bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of LPS-mediated bystander activation in the innate immune system
Authors: Yadav Rajwardhan , Zammit David J , Lefrancois Leo , Vella Anthony T 
Published: September 2006

Abstract
LPS induces dendritic cell (DC) activation, but the precise in vivo mechanism is unclear since DCs express low levels of TLR4. Here, it is shown that DCs can be activated in response to LPS through a bystander mechanism. This result was obtained using chimeric mice reconstituted with LPS-responsive and nonresponsive bone marrow cells. Thus, after indirect in vivo conditioning by LPS, bystander-activated DCs (LPS nonresponsive) up-regulated CD86. This up-regulation occurred even when LPS-responsive cells were MyD88 deficient. Functional analysis demonstrated that in vivo LPS conditioning endowed both the LPS-responsive and bystander cells with the ability to produce IFN-γ in response to TLR9 stimulation in vitro. IFN-γ production was also shown to be important for enhanced T-bet gene expression but not important for up-regulation of CD86. To investigate aspects of the mechanism, we used intracellular cytokine staining and found that NKDCs were responsible for at least some of the IFN-γ production. Thus, our in vivo results demonstrated that bacterial LPS can bridge activation of various cellular populations of the innate immune system through a bystander mechanism.
Transgenic expression of CSF-1 in CSF-1 receptor-expressing cells leads to macrophage activation, osteoporosis, and early death
Authors: Wei Suwen , Dai Xu-Ming , Stanley E Richard 
Published: September 2006

Abstract
CSF-1 is the primary mononuclear phagocyte and osteoclast growth factor. Autocrine regulation by CSF-1 has been reported in macrophages during inflammatory responses and in neoplastic cells. To investigate whether inflammatory disease or neoplasia was the dominant consequence of autocrine regulation by CSF-1 in CSF-1 receptor (CSF-1R)-expressing cells, we created mice that express CSF-1 under the control of the CSF-1R promoter/first intron driver [transgene TgN(Csf1r-Csf1)Ers (TgRC) mice], which have reduced thymic size, a short lifetime, and low body weight and develop osteoporosis. In 4-week-old TgRC mice, osteoclast numbers are elevated, and macrophage densities are increased in bone marrow, spleen, liver, and brain. Cultured TgRC macrophages express CSF-1 and proliferate without exogenous CSF-1 and in the presence of neutralizing antimouse CSF-1 antibody. Compared with macrophages from nontransgenic littermates, TgRC macrophages exhibit a stellate morphology, express elevated mRNAs for proinflammatory cytokines, and despite a lower, steady-state cytokine secretion, secrete elevated levels of inflammatory cytokines in response to LPS, indicating that TgRC macrophages are functionally primed through the CSF-1R. Thus, autocrine regulation of CSF-1R-expressing cells by CSF-1 leads to a severe phenotype that emphasizes the importance of the known, local production of CSF-1 in inflammatory disease.
Conserved Amino Acid Residues that Are Important for Ligand Binding in the Type I Gonadotropin-Releasing Hormone (GnRH) Receptor Are Required for High Potency of GnRH II at the Type II GnRH Receptor
Authors: Mamputha Sipho , Lu Zhi-liang , Roeske Roger W. , Millar Robert P. , Katz Arieh A. , Flanagan Colleen A. 
Published: September 2006

AbstractGnRH I regulates reproduction. A second form, designated GnRH II, selectively binds type II GnRH receptors. Amino acids of the type I GnRH receptor required for binding of GnRH I (Asp2.61(98), Asn2.65(102), and Lys3.32(121)) are conserved in the type II GnRH receptor, but their roles in receptor function are unknown. We have delineated their functions using mutagenesis, signaling and binding assays, immunoblotting, and computational modeling. Mutating Asp2.61(97) to Glu or Ala, Asn2.65(101) to Ala, or Lys3.32(120) to Gln decreased potency of GnRH II-stimulated inositol phosphate production. Consistent with proposed roles in ligand recognition, mutations eliminated measurable binding of GnRH II, whereas expression of mutant receptors was not decreased. In detailed analysis of how these residues affect ligand-dependent signaling, [Trp2]-GnRH I showed lesser decreases in potency than GnRH I at the Asp2.61(97)Glu mutant. In contrast, [Trp2]-GnRH II showed the same loss of potency as GnRH II at this mutant. This suggests that Asp2.61(97) contributes to recognition of His2 of GnRH I, but not of GnRH II. GnRH II showed a large decrease in potency at the Asn2.65(101)Ala mutant compared with analogs lacking the C⋕O group of Gly10NH2. This suggests that Asn2.65(101) recognizes Gly10NH2 of GnRH II. GnRH agonists showed large decreases in potency at the Lys3.32(120)Gln mutant, but antagonist activity was unaffected. This suggests that Lys3.32(120) recognizes agonists, but not antagonists, as in the type I receptor. These data indicate that roles of conserved residues are similar, but not identical, in the type I and II GnRH receptors.
Liver X Receptors Regulate Adrenal Steroidogenesis and Hypothalamic-Pituitary-Adrenal Feedback
Authors: Nilsson Maria , Stulnig Thomas M. , Lin Chin-Yo , Yeo Ai Li , Nowotny Peter , Liu Edison T. , Steffensen Knut R. 
Published: September 2006

Abstract
The nuclear hormone receptors liver X receptor α (LXRα) (NR1H3) and LXRβ (NR1H2) are established regulators of cholesterol, lipid, and glucose metabolism and are attractive drug targets for the treatment of diabetes and cardiovascular disease. Adrenal steroid hormones including glucocorticoids and mineralocorticoids are known to interfere with glucose metabolism, insulin signaling, and blood pressure regulation. Here we present genome-wide expression profiles of LXR-responsive genes in both the adrenal and the pituitary gland. LXR activation in cultured adrenal cells inhibited expression of multiple steroidogenic genes and consequently decreased adrenal steroid hormone production. In addition, LXR agonist treatment elevated ACTH mRNA expression and hormone secretion from pituitary cells both in vitro and in vivo. Reduced expression of the glucocortioid-activating enzyme 11β-hydroxysteroid dehydrogenase 1 in pituitary cells upon LXR activation suggests blunting of the negative feedback of glucocorticoids by LXRs. In conclusion, LXRs independently interfere with the hypothalamic-pituitary-adrenal axis regulation at the level of the pituitary and the adrenal gland.
Activation of Pregnane X Receptor Disrupts Glucocorticoid and Mineralocorticoid Homeostasis
Authors: Zhai Yonggong , Pai Harish V. , Zhou Jie , Amico Janet A. , Vollmer Regis R. , Xie Wen 
Published: September 2006

AbstractThe pregnane X receptor (PXR) was isolated as a xenobiotic receptor that regulates responses to various xenobiotic agents. In this study, we show that PXR plays an important endobiotic role in adrenal steroid homeostasis. Activation of PXR by genetic (transgene) or pharmacological (ligand, such as rifampicin) markedly increased plasma concentrations of corticosterone and aldosterone, the respective primary glucocorticoid and mineralocorticoid in rodents. The increased levels of corticosterone and aldosterone were associated with activation of adrenal steroidogenic enzymes, including cytochrome P450 (CYP)11a1, CYP11b1, CYP11b2, and 3β-hydroxysteroid dehydrogenase. The PXR-activating transgenic mice also exhibited hypertrophy of the adrenal cortex, loss of glucocorticoid circadian rhythm, and lack of glucocorticoid responses to psychogenic stress. Interestingly, the transgenic mice had normal pituitary secretion of ACTH and the corticosterone-suppressing effect of dexamethasone was intact, suggesting a functional hypothalamus-pituitary-adrenal axis despite a severe disruption of adrenal steroid homeostasis. The ACTH-independent hypercortisolism in the PXR-activating transgenic mice is reminiscent of the pseudo-Cushing’s syndrome in patients. The glucocorticoid effect appears to be PXR specific, as the activation of constitutive androstane receptor in transgenic mice had little effect. We propose that PXR is a potential endocrine disrupting factor that may have broad implications in steroid homeostasis and drug-hormone interactions.
There is no opposition between Formal and Cognitive Semantics
Authors: Hamm Fritz , Kamp Hans , Lambalgen Michiel van 
Published: September 2006

Abstract

1. Introduction

The history of modern semantics is characterised by two research traditions which are based on radically different views concerning both conceptual motivation and the purpose of semantic research.
Realistic semantics conceives of semantics as characterising the relationsship between linguistic expressions and reality. In most cases this relationship is explicated by means of modeltheoretic concepts. The following quote from one of the founding fathers of realistic semantics clearly rejects a mentalist stance.
Comments on: Fritz Hamm, Hans Kamp, Michiel van Lambalgen, There is no opposition between Formal and Cognitive Semantics
Authors: Bierwisch Manfred 
Published: September 2006

Abstract
Although I am strongly inclined to agree with the headline of the target-paper, it is not clear to me to what extent it contributes to this position. This is primarily due to the unfortunate strategy to defer crucial parts of its demonstration and of the supporting arguments to Lambalgen and Hamm (2004). Either the reader is assumed to be familiar with this reference, but then he doesn't need the paper under discussion, or he is not, and then he is left in doubt about crucial points. My comments are made from of the latter position.
Ontology for human talk and thought (not robotics)
Authors: Bittner Maria 
Published: September 2006

Abstract

1. Introduction

Hamm, Kamp, and van Lambalgen 2006 (hereafter HKL) propose to relate NL discourse to cognitive representations that also deal with world knowledge, planning, belief revision, etc. Their implementation involves translating NL discourse first into DRT, which explicates the linguistic information, and then into an event calculus, which uses world knowledge and non-monotonic reasoning to arrive at the final cognitive representation.
Representing events and discourse; comments on Hamm, Kamp and van Lambalgen
Authors: Fernando Tim 
Published: September 2006

Abstract
In [HKL00] (henceforth HKL), Hamm, Kamp and van Lambalgen declare “there is no opposition between formal and cognitive semantics,” notwithstanding the realist/mentalist divide. That divide separates two sides Jackendoff has (in [Jac96], following Chomsky) labeled E(xternalized)-semantics, relating language to a reality independent of speakers, and I(nternalized)-semantics, revolving around mental representations and thought. Although formal semanticists have (following David Lewis) traditionally leaned towards E-semantics, it is reasonable to apply formal methods also to I-semantics. This point is made clear in HKL via two computational approaches to natural language semantics, Discourse Representation Theory (DRT, [KR93]) and the Event Calculus (EC) presented in [LH05]. In this short note, I wish to raise certain questions about EC that can be traced to the applicability of formal methods to E-semantics and I-semantics alike. These opposing orientations suggest different notions of time, event and representation.
What is an action-based model of interpretation?
Authors: Michaelis Laura A 
Published: September 2006

Abstract
Scholars of linguistic meaning have always talked about sentences in terms of the things that they instruct their interpreters to do, find or check, and so the idea of an action-based model of interpretation is not entirely new. In denotational or ‘realist’ semantics, a sentence tells its interpreter how to determine its truth or falsity. In representational semantics, a sentence tells its interpreter to retrieve an array of semantic frames and make them fit together. When denotational semanticists started paying attention to narratives, they found an ingenious way to combine the representationalist idea of meaning as the integration of knowledge structures with the realist's view of meaning as truth conditions: they proposed that a sentence, rather than merely having a truth value, has a truth interval – the time for which it is true (Herweg 1991) – and that the interpreter can use linguistic and extralinguistic cues to determine whether or not two truth intervals overlap. Sometimes, however, the necessary contextual cues are lacking. For example, the English past tense, unlike its French analog, is aspectually neutral; therefore, the narrative passage in (1) is ambiguous:
Is semantics computational?
Authors: Steedman Mark , Stone Matthew 
Published: September 2006

Abstract

1. Introduction

Both formal semantics and cognitive semantics are the source of important insights about language. By developing precise statements of the rules of meaning in fragmentary, abstract languages, formalists have been able to offer perspicuous accounts of how we might come to know such rules and use them to communicate with others. Conversely, by charting the overall landscape of interpretations, cognitivists have documented how closely interpretations draw on the commonsense knowledge that lets us make our way in the world. There is no opposition between these insights. Sooner or later we will have a semantics that responds to both.
The future of semantics?
Authors: Stokhof Martin 
Published: September 2006

Abstract
The paper by Fritz Hamm, Hans Kamp and Michiel van Lambalgen (in what follows abbreviated as ‘hkl’) is a very rich one. Not only does it contain a wealth of empirical and formal insights concerning the analysis of tense and aspect, planning and causality, and other phenomena, it also contains some penetrating remarks concerning the scope and method of semantic theory. It is the latter aspect of the paper that I want to make a few comments on in what follows.
Replies to comments
Authors: Hamm Fritz , Kamp Hans , Lambalgen Michiel van 
Published: September 2006

Abstract

1. Bierwisch

Manfred Bierwisch starts his comment with the complaint that crucial parts of our paper rely on van Lambalgen and Hamm (2005). This is of course true, and it points to a predicament of which we have been aware: In order that we could say, within the space allotted to us, that which we wanted to say in this paper almost all the technical details of van Lambalgen and Hamm (2005) had to be left out. We do not agree, however, with Bierwisch' contention that someone familiar with the book could just as well have done without the paper. For one thing, the book, while acknowledging DRT as an important motivation for the ‘Proper Treatment of Events’ approach it presents, has no explicit discussion of the formal relations between the two theories, let alone any hints of how they could be put together. And precisely this is a central message of the paper: that there is a way of combining the two and that a combination of DRT and PTE techniques can help to bridge the gap between formal and cognitive aspects of linguistic structure and meaning.
Force Measurements of Human Embryonic Stem Cell-Derived Cardiomyocytes in an In Vitro Transplantation Model
Authors: Pillekamp Frank , Reppel Michael , Rubenchyk Olga , Pfannkuche Kurt , Matzkies Matthias , Bloch Wilhelm , Sreeram Narayanswami , Brockmeier Konrad , Hescheler Jürgen 
Published: September 2006

AbstractHuman embryonic stem cell (hESC)-derived cardiomyocytes have been suggested for cardiac cell replacement therapy. However, there are no data on loaded contractions developed by these cells and the regulation thereof. We developed a novel in vitro transplantation model in which beating cardiomyocytes derived from hESCs (line H1) were isolated and transplanted onto noncontractile, ischemically damaged ventricular slices of murine hearts. After 2–3 days, transplanted cells started to integrate mechanically into the existing matrix, resulting in spontaneous movements of the whole preparation. Preparations showed a length-dependent increase of active tension. In transplanted early beating hESC-derived cardiomyocytes, frequency modulation by field stimulation was limited to a small range around their spontaneous beating rate. Our data demonstrate that this novel in vitro transplantation model is well suited to assess the mechanical properties and functional integration of cells suggested for cardiac replacement strategies.
In Vitro Expanded Cells Contributing to Rapid Severe Combined Immunodeficient Repopulation Activity Are CD34+38−33+90+45RA−
Authors: Vanheusden Katrien , Van Coppernolle Stefanie , De Smedt Magda , Plum Jean , Vandekerckhove Bart 
Published: September 2006

Abstract
Expansion of hematopoietic stem cells could be used clinically to shorten the prolonged aplastic phase after umbilical cord blood (UCB) transplantation. In this report, we investigated rapid severe combined immunodeficient (SCID) repopulating activity (rSRA) 2 weeks after transplantation of CD34+ UCB cells cultured with serum on MS5 stromal cells and in serum- and stroma-free cultures. Various subpopulations obtained after culture were studied for rSRA. CD34+ expansion cultures resulted in vast expansion of CD45+ and CD34+ cells. Independent of the culture method, only the CD34+33+38− fraction of the cultured cells contained rSRA. Subsequently, we subfractionated the CD34+38− fraction using stem cell markers CD45RA and CD90. In vitro differentiation cultures showed CD34+ expansion in both CD45RA− and CD90+ cultures, whereas little increase in CD34+ cells was observed in both CD45RA+ and CD90− cultures. By four-color flow cytometry, we could demonstrate that CD34+38−45RA− and CD34+38−90+ cell populations were largely overlapping. Both populations were able to reconstitute SCID/nonobese diabetic mice at 2 weeks, indicating that these cells contained rSRA activity. In contrast, CD34+38−45RA+ or CD34+38−90− cells contributed only marginally to rSRA. Similar results were obtained when cells were injected intrafemorally, suggesting that the lack of reconstitution was not due to homing defects. In conclusion, we show that after in vitro expansion, rSRA is mediated by CD34+38−90+45RA− cells. All other cell fractions have limited reconstitutive potential, mainly because the cells have lost stem cell activity rather than because of homing defects. These findings can be used clinically to assess the rSRA of cultured stem cells.
Higher Expression of Transcription Targets and Components of the Nuclear Factor-κB Pathway Is a Distinctive Feature of Umbilical Cord Blood CD34+ Precursors
Authors: Panepucci Rodrigo Alexandre , Calado Rodrigo Tocantins , Rocha Vanderson , Proto-Siqueira Rodrigo , Silva Wilson Araujo , Zago Marco Antonio 
Published: September 2006

AbstractDelayed engraftment, better reconstitution of progenitors, higher thymic function, and a lower incidence of the graft-versus-host disease are characteristics associated with umbilical cord blood (UCB) transplants, compared with bone marrow (BM). To understand the molecular mechanisms causing these intrinsic differences, we analyzed the differentially expressed genes between BM and UCB hematopoietic stem and progenitor cells (HSPCs). The expressions of approximately 10,000 genes were compared by serial analysis of gene expression of magnetically sorted CD34+ cells from BM and UCB. Differential expression of selected genes was evaluated by real-time polymerase chain reaction on additional CD34+ samples from BM (n = 22), UCB (n = 9), and granulocyte colony stimulating factor-mobilized peripheral blood (n = 6). The overrepresentation of nuclear factor-κB (NF-κB) pathway components and targets was found to be a major characteristic of UCB HSPCs. Additional promoter analysis of 41 UCB-overrepresented genes revealed a significantly higher number of NF-κB cis-regulatory elements (present in 22 genes) than would be expected by chance. Our results point to an important role of the NF-κB pathway on the molecular and functional differences observed between BM and UCB HSPCs. Our study forms the basis for future studies and potentially for new strategies to stem cell graft manipulation, by specific NF-κB pathway modulation on stem cells, prior to transplant.
Concise Review: Multipotent Mesenchymal Stromal Cells in Blood
Authors: He Qiling , Wan Chao , Li Gang 
Published: September 2006

AbstractPeripheral blood-derived multipotent mesenchymal stromal cells circulate in low number. They share, most although not all, of the surface markers with bone marrow-derived multipotent mesenchymal stromal cells, possess diverse and complicated gene expression characteristics, and are capable of differentiating along and even beyond mesenchymal lineages. Although their origin and physio-pathological function are still unclear, their presence in the adult peripheral blood might relate to some interesting but controversial subjects in the field of adult stem cell biology, such as systemic migration of bone marrow-derived multipotent mesenchymal stromal cells and the existence of common hematopoietic-mesenchymal precursors. In this review, current studies/knowledge about peripheral blood-derived multipotent mesenchymal stromal cells is summarized, and the above-mentioned topics are discussed.
Concise Review: Bone Morphogenetic Protein Pleiotropism in Neural Stem Cells and Their Derivatives—Alternative Pathways, Convergent Signals
Authors: Chen Hui-Ling , Panchision David M. 
Published: September 2006

Abstract
Bone morphogenetic proteins (BMPs) are a class of morphogens that are critical regulators of the central nervous system (CNS), peripheral nervous system, and craniofacial development. Modulation of BMP signaling also appears to be an important component of the postnatal stem cell niche. However, describing a comprehensive model of BMP actions is complicated by their paradoxical effects in precursor cells, which include dorsal specification, promoting proliferation or mitotic arrest, cell survival or death, and neuronal or glial fate. In addition, in postmitotic neurons BMPs can promote dendritic growth, act as axonal chemorepellants, and stabilize synapses. Although many of these responses depend on interactions with other incoming signals, some reflect the recruitment of distinct BMP signal transduction pathways. In this review, we classify the diverse effects of BMPs on neural cells, focus on the known mechanisms that specify distinct responses, and discuss the remaining challenges in identifying the cellular basis of BMP pleiotropism. Addressing these issues may have importance for stem cell mobilization, differentiation, and cell integration/survival in reparative therapies.