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August 31,2005 Oxidative stress and the use of antioxidants in diabetes
  Cardiovascular complications, characterized by endothelial dysfunction and accelerated atherosclerosis, are the leading cause of morbidity and mortality associated with diabetes. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Overproduction and/or insufficient removal of these free radicals result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids.
August 30,2005 Selective chemical labeling of proteins in living cells
  Labeling proteins with fluorophores, affinity labels or other chemically or optically active species is immensely useful for studying protein function in living cells or tissue. The use of genetically encoded green fluorescent protein and its variants has been particularly valuable in this regard. In an effort to increase the diversity of available protein labels, various efforts to append small molecules to selected proteins in vivo have been reported. This review discusses recent advances in selective, in vivo protein labeling based on small molecule ligand–receptor interactions, intein-mediated processes, and enzyme-catalyzed protein modifications.
August 29,2005 Cell Death Independent of Caspases
  Patterns of cell deathhave been divided into apoptosis,whichis actively executed by specific proteases, the caspases, and accidental necrosis.However, there is now accumulating evidence indicating that cell death can occur in a programmed fashion but incomplete absence and independent of caspase activation. Alternative models of programmed cell death (PCD) have therefore been proposed, including autophagy, paraptosis,mitotic catastrophe, and the descriptive model of apoptosis- like and necrosis-like PCD.
August 28,2005 Thrombosis of the Cerebral Veins and Sinuses
  Thrombosis of the cerebral veins and sinuses is a distinct cerebrovascular disorder that, unlike arterial stroke, most often affects young adults and children. The symptoms and clinical course are highly variable. A teenager who has had recent headaches after starting oral contraception, a woman who has had seizures after delivery in the obstetrical ward, and a comatose man with a dilated pupil in the emergency room all may have sinus thrombosis. The estimated annual incidence is 3 to 4 cases per 1 million population and up to 7 cases per 1 million among children. About 75 percent of the adult patients are women.
August 27,2005 GENE DISCOVERY BY RIBOZYME AND siRNA LIBRARIES
  Catalytic RNAs, also known as ribozymes, can be engineered to optimize their activities in the intracellular environment. The introduction of a library of active ribozymes into cells, and the subsequent screening for phenotypic changes, allows the rapid identification of gene function. For the determination of gene function, ribozyme technology complements another RNA-based tool that is based on libraries of small interfering RNAs.
August 26,2005 The SARS-CoV S glycoprotein
  The severe acute respiratory syndrome-coronavirus (SARS-CoV) spike (S) glycoprotein alone can mediate the membrane fusion required for virus entry and cell fusion. It is also a major immunogen and a target for entry inhibitors. Recent rapid advances in our knowledge of the structure and function of this protein have lead to the development of a number of candidate vaccine immunogens and SARS-CoV entry inhibitors.
August 25,2005 Transcriptional Regulation of Renin
  Renin, as a component of the renin-angiotensin system, plays important roles in the regulation of blood pressure, electrolyte homeostasis, and mammalian renal development. Transcription of renin genes is subject to complex developmental and tissue-specific regulation. Progress has been made recently in elucidating the molecular mechanisms involved in renin gene expression. Using mouse As4.1 cells, which have many features characteristic of the renin-expressing juxtaglomerular cells of kidney, a proximal promoter region and an enhancer have been identified in the mouse renin gene, Ren-1c, that are critical for its expression.
August 24,2005 DNA and the chromosome – varied targets for chemotherapy
  The nucleus of the cell serves to maintain, regulate, and replicate the critical genetic information encoded by the genome. Genomic DNA is highly associated with proteins that enable simple nuclear structures such as nucleosomes to form higher-order organisation such as chromatin fibres. The temporal association of regulatory proteins with DNA creates a dynamic environment capable of quickly responding to cellular requirements and distress. The response is often mediated through alterations in the chromatin structure, resulting in changed accessibility of specific DNA sequences that are then recognized by specific proteins.
August 23,2005 Fusion oncogenes in tumor development
  Currently, all identified fusion oncogenes are found in rare tumor forms, and most of them only in specific tumor types. Some fusion oncogenes are frequent in healthy individuals suggesting that they rarely induce tumor growth. Multiple double-strand breaks that cluster in time and space increases the risk for formation of fusion oncogenes genes. The normal cell type specific spatial distribution of chromatin and genes in interphase nuclei may affect the risk for fusion of specific genes. Transcriptional orientation, splicing of reading frames, size and sequences of breakpoint introns are other risk factors. The biological activity of fusion oncoproteins is the most important factor for penetrance. The effects in specific target cells may explain the tumor type specificity of most fusion oncogenes.
August 22,2005 The Year in Cardiovascular Surgery
  This paper highlights information from cardiovascular surgery articles published in 2004 that are likely to have a broad impact on the practice of cardiovascular specialists in the years ahead. A scan of major general and cardiovascular journals, complemented by a formal MEDLINE search, focused on identifying well-conducted randomized or observational studies of clinical outcomes that should inform cardiovascular surgery care management decisions for individual patients with specific cardiovascular disease presentations.
August 21,2005 New developments in dendritic cell–based vaccinations
  Dendritic cells (DCs) are the most powerful antigen-presenting cells that induce and maintain primary immune responses in vitro and in vivo. The development of protocols for the ex vivo generation of DCs provided a rationale for designing and developing DC-based vaccination studies for the treatment of infectious and malignant diseases. Recently, it was shown that DCs transfected with ribonucleic acid (RNA) coding for a tumour-associated antigen or whole tumour RNA are able to induce potent antigen and tumour-specific T-cell responses directed against multiple epitopes.
August 20,2005 Genomic studies of transcription factor–DNA interactions
  A central issue in the regulation of gene expression is the physical association of transcription factors with relevant promoter sequences. Recently, technological advances have allowed researchers to analyze these processes on a genomic scale. In particular, the combination of the chromatin immunoprecipitation (ChIP) technique with microarray analysis (the ‘ChIP to chip’ experiment) is providing a wealth of new and surprising data on transcription factor–chromatin interactions. These advances are reviewed here. We also discuss future challenges in the area.
August 19,2005 Immunomodulation of Atherosclerosis
  A number of studies have shown activation of the immune system throughout various stages of atherosclerosis. Recent observations have suggested that activation of immune responses may promote atherosclerosis on one hand by inducing and perpetuating arterial inflammation, whereas on the other hand, selective activation of certain immune functions may inhibit atherosclerosis and arterial inflammation. These observations suggest the possibility that selective suppression of proatherogenic immune responses or selective activation of antiatherogenic immune responses may provide new approaches for atherosclerosis prevention and treatment. Several antigens activating immune responses affecting development of atherosclerosis have been identified.
August 18,2005 Imaging genome abnormalities in cancer research
  Increasing attention is focusing on chromosomal and genome structure in cancer research due to the fact that genomic instability plays a principal role in cancer initiation, progression and response to chemotherapeutic agents. The integrity of the genome (including structural, behavioral and functional aspects) of normal and cancer cells can be monitored with direct visualization by using a variety of cutting edge molecular cytogenetic technologies that are now available in the field of cancer research. Examples are presented in this review by grouping these methodologies into four categories visualizing different yet closely related major levels of genome structures.
August 17,2005 Cell cycle control by homeobox genes in development and disease
  Homeobox-containing transcription factors are among the most studied players during normal embryonic development. In the last few years, they have also been shown to act as modulators of cell proliferation. In the present review, we highlight recent studies that demonstrated the influences of homeobox genes on crucial components of the cell cycle machinery. Homeobox genes may have direct or indirect influence on their transcription levels but can also interact with those components via protein–protein interaction. In many cases, these studies were done in the context of pathological states like cancer as well as during vertebrate development.
August 16,2005 OVCA1: tumor suppressor gene
  OVCA1, also known as DPH2L1, is a tumor suppressor gene associated with ovarian carcinoma and other tumors. Ovca1 homozygous mutant mice die at birth with developmental delay and cell-autonomous proliferation defects. Ovca1 heterozygous mutant mice are tumor-prone but rarely develop ovarian tumors. OVCA1 appears to be the homolog of yeast DPH2, which participates in the first biosynthetic step of diphthamide, by modification of histidine on translation elongation factor 2 (EF-2). Yeast dph2 mutants are resistant to diphtheria toxin, which catalyses ADP ribosylation of EF-2 at diphthamide. Thus, there appears to be growing evidence implicating alterations in protein translation with tumorigenesis.
August 15,2005 Methods for Expansion of Human Embryonic Stem Cells
  The manipulation of human embryonic stem cells (hESCs) requires refined skills. Here we introduce both mechanical and enzymatic transfer methods for hESCs depending on experimental purpose. We use the mechanical transfer method for maintenance of hESC lines. Although the method is laborious and time-consuming, the technique permits efficient transfer of undifferentiated hESCs and results in similar clump sizes. We implement the enzymatic transfer method when we need the bulk production of cells for various experiments. The enzyme-treated expansion rapidly produces greater amounts of hESCs within a limited time frame.
August 14,2005 Molecular mechanisms of severe acute respiratory syndrome (SARS)
  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus.
August 13,2005 Controversies in Antiplatelet Therapy for Patients With Cardiovascular Disease
  Case presentation: An asymptomatic man (J.D.) is referred for a cardiovascular evaluation. He has a strong family history of coronary artery disease and has received more than 10 years of treatment for hypertension and dyslipidemia. Past medical history is significant for symptomatic degenerative joint disease. Medications include hydrochlorothiazide, lisinopril, atorvastatin, and celecoxib. How should he be counseled about antiplatelet therapy?
August 12,2005 Artificial and engineered chromosomes: non-integrating vectors for gene therapy
  Non-integrating gene-delivery platforms demonstrate promise as potentially ideal gene-therapy vector systems. Although several approaches are under development, there is little consensus as to what constitutes a true ‘artificial’ versus an ‘engineered’ human chromosome. Recent progress must be evaluated in light of significant technical challenges that remain before such vectors achieve clinical utility. Here, we examine the principal classes of non-integrating vectors, ranging from episomes to engineered mini-chromosomes to true human artificial chromosomes. We compare their potential as practical gene-transfer platforms and summarize recent advances towards eventual applications in gene therapy.
August 11,2005 GENETICS OF CROHN DISEASE, AN ARCHETYPAL INFLAMMATORY BARRIER DISEASE
  Chronic inflammatory disorders such as Crohn disease, atopic eczema, asthma and psoriasis are triggered by hitherto unknown environmental factors that function on the background of some polygenic susceptibility. Recent technological advances have allowed us to unravel the genetic aetiology of these and other complex diseases. Using Crohn disease as an example, we show how the discovery of susceptibility genes furthers our understanding of the underlying disease mechanisms and how it will, ultimately, give rise to new therapeutic developments. The long-term goal of such endeavours is to develop targeted prophylactic strategies.
August 10,2005 Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis
  Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors. FGFs exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Their activity is modulated by a variety of free and extracellular matrix-associated molecules. Also, the cross-talk among FGFs, vascular endothelial growth factors (VEGFs), and inflammatory cytokines/chemokines may play a role in the modulation of blood vessel growth in different pathological conditions, including cancer.
August 9,2005 MITOCHONDRIAL DNA MUTATIONS IN HUMAN DISEASE
  The human mitochondrial genome is extremely small compared with the nuclear genome, and mitochondrial genetics presents unique clinical and experimental challenges. Despite the diminutive size of the mitochondrial genome, mitochondrial DNA (mtDNA) mutations are an important cause of inherited disease. Recent years have witnessed considerable progress in understanding basic mitochondrial genetics and the relationship between inherited mutations and disease phenotypes, and in identifying acquired mtDNA mutations in both ageing and cancer. However, many challenges remain, including the prevention and treatment of these diseases. This review explores the advances that have been made and the areas in which future progress is likely.
August 8,2005 Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming
  The “fetal” or “early” origins of adult disease hypothesis was originally put forward by David Barker and colleagues and stated that environmental factors, particularly nutrition, act in early life to program the risks for adverse health outcomes in adult life. This hypothesis has been supported by a worldwide series of epidemiological studies that have provided evidence for the association between the perturbation of the early nutritional environment and the major risk factors for cardiovascular disease, diabetes, and the metabolic syndrome in adult life.
August 7,2005 Mechanisms of Insulin Resistance in Humans and Possible Links With Inflammation
  Insulin resistance is a major player in the pathogenesis of the metabolic syndrome and type 2 diabetes, and yet, the mechanisms responsible for it remain poorly understood. Magnetic resonance spectroscopy studies in humans suggest that a defect in insulin-stimulated glucose transport in skeletal muscle is the primary metabolic abnormality in insulin-resistant type 2 diabetics. Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1 associated phosphatidylinositol 3-kinase activity.
August 6,2005 CHOOSING THE GREATER OF TWO GOODS: NEURAL CURRENCIES FOR VALUATION AND DECISION MAKING
  To make adaptive decisions, animals must evaluate the costs and benefits of available options. The nascent field of neuroeconomics has set itself the ambitious goal of understanding the brain mechanisms that are responsible for these evaluative processes. A series of recent neurophysiological studies in monkeys has begun to address this challenge using novel methods to manipulate and measure an animal’s internal valuation of competing alternatives. By emphasizing the behavioural mechanisms and neural signals that mediate decision making under conditions of uncertainty, these studies might lay the foundation for an emerging neurobiology of choice behaviour.
August 5,2005 DNA looping in gene regulation: from the assembly of macromolecular complexes to the control of transcriptional noise
  The formation of DNA loops by the binding of proteins and protein complexes at distal DNA sites plays a central role in many cellular processes, such as transcription, recombination and replication. Important thermodynamic concepts underlie the assembly of macromolecular complexes on looped DNA. The effects that this process has on the properties of gene regulation extend beyond the traditional view of DNA looping as a mechanism to increase the affinity of regulatory molecules for their cognate sites. Recent developments indicate that DNA looping can also lead to the suppression of cell-to-cell variability, the control of transcriptional noise, and the activation of cooperative interactions on demand.
August 4,2005 Bone marrow stem cell transplantation for cardiac repair
  Cardiomyocytes respond to physiological or pathological stress only by hypertrophy and not by an increase in the number of functioning cardiomyocytes. However, recent evidence suggests that adult cardiomyocytes have the ability, albeit limited, to divide to compensate for the cardiomyocyte loss in the event of myocardial injury. Similarly, the presence of stem cells in the myocardium is a good omen. Their activation to participate in the repair process is, however, hindered by some as-yet-undetermined biological impediments. The rationale behind the use of adult stem cell transplantation is to supplement the inadequacies of the intrinsic repair mechanism of the heart and compensate for the cardiomyocyte loss in the event of injury.
August 3,2005 RNA silencing and genome regulation
  Closely related RNA silencing phenomena such as posttranscriptional and transcriptional gene silencing (PTGS and TGS), quelling and RNA interference (RNAi) represent different forms of a conserved ancestral process. The biological relevance of these RNA-directed mechanisms of silencing in gene regulation, genome defence and chromosomal structure is rapidly being unravelled. Here, we review the recent developments in the field of RNA silencing in relation to other epigenetic phenomena and discuss the significance of this process and its targets in the regulation of modern eukaryotic genomes.
August 2,2005 MicroRNA Biogenesis and Cancer
  MicroRNAs (miRNA) are a recently discovered family of short non–protein-coding RNAs that negatively regulate gene expression. Recent studies of miRNAs highlight a requirement for cell viability. Posttranscriptional silencing of target genes by miRNAs occurs either by targeting specific cleavage of homologous mRNAs, or by targeting specific inhibition of protein synthesis. We recently identified a multisubunit protein complex termed Microprocessor that is necessary and sufficient for processing miRNA precursor RNAs. Microprocessor contains Drosha, an RNase III endonuclease, and DGCR8, a gene deleted in DiGeorge syndrome. We consider recent findings that link miRNA perturbation to cancer.
August 1,2005 Diets and Cardiovascular Disease
  With rising obesity, despite low-fat diet recommendations, there is an increased interest in weight loss and alternative dietary approaches for cardiovascular health. Physicians must have an understanding of the literature to better counsel their patients about diets and cardiovascular disease. This review examines several dietary approaches to cardiovascular health and evaluates the available scientific evidence regarding these diets.

July June May April March February January 2004 2003 2002 2001