bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of Inflammasome Activation by Vibrio cholerae Secreted Toxins Vary with Strain Biotype
Authors: Queen Jessica , Agarwal Shivani , Dolores Jazel S. , Stehlik Christian , Satchell Karla J. F. 
Published: April 2015

ABSTRACT

Activation of inflammasomes is an important aspect of innate immune responses to bacterial infection. Recent studies have linked
Vibrio cholerae
secreted toxins to inflammasome activation by using murine macrophages. To increase relevance to human infection, studies of inflammasome-dependent cytokine secretion were conducted with the human THP-1 monocytic cell line and corroborated in primary human peripheral blood mononuclear cells (PBMCs). Both El Tor and classical strains of
V. cholerae
activated ASC (apoptosis-associated speck-like protein-containing a CARD domain)-dependent release of interleukin-1β (IL-1β) when cultured with human THP-1 cells, but the pattern of induction was distinct, depending on the repertoire of toxins the strains produced. El Tor biotype strains induced release of IL-1β dependent on NOD-like receptor family pyrin domain-containing 3 (NLRP3) and ASC due to the secreted pore-forming toxin hemolysin. Unlike in studies with mouse macrophages, the MARTX toxin did not contribute to IL-1β release from human monocytic cells. Classical biotype strains, which do not produce either hemolysin or the MARTX toxin, activated low-level IL-1β release that was induced by cholera toxin (CT) and dependent on ASC but independent of NLRP3 and pyroptosis. El Tor strains likewise showed increased IL-1β production dependent on CT when the hemolysin gene was deleted. In contrast to studies with murine macrophages, this phenotype was dependent on a catalytically active CT A subunit capable of inducing production of cyclic AMP and not on the B subunit. These studies demonstrate that the induction of the inflammasome in human THP-1 monocytes and in PBMCs by
V. cholerae
varies with the biotype and is mediated by both NLRP3-dependent and -independent pathways.
AMA1-Deficient Toxoplasma gondii Parasites Transiently Colonize Mice and Trigger an Innate Immune Response That Leads to Long-Lasting Protective Immunity
Authors: Lagal Vanessa , Dinis Márcia , Cannella Dominique , Bargieri Daniel , Gonzalez Virginie , Andenmatten Nicole , Meissner Markus , Tardieux Isabelle 
Published: April 2015

ABSTRACT

The apical membrane antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera,
Plasmodium
and
Toxoplasma
, until we genetically engineered viable parasites lacking
AMA1
. The reduction in invasiveness of the
Toxoplasma gondii
RH-AMA1 knockout (RH-AMA1
KO
) tachyzoite population,
in vitro
, raised key questions about the outcome associated with these tachyzoites once inoculated in the peritoneal cavity of mice. In this study, we used AMNIS technology to simultaneously quantify and image the parasitic process driven by AMA1
KO
tachyzoites. We report their ability to colonize and multiply in mesothelial cells and in both resident and recruited leukocytes. While the RH-AMA1
KO
population amplification is rapidly lethal in immunocompromised mice, it is controlled in immunocompetent hosts, where immune cells in combination sense parasites and secrete proinflammatory cytokines. This innate response further leads to a long-lasting status immunoprotective against a secondary challenge by high inocula of the homologous type I or a distinct type II
T. gondii
genotypes. While AMA1 is definitively not an essential protein for tachyzoite entry and multiplication in host cells, it clearly assists the expansion of parasite population
in vivo
.
Air Pollution Particulate Matter Alters Antimycobacterial Respiratory Epithelium Innate Immunity
Authors: Rivas-Santiago César E. , Sarkar Srijata , Cantarella Pasquale , Osornio-Vargas Álvaro , Quintana-Belmares Raúl , Meng Qingyu , Kirn Thomas J. , Ohman Strickland Pamela , Chow Judith C. , Watson John G. , Torres Martha , Schwander Stephan 
Published: April 2015

ABSTRACTInhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses againstMycobacterium tuberculosishas been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm (PM2.5) and 10 μm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5or PM10deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection withM. tuberculosisand increased intracellularM. tuberculosisgrowth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhancedM. tuberculosisgrowth represent mechanisms by which exposure to air pollution PM may increase the risk ofM. tuberculosisinfection and the development of TB.
Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of
l
-Lysine
Authors: Pathania Amit , Sardesai Abhijit A. 
Published: April 2015

ABSTRACT

In
Escherichia coli
,
argO
encodes an exporter for
l
-arginine (Arg) and its toxic analogue canavanine (CAN), and its transcriptional activation and repression, by Arg and
l
-lysine (Lys), respectively, are mediated by the regulator ArgP. Accordingly
argO
and
argP
mutants are CAN supersensitive (CAN
ss
). We report the identification of
ybjE
as a gene encoding a predicted inner membrane protein that mediates export of Lys, and our results confirm the previous identification with a different approach of YbjE as a Lys exporter, reported by Ueda and coworkers (T. Ueda, Y. Nakai, Y. Gunji, R. Takikawa, and Y. Joe, U.S. patents 7,629,142 B2 [December 2009] and 8,383,363 B1 [February 2013] and European patent 1,664,318 B1 [September 2009]).
ybjE
was isolated as a multicopy suppressor of the CAN
ss
phenotype of a strain lacking ArgO. The absence of YbjE did not confer a CAN
ss
phenotype but instead conferred hypersensitivity to the lysine antimetabolite thialysine and led to growth inhibition by the dipeptide lysylalanine, which is associated with elevated cellular Lys content. YbjE overproduction resulted in Lys excretion and syntrophic cross-feeding of a Lys auxotroph. Constitutive overexpression of
argO
promoted Lys cross-feeding that is indicative of a latent Lys export potential of ArgO. Arg modestly repressed
ybjE
transcription in an ArgR-dependent manner, and ArgR displayed Arg-sensitive binding to the
ybjE
promoter region
in vitro
. Our studies suggest that the reciprocal repression of
argO
and
ybjE
, respectively, by Lys and Arg confers the specificity for basic amino acid export by distinct paths and that such cross-repression contributes to maintenance of cytoplasmic Arg/Lys balance. We propose that YbjE be redesignated LysO.

IMPORTANCE
This work ascribes a lysine export function to the product of the
ybjE
gene of
Escherichia coli
, leading to a physiological scenario wherein two proteins, ArgO and YbjE, perform the task of separately exporting arginine and lysine, respectively, which is distinct from that seen for
Corynebacterium glutamicum
, where the ortholog of ArgO, LysE, mediates export of both arginine and lysine. Repression of
argO
transcription by lysine is thought to effect this separation. Accordingly, ArgO mediates lysine export when repression of its transcription by lysine is bypassed. Repression of
ybjE
transcription by arginine via the ArgR repressor, together with the lysine repression of
argO
effected by ArgP, is indicative of a mechanism of maintenance of arginine/lysine balance in
E. coli
.
Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 “Gatekeeper” F691L Mutation with PLX3397
Authors: Smith Catherine C. , Zhang Chao , Lin Kimberly C. , Lasater Elisabeth A. , Zhang Ying , Massi Evan , Damon Lauren E. , Pendleton Matthew , Bashir Ali , Sebra Robert , Perl Alexander , Kasarskis Andrew , Shellooe Rafe , Tsang Garson , Carias Heidi , Powell Ben , Burton Elizabeth A. , Matusow Bernice , Zhang Jiazhong , Spevak Wayne , Ibrahim Prabha N. , Le Mai H. , Hsu Henry H. , Habets Gaston , West Brian L. , Bollag Gideon , Shah Neil P. 
Published: April 2015

Abstract
Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKI) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase “gatekeeper” residues, which control access to an allosteric pocket adjacent to the ATP-binding site, has been frequently implicated in TKI resistance. The molecular underpinnings of gatekeeper mutation–mediated resistance are incompletely understood. We report the first cocrystal structure of FLT3 with the TKI quizartinib, which demonstrates that quizartinib binding relies on essential edge-to-face aromatic interactions with the gatekeeper F691 residue, and F830 within the highly conserved Asp-Phe-Gly motif in the activation loop. This reliance makes quizartinib critically vulnerable to gatekeeper and activation loop substitutions while minimizing the impact of mutations elsewhere. Moreover, we identify PLX3397, a novel FLT3 inhibitor that retains activity against the F691L mutant due to a binding mode that depends less vitally on specific interactions with the gatekeeper position.
Significance: We report the first cocrystal structure of FLT3 with a kinase inhibitor, elucidating the structural mechanism of resistance due to the gatekeeper F691L mutation. PLX3397 is a novel FLT3 inhibitor with in vitro activity against this mutation but is vulnerable to kinase domain mutations in the FLT3 activation loop. Cancer Discov; 5(6); 668–79. ©2015 AACR.
This article is highlighted in the In This Issue feature, p. 565
Read My Lips: Brain Dynamics Associated with Audiovisual Integration and Deviance Detection
Authors: Tse Chun-Yu , Gratton Gabriele , Garnsey Susan M. , Novak Michael A. , Fabiani Monica 
Published: April 2015

Abstract
Information from different modalities is initially processed in different brain areas, yet real-world perception often requires the integration of multisensory signals into a single percept. An example is the McGurk effect, in which people viewing a speaker whose lip movements do not match the utterance perceive the spoken sounds incorrectly, hearing them as more similar to those signaled by the visual rather than the auditory input. This indicates that audiovisual integration is important for generating the phoneme percept. Here we asked when and where the audiovisual integration process occurs, providing spatial and temporal boundaries for the processes generating phoneme perception. Specifically, we wanted to separate audiovisual integration from other processes, such as simple deviance detection. Building on previous work employing ERPs, we used an oddball paradigm in which task-irrelevant audiovisually deviant stimuli were embedded in strings of non-deviant stimuli. We also recorded the event-related optical signal, an imaging method combining spatial and temporal resolution, to investigate the time course and neuroanatomical substrate of audiovisual integration. We found that audiovisual deviants elicit a short duration response in the middle/superior temporal gyrus, whereas audiovisual integration elicits a more extended response involving also inferior frontal and occipital regions. Interactions between audiovisual integration and deviance detection processes were observed in the posterior/superior temporal gyrus. These data suggest that dynamic interactions between inferior frontal cortex and sensory regions play a significant role in multimodal integration.
“The Cooties Effect”: Amygdala Reactivity to Opposite- versus Same-sex Faces Declines from Childhood to Adolescence
Authors: Telzer Eva H. , Flannery Jessica , Humphreys Kathryn L. , Goff Bonnie , Gabard-Durman Laurel , Gee Dylan G. , Tottenham Nim 
Published: April 2015

Abstract
One of the most important social identities that children learn to define themselves and others by is sex, becoming a salient social category by early childhood. Although older children begin to show greater flexibility in their gendered behaviors and attitudes, gender rigidity intensifies again around the time of puberty. In the current study, we assessed behavioral and neural biases to sex across a wide age group. Ninety-three youth (ages 7–17 years) provided behavioral rating of same- and opposite-sex attitudes, and 52 youth (ages 4–18 years) underwent an fMRI scan as they matched the emotion of same- and opposite-sex faces. We demonstrate significant age-related behavioral biases of sex that are mediated by differential amygdala response to opposite-sex relative to same-sex faces in children, an effect that completely attenuates by the teenage years. Moreover, we find a second peak in amygdala sensitivity to opposite-sex faces around the time of puberty. Thus, the amygdala codes for developmentally dependent and motivationally relevant social identification across development.
Cloud-Resolving Large-Eddy Simulation of Tropical Convective Development and Surface Fluxes
Authors: Skyllingstad Eric D. , de Szoeke Simon P. 
Published: April 2015

Abstract
Cloud-resolving large-eddy simulations (LES) on a 500 km × 500 km periodic domain coupled to a thermodynamic ocean mixed layer are used to study the effect of large-scale moisture convergence M on the convective population and heat and moisture budgets of the tropical atmosphere, for several simulations with M representative of the suppressed, transitional, and active phases of the Madden–Julian oscillation (MJO). For a limited-area model without an imposed vertical velocity, M controls the overall vertical temperature structure. Moisture convergence equivalent to ~200 W m−2 (9 mm day−1) maintains the observed temperature profile above 5 km. Increased convective heating for simulations with higher M is partially offset by greater infrared cooling, suggesting a potential negative feedback that helps maintain the weak temperature gradient conditions observed in the tropics. Surface evaporation decreases as large-scale moisture convergence increases, and is only a minor component of the overall water budget for convective conditions representing the active phase of the MJO. Cold pools generated by evaporation of precipitation under convective conditions are gusty, with roughly double the wind stress of their surroundings. Consistent with observations, enhanced surface evaporation due to cold pool gusts is up to 40% of the mean, but has a small effect on the total moisture budget compared to the imposed large-scale moisture convergence.
Performance in Tangible and in Cognitive Stock-Flow Tasks
Authors: Strohhecker Jürgen , Größler Andreas 
Published: April 2015

Background. Most research in the area of dynamic decision making in general and stock-flow failures in particular is conducted with the help of computerized simulations as task environments or paper-based tasks of simple dynamic systems. Purpose. The purpose of this article is to investigate if stock-flow failures persist in naturalistic decision making environments. Methods. For this purpose, a tangible stock-flow experiment is used. It asks participants to meet a target level of water in a glass by pouring water through a funnel as fast as possible. We then compare their performance with a purely cognitive task (a manufacturing task). Results. Participants on average did not significantly perform better in a tangible stock-flow task than in a paper-based test of a comparable task. In addition, individual performance in the tangible task cannot be related to performance in a similar paper-pencil stock-flow task. Conclusions. An implication of this study is that tangible stock-flow tasks are as difficult for humans to control as are purely cognitive tasks. Further research should address individual differences between the two task modes (tangible vs. cognitive). A limitation of this study is the usage of only one tangible stock-flow task.
Nutrition Science and Behavioral Theories Integrated in a Serious Game for Adolescents
Authors: Majumdar Dalia , Koch Pamela A. , Lee Gray Heewon , Contento Isobel R. , de Lourdes Islas-Ramos Ana , Fu Daniel 
Published: April 2015

Purpose. Serious games have demonstrated positive effects on adolescent eating and physical activity. The purpose of this paper is to describe how constructs from social cognitive theory (SCT) and self-determination theory (SDT) were operationalized in the development of the serious game CREATURE 101 (C-101) to engage players in acquiring motivation, knowledge, skills, and personal agency. Approach. C-101 was developed from an evaluated nutrition and science curriculum for middle school youth, Choice, Control & Change (C3). Its behavior change goals are three pairs of “increase/decrease” behaviors: increase water / decease sweetened beverages, increase fruit and vegetables / decrease processed snacks (chips, candy etc), and increase physical activity (light, medium, intense) / decrease recreational screen time (watching TV, playing video games for fun) through a “virtual companion care” motif where the players bring their adopted creatures back to health. Several procedures or strategies were used to develop the story line and activities in C-101 to address autonomy, competence and relatedness from SDT and outcome expectations, self-efficacy, and behavioral capability from SCT, constructs shown in previous studies as likely to enhance effectiveness of nutrition and physical activity interventions. Implications. This description of how the theory constructs and procedures were used to create an entertaining serious game based on an existing evaluated health-related curriculum can help game developers, curriculum developers, and educators who wish to expand existing curricula through the development and integration of games into their work.
“The Letter after Your Name”: Party Labels on Virginia Ballots
Authors: Garlick Alex 
Published: April 2015

AbstractIn 2000, Virginia became the last state in the nation to add party labels to its ballots for state-level races. This article assesses the impact of this reform on citizen participation and the partisan behavior of down-ballot voters using precinct-level election returns. It finds that after the application of labels, roll-off in contested, down-ballot races dropped by about a percentage point, a reduction of approximately 15%. Roll-off dropped more in precincts with a larger share of African Americans. Also, the association between Republican vote shares in the Lt. Governor and state legislative races and presidential vote share in the 2000 general election became stronger in the presence of party labels. This result suggests that the labels made voters behave more as national partisans in state-level contests.
Temporal Change in the Density of State Interest Communities: 1980 to 2007
Authors: Lowery David , Gray Virginia , Cluverius John 
Published: April 2015

AbstractTwo very different kinds of models—cross-sectional models based on the logic of island biogeography and time series models of density dependence—are used to understand interest system density. While they share much in common, it is not at all clear how results derived from cross-sectional models are to be understood in terms of the temporal focus of the time series approach. Thus, the first purpose of this article is to more thoroughly think through how these two modeling strategies and their empirical findings are related to each other. We empirically assess several theoretical conjectures about the relationship of the two modeling strategies by adding a temporal element to the typical cross-sectional analysis of state interest systems via modeling density dependence pooled across four cross-sections from 1980, 1990, 1997, and 2007. By doing so, we add to the literature on state interest system density by examining how it has changed since 1980. Finally, we discuss the nature of this change and what it implies for the temporal development of state interest communities, the second focus of this analysis.
Advantage of impulse oscillometry over spirometry to diagnose chronic obstructive pulmonary disease and monitor pulmonary responses to bronchodilators: An observational study
Authors: Saadeh Constantine , Saadeh Charles , Cross Blake , Gaylor Michael , Griffith Melissa 
Published: April 2015

Objectives: This retrospective study was a comparative analysis of sensitivity of impulse oscillometry and spirometry techniques for use in a mixed chronic obstructive pulmonary disease group for assessing disease severity and inhalation therapy. Methods: A total of 30 patients with mild-to-moderate chronic obstructive pulmonary disease were monitored by impulse oscillometry, followed by spirometry. Lung function was measured at baseline after bronchodilation and at follow-up (3–18 months). The impulse oscillometry parameters were resistance in the small and large airways at 5 Hz (R5), resistance in the large airways at 15 Hz (R15), and lung reactance (area under the curve X; AX). Results: After the bronchodilator therapy, forced expiratory volume in 1 second (FEV1) readings evaluated by spirometry were unaffected at baseline and at follow-up, while impulse oscillometry detected an immediate improvement in lung function, in terms of AX ( p = 0.043). All impulse oscillometry parameters significantly improved at follow-up, with a decrease in AX by 37% ( p = 0.0008), R5 by 20% ( p = 0.0011), and R15 by 12% ( p = 0.0097). Discussion: Impulse oscillometry parameters demonstrated greater sensitivity compared with spirometry for monitoring reversibility of airway obstruction and the effect of maintenance therapy. Impulse oscillometry may facilitate early treatment dose optimization and personalized medicine for chronic obstructive pulmonary disease patients.
Temporal and technical variability of human gut metagenomes
Authors: Voigt Anita Y , Costea Paul I , Kultima Jens Roat , Li Simone S , Zeller Georg , Sunagawa Shinichi , Bork Peer 
Published: April 2015

Abstract
Background
Metagenomics has become a prominent approach for exploring the role of the gut microbiota in human health. However, the temporal variability of the healthy gut microbiome has not yet been studied in depth using metagenomics and little is known about the effects of different sampling and preservation approaches. We performed metagenomic analysis on fecal samples from seven subjects collected over a period of up to two years to investigate temporal variability and assess preservation-induced variation, specifically, fresh frozen compared to RNALater. We also monitored short-term disturbances caused by antibiotic treatment and bowel cleansing in one subject.

Results
We find that the human gut microbiome is temporally stable and highly personalized at both taxonomic and functional levels. Over multiple time points, samples from the same subject clustered together, even in the context of a large dataset of 888 European and American fecal metagenomes. One exception was observed in an antibiotic intervention case where, more than one year after the treatment, samples did not resemble the pre-treatment state. Clustering was not affected by the preservation method. No species differed significantly in abundance, and only 0.36% of gene families were differentially abundant between preservation methods.

Conclusions
Technical variability is small compared to the temporal variability of an unperturbed gut microbiome, which in turn is much smaller than the observed between-subject variability. Thus, short-term preservation of fecal samples in RNALater is an appropriate and cost-effective alternative to freezing of fecal samples for metagenomic studies.