bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of synaptic input by GABAB receptors improves coincidence detection for computation of sound location
Authors: Fischl Matthew J. , Combs T. Dalton , Klug Achim , Grothe Benedikt , Burger R. Michael 
Published: April 2012

Key points
Organisms localise low frequencies using interaural time disparities (ITDs) in which specialized neurones in the medial superior olive (MSO) compute submillisecond differences in arrival time of sounds to each ear, a value that varies systematically with sound location.
These neurones compute sound location over a 1012 fold range in sound intensities, despite large intensity‐dependent changes in input strength. Modulation of synaptic gain has been suggested as a mechanism to maintain accurate ITD processing.
Here we show that activation of GABAB receptors suppresses both the excitatory and inhibitory inputs to the MSO and alters the kinetics of inhibitory synaptic currents.
Using in vitro physiological methods and computational modelling, we show that the modulation by GABAB receptor activation contributes to spatial tuning of MSO neurones.
These results contribute to the understanding of how neurones maintain computational stability under widely varying input conditions.
Abstract  Interaural time disparities (ITDs) are the primary cues for localisation of low‐frequency sound stimuli. ITDs are computed by coincidence‐detecting neurones in the medial superior olive (MSO) in mammals. Several previous studies suggest that control of synaptic gain is essential for maintaining ITD selectivity as stimulus intensity increases. Using acute brain slices from postnatal day 7 to 24 (P7–P24) Mongolian gerbils, we confirm that activation of GABAB receptors reduces the amplitude of excitatory and inhibitory synaptic currents to the MSO and, moreover, show that the decay kinetics of IPSCs are slowed in mature animals. During repetitive stimuli, activation of GABAB receptors reduced the amount of depression observed, while PSC suppression and the slowed kinetics were maintained. Additionally, we used physiological and modelling approaches to test the potential impact of GABAB activation on ITD encoding in MSO neurones. Current clamp recordings from MSO neurones were made while pharmacologically isolated excitatory inputs were bilaterally stimulated using pulse trains that simulate ITDs in vitro. MSO neurones showed strong selectivity for bilateral delays. Application of both GABAB agonists and antagonists demonstrate that GABAB modulation of synaptic input can sharpen ITD selectivity. We confirmed and extended these results in a computational model that allowed for independent manipulation of each GABAB‐dependent effect. Modelling suggests that modulation of both amplitude and kinetics of synaptic inputs by GABAB receptors can improve precision of ITD computation. Our studies suggest that in vivo modulation of synaptic input by GABAB receptors may act to preserve ITD selectivity across various stimulus conditions.
Influence of Antituberculosis Drug Resistance and Mycobacterium tuberculosis Lineage on Outcome in HIV-Associated Tuberculous Meningitis
Authors: Tho Dau Quang , Török M. Estée , Yen Nguyen Thi Bich , Bang Nguyen Duc , Lan Nguyen Thi Ngoc , Kiet Vo Sy , van Vinh Chau Nguyen , Dung Nguyen Huy , Day Jeremy , Farrar Jeremy , Wolbers Marcel , Caws Maxine 
Published: April 2012

ABSTRACT

HIV-associated tuberculous meningitis (TBM) has high mortality. Aside from the devastating impact of multidrug resistance (MDR) on survival, little is understood about the influence of other bacterial factors on outcome. This study examined the influence of
Mycobacterium tuberculosis
drug resistance, bacterial lineage, and host vaccination status on outcome in patients with HIV-associated TBM.
Mycobacterium tuberculosis
isolates from the cerebrospinal fluid of 186 patients enrolled in two studies of HIV-associated TBM in Ho Chi Minh City, Vietnam, were tested for resistance to first-line antituberculosis drugs. Lineage genotyping was available for 122 patients. The influence of antituberculosis drug resistance and
M. tuberculosis
lineage on 9-month mortality was analyzed using Kaplan-Meier survival analysis and Cox multiple regression models. Isoniazid (INH) resistance without rifampin resistance was associated with increased mortality (adjusted hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.18 to 2.66;
P
= 0.005), and multidrug resistance was uniformly fatal (
n
= 8/8; adjusted HR, 5.21, 95% CI, 2.38 to 11.42;
P
< 0.0001). The hazard ratio for INH-resistant cases was greatest during the continuation phase of treatment (after 3 months; HR, 5.05 [95% CI, 2.23 to 11.44];
P
= 0.0001). Among drug-susceptible cases, patients infected with the “modern” Beijing lineage strains had lower mortality than patients infected with the “ancient” Indo-Oceanic lineage (HR, 0.29 [95% CI, 0.14 to 0.61];
P
= 0.001). Isoniazid resistance, multidrug resistance, and
M. tuberculosis
lineage are important determinants of mortality in patients with HIV-associated TBM. Interventions which target these factors may help reduce the unacceptably high mortality in patients with TBM.
Antischistosomal Activities of Mefloquine-Related Arylmethanols
Authors: Ingram Katrin , Ellis William , Keiser Jennifer 
Published: April 2012

ABSTRACT

Interesting antischistosomal properties have been documented for the antimalarial mefloquine, a 4-quinolinemethanol. We evaluated the antischistosomal activities of nine mefloquine-related compounds belonging to the 4-pyridinemethanols, 9-phenanthrenmethanols, and 4-quinolinemethanols. Eight compounds revealed high activities against
Schistosoma mansoni in vitro
, with two drugs (the 4-quinolinemethanols WR7573 and WR7930) characterized by significantly lower half-maximal inhibitory concentrations (IC
50
s) (2.7 and 3.5 μM, respectively) compared to mefloquine (11.4 μM). Mefloquine and WR7930 showed significantly decreased IC
50
s when incubated in the presence of hemoglobin. High worm burden reductions (WBR) were obtained with enpiroline (WBR, 82.7%; dosage, 200 mg/kg of body weight) and its
threo
isomers (+)-
threo
(WBR, 100%) and (−)-
threo
(WBR, 89%) and with WR7930 (WBR, 87%; dosage, 100 mg/kg) against adult
S. mansoni
in mice. Furthermore, excellent
in vitro
and
in vivo
antischistosomal activity was observed for two WR7930-related structures (WR29252 and WR7524). In addition, mefloquine (WBR, 81%), enpiroline (WBR, 77%), and WR7930 (WBR, 100%) showed high activities against
S. haematobium
harbored in mice following single oral doses of 200 mg/kg. These results provide a deeper insight into the structural features of the arylmethanols that rule antischistosomal activity. Further studies should be launched with enpiroline and WR7930.
Contribution of Bordetella Filamentous Hemagglutinin and Adenylate Cyclase Toxin to Suppression and Evasion of Interleukin-17-Mediated Inflammation
Authors: Henderson Michael W. , Inatsuka Carol S. , Sheets Amanda J. , Williams Corinne L. , Benaron David J. , Donato Gina M. , Gray Mary C. , Hewlett Erik L. , Cotter Peggy A. 
Published: April 2012

ABSTRACTBordetella pertussisandBordetella bronchisepticaestablish respiratory infections with notorious efficiency. Our previous studies showed that thefhaBgenes ofB. pertussisandB. bronchiseptica, which encode filamentous hemagglutinin (FHA), are functionally interchangeable and provided evidence that FHA-deficientB. bronchisepticainduces more inflammation in the lungs of mice than wild-typeB. bronchiseptica. We show here that the robust inflammatory response to FHA-deficientB. bronchisepticais characterized by the early and sustained influx of interleukin-17 (IL-17)-positive neutrophils and macrophages and, at 72 h postinoculation, IL-17-positive CD4+T cells, suggesting that FHA allows the bacteria to suppress the development of an IL-17-mediated inflammatory response. We also show that thecyaAgenes ofB. pertussisandB. bronchiseptica, which encode adenylate cyclase toxin (ACT), are functionally interchangeable and that ACT, specifically its catalytic activity, is required forB. bronchisepticato resist phagocytic clearance but is neither required for nor inhibitory of the induction of inflammation if bacteria are present in numbers sufficient to persist during the first 3 days postinoculation. Incubation of bone marrow-derived macrophages with a ΔcyaAstrain caused decreased production of IL-1β and increased production of tumor necrosis factor alpha (TNF-α) and IL-12, while incubation with a ΔcyaAΔfhaBstrain caused increased production of IL-23. These data suggest that FHA and ACT both contribute to suppress the recruitment of neutrophils and the development of an IL-17-mediated immune response. To our knowledge, this is the first demonstration of a microbial pathogen suppressing IL-17-mediated inflammationin vivoas a strategy to evade innate immunity.
Entamoeba histolytica Cell Surface Calreticulin Binds Human C1q and Functions in Amebic Phagocytosis of Host Cells
Authors: Vaithilingam Archana , Teixeira Jose E. , Miller Peter J. , Heron Bradley T. , Huston Christopher D. 
Published: April 2012

ABSTRACTPhagocytosis of host cells is characteristic of tissue invasion by the intestinal amebaEntamoeba histolytica, which causes amebic dysentery and liver abscesses.Entamoeba histolyticainduces host cell apoptosis and uses ligands, including C1q, on apoptotic cells to engulf them. Two mass spectrometry analyses identified calreticulin in amebic phagosome preparations, and, in addition to its function as an endoplasmic reticulum chaperone, calreticulin is believed to be the macrophage receptor for C1q. The purpose of this study was to determine if calreticulin functions as anE. histolyticaC1q receptor during phagocytosis of host cells. Calreticulin was localized to the surface ofE. histolyticaduring interaction with both Jurkat lymphocytes and erythrocytes and was present in over 75% of phagocytic cups during amebic erythrophagocytosis. Presence of calreticulin on the cell surface was further demonstrated using a method that selectively biotinylated cell surface proteins and by flow cytometry using trophozoites overexpressing epitope-tagged calreticulin. Regulated overexpression of calreticulin increasedE. histolytica's ability to phagocytose apoptotic lymphocytes and calcium ionophore-treated erythrocytes but had no effect on amebic adherence to or destruction of cell monolayers or surface expression of the GalNAc lectin and serine-richE. histolyticaprotein (SREHP) receptors. Finally,E. histolyticacalreticulin bound specifically to apoptotic lymphocytes and to human C1q. Collectively, these data implicate cell surface calreticulin as a receptor for C1q duringE. histolyticaphagocytosis of host cells.
Reactive Oxygen Species-Triggered Trophoblast Apoptosis Is Initiated by Endoplasmic Reticulum Stress via Activation of Caspase-12, CHOP, and the JNK Pathway in Toxoplasma gondii Infection in Mice
Authors: Xu Xiucai , Liu Tingting , Zhang Aimei , Huo Xingxing , Luo Qingli , Chen Zhaowu , Yu Li , Li Qing , Liu Lili , Lun Zhao-rong , Shen Jilong 
Published: April 2012

ABSTRACT

Toxoplasma gondii
infection in pregnant women may result in abortion or in fetal teratogenesis; however, the underlying mechanisms are still unclear. In this paper, based on a murine model, we showed that maternal infection with RH strain
T. gondii
tachyzoites induced elevated production of reactive oxygen species (ROS), local oxidative stress, and subsequent apoptosis of placental trophoblasts. PCR array analysis of 84 oxidative stress-related genes demonstrated that 27 genes were upregulated at least 2-fold and that 9 genes were downregulated at least 2-fold in the
T. gondii
infection group compared with levels in the control group. The expression of NADPH oxidase 1 (Nox1) and glutathione peroxidase 6 (Gpx6) increased significantly, about 25-fold. The levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) increased significantly with
T. gondii
infection, and levels of glutathione (GSH) decreased rapidly.
T. gondii
infection increased the early expression of endoplasmic reticulum stress (ERS) markers, followed by cleavage of caspase-12, activation of ASK1/JNK, and increased apoptosis of trophoblasts, both
in vivo
and
in vitro
. The apoptosis of trophoblasts, the activation of caspase-12 and the ASK1/JNK pathway, and the production of peroxides were dramatically inhibited by pretreatment with
N
-acetylcysteine (NAC). The upregulation of Nox1 was contact dependent and preceded the increase in levels of ERS markers and the activation of the proapoptosis cascade. Thus, we concluded that apoptosis in placental trophoblasts was initiated predominantly by ROS-mediated ERS via activation of caspase-12, CHOP, and the JNK pathway in acute
T. gondii
infection. Elevated ROS production is the central event in
T. gondii
-induced apoptosis of placental trophoblasts.
Retrospective study of 155 cases of prolapse of the nictitating membrane gland in dogs
Authors: Mazzucchelli S. , Vaillant M. D. , Wéverberg F. , Arnold‐Tavernier H. , Honegger N. , Payen G. , Vanore M. , Liscoet L. , Thomas O. , Clerc B. , Chahory S. 
Published: April 2012

A retrospective study of 155 cases (114 dogs). The breed, sex and age at the time of the first and opposite onset of nictitans gland prolapse were recorded. Long‐term follow‐up with a minimum of one‐year duration was performed by telephone conversations. One hundred and fourteen dogs representing 155 nictitans gland prolapses were included. 75.4 per cent of the first prolapse occur before one year of age. Unilateral nictitans gland prolapse was observed in 64 per cent of cases. When the condition was bilateral, it occurred simultaneously in 41.4 per cent. When it was bilateral but not simultaneous (24/41), the opposite gland prolapse occurred within three months in 70.8 per cent of the cases. Five breeds were most commonly affected by the bilateral condition: French bulldog, shar pei, great dane, English bulldog and cane corso.
When Prefetching Works, When It Doesn’t, and Why
Authors: Lee Jaekyu , Kim Hyesoon , Vuduc Richard 
Published: April 2012

In emerging and future high-end processor systems, tolerating increasing cache miss latency and properly managing memory bandwidth will be critical to achieving high performance. Prefetching, in both hardware and software, is among our most important available techniques for doing so; yet, we claim that prefetching is perhaps also the least well-understood.
Thus, the goal of this study is to develop a novel, foundational understanding of both the benefits and limitations of hardware and software prefetching. Our study includes: source code-level analysis, to help in understanding the practical strengths and weaknesses of compiler- and software-based prefetching; a study of the synergistic and antagonistic effects between software and hardware prefetching; and an evaluation of hardware prefetching training policies in the presence of software prefetching requests. We use both simulation and measurement on real systems. We find, for instance, that although there are many opportunities for compilers to prefetch much more aggressively than they currently do, there is also a tangible risk of interference with training existing hardware prefetching mechanisms. Taken together, our observations suggest new research directions for cooperative hardware/software prefetching.
Secure reconfiguration of software-defined radio
Authors: Li Chunxiao , Jha Niraj K. , Raghunathan Anand 
Published: April 2012

Software-defined radio (SDR) implements a radio system in software that executes on a programmable processor. The components of SDR, such as the filters, amplifiers, and modulators, can be easily reconfigured to adapt to the operating environment and user preferences. However, the flexibility of radio reconfiguration brings along the serious security concern of malicious modification of software in the SDR system, leading to radio malfunction and interference with other users' communications. Both the SDR device and the network need to be protected from such malicious radio reconfiguration.
In this article, a new architecture targeted at protecting SDR devices from malicious reconfiguration is proposed. The architecture is based on robust separation of the radio operation environment and user application environment, through the use of virtualization. A new radio middleware layer is designed to securely intercept all attempts to reconfigure the radio, and a security policy monitor checks the target configuration against security policies that represent the interests of various parties. Even if the operating system in the user application environment is compromised, the proposed architecture can ensure secure reconfiguration in the radio operation environment. We have prototyped the proposed secure SDR architecture using VMware and the GNU Radio toolkit and demonstrate that overheads incurred by the architecture are small and tolerable. Therefore, we believe that the proposed solution could be applied to address secure SDR reconfiguration in both general-purpose and embedded computing systems.
A Comparison of Inner and Outer Spiral Rainbands in a Numerically Simulated Tropical Cyclone
Authors: Li Qingqing , Wang Yuqing 
Published: April 2012

Abstract
The simulated inner and outer spiral rainbands in a tropical cyclone are compared in this study. The inner rainbands are generally active immediately outside the eyewall in the rapid filamentation zone, while the outer rainbands are active in regions outside about 3 times the radius of maximum wind. The inner rainbands are characterized by the convectively coupled vortex Rossby waves. The movement of the outer rainbands follows the low-level vector winds associated with the azimuthally averaged low-level flow and the radially outward cross-band flow caused by the downdraft-induced cold pool in the boundary layer. Convective cells in outer rainbands are typical of convective systems and move cyclonically and radially outward (inward) at large (small) radii.
Net upward vertical mass transports (VMTs) appear throughout the depth of the troposphere in the whole inner-rainband region, while net downward VMTs are found below 4-km height in the outer-rainband region. In the whole inner-rainband region, only a very shallow layer with net horizontal convergence appears below 2-km height, while a deep layer with net convergence is found below 7.5-km height with net divergence aloft in the outer-rainband region. The inner rainband shows two tangential wind maxima, respectively, located near the top of the inflow boundary layer and immediately below the upper-tropospheric outflow layer. A secondary horizontal wind maximum occurs at about 4-km height on the inner edge of the outer rainband. Distinct features of the upwind, middle, and downwind sectors of the outer rainband are also discussed.
Integrative Analysis in Oral Squamous Cell Carcinoma Reveals DNA Copy Number–Associated miRNAs Dysregulating Target Genes
Authors: Serrano Nicholas A. , Xu Chang , Liu Yan , Wang Pei , Fan Wenhong , Upton Melissa P. , Houck John R. , Lohavanichbutr Pawadee , Kao Michael , Zhao Lue Ping , Schwartz Stephen M. , Chen Chu , Méndez Eduardo 
Published: April 2012

ObjectiveTo better understand possible mechanisms involved in the dysregulation of gene expression unique to oral squamous cell carcinoma (OSCC) metastasis, the investigators examined the differential expression of microRNAs (miRNAs) in OSCC metastasis and their functional impact on target gene expression.Study DesignObservational assessment of DNA copy number, miRNA, and RNA expression in primary and metastatic OSCC.SettingUniversity of Washington Medical Center and affiliated hospitals.SubjectsTumor samples were taken from patients with primary incident OSCC; cells were laser‐capture microdissected from 17 nonmetastatic primary tumors and 20 metastatic lymph nodes.MethodsDNA copy number aberrations and gene expression profiles were previously determined using Affymetrix 250K Nsp I SNP arrays and HU133 plus 2.0 expression arrays. miRNAs were interrogated with Exiqon’s Ready‐to‐Use PCR Panels assessing the expression of 368 human miRNAs.ResultsInvestigators found 31 miRNAs differentially expressed between metastatic and nonmetastatic samples (false discovery rate <0.4; 26 overexpressed and 5 underexpressed in metastatic samples). Expression of 7 of these miRNAs was significantly associated with their DNA copy numbers, and expressions of 8 of these miRNAs were significantly associated with their target genes. Among these unique miRNAs, miR‐140‐3p, miR‐29c, and miR‐29a were differentially expressed in metastasis versus nonmetastatic samples and had a strong positive correlation with their DNA copy numbers and a negative correlation with the expression of their target genes.ConclusionResults suggest that DNA copy number aberration may play a role in the dysregulation of some differentially expressed miRNAs in OSCC metastasis, warranting further investigation.
Quantitative Crawling Wave Sonoelastography of Benign and Malignant Thyroid Nodules
Authors: Walsh Jonathan , An Liwei , Mills Brad , Hah Zaegyoo , Moalem Jacob , Miller Matthew , Giampoli Ellen , Parker Kevin , Rubens Deborah 
Published: April 2012

ObjectiveThe purpose of this study is to determine if crawling wave elastography, a novel sonoelastography technique, can be used to provide quantitative measurements of thyroid tissue shear velocity (a measure of tissue stiffness) and distinguish between benign and malignant thyroid nodules.Study DesignDiagnostic test assessment.SettingAcademic university.Subjects and MethodsFresh thyroid specimens (n = 20) with 44 regions of interest were imaged ex vivo with crawling wave sonoelastography over a 9‐month period in 2010 at a single institution. Using the sonoelastography technique, shear velocity estimations and contrast‐to‐noise ratios were calculated. The higher the shear velocity (SV) and contrast‐to‐noise ratio (CNR), the greater the tissue stiffness. Histological diagnosis was correlated with shear velocity and contrast‐to‐noise ratio values.ResultsBoth the shear velocity and contrast‐to‐noise values of papillary thyroid carcinoma (n = 10, CNR = 5.29, SV = 2.45 m/s) were significantly higher than benign nodules (n = 22, CNR = −0.41, SV = 1.90 m/s). There is a maximum sensitivity and specificity of 100% and 90.9%, respectively, for differentiating papillary thyroid carcinoma from benign nodules using contrast‐to‐noise ratio values. There is a maximum sensitivity and specificity of 83.3% and 72.7%, respectively, for differentiating papillary thyroid carcinoma from benign nodules using shear velocity values. Insufficient samples were obtained for comparison with other histological types.ConclusionCrawling wave sonoelastography can provide quantitative estimations of shear velocity, thereby depicting the elastic properties of thyroid nodules. The shear velocity and contrast‐to‐noise ratio can differentiate between benign thyroid nodules and papillary thyroid carcinoma with high specificity and sensitivity.