection topography of the human splenium. Homotopic and heterotopic connections were revealed between the splenium and the posterior visual areas, including the occipital and the posterior parietal cortices. In nearly one third of participants, there were homotopic connections between the primary visual cortices, suggesting interindividual differences in splenial connectivity. There were also more instances of connections with the right hemisphere, indicating a hemispheric asymmetry in interhemispheric connectivity within the splenium. Combined, these findings demonstrate unique aspects of human interhemispheric connectivity and provide anatomical bases for hemispheric asymmetries in visual processing and a long-described hemispheric asymmetry in speed of interhemispheric communication for visual information.
Effect of Attention on Early Cortical Processes Associated with the Sound-induced Extra Flash Illusion
Authors: Mishra Jyoti , Martínez Antigona , Hillyard Steven A. 
Published: July 2009

AbstractWhen a single flash of light is presented interposed between two brief auditory stimuli separated by 60–100 msec, subjects typically report perceiving two flashes [Shams, L., Kamitani, Y., & Shimojo, S. Visual illusion induced by sound. Brain Research, Cognitive Brain Research, 14, 147–152, 2002; Shams, L., Kamitani, Y., & Shimojo, S. Illusions. What you see is what you hear. Nature, 408, 788, 2000]. Using ERP recordings, we previously found that perception of the illusory extra flash was accompanied by a rapid dynamic interplay between auditory and visual cortical areas that was triggered by the second sound [Mishra, J., Martínez, A., Sejnowski, T. J., & Hillyard, S. A. Early cross-modal interactions in auditory and visual cortex underlie a sound-induced visual illusion. Journal of Neuroscience, 27, 4120–4131, 2007]. In the current study, we investigated the effect of attention on the ERP components associated with the illusory extra flash in 15 individuals who perceived this cross-modal illusion frequently. All early ERP components in the cross-modal difference wave associated with the extra flash illusion were significantly enhanced by selective spatial attention. The earliest attention-related modulation was an amplitude increase of the positive-going PD110/PD120 component, which was previously shown to be correlated with an individual's propensity to perceive the illusory second flash [Mishra, J., Martínez, A., Sejnowski, T. J., & Hillyard, S. A. Early cross-modal interactions in auditory and visual cortex underlie a sound-induced visual illusion. Journal of Neuroscience, 27, 4120–4131, 2007]. The polarity of the early PD110/PD120 component did not differ as a function of the visual field (upper vs. lower) of stimulus presentation. This, along with the source localization of the component, suggested that its principal generator lies in extrastriate visual cortex. These results indicate that neural processes previously shown to be associated with the extra flash illusion can be modulated by attention, and thus are not the result of a wholly automatic cross-modal integration process.
Human Visual System Automatically Encodes Sequential Regularities of Discrete Events
Authors: Kimura Motohiro , Schröger Erich , Czigler István , Ohira Hideki 
Published: July 2009

AbstractFor our adaptive behavior in a dynamically changing environment, an essential task of the brain is to automatically encode sequential regularities inherent in the environment into a memory representation. Recent studies in neuroscience have suggested that sequential regularities embedded in discrete sensory events are automatically encoded into a memory representation at the level of the sensory system. This notion is largely supported by evidence from investigations using auditory mismatch negativity (auditory MMN), an event-related brain potential (ERP) correlate of an automatic memory-mismatch process in the auditory sensory system. However, it is still largely unclear whether or not this notion can be generalized to other sensory modalities. The purpose of the present study was to investigate the contribution of the visual sensory system to the automatic encoding of sequential regularities using visual mismatch negativity (visual MMN), an ERP correlate of an automatic memory-mismatch process in the visual sensory system. To this end, we conducted a sequential analysis of visual MMN in an oddball sequence consisting of infrequent deviant and frequent standard stimuli, and tested whether the underlying memory representation of visual MMN generation contains only a sensory memory trace of standard stimuli (trace-mismatch hypothesis) or whether it also contains sequential regularities extracted from the repetitive standard sequence (regularity-violation hypothesis). The results showed that visual MMN was elicited by first deviant (deviant stimuli following at least one standard stimulus), second deviant (deviant stimuli immediately following first deviant), and first standard (standard stimuli immediately following first deviant), but not by second standard (standard stimuli immediately following first standard). These results are consistent with the regularity-violation hypothesis, suggesting that the visual sensory system automatically encodes sequential regularities. In combination with a wide range of auditory MMN studies, the present study highlights the critical role of sensory systems in automatically encoding sequential regularities when modeling the world.
The Evocative Power of Sounds: Conceptual Priming between Words and Nonverbal Sounds
Authors: Schön Daniele , Ystad Sølvi , Kronland-Martinet Richard , Besson Mireille 
Published: July 2009

Abstract
Two experiments were conducted to examine the conceptual relation between words and nonmeaningful sounds. In order to reduce the role of linguistic mediation, sounds were recorded in such a way that it was highly unlikely to identify the source that produced them. Related and unrelated sound–word pairs were presented in Experiment 1 and the order of presentation was reversed in Experiment 2 (word–sound). Results showed that, in both experiments, participants were sensitive to the conceptual relation between the two items. They were able to correctly categorize items as related or unrelated with good accuracy. Moreover, a relatedness effect developed in the event-related brain potentials between 250 and 600 msec, although with a slightly different scalp topography for word and sound targets. Results are discussed in terms of similar conceptual processing networks and we propose a tentative model of the semiotics of sounds.
Neural Representations and Mechanisms for the Performance of Simple Speech Sequences
Authors: Bohland Jason W. , Bullock Daniel , Guenther Frank H. 
Published: July 2009

AbstractSpeakers plan the phonological content of their utterances before their release as speech motor acts. Using a finite alphabet of learned phonemes and a relatively small number of syllable structures, speakers are able to rapidly plan and produce arbitrary syllable sequences that fall within the rules of their language. The class of computational models of sequence planning and performance termed competitive queuing models have followed K. S. Lashley [The problem of serial order in behavior. In L. A. Jeffress (Ed.), Cerebral mechanisms in behavior (pp. 112–136). New York: Wiley, 1951] in assuming that inherently parallel neural representations underlie serial action, and this idea is increasingly supported by experimental evidence. In this article, we developed a neural model that extends the existing DIVA model of speech production in two complementary ways. The new model includes paired structure and content subsystems [cf. MacNeilage, P. F. The frame/content theory of evolution of speech production. Behavioral and Brain Sciences, 21, 499–511, 1998] that provide parallel representations of a forthcoming speech plan as well as mechanisms for interfacing these phonological planning representations with learned sensorimotor programs to enable stepping through multisyllabic speech plans. On the basis of previous reports, the model's components are hypothesized to be localized to specific cortical and subcortical structures, including the left inferior frontal sulcus, the medial premotor cortex, the basal ganglia, and the thalamus. The new model, called gradient order DIVA, thus fills a void in current speech research by providing formal mechanistic hypotheses about both phonological and phonetic processes that are grounded by neuroanatomy and physiology. This framework also generates predictions that can be tested in future neuroimaging and clinical case studies.
Responding with Restraint: What Are the Neurocognitive Mechanisms?
Authors: Jahfari Sara , Stinear Cathy M. , Claffey Mike , Verbruggen Frederick , Aron Adam R. 
Published: July 2009

Abstract
An important aspect of cognitive control is the ability to respond with restraint. Here, we modeled this experimentally by measuring the degree of response slowing that occurs when people respond to an imperative stimulus in a context where they might suddenly need to stop the initiated response compared with a context in which they do not need to stop. We refer to the RT slowing that occurs as the “response delay effect.” We conjectured that this response delay effect could relate to one or more neurocognitive mechanism(s): partial response suppression (i.e., “active braking”), prolonged decision time, and slower response facilitation. These accounts make different predictions about motor system excitability and brain activation. To test which neurocognitive mechanisms underlie the response delay effect, we performed two studies with TMS and we reanalyzed fMRI data. The results suggest that the response delay effect is at least partly explained by active braking, possibly involving a mechanism that is similar to that used to stop responses completely. These results further our understanding of how people respond with restraint by pointing to proactive recruitment of a neurocognitive mechanism heretofore associated with outright stopping.