bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of Colitis-Associated Colorectal Cancer with 8-Hydroxydeoxyguanosine
Authors: Ock Chan Young , Kim Eun-Hee , Hong Hua , Hong Kyung Sook , Han Young-Min , Choi Ki-Seok , Hahm Ki-Baik , Chung Myung-Hee 
Published: July 2011

Abstract
Colitis-associated cancer (CAC) is one of clear examples of inflammation–carcinogenesis sequence, by which the strict control of colitis with potent anti-inflammatory or antioxidative agent offers the chance of cancer prevention. Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1–STAT3 and COX–NF-κB pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC. Before commencing carcinogenesis model, we checked whether exogenous 8-OHdG can alleviate IBD, for which interleukin (IL)-10 knockout mice were designed to ingest 5% DSS for 1 week, and 8-OHdG is given through intraperitoneal route daily. 8-OHdG treatment groups significantly reduced pathologic grade of DSS-induced colitis as well as various inflammatory mediators such as TNF-α, IL-6, COX-2, and iNOS in a dose-dependent manner. To document the cancer prevention effects of 8-OHdG, mice were injected azoxymethane followed by drinking 2.5% DSS for 1 week, after which 8-OHdG–containing diets were given for 20 weeks. As results, mice that consumed 8-OHdG–containing diet significantly reduced both tumor incidence and multiplicity. Rac1 activity and phosphorylated STAT3 level were significantly attenuated in the 8-OHdG–treated group. Significantly decreased levels of malondialdehyde, monocyte chemotactic protein-1, matrix metalloproteinasess, COX-2, NOX4, and β-catenin nuclear accumulation were responsible for cancer prevention effects of exogenous 8-OHdG. In conclusion, we clearly showed cancer-preventive effect of exogenous 8-OHdG against CAC. Cancer Prev Res; 4(9); 1507–21. ©2011 AACR.
Neural Correlates of Confidence during Item Recognition and Source Memory Retrieval: Evidence for Both Dual-process and Strength Memory Theories
Authors: Hayes Scott M. , Buchler Norbou , Stokes Jared , Kragel James , Cabeza Roberto 
Published: July 2011

Abstract
Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval.
Attention Modulates Maintenance of Representations in Visual Short-term Memory
Authors: Kuo Bo-Cheng , Stokes Mark G. , Nobre Anna Christina 
Published: July 2011

Abstract
Recent studies have shown that selective attention is of considerable importance for encoding task-relevant items into visual short-term memory (VSTM) according to our behavioral goals. However, it is not known whether top–down attentional biases can continue to operate during the maintenance period of VSTM. We used ERPs to investigate this question across two experiments. Specifically, we tested whether orienting attention to a given spatial location within a VSTM representation resulted in modulation of the contralateral delay activity (CDA), a lateralized ERP marker of VSTM maintenance generated when participants selectively encode memory items from one hemifield. In both experiments, retrospective cues during the maintenance period could predict a specific item (spatial retrocue) or multiple items (neutral retrocue) that would be probed at the end of the memory delay. Our results revealed that VSTM performance is significantly improved by orienting attention to the location of a task-relevant item. The behavioral benefit was accompanied by modulation of neural activity involved in VSTM maintenance. Spatial retrocues reduced the magnitude of the CDA, consistent with a reduction in memory load. Our results provide direct evidence that top–down control modulates neural activity associated with maintenance in VSTM, biasing competition in favor of the task-relevant information.
Observing Degradation of Visual Representations over Short Intervals When Medial Temporal Lobe Is Damaged
Authors: Warren David E. , Duff Melissa C. , Tranel Daniel , Cohen Neal J. 
Published: July 2011

Abstract
Medial temporal lobe (MTL) contributions to the brief maintenance of visual representations were evaluated by studying a group of patients with MTL damage. Eye movements of patients and healthy comparison subjects were tracked while performing a visual search for a target among complex stimuli of varying similarity to that target. Despite the task having no imposed delays, patients were impaired behaviorally, and eye movement measures showed abnormally rapid degradation of target representations in the patients. Eye movement data showed a modulation of the duration of fixations as a function of the similarity of fixated array lures to the target, but the effect was attenuated in patients during long fixation paths away from the sample target. This effect manifested despite patients' shorter searches and more frequent fixations of the sample target. Novel techniques provided unique insight into visual representation without healthy MTL, which may support maintenance of information through hippocampal-dependent relational binding.
Vigor in the Face of Fluctuating Rates of Reward: An Experimental Examination
Authors: Guitart-Masip Marc , Beierholm Ulrik R. , Dolan Raymond , Duzel Emrah , Dayan Peter 
Published: July 2011

Abstract
Two fundamental questions underlie the expression of behavior, namely what to do and how vigorously to do it. The former is the topic of an overwhelming wealth of theoretical and empirical work particularly in the fields of reinforcement learning and decision-making, with various forms of affective prediction error playing key roles. Although vigor concerns motivation, and so is the subject of many empirical studies in diverse fields, it has suffered a dearth of computational models. Recently, Niv et al. [Niv, Y., Daw, N. D., Joel, D., & Dayan, P. Tonic dopamine: Opportunity costs and the control of response vigor. Psychopharmacology (Berlin), 191, 507–520, 2007] suggested that vigor should be controlled by the opportunity cost of time, which is itself determined by the average rate of reward. This coupling of reward rate and vigor can be shown to be optimal under the theory of average return reinforcement learning for a particular class of tasks but may also be a more general, perhaps hard-wired, characteristic of the architecture of control. We, therefore, tested the hypothesis that healthy human participants would adjust their RTs on the basis of the average rate of reward. We measured RTs in an odd-ball discrimination task for rewards whose magnitudes varied slowly but systematically. Linear regression on the subjects' individual RTs using the time varying average rate of reward as the regressor of interest, and including nuisance regressors such as the immediate reward in a round and in the preceding round, showed that a significant fraction of the variance in subjects' RTs could indeed be explained by the rate of experienced reward. This validates one of the key proposals associated with the model, illuminating an apparently mandatory form of coupling that may involve tonic levels of dopamine.
Division of Labor between Lateral and Ventral Extrastriate Representations of Faces, Bodies, and Objects
Authors: Taylor John C. , Downing Paul E. 
Published: July 2011

AbstractThe occipito-temporal cortex is strongly implicated in carrying out the high-level computations associated with vision. In human neuroimaging studies, focal regions are consistently found within this broad region that respond strongly and selectively to faces, bodies, or objects. A notable feature of these selective regions is that they are found in pairs. In the posterior-lateral occipito-temporal cortex, focal selectivity is found for faces (occipital face area), bodies (extrastriate body area), and objects (lateral occipital). These three areas are found bilaterally and at close quarters to each other. Likewise, in the ventro-medial occipito-temporal cortex, three similar category-selective regions are found, also in proximity to each other: for faces (fusiform face area), bodies (fusiform body area), and objects (posterior fusiform). Here we review some of the extensive evidence on the functional properties of these areas with two aims. First, we seek to identify principles that distinguish the posterior-lateral and ventro-medial clusters of selective regions but that apply generally within each cluster across the three stimulus kinds. Our review identifies and elaborates several principles by which these relationships hold. In brief, the posterior-lateral representations are more primitive, local, and stimulus-driven relative to the ventro-medial representations, which in contrast are more invariant to visual features, global, and linked to the subjective percept. Second, because the evidence base of studies that compare both posterior-lateral and ventro-medial representations of faces, bodies, and objects is still relatively small, we seek to provoke more cross-talk among the research strands that are traditionally separate. We identify several promising approaches for such future work.
Opposite Effects of Cortisol on Consolidation of Temporal Sequence Memory during Waking and Sleep
Authors: Wilhelm Ines , Wagner Ullrich , Born Jan 
Published: July 2011

Abstract
Memory functions involve three stages: encoding, consolidation, and retrieval. Modulating effects of glucocorticoids (GCs) have been consistently observed for declarative memory with GCs enhancing encoding and impairing retrieval, but surprisingly, little is known on how GCs affect memory consolidation. Studies in rats suggest a beneficial effect of GCs that were administered during postlearning wake periods, whereas in humans, cortisol impaired memory consolidation when administered during postlearning sleep. These inconsistent results raise the question whether effects of GCs critically depend on the brain state during consolidation (sleep vs. wake). Here, we compare for the first time directly the effects of cortisol on memory consolidation during postlearning sleep and wakefulness in different measures of declarative memory. Cortisol (13 mg vs. placebo) was intravenously infused during a postlearning nap or a time-matched period of wakefulness after participants had encoded neutral and emotional text material. Memory for the texts was tested (a) by asking for the contents of the texts (“item” memory) and (b) for the temporal order of the contents within the texts (“relational” memory). Neither postlearning infusion of cortisol during sleep nor during wakefulness affected retention of content words of emotional or neutral texts. Critically, however, the retention of temporal order within the texts, known to rely most specifically on the hippocampus proper within the medial-temporal lobe memory system, was distinctly improved by cortisol infusion during the wake phase but impaired by cortisol during sleep. These results point toward fundamentally different mechanisms of hippocampal memory consolidation, depending on the brain state.
EGFR inhibitors as first-line therapy in EGFR mutation-positive patients with NSCLC
Authors: Gorden Kimberly J , Mesbah Parvin , Kolesar Jill M 
Published: July 2011

Purpose: The purpose of this review article is to describe the recent data supporting the use of epidermal growth factor receptor (EGFR) receptor tyrosine kinase inhibitors (TKIs) in the first-line setting of EGFR mutation-positive non-small cell lung cancer (NSCLC). Summary: EGFR receptor TKIs were originally developed in unselected NSCLC patients and demonstrated modest clinical benefit compared to placebo. With the discovery of improved benefits in the approximately 16% of NSCLC patients with an EGFR mutation, trials in selected populations were undertaken, demonstrating comparable efficacy to standard chemotherapy with an improved toxicity profile. The most common toxicity is rash, sometimes requiring dose adjustment and discontinuation and the most serious toxicity is interstitial lung disease, which occurs in about 1% of patients treated with EGFR receptor TKIs and is fatal in 30% who develop this toxicity. Conclusion: The EGFR receptor TKIs are an effective therapy in EGFR-mutated NSCLC and are recommended as first-line therapy for those with advanced or metastatic disease.
Pervasive Refusal Syndrome
Authors: Wright Barry , Beverley David 
Published: July 2011

We report here on a case of severe pervasive refusal syndrome. This is of interest for three reasons. Firstly, most reported cases are adolescent girls; our case is regarding an adolescent boy. Secondly, he was successfully treated at home and thirdly, the serology showed an apparent infective pre-cursor to the illness with evidence of possible autoimmune serology. A 14-year old boy deteriorated from a picture where diagnosed CFS/ME developed into Pervasive Refusal Syndrome. This included the inability to move or speak, with closed eyes, multiple tics, facial grimacing, heightened sensitivity to noise (hyperacusis) and touch (hyperaesthesia), and inability or unwillingness to eat anything except small amounts of sloppy food. Successful rehabilitation is reported. Finally the issue of nomenclature is discussed, raising the question whether Pervasive Refusal Syndrome would be better renamed in a way that does not imply that the condition is always volitional and oppositional, as this can distract focus away from an alliance between family and clinicians.
Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors
Authors: Pronier Elodie , Almire Carole , Mokrani Hayat , Vasanthakumar Aparna , Simon Audrey , da Costa Reis Monte Mor Barbara , Massé Aline , Le Couédic Jean-Pierre , Pendino Frédéric , Carbonne Bruno , Larghero Jérôme , Ravanat Jean-Luc , Casadevall Nicole , Bernard Olivier A. , Droin Nathalie , Solary Eric , Godley Lucy A. , Vainchenker William , Plo Isabelle , Delhommeau François 
Published: July 2011

Abstract
TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is frequently mutated in myeloid malignancies, including myeloproliferative neoplasms. Here we show that the level of 5-hmC is decreased in granulocyte DNA from myeloproliferative neoplasm patients with TET2 mutations compared with granulocyte DNA from healthy patients. Inhibition of TET2 by RNA interference decreases 5-hmC levels in both human leukemia cell lines and cord blood CD34+ cells. These results confirm the enzymatic function of TET2 in human hematopoietic cells. Knockdown of TET2 in cord blood CD34+ cells skews progenitor differentiation toward the granulomonocytic lineage at the expense of lymphoid and erythroid lineages. In addition, by monitoring in vitro granulomonocytic development we found a decreased granulocytic differentiation and an increase in monocytic cells. Our results indicate that TET2 disruption affects 5-hmC levels in human myeloid cells and participates in the pathogenesis of myeloid malignancies through the disturbance of myeloid differentiation.
Escape from highly effective public CD8+ T-cell clonotypes by HIV
Authors: Iglesias Maria Candela , Almeida Jorge R. , Fastenackels Solène , van Bockel David J. , Hashimoto Masao , Venturi Vanessa , Gostick Emma , Urrutia Alejandra , Wooldridge Linda , Clement Mathew , Gras Stéphanie , Wilmann Pascal G. , Autran Brigitte , Moris Arnaud , Rossjohn Jamie , Davenport Miles P. , Takiguchi Masafumi , Brander Christian , Douek Daniel C. , Kelleher Anthony D. , Price David A. , Appay Victor 
Published: July 2011

AbstractMapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8+ T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8+ T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These “public” clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L268M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8+ T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8+ T-cell response against HIV.
Antiphospholipid antibodies induce translocation of TLR7 and TLR8 to the endosome in human monocytes and plasmacytoid dendritic cells
Authors: Prinz Nadine , Clemens Natascha , Strand Dennis , Pütz Inge , Lorenz Mareike , Daiber Andreas , Stein Pamela , Degreif Adriana , Radsak Markus , Schild Hansjörg , Bauer Stefan , von Landenberg Philipp , Lackner Karl J. 
Published: July 2011

Abstract
The antiphospholipid syndrome (APS) is an autoimmune disease characterized by thromboembolic events and/or fetal loss in the presence of antiphospholipid antibodies (aPLs). The mechanisms underlying the pathogenicity of aPLs are still poorly understood. Here we show that 3 human monoclonal aPLs as well as IgG fractions from patients with the APS increase mRNA expression of the intracellular toll-like receptor (TLR) 7 in plasmacytoid dendritic cells and TLR8 in monocytes. Simultaneously they induce the translocation of TLR7 or TLR8 from the endoplasmic reticulum to the endosome. These effects depend on the uptake of aPLs into the endosome, subsequent activation of endosomal NADPH oxidase, and generation of superoxide. As a consequence cells are dramatically sensitized to ligands for TLR7 and TLR8. This observation delineates a novel signal transduction pathway in innate immunity originating from the endosome. Because the overexpression of TLR7 can also be detected in plasmacytoid dendritic cells from patients with the APS ex vivo, our results provide an explanation for proinflammatory and procoagulant effects of aPLs. Because inappropriate expression of TLR7 has been implicated in the development of systemic autoimmunity, these findings may also be relevant for the understanding of autoimmunity.
Next-generation leukemia immunotherapy
Authors: Vincent Krystel , Roy Denis-Claude , Perreault Claude 
Published: July 2011

AbstractAllogeneic hematopoietic cell transplantation led to the discovery of the allogeneic GVL effect, which remains the most convincing evidence that immune cells can cure cancer in humans. However, despite its great paradigmatic and clinical relevance, induction of GVL by conventional allogeneic hematopoietic cell transplantation remains a quite rudimentary form of leukemia immunotherapy. It is toxic and its efficacy is far from optimal. It is therefore sobering that since the discovery of the GVL effect 3 decades ago, the way GVL is induced and manipulated has practically not changed. Preclinical and clinical studies suggest that injection of T cells primed against a single Ag present on neoplastic cells could enhance the GVL effect without causing any GVHD. We therefore contend that Ag-targeted adoptive T-cell immunotherapy represents the future of leukemia immunotherapy, and we discuss the specific strategies that ought to be evaluated to reach this goal. Differences between these strategies hinge on 2 key elements: the nature of the target Ag and the type of Ag receptor expressed on T cells.
Anti-inflammatory function of arctiin by inhibiting COX-2 expression via NF-κB pathways
Authors: Lee Sungwon , Shin Seulmee , Kim Hyunyul , Han Shinha , Kim Kwanghee , Kwon Jeunghak , Kwak Jin-Hwan , Lee Chong-Kil , Ha Nam-Joo , Yim Dongsool , Kim Kyungjae 
Published: July 2011

Abstract

Background
Arctiin, isolated from Forsythia suspensa has been reported to have anti-inflammatory, anti-oxidant, antibacterial, and antiviral effects in vitro. However, there has been a lack of studies regarding its effects on immunological activity. The aim of this study is to investigate the anti-inflammatory potential and possible mechanisms of arctiin in LPS-induced macrophages.

Methods
We investigated the mRNA and protein levels of proinflammatory cytokines through RT-PCR and western blot analysis, followed by a FACS analysis for surface molecule changes.

Results
Arctiin dose dependently decreased the production of NO and proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE2, and it reduced the gene and protein levels as determined by RT-PCR and western blot analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 were also inhibited by arctiin. Furthermore, the activation of the nuclear transcription factor, NF-κB in macrophages was inhibited by arctiin.

Conclusion
Taken together these results provide evidence of the bioactivity of arctiin in inflammatory diseases and suggest that arctiin may exert anti-inflammatory effect by inhibiting the pro-inflammatory mediators through the inactivation of NF-kB.