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Increased Potential (increased + potential)
Selected AbstractsTLR9 stimulation drives naïve B cells to proliferate and to attain enhanced antigen presenting functionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Wei Jiang Abstract Mechanisms that regulate naïve B cell proliferation and function are incompletely defined. In this study, we test the hypothesis that naïve B cell expansion, survival and ability to present antigen to T,lymphocytes can be directly modulated by Toll-like receptor (TLR) agonists. In the absence of B cell receptor stimulation, CpG oligonucleotide, a TLR9 agonist, was particularly efficient in inducing naïve B cell proliferation and survival. Although the expanded naïve B cells did not mature into CD27+ or IgG+ memory B cells, these cells did differentiate into IgM-secreting cells with increased surface expression of HLA-DR, CD40 and CD80. This was associated with an increased potential for these B cells to activate allogeneic T cells. We propose that the activation and expansion of naïve B cells induced by TLR9 agonists could enhance the potential of these cells to interact with cognate antigens and facilitate cell-mediated immune responses. [source] Glutamate enhances proliferation and neurogenesis in human neural progenitor cell cultures derived from the fetal cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006Masatoshi Suzuki Abstract Excitatory amino acids such as glutamate play important roles in the central nervous system. We previously demonstrated that a neurosteroid, dehydroepiandrosterone (DHEA), has powerful effects on the cell proliferation of human neural progenitor cells (hNPC) derived from the fetal cortex, and this effect is modulated through NMDA receptor signaling. Here, we show that glutamate can significantly increase the proliferation rates of hNPC. The increased proliferation could be blocked by specific NMDA receptor antagonists, but not other glutamate antagonists for kainate,AMPA or metabotropic receptors. The NR1 subunit of the NMDA receptor was detectable in elongated bipolar or unipolar cells with small cell bodies. These NR1-positive cells were colocalized with GFAP immunoreactivity. Detection of the phosphorylation of cAMP response element-binding protein (pCREB) revealed that a subset of NR1-positive hNPC could respond to glutamate. Furthermore, we hypothesized that glutamate treatment may affect mainly the hNPC with a radial morphology and found that glutamate as well as DHEA selectively affected elongated hNPC; these elongated cells may be a type of radial glial cell. Finally we asked whether the glutamate-responsive hNPC had an increased potential for neurogenesis and found that glutamate-treated hNPC produced significantly more neurons following differentiation. Together these data suggest that glutamate stimulates the division of human progenitor cells with neurogenic potential. [source] Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer diseaseHIPPOCAMPUS, Issue 10 2009Sebastian Mirochnic Abstract An active lifestyle is to some degree protective against Alzheimer's disease (AD), but the biological basis for this benefit is still far from clear. We hypothesize that physical and cognitive activity increase a reserve for plasticity by increasing adult neurogenesis in the hippocampal dentate gyrus (DG). We thus assessed how age affects the response to activity in the murine APP23 model of AD compared with wild type (WT) controls and studied the effects of physical exercise (RUN) and environmental enrichment (ENR) in comparison with standard housing (CTR) at two different ages (6 months and 18 months) and in both genotypes. At 18 months, both activity paradigms reduced the hippocampal human A,1-42/A,1-40 ratio when compared with CTR, despite a stable plaque load in the hippocampus. At this age, both RUN and ENR increased the number of newborn granule cells in the DG of APP23 mice when compared with CTR, whereas the levels of regulation were equivalent to those in WT mice under the same housing conditions. At 6 months, however, neurogenesis in ENR but not RUN mice responded like the WT. Quantifying the number of cells at the doublecortin-positive stage in relation to the number of cells on postmitotic stages we found that ENR overproportionally increased the number of the DCX-positive "late" progenitor cells, indicative of an increased potential to recruit even more new neurons. In summary, the biological substrates for activity-dependent regulation of adult hippocampal neurogenesis were preserved in the APP23 mice. We thus propose that in this model, ENR even more than RUN might contribute to a "neurogenic reserve" despite a stable plaque load and that age affects the outcome of an interaction based on "activity." © 2009 Wiley-Liss, Inc. [source] Improving lipid management , to titrate, combine or switchINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2004H. Schuster Summary Despite the benefits of statin therapy, cholesterol management remains suboptimal and many patients do not achieve their recommended low-density lipoprotein cholesterol (LDL-C) goals. The use of insufficient doses, limited drug effectiveness and poor patient compliance may contribute to the treatment gap. Options for improving lipid management include dose titration, combination therapy or prescribing a more efficacious statin. LDL-C reductions are generally modest when patients' current statin dose is titrated, and there may be an increased potential for adverse effects. Combining statin therapy with another lipid-modifying agent can provide additional LDL-C reductions, but cost, tolerability and compliance should be considered. In general, switching to a more efficacious statin is a cost-effective way of enabling more patients to achieve recommended targets without increasing dosages. When considering the options available, physicians should balance efficacy, cost and safety to enable more patients to attain LDL-C goals and achieve greater therapeutic gain from statin treatment. [source] Evaluation of the Mini-Mental State Examination's Internal Consistency in a Community-Based Sample of Mexican-American and European-American Elders: Results from the San Antonio Longitudinal Study of AgingJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2004David V. Espino MD This study examined the effect of scoring method, education, and language usage on internal consistency of the Folstein Mini-Mental State Examination (MMSE). Trained bilingual staff administered the MMSE in participants' homes as part of the San Antonio Longitudinal Study of Aging home-based assessment battery. Subjects included 833 community-dwelling Mexican-American (MA) and European-American (EA) elders, aged 65 and older, residing in three socioculturally distinct neighborhoods in San Antonio, Texas. Three methods of scoring the MMSE were examined: serial sevens only, spelling only, and serial sevens or spelling, whichever was higher. Mean MMSE scores±standard deviation ranged from 27.7±2.4 to 28.5±1.9 for EAs, from 25.6±3.2 to 27.2±2.9 for MAs interviewed in English, and from 22.5±4.5 to 25.5±3.5 for MAs interviewed in Spanish, depending on scoring method. Across the three ethnic-language subgroups, the lowest mean scores, largest coefficients of variation, and highest alpha coefficients were observed using serial sevens only. Stratification by educational level showed that alpha coefficients for all three scoring methods were consistently lower in high school graduates than in less-educated groups. Serial sevens only was the only scoring method that yielded acceptably high alpha coefficients across all ethnic, language, and education subgroups. Thus, clinicians should use the serial sevens,only method when administering the MMSE and be alert to the increased potential for false-negatives in more highly educated EA and MA elders, particularly in EAs and MAs proficient in English. [source] Multiple Encounter Simulation for High-acuity Multipatient Environment TrainingACADEMIC EMERGENCY MEDICINE, Issue 12 2007Leo Kobayashi MD Patient safety interventions for multitasking, multipatient, error-prone work settings such as the emergency department (ED) must improve assorted clinical abilities, specific cognitive strategies, and teamwork functions of the staff to be effective. Multiple encounter simulation scenarios explore and convey this specialized mental work-set through use of multiple high-fidelity medical simulation (SIM) manikins in realistic surroundings. Multipatient scenarios reflect the work situations being targeted yet have the benefit of scripted control and instructor guidance to advance specific educational objectives. The use of two or more SIM patients promotes the exploration not only of multiple distinct clinical issues but also of interdependent processes pervasive in EDs. Cascading shortages of time, personnel, equipment, and supplies are re-created, thereby replicating process limitations at various levels, in a safe environment in which compensatory actions and adaptive behaviors can be learned. Distinguishing features of multipatient exercises include 1) broadened educational scope and expanded indications for SIM application, 2) enhanced scenario complexity, 3) controlled exposure to high workload environments, 4) expanded communication requirements, and 5) increased potential for reflective learning. Widespread and effective training in well-replicated, carefully coordinated representations of complex multipatient work environments may strengthen educational interventions for personnel working in high acuity and work-overloaded settings such as the ED. The use of concurrent patient encounter SIM exercises to elicit calculated stressors and to foster compensatory staff behaviors is an educational advance toward this objective. The authors present SIM methodology using concurrent patient encounters to replicate these environments. [source] Life, information, entropy, and time: Vehicles for semantic inheritanceCOMPLEXITY, Issue 1 2007Antony R. Crofts Abstract Attempts to understand how information content can be included in an accounting of the energy flux of the biosphere have led to the conclusion that, in information transmission, one component, the semantic content, or "the meaning of the message," adds no thermodynamic burden over and above costs arising from coding, transmission and translation. In biology, semantic content has two major roles. For all life forms, the message of the genotype encoded in DNA specifies the phenotype, and hence the organism that is tested against the real world through the mechanisms of Darwinian evolution. For human beings, communication through language and similar abstractions provides an additional supra-phenotypic vehicle for semantic inheritance, which supports the cultural heritages around which civilizations revolve. The following three postulates provide the basis for discussion of a number of themes that demonstrate some important consequences. (i) Information transmission through either pathway has thermodynamic components associated with data storage and transmission. (ii) The semantic content adds no additional thermodynamic cost. (iii) For all semantic exchange, meaning is accessible only through translation and interpretation, and has a value only in context. (1) For both pathways of semantic inheritance, translational and copying machineries are imperfect. As a consequence both pathways are subject to mutation and to evolutionary pressure by selection. Recognition of semantic content as a common component allows an understanding of the relationship between genes and memes, and a reformulation of Universal Darwinism. (2) The emergent properties of life are dependent on a processing of semantic content. The translational steps allow amplification in complexity through combinatorial possibilities in space and time. Amplification depends on the increased potential for complexity opened by 3D interaction specificity of proteins, and on the selection of useful variants by evolution. The initial interpretational steps include protein synthesis, molecular recognition, and catalytic potential that facilitate structural and functional roles. Combinatorial possibilities are extended through interactions of increasing complexity in the temporal dimension. (3) All living things show a behavior that indicates awareness of time, or chronognosis. The ,4 billion years of biological evolution have given rise to forms with increasing sophistication in sensory adaptation. This has been linked to the development of an increasing chronognostic range, and an associated increase in combinatorial complexity. (4) Development of a modern human phenotype and the ability to communicate through language, led to the development of archival storage, and invention of the basic skills, institutions and mechanisms that allowed the evolution of modern civilizations. Combinatorial amplification at the supra-phenotypical level arose from the invention of syntax, grammar, numbers, and the subsequent developments of abstraction in writing, algorithms, etc. The translational machineries of the human mind, the "mutation" of ideas therein, and the "conversations" of our social intercourse, have allowed a limited set of symbolic descriptors to evolve into an exponentially expanding semantic heritage. (5) The three postulates above open interesting epistemological questions. An understanding of topics such dualism, the élan vital, the status of hypothesis in science, memetics, the nature of consciousness, the role of semantic processing in the survival of societies, and Popper's three worlds, require recognition of an insubstantial component. By recognizing a necessary linkage between semantic content and a physical machinery, we can bring these perennial problems into the framework of a realistic philosophy. It is suggested, following Popper, that the ,4 billion years of evolution of the biosphere represents an exploration of the nature of reality at the physicochemical level, which, together with the conscious extension of this exploration through science and culture, provides a firm epistemological underpinning for such a philosophy. © 2007 Wiley Periodicals, Inc. Complexity, 2007 [source] | |||||||||||||