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每日一文(0401) |
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| January 31,2004 | Implantable Cardioverter–Defibrillators | |||||
| despite advances in emergency medical systems and in tech- niques of resuscitation, sudden death from cardiac arrest remains a major public health problem. Most persons who have an out-of-hospital cardiac arrest do not survive. 1,2 Those who are resuscitated may have severe, long-term cognitive impairment and motor impairment due to delays before a stable rhythm could be restored. | ||||||
| January 30,2004 | Regulation of protein phosphatases in disease and behaviour | |||||
| The biennial EuroPhosphatases meeting was held near the Sagrada Familia, Antonio Gaudi's unfinished architectural masterpiece, which could be a metaphor for the phosphatase field: a lot has been achieved, but much more work still needs to be done. Protein phosphorylation is reversible and has a regulatory role in many-if not all-biological processes. | ||||||
| January 29,2004 | Dynamic Equilibrium of Neurotransmitter Transporters | |||||
| Many electrophysiologists view neurotransmitter transporters as tiny vacuum cleaners, operating continuously to lower extracellular neurotransmitter concentration to zero. However, this is not consistent with their known behavior, instead only reducing extracellular neurotransmitter concentration to a finite, nonzero value at which an equilibrium is reached. In addition, transporters are equally able to go in either the forward or reverse direction, and when they reverse, they release their substrate in a calcium-independent manner. | ||||||
| January 28,2004 | Bone marrow-derived stem cells and “plasticity” | |||||
| Studies describing plasticity of somatic stem cells have become a focus of interest because clinical applications in the treatment of degenerative diseases would be at hand. In particular, bone marrow-derived cells and their potential to contribute to skeletal and cardiac muscle, liver, neurons and epithelium have recently been studied extensively. Nevertheless, results of these studies have not always been consistent with each other, and yet it remains to be resolved whether plasticity of adult stem cells truly exists. | ||||||
| January 27,2004 | The DNA sequence and analysis of human chromosome 6 | |||||
| Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to highquality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. | ||||||
| January 26,2004 | HIF-1 AS A TARGET FOR DRUG DEVELOPMENT | |||||
| Sensing and responding to fluxes in oxygen tension is perhaps the single most important variable in physiology, and animal tissues have developed a number of essential mechanisms to cope with the stress of low physiological oxygen levels, or hypoxia. Among these coping mechanisms is the response mediated by the hypoxia-inducible transcription factor, or HIF-1. | ||||||
| January 25,2004 | Molecular mechanisms in lymphangiogenesis | |||||
| The basic science and development of therapies targeting the blood vascular system has enjoyed much focus due to the knowledge of the molecular mechanisms behind its development and roles in disease. However, the closely associated lymphatic system, while also being responsible for a number of serious and debilitating diseases, has not garnered as much attention due to the lack of specific molecular markers, thereby limiting this field to no more than descriptive analysis. | ||||||
| January 24,2004 | Anti-inflammatory properties of lipid oxidation products | |||||
| Oxidative modification of lipids occurs during inflammatory processes and leads to the formation and accumulation of biologically active lipid oxidation products that induce specific cellular reactions. These reactions lead to a modulation of the inflammatory process and may determine the fate and outcome of the body's reaction in acute inflammation during host defense. The processes by which oxidized lipids may play an important role include resolution of inflammation involving apoptosis, chronic inflammatory processes, and innate and adaptive immune responses. | ||||||
| January 23,2004 | Role of Monocytes in Atherogenesis | |||||
| This review focuses on the role of monocytes in the early phase of atherogenesis, before foam cell formation. An emerging consensus underscores the importance of the cellular inflammatory system in atherogenesis. Initiation of the process apparently hinges on accumulating low-density lipoproteins (LDL) undergoing oxidation and glycation, providing stimuli for the release of monocyte attracting chemokines and for the upregulation of endothelial adhesive molecules. | ||||||
| January 22,2004 | The vascular network of tumours — what is it not for? | |||||
| It is becoming almost a dogma that tumours cannot grow beyond 1-2 mm3 unless they are supported by a rich vascular supply [1]. It is true that tumours promote angiogenesis and that highly vascularized carcinomas have, in general, a more aggressive clinical course than carcinomas of low vascularization [2,3]. However, a study of intratumoral angiogenesis reveals that the newly formed vessels are commonly deprived of those structural qualities that would allow them to perform an optimal oxygenation function [3]. | ||||||
| January 21,2004 | Evidence for Ozone Formation in Human Atherosclerotic Arteries | |||||
| Here, we report evidence for the production of ozone in human disease. Signature products unique to cholesterol ozonolysis are present within atherosclerotic tissue at the time of carotid endarterectomy, suggesting that ozone production occurred during lesion development. Furthermore, advanced atherosclerotic plaques generate ozone when the leukocytes within the diseased arteries are activated in vitro. | ||||||
| January 20,2004 | Endothelin, hypercholesterolemia and atherosclerosis | |||||
| Atherosclerosis, a chronic systemic disease of the vasculature with an inflammatory component, remains the major cause of disease and death in industrialized countries [1-3]. Early atheromatous vascular changes are already present during fetal life and maternal plasma cholesterol levels determine the severity of fatty streak formation in the aorta of the fetus [4,5]. Intimal accumulation of low-density lipoproteins (LDLs) precedes monocyte recruitment [4], thus a direct inflammatory effect of native, non-oxidized LDLs is likely to be involved in vascular lesion formation [6]. | ||||||
| January 19,2004 | Angiotensin AT2 receptors: cardiovascular hope or hype? | |||||
| It is widely accepted that the angiotensin II type 1 receptor (AT1R) accounts for the majority of cardiovascular effects evoked by angiotensin II (Ang II), such as contraction/pressor activity and growth-promoting effects leading to cardiac and vascular hypertrophy. However, there has been an increasing body of evidence that indicates that the angiotensin II type 2 receptor (AT2R) may exert pharmacological actions per se as well as play a role in pathophysiological processes. | ||||||
| January 18,2004 | DNA electronics | |||||
| DNA, the blueprint of life, has taken centre stage in biological research during the past few decades. The elucidation of the molecule’s structure 50 years ago and the unravelling of the genetic code revolutionized the field of biotechnology. They sparked the creation of whole new industries based on this knowledge and on the various tools and technologies that have subsequently developed. Biologically, the well-known function of DNA is to code for functional proteins that are the expressed form of hereditary, genetic information. | ||||||
| January 17,2004 | Update: Influenza Activity-United States, 2003-04 Season | |||||
| Influenza began circulating in the United States unusually early this season, and influenza activity nationwide is expected to increase.Cases of severe disease, including deaths, have been reported in children.This report summarizes influenza activity in the United States during the weeks ending October 4-December 6, 2003.During the week ending December 6, influenzaacitivity was reported to CDC as wide-spread in 24 states.The early reason and the unusually high and persistent demand for vaccine have resulted in a decreasing supply of trivalent inactivated vaccine. | ||||||
| January 16,2004 | Control Mechanism of the Circadian Clock for Timing of Cell Division in Vivo | |||||
| Cell division in many mammalian tissues is associated with specic times of day, but just how the circadian clock controls this timing has not been clear. Here, we show in the regenerating liver (of mice) that the circadian clock controls the expression of cell cycle-related genes that in turn modulate the expression of active Cyclin B1-Cdc2 kinase, a key regulator of mitosis. Among these genes, expression of wee1 was directly regulated by the molecular components of the circadian clockwork. | ||||||
| January 15,2004 | Apoptotic cell death in atherosclerosis | |||||
| Apoptosis is a critical regulator of homeostasis in many tissues, including the vasculature. Apoptosis in atherosclerotic lesions is triggered by inflammatory processes, both via cell-Ccell contact and by cytokines and oxidized lipids. Apoptosis of vascular smooth muscle cells, endothelial cells and macrophages may promote plaque growth and pro-coagulation and may induce rupture, the major consequence of atherosclerosis in humans. | ||||||
| January 14,2004 | New Concepts in Regulation of G Protein-Coupled Receptor Signaling and Trafficking | |||||
| Most G protein-coupled receptors (GPCRs) are reversibly activated upon ligand binding. However, activation of proteaseactivated G protein-coupled receptors (PARs) occurs through an irreversible proteolytic event that results in the generation of a tethered ligand that cannot diffuse away. This unusual mode of PAR activation raises important questions regarding the mechanisms responsible for termination of receptor signaling. There are currently four members of the PAR family. | ||||||
| January 13,2004 | Receptor tyrosine kinases in normal and malignant haematopoiesis | |||||
| Haematopoiesis is controlled by a number of growth factors and cytokines, a number of which act through binding to high-affinity receptor tyrosine kinases (RTKs). Approximately 20 different RTK classes have been identified, all of which share a similar structure that includes a ligand binding extracellular domain, a single transmembrane domain and an intracellular tyrosine kinase domain. Recent studies have linked an increasing number of mutations in the RTKs to the pathogenesis of both acute and chronic leukaemia. | ||||||
| January 12,2004 | New tools for cancer chemotherapy: computational assistance for tailoring treatments | |||||
| Computational models of cancer chemotherapy have the potential to streamline clinical trial design, contribute to the design of rational, tailored treatments, and facilitate our understanding of experimental results. Mechanistic models based on functional data from tumor biopsies will enable physicians to predict response to treatment for a specific patient, in contrast to statistical models in which the probability of response for a given patient may differ substantially from the population average. | ||||||
| January 11,2004 | In through the out door: nuclear localization of the regulators of G protein signaling | |||||
| The regulators of G protein signaling (RGS) are an extraordinary class of diverse multifunctional signaling proteins best known for their potent capacity to down-regulate the activity of Ga subunits at the plasma membrane. In certain circumstances, some RGS proteins undergo translocation to the nucleus or plasma membrane from the cytoplasm. Translocation demonstrates a potentially dynamic alternative mechanism for Ga subunit or effector regulation. | ||||||
| January 10,2004 | TMolecular responses to hypoxia in tumor cells | |||||
| Highly aggressive, rapidly growing tumors are exposed to hypoxia or even anoxia which occurs as a consequence of inadequate blood supply. Both hypoxia and consecutive hypoxia/reoxygenation exert a variety of influences on tumor cell biology. Among these are activation of certain signal transduction pathways and gene regulatory mechanisms, induction of selection processes for gene mutations, tumor cell apoptosis and tumor angiogenesis. Most of these mechanisms contribute to tumor progression. | ||||||
| January 9,2004 | The Posttranslational Phase of Gene Expression: New Possibilities in Molecular Diagnosis | |||||
| Proteins in general and secretory proteins in particular undergo posttranslational processes before they reach the structure in which they can fulfill their functional purpose. The protein precursor may undergo a wide variety of proteolytic cleavages, N- and C-terminal trimmings and amino acid derivatizations in cells that express the protein. Occasionally, the same precursor is differently processed in different cell types and, in addition, diseased cells may process a given precursor abnormally. | ||||||
| January 8,2004 | RNA sensors: novel regulators of gene expression | |||||
| RNA-mediated control can evolve far more rapidly than mechanisms that rely on proteins, creating selective advantages in adaptive gene regulation. Recently, evidence has emerged that messenger RNA is a source of cis-acting RNA elements that sense external signals and thereby regulate gene expression. With exquisite specificity, metabolite-sensing riboswitches control the formation or translation of prokaryotic mRNA. In eukaryotes, RNA sensors in human antiviral cytokine genes that encode tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) have been shown to activate strongly the RNA-dependent protein kinase PKR, a stress kinase that is also activated by double-stranded RNA-a hallmark of viral infection. | ||||||
| January 7,2004 | Guanylyl cyclases, nitric oxide, natriuretic peptides, and airway smooth muscle function | |||||
| Airway smooth muscle (ASM) plays an important role in asthma pathophysiology through its contractile and proliferative functions. The cyclic nucleotides adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) are second messengers capable of mediating the effects of a variety of drugs and hormones. There is a large body of evidence to support the hypothesis that cAMP is a mediator of the ASM's relaxant effects of drugs, such as β2-adrenoceptor agonists, in human airways. | ||||||
| January 6,2004 | Life-on-a-chip | |||||
| Mechanistic studies of cellular processes are usually carried out with large populations of cells. However, parameters that are measured as averages of large populations can be misleading. For instance, an apparently linear response to a signal could, in fact, reflect an increasing number of cells in the population that have switched from ‘off’to‘on’, rather than a graded increase in response by all the cells. At present, the study of single cells is challenging, but new technologies mean it might soon be a reality. | ||||||
| January 5,2004 | Immunotherapy as a therapeutic treatment for neurodegenerative disorders | |||||
| Human neurodegenerative illnesses such as Alzheimer's disease and Creutzfeldt-Jakob disease exact an enormous cost on individuals, families and society. For these and related disorders, current treatment is largely symptomatic without influencing the underlying disease process. Until recently, the development of immunotherapeutic approaches to neurodegenerative disorders had been almost completely ignored despite growing successes against other non-infectious diseases such as cancer. | ||||||
| January 4,2004 | Regulation of Dendritic Cell Function Through Toll-like Receptors | |||||
| Higher animals establish host defense by orchestrating innate and adaptive immunity. This is mediated by professional antigen presenting cells, i.e. dendritic cells (DCs). DCs can incorporate pathogens, produce a variety of cytokines, maturate, and present pathogen-derived peptides to T cells, thereby inducing T cell activation and differentiation. These responses are triggered by microbial recognition through type I transmembrane proteins, Toll-like receptors (TLRs) on DCs. TLRs consist of ten members and each TLR is involved in recognizing a variety of microorganism-derived molecular structures. | ||||||
| January 3,2004 | Disease genes and intracellular protein networks | |||||
| By a computational approach we reconstructed genomic transcriptional profiles of 19 different adult human tissues, based on information on activity of 27,924 genes obtained from unbiased UniGene cDNA libraries. In each considered tissue, a small number of genes resulted highly expressed or "tissue specific." Distribution of gene expression levels in a tissue appears to follow a power law, thus suggesting a correspondence between transcriptional profile and "scale-free" topology of protein networks. The expression of 737 genes involved in Mendelian diseases was analyzed, compared with a large reference set of known human genes. | ||||||
| January 2,2004 | Ontogenesis of β-Adrenoceptor Signaling | |||||
| G-Protein-coupled receptors play an instrumental role in cellular development and function. In the mature organism, receptor signaling is controlled through the processes of desensitization and down-regulation. Recent evidence suggests that these regulatory mechanisms are not inherent properties, however, but rather are acquired during ontogenesis. This review focuses on β-adrenoceptors (βARs), which are found in fetal and neonatal tissues and are effectively linked through adenylyl cyclase (AC) to the production of cAMP. Agonist-induced stimulation of βARs in the immature organism fails to produce desensitization, and instead, responsiveness increases. | ||||||
| January 1,2004 | 5-Lipoxygenase and atherosclerosis | |||||
| 5-Lipoxygenase (5LO) was recently identified as a gene that makes an important contribution to atherosclerosis in mice and humans, but the underlying mechanism(s) remains unknown. Studies of the 5LO pathway in other disease areas suggest that 5LO could contribute to atherosclerosis at different levels, such as lesion initiation, growth and cellular proliferation within the lesion, and/or destabilization of plaques that can lead to their rupture. Recent advances in our understanding of how 5LO is involved in the atherosclerotic process will have important implications for diagnostic and therapeutic strategies in the future. |
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