bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of a Human-Like Low-Grade Bacteremia Model of Experimental Endocarditis To Study the Role of Staphylococcus aureus Adhesins and Platelet Aggregation in Early Endocarditis
Authors: Veloso Tiago Rafael , Chaouch Aziz , Roger Thierry , Giddey Marlyse , Vouillamoz Jacques , Majcherczyk Paul , Que Yok-Ai , Rousson Valentin , Moreillon Philippe , Entenza José Manuel 
Published: December 2012

ABSTRACTAnimal models of infective endocarditis (IE) induced by high-grade bacteremia revealed the pathogenic roles ofStaphylococcus aureussurface adhesins and platelet aggregation in the infection process. In humans, however,S. aureusIE possibly occurs through repeated bouts of low-grade bacteremia from a colonized site or intravenous device. Here we used a rat model of IE induced by continuous low-grade bacteremia to explore further the contributions ofS. aureusvirulence factors to the initiation of IE. Rats with aortic vegetations were inoculated by continuous intravenous infusion (0.0017 ml/min over 10 h) with 106CFU ofLactococcus lactispIL253 or a recombinantL. lactisstrain expressing an individualS. aureussurface protein (ClfA, FnbpA, BCD, or SdrE) conferring a particular adhesive or platelet aggregation property. Vegetation infection was assessed 24 h later. Plasma was collected at 0, 2, and 6 h postinoculation to quantify the expression of tumor necrosis factor (TNF), interleukin 1α (IL-1α), IL-1β, IL-6, and IL-10. The percentage of vegetation infection relative to that with strain pIL253 (11%) increased when binding to fibrinogen was conferred onL. lactis(ClfA strain) (52%;P= 0.007) and increased further with adhesion to fibronectin (FnbpA strain) (75%;P< 0.001). Expression of fibronectin binding alone was not sufficient to induce IE (BCD strain) (10% of infection). Platelet aggregation increased the risk of vegetation infection (SdrE strain) (30%). Conferring adhesion to fibrinogen and fibronectin favored IL-1β and IL-6 production. Our results, with a model of IE induced by low-grade bacteremia, resembling human disease, extend the essential role of fibrinogen binding in the initiation ofS. aureusIE. Triggering of platelet aggregation or an inflammatory response may contribute to or promote the development of IE.
History of the pharmaceutical use of pumice
Authors: Duffin Christopher J. 
Published: December 2012

Abstract
Pumice has been used as an abrasive with medical applications for over 2000 years. Introduced into traditional Chinese medicine in the mid-eighteenth century, it has been employed as part of a decoction (tea) in combination with a range of herbs and other geopharmaceuticals (including amber, cinnabar, mica and the bones of fossil vertebrates) in the treatment of gall bladder cancer, urinary conditions, dry and hacking coughs, and anxiety disorders. Pumice has had a relatively stable literary history in Western medicine. ‘Spuma maris’ (sea foam) has been a source of some confusion in classical literature, a situation exacerbated by some medieval revisionist texts. In a medical context, the term most commonly refers to pumice. Pumice has been employed since classical times in preparations acting as dentifrices, cleansers for ulcers (particularly of the skin and cornea), cicatrizing agents to help wounds scar efficiently, an active ingredient in eye ointments and powders in both farriery and human medicine, sneeze-inducing powders, and abrasives for removing body hair and assisting in the production of fine powders of resistant pharmaceutical ingredients.
Dietary Resveratrol Prevents Development of High-Grade Prostatic Intraepithelial Neoplastic Lesions: Involvement of SIRT1/S6K Axis
Authors: Li Guiming , Rivas Paul , Bedolla Roble , Thapa Dinesh , Reddick Robert L. , Ghosh Rita , Kumar Addanki P. 
Published: December 2012

Abstract
SIRT1 (mammalian ortholog of the yeast silent information regulator 2) is a NAD-dependent histone deacetylase belonging to the multigene family of sirtuins. Anecdotal and epidemiologic observations provide evidence for beneficial effects of the calorie restriction mimetic resveratrol (RES), a SIRT1 activator in preventing cardiovascular diseases and cancer. Although SIRT1 possesses both tumorigenic and antitumorigenic potential, the molecular mechanisms underlying SIRT1-mediated tumor progression or inhibition are poorly understood. In this study, we investigated the role of SIRT1 in multiple human prostate cancer cell lines and prostate-specific PTEN knockout mouse model using resveratrol. Androgen-independent prostate cancer cell lines (C42B, PC3, and DU145) express higher levels of SIRT1 than androgen-responsive (LNCaP) and nontumorigenic prostate cells (RWPE-1). Resveratrol enhanced this expression without any significant effect on SIRT1 enzymatic activity. Inhibition of SIRT1 expression using shRNA enhanced cell proliferation and inhibited autophagy by repressing phosphorylation of S6K and 4E-BP1. These biologic correlates were reversed in the presence of resveratrol. Analysis of prostates from dietary intervention with resveratrol showed a significant reduction in prostate weight and reduction in the incidence of high-grade prostatic intraepithelial neoplastic (HGPIN) lesions by approximately 54% with no significant change in body weight. Consistent with the in vitro findings, resveratrol intervention in the PTEN knockout mouse model was associated with reduction in the prostatic levels of mTOR complex 1 (mTORC1) activity and increased expression of SIRT1. These data suggest that SIRT1/S6K-mediated inhibition of autophagy drives prostate tumorigenesis. Therefore, modulation of SIRT1/S6K signaling represents an effective strategy for prostate cancer prevention. Cancer Prev Res; 6(1); 27–39. ©2012 AACR.
Genome-Wide Association Study Pinpoints a New Functional Apolipoprotein B Variant Influencing Oxidized Low-Density Lipoprotein Levels But Not Cardiovascular Events
Authors: Mäkelä Kari-Matti , Seppälä Ilkka , Hernesniemi Jussi A. , Lyytikäinen Leo-Pekka , Oksala Niku , Kleber Marcus E. , Scharnagl Hubert , Grammer Tanja B. , Baumert Jens , Thorand Barbara , Jula Antti , Hutri-Kähönen Nina , Juonala Markus , Laitinen Tomi , Laaksonen Reijo , Karhunen Pekka J. , Nikus Kjell C. , Nieminen Tuomo , Laurikka Jari , Kuukasjärvi Pekka , Tarkka Matti , Viik Jari , Klopp Norman , Illig Thomas , Kettunen Johannes , Ahotupa Markku , Viikari Jorma S.A. , Kähönen Mika , Raitakari Olli T. , Karakas Mahir , Koenig Wolfgang , Boehm Bernhard O. , Winkelmann Bernhard R. , März Winfried , Lehtimäki Terho 
Published: December 2012

Background—
Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events.

Methods and Results—

A discovery genome-wide association study was performed on a population of young healthy white individuals (N=2080), and the SNPs associated with a
P
<5×10
–8
were replicated in 2 independent samples (A: N=2912; B: N=1326). Associations with cardiovascular endpoints were also assessed with 2 additional clinical cohorts (C: N=1118; and D: N=808). We found 328 SNPs associated with oxidized low-density lipoprotein. The genetic variant rs676210 (Pro2739Leu) in apolipoprotein B was the proxy SNP behind all associations (
P
=4.3×10
–136
, effect size=13.2 U/L per allele). This association was replicated in the 2 independent samples (A and B,
P
=2.5×10
–47
and 1.1×10
–11
, effect sizes=10.3 U/L and 7.8 U/L, respectively). In the meta-analyses of cohorts A, C, and D (excluding cohort B without angiographic data), the top SNP did not associate significantly with the age of onset of angiographically verified coronary artery disease (hazard ratio=1.00 [0.94–1.06] per allele), 3-vessel coronary artery disease (hazard ratio=1.03 [0.94–1.13]), or myocardial infarction (hazard ratio=1.04 [0.96–1.12]).

Conclusions—
This novel genetic marker is an important factor regulating oxidized low-density lipoprotein levels but not a major genetic factor for the studied cardiovascular endpoints.
Muscle and Timing-specific Functional Connectivity between the Dorsolateral Prefrontal Cortex and the Primary Motor Cortex
Authors: Hasan Alkomiet , Galea Joseph M. , Casula Elias P. , Falkai Peter , Bestmann Sven , Rothwell John C. 
Published: December 2012

AbstractThe pFC has a crucial role in cognitive control, executive function, and sensory processing. Functional imaging, neurophysiological, and animal studies provide evidence for a functional connectivity between the dorsolateral pFC (DLPFC) and the primary motor cortex (M1) during free choice but not instructed choice selection tasks. In this study, twin coil, neuronavigated TMS was used to examine the precise timing of the functional interaction between human left DLPFC and ipsilateral M1 during the execution of a free/specified choice selection task involving the digits of the right hand. In a thumb muscle that was not involved in the task, a conditioning pulse to the left DLPFC enhanced the excitability of the ipsilateral M1 during free selection more than specified selection 100 msec after presentation of the cue; the opposite effect was seen at 75 msec. However, the difference between free and externally specified conditions disappeared when a task-specific muscle was investigated. In this case, the influence from DLPFC was dominated by task involvement rather than mode of selection, suggesting that other processes related to movement execution were also operating. Finally, we show that the effects were spatially specific because they were absent when an adjacent area of DLPFC was stimulated. These results reveal temporally and spatially selective interactions between BA 46 and M1 that are both task and muscle specific.
The Biology of Linguistic Expression Impacts Neural Correlates for Spatial Language
Authors: Emmorey Karen , McCullough Stephen , Mehta Sonya , Ponto Laura L. B. , Grabowski Thomas J. 
Published: December 2012

AbstractBiological differences between signed and spoken languages may be most evident in the expression of spatial information. PET was used to investigate the neural substrates supporting the production of spatial language in American Sign Language as expressed by classifier constructions, in which handshape indicates object type and the location/motion of the hand iconically depicts the location/motion of a referent object. Deaf native signers performed a picture description task in which they overtly named objects or produced classifier constructions that varied in location, motion, or object type. In contrast to the expression of location and motion, the production of both lexical signs and object type classifier morphemes engaged left inferior frontal cortex and left inferior temporal cortex, supporting the hypothesis that unlike the location and motion components of a classifier construction, classifier handshapes are categorical morphemes that are retrieved via left hemisphere language regions. In addition, lexical signs engaged the anterior temporal lobes to a greater extent than classifier constructions, which we suggest reflects increased semantic processing required to name individual objects compared with simply indicating the type of object. Both location and motion classifier constructions engaged bilateral superior parietal cortex, with some evidence that the expression of static locations differentially engaged the left intraparietal sulcus. We argue that bilateral parietal activation reflects the biological underpinnings of sign language. To express spatial information, signers must transform visual–spatial representations into a body-centered reference frame and reach toward target locations within signing space.
Frontoparietal Traffic Signals: A Fast Optical Imaging Study of Preparatory Dynamics in Response Mode Switching
Authors: Baniqued Pauline L. , Low Kathy A. , Fabiani Monica , Gratton Gabriele 
Published: December 2012

Abstract
Coordination between networks of brain regions is important for optimal cognitive performance, especially in attention demanding tasks. With the event-related optical signal (a measure of changes in optical scattering because of neuronal activity) we can characterize rapidly evolving network processes by examining the millisecond-scale temporal correlation of activity in distinct regions during the preparatory period of a response mode switching task. Participants received a precue indicating whether to respond vocally or manually. They then saw or heard the letter “L” or “R,” indicating a “left” or “right” response to be implemented with the appropriate response modality. We employed lagged cross-correlations to characterize the dynamic connectivity of preparatory processes. Our results confirmed coupling of frontal and parietal cortices and the trial-dependent relationship of the right frontal cortex with response preparation areas. The frontal-to-modality-specific cortex cross-correlations revealed a pattern in which first irrelevant regions were deactivated, and then relevant regions were activated. These results provide a window into the subsecond scale network interactions that flexibly tune to task demands.
Seeing It My Way or Your Way: Frontoparietal Brain Areas Sustain Viewpoint-independent Perspective Selection Processes
Authors: Ramsey Richard , Hansen Peter , Apperly Ian , Samson Dana 
Published: December 2012

AbstractA hallmark of human social interaction is the ability to consider other people's mental states, such as what they see, believe, or desire. Prior neuroimaging research has predominantly investigated the neural mechanisms involved in computing one's own or another person's perspective and largely ignored the question of perspective selection. That is, which brain regions are engaged in the process of selecting between self and other perspectives? To address this question, the current fMRI study used a behavioral paradigm that required participants to select between competing visual perspectives. We provide two main extensions to current knowledge. First, we demonstrate that brain regions within dorsolateral prefrontal and parietal cortices respond in a viewpoint-independent manner during the selection of task-relevant over task-irrelevant perspectives. More specifically, following the computation of two competing visual perspectives, common regions of frontoparietal cortex are engaged to select one's own viewpoint over another's as well as select another's viewpoint over one's own. Second, in the absence of conflict between the content of competing perspectives, we showed a reduced engagement of frontoparietal cortex when judging another's visual perspective relative to one's own. This latter finding provides the first brain-based evidence for the hypothesis that, in some situations, another person's perspective is automatically and effortlessly computed, and thus, less cognitive control is required to select it over one's own perspective. In doing so, we provide stronger evidence for the claim that we not only automatically compute what other people see but also, in some cases, we compute this even before we are explicitly aware of our own perspective.
Neuromodulation of Early Multisensory Interactions in the Visual Cortex
Authors: Convento Silvia , Vallar Giuseppe , Galantini Chiara , Bolognini Nadia 
Published: December 2012

Abstract
Merging information derived from different sensory channels allows the brain to amplify minimal signals to reduce their ambiguity, thereby improving the ability of orienting to, detecting, and identifying environmental events. Although multisensory interactions have been mostly ascribed to the activity of higher-order heteromodal areas, multisensory convergence may arise even in primary sensory-specific areas located very early along the cortical processing stream. In three experiments, we investigated early multisensory interactions in lower-level visual areas, by using a novel approach, based on the coupling of behavioral stimulation with two noninvasive brain stimulation techniques, namely, TMS and transcranial direct current stimulation (tDCS). First, we showed that redundant multisensory stimuli can increase visual cortical excitability, as measured by means of phosphene induction by occipital TMS; such physiological enhancement is followed by a behavioral facilitation through the amplification of signal intensity in sensory-specific visual areas. The more sensory inputs are combined (i.e., trimodal vs. bimodal stimuli), the greater are the benefits on phosphene perception. Second, neuroelectrical activity changes induced by tDCS in the temporal and in the parietal cortices, but not in the occipital cortex, can further boost the multisensory enhancement of visual cortical excitability, by increasing the auditory and tactile inputs from temporal and parietal regions, respectively, to lower-level visual areas.
Building Blocks of Visual Working Memory: Objects or Boolean Maps?
Authors: Shen Mowei , Yu Wenjun , Xu Xiaotian , Gao Zaifeng 
Published: December 2012

Abstract
The nature of the building blocks of information in visual working memory (VWM) is a fundamental issue that has not been well resolved. Most researchers take objects as the building blocks, although this perspective has received criticism. The objects could be physically separated ones (strict object hypothesis) or hierarchical objects created from separated individuals (broad object hypothesis). Meanwhile, a newly proposed Boolean map theory for visual attention suggests that Boolean maps may be the building blocks of VWM (Boolean map hypothesis); this perspective could explain many critical findings of VWM. However, no previous study has examined these hypotheses. We explored this issue by focusing on a critical point on which they make distinct predictions. We asked participants to remember two distinct objects (2-object), three distinct objects (3-object), or three objects with repeated information (mixed-3-object, e.g., one red bar and two green bars, green bars could be represented as one hierarchical object) and adopted contralateral delay activity (CDA) to tap into the maintenance phase of VWM. The mixed-3-object condition could generate two Boolean maps, three objects, or three objects most of the time (hierarchical objects are created in certain trials, retaining two objects). Simple orientations (Experiment 1) and colors (Experiments 2 and 3) were used as stimuli. Although the CDA of the mixed-3-object condition was slightly lower than that of the 3-object condition, no significant difference was revealed between them. Both conditions displayed significantly higher CDAs than the 2-object condition. These findings support the broad object hypothesis. We further suggest that Boolean maps might be the unit for retrieval/comparison in VWM.
Multiple Object Individuation and Exact Enumeration
Authors: Mazza Veronica , Pagano Silvia , Caramazza Alfonso 
Published: December 2012

AbstractExact computation of numerosity requires the selective individuation of the elements to be enumerated so that each element is counted once and only once. Such a mechanism should operate not only when the elements to be enumerated are presented in isolation but also when they are presented in cluttered scenes. To uncover the electrophysiological correlates of the level of object representation necessary for exact enumeration, we examined ERP measures during the execution of a target enumeration task. A variable number (1–4) of lateralized targets were presented with or without distracters on the target side. An early nonlateralized response (N1, 120–180 msec) was modulated by target numerosity only when presented without distracters. By contrast, the amplitudes of a lateralized and later response (N2pc, 180–300 msec) increased as a function of target numerosity both with and without distracters, reaching a plateau at three targets. We propose that the stage of processing reflected in the N2pc corresponds to the component of individuation that binds specific indexes to properties and locations and that this provides the representation type necessary for exact enumeration.
Origin and Demise of Socio-cultural Presentations of Self from Birth to Death: Caregiver ‘Scaffolding’ Practices Necessary for Guiding and Sustaining Communal Social Structure Throughout the Life Cycle
Authors: Cicourel Aaron V 
Published: December 2012

The emergence, social differentiation, and reproduction of human communities require socialization of the young. Socialization practices require caregivers and socially distributed, intuitive, normative knowledge systems to enable progeny to acquire and sustain habitual, socially organized skills and belief systems. Neurobiological, cognitive, emotional, and socio-cultural evolution enabled and paralleled the acquisition of communicative and socio-cultural skills indispensable for the emergence and reproduction of a sense of others. Stable adult capacities differentially weaken over the life cycle. This ‘reverse socialization’ means gradual loss of self, sense of others, and decline of routine practices necessary for reproduction of communal life. A modest corpus of data (10 minutes of discourse between six couples, two deemed ‘normal’, and four where one spouse diagnosed with Alzheimer’s Disease or Frontotemporal Dementia) is used to illustrate caregiver scaffolding simulation of appropriate socio-cultural interaction, illuminating the origin and demise of socio-cultural presentations of self from birth to death.
T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production
Authors: Riches John C. , Davies Jeffrey K. , McClanahan Fabienne , Fatah Rewas , Iqbal Sameena , Agrawal Samir , Ramsay Alan G. , Gribben John G. 
Published: December 2012

AbstractT-cell exhaustion, originally described in chronic viral infections, was recently reported in solid and hematologic cancers. It is not defined whether exhaustion contributes to T-cell dysfunction observed in chronic lymphocytic leukemia (CLL). We investigated the phenotype and function of T cells from CLL patients and age-matched controls. CD8+ and CD4+ T cells from CLL patients had increased expression of exhaustion markers CD244, CD160, and PD1, with expansion of a PD1+BLIMP1HI subset. These molecules were most highly expressed in the expanded population of effector T cells in CLL. CLL CD8+ T cells showed functional defects in proliferation and cytotoxicity, with the cytolytic defect caused by impaired granzyme packaging into vesicles and nonpolarized degranulation. In contrast to virally induced exhaustion, CLL T cells showed increased production of interferon-γ and TNFα and increased expression of TBET, and normal IL2 production. These defects were not restricted to expanded populations of cytomegalovirus (CMV)–specific cells, although CMV seropositivity modulated the distribution of lymphocyte subsets, the functional defects were present irrespective of CMV serostatus. Therefore, although CLL CD8+ T cells exhibit features of T-cell exhaustion, they retain the ability to produce cytokines. These findings also exclude CMV as the sole cause of T-cell defects in CLL.