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Major Advances (major + advance)
Selected AbstractsCobalt Deposits of China: Classification, Distribution and Major AdvancesACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 2 2004FENG Chengyou Abstract, The important strategic metal cobalt has diverse uses and the majority of world cobalt deposits have been found in China. The deposits can be classified into four types, i.e., magmatic Ni-Cu-Co sulfide deposits, hydrothermal and volcanogenic cobalt polymetallic deposits, strata-bound Cu-Co deposits hosted by sedimentary rocks and lateritic Ni-Co deposits, of which the former two types are the most important. There are six principal metallogenic epochs and seven important metallogenic belts according to their distribution and tectonic position. Although cobalt generally occurs in nickel-copper, copper and iron deposits as an associated metal, great developments in exploration for independent cobalt deposits have happened in China, and, in recent years, many independent deposits with different elementary assemblages and different genetic types have been discovered in the eastern part of the northern margin of the North China platform, the Central Orogenic Belt of China, western Jiangxi and northeastern Hunan. In addition, it is inferred that the Kunlun-Qinling Orogenic Belt has great potential for further exploration of new types of independent cobalt deposits. [source] The current status of investigative dermatology IIEXPERIMENTAL DERMATOLOGY, Issue 10 2010Stephen I. Katz Abstract:, Major advances in skin biology and skin diseases are heralding new and more specific forms of treatment that are based on better characterization of pathological mechanisms involved in the individual diseases. The advances that we have seen are being made by dermatologists, skin biologists, and others who have come to appreciate the skin as an organ that is reflective of many important systemic mechanisms. In this commentary, I identify some of what I feel are the most important advances that will be the basis for many future studies. [source] Transmitting the signal of excess nitrogen in Saccharomyces cerevisiae from the Tor proteins to the GATA factors: connecting the dotsFEMS MICROBIOLOGY REVIEWS, Issue 3 2002Terrance G. Cooper Abstract Major advances have recently occurred in our understanding of GATA factor-mediated, nitrogen catabolite repression (NCR)-sensitive gene expression in Saccharomyces cerevisiae. Under nitrogen-rich conditions, the GATA family transcriptional activators, Gln3 and Gat1, form complexes with Ure2, and are localized to the cytoplasm, which decreases NCR-sensitive expression. Under nitrogen-limiting conditions, Gln3 and Gat1 are dephosphorylated, move from the cytoplasm to the nucleus, in wild-type but not rna1 and srp1 mutants, and increase expression of NCR-sensitive genes. ,Induction' of NCR-sensitive gene expression and dephosphorylation of Gln3 (and Ure2 in some laboratories) when cells are treated with rapamycin implicates the Tor1/2 signal transduction pathway in this regulation. Mks1 is posited to be a negative regulator of Ure2, positive regulator of retrograde gene expression and to be itself negatively regulated by Tap42. In addition to Tap42, phosphatases Sit4 and Pph3 are also argued by some to participate in the regulatory pathway. Although a treasure trove of information has recently become available, much remains unknown (and sometimes controversial) with respect to the precise biochemical functions and regulatory pathway connections of Tap42, Sit4, Pph3, Mks1 and Ure2, and how precisely Gln3 and Gat1 are prevented from entering the nucleus. The purpose of this review is to provide background information needed by students and investigators outside of the field to follow and evaluate the rapidly evolving literature in this exciting field. [source] How you count counts: the importance of methods research in applied ecologyJOURNAL OF APPLIED ECOLOGY, Issue 5 2008Chris S. Elphick Summary 1Methods papers play a crucial role in advancing applied ecology. Counting organisms, in particular, has a rich history of methods development with many key advances both in field sampling and the treatment of resulting data. 2Most counts, however, have associated errors due to portions of the population of interest being unavailable for detection (e.g. target population not fully sampled; individuals present but not detectable), detection mistakes (e.g. detectable individuals missed; non-existent individuals recorded), or erroneous counts (e.g. large groups miscounted; individuals misidentified). 3Developments in field methods focus on reducing biases in the actual counts. Simultaneously, statisticians have developed many methods for improving inference by quantifying and correcting for biases retrospectively. Prominent examples of methods used to account for detection errors include distance sampling and multiple-observer methods. 4Simulations, in which population characteristics are set by the investigator, provide an efficient means of testing methods. With good estimates of sampling biases, computer simulations can be used to evaluate how much a given counting problem affects estimates of parameters such as population size and decline, thereby allowing applied ecologists to test the efficacy of sampling designs. Combined with cost estimates for each field method, such models would allow the cost-effectiveness of alternative protocols to be assessed. 5Synthesis and applications. Major advances are likely to come from research that looks for systematic patterns, across studies, in the effects of different types of bias and assumption violation on the ecological conclusions drawn. Specifically, determining how often, and under what circumstances, errors contribute to poor management and policy would greatly enhance future application of ecological knowledge. [source] Functional and molecular MR imaging of angiogenesis: Seeing the target, seeing it workJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002Michal NeemanArticle first published online: 16 JAN 200 Abstract Intensive research over the last years led to the discovery of multiple molecular pathways and intricate regulatory network controlling the growth and regression of blood vessels in general and angiogenesis in particular. The difficulties in elucidation of the regulation of angiogenesis, stems from the inherent complexity due to participation of many cell types, under a dominant impact of physiological and environmental effects of flow, perfusion, and oxygenation. Major advances were achieved with the use of sophisticated transgenic mice models engineered so as to provide spatially and temporally controlled expression of specific factors alone or in combination. In vivo analysis of these models frequently requires the use of non-invasive imaging modalities for measurement of functional parameters of the vasculature along with dynamic molecular information. Optical methods are extensively applied for the study of angiogenesis [Brown et al., 2001] but provide very limited tissue penetration. MRI offers the advantage of being non-invasive with uniform and relatively high spatial resolution for deep tissues. Multiple MRI approaches for monitoring angiogenesis were developed over the last years, each looking at a particular step in the process. The aim of this paper is to analyze the clinical, pharmaceutical, and biological needs for imaging of angiogenesis, and to critically evaluate the strengths and weaknesses of functional and molecular imaging for monitoring angiogenesis. The inherent problem of validation of different measures of angiogenesis, and the advantages and limitations associated with application of MRI based methods, as surrogates for other measurements of angiogenesis will be discussed. The terms molecular imaging and functional imaging are frequently loosely defined with a significant overlap between the two. For the sake of this paper we will apply a narrower definition of both terms, where molecular imaging will apply to methods directed towards detection of specific biological molecules that participate directly in (regulation of) a physiological process; while functional imaging will be used to describe those methods that aim to detect the physiological response to a defined (molecular) stimulus. J. Cell. Biochem. Suppl. 39: 11,17, 2002. © 2002 Wiley-Liss, Inc. [source] Lifespan extension in genetically modified miceAGING CELL, Issue 4 2009Warren Ladiges Summary Major advances in aging research have been made by studying the effect of genetic modifications on the lifespan of organisms, such as yeast, invertebrates (worms and flies) and mice. Data from yeast and invertebrates have been the most plentiful because of the ease in which genetic manipulations can be made and the rapidity by which lifespan experiments can be performed. With the ultimate focus on advancing human health, testing genetic interventions in mammals is crucial, and the mouse has proven to be the mammal most amenable to this task. Lifespan studies in mice are resource intensive, requiring up to 4 years to complete. Therefore, it is critical that a set of scientifically-based criteria be followed to assure reliable results and establish statistically significant findings so other laboratories can replicate and build on the data. Only then will it be possible to confidently determine that the genetic modification extends lifespan and alters aging. [source] Cellulose structure and biosynthesis: What is in store for the 21st century?JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 3 2004R. Malcolm Brown Jr. Abstract This article briefly summarizes historical developments in fundamental research related to the structure and biosynthesis of cellulose. Major advances concerning the structure of cellulose include the discovery of a new suballomorph of cellulose I, the lattice imaging of glucan chains showing no fringe micelle structure, parallel chain orientation in cellulose I, and the discovery of nematic ordered cellulose. Major advances in biosynthesis include the discovery of the terminal synthesizing complex, the isolation and purification of cellulose synthase, the in vitro synthesis of cellulose I, and synthetic cellulose assembly. This article focuses on recent advances in molecular biology with cellulose, including the cloning and sequencing of cellulose synthase genes from bacteria, cyanobacteria, and vascular plants; proof of the terminal synthesizing complex as the site of the catalytic subunit of cellulose synthase; cellulose and callose synthase expression during growth and development; and phylogenetic aspects of cellulose synthase evolution. This article concludes with thoughts about future uses for the accumulating genetic information on cellulose biosynthesis for textiles and forest products and discusses possibilities of new global resources for cellulose production. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 487,495, 2004 [source] Liver tumors: Pediatric population,LIVER TRANSPLANTATION, Issue 11 2008Milton J. Finegold Liver tumors in childhood are rare and are typically not detected clinically until they reach a large size and often spread within the organ or metastasize. This can make surgical resection problematic, and almost all of them require extirpation for cure. With very effective chemotherapy for hepatoblastoma and to some extent for sarcomas, many cancers can be shrunk to permit partial hepatectomy, but for most hepatocarcinomas, some of the other malignancies, and even some benign proliferations, their location at the hilum and multiplicity of masses in multiple lobes make transplantation the treatment of choice. Major advances in diagnostic imaging, especially enhanced computed tomography and magnetic resonance imaging, permit a preoperative choice of resection versus transplantation to be achieved in almost all instances, and for the remainder, intraoperative ultrasonography can further help to determine the most desirable approach. The outcome is very much better in the case of hepatoblastoma when transplantation is a primary modality rather than following unsuccessful attempts at resection. In this review, transplantation for liver tumors in children is considered from all aspects, including the importance of screening for tumors whenever possible to avoid the need for transplantation. Liver Transpl 14:1545,1556, 2008. © 2008 AASLD. [source] DOE genomics: Applications to in situ subsurface bioremediationREMEDIATION, Issue 1 2006Robert T. AndersonArticle first published online: 22 DEC 200 Microbial communities can greatly affect the mobility and fate of subsurface contaminants, yet relatively little is known about the functioning of microorganisms in subsurface environments. Major advances in DNA sequencing capability and the advent of genome-enabled studies have produced key insights into how microorganisms adapt to environmental conditions and/or biotransform subsurface contaminants starting from analyses of genome content. These techniques enable the researcher to detect how an organism responds to its environment and, potentially, to devise better methods to promote specific microbial activity in subsurface environments. The U.S. Department of Energy sponsors genome research through the Genomics:GTL program. One of the applications of this research is to better understand and control biological processes influencing the mobility of contaminants of concern to DOE such as metals and radionuclides. Genome and gene expression techniques have led to new insights into the functioning of subsurface microbial communities, but the true potential of these techniques is still to be revealed. As genome-enabled science progresses, techniques for evaluating gene expression patterns of whole communities will advance the understanding and development of optimized in situ bioremediation and more realistic simulations of microbial contaminant biotransformation. © 2006 Wiley Periodicals, Inc.* [source] Genetic control of susceptibility to bacterial infections in mouse modelsCELLULAR MICROBIOLOGY, Issue 5 2003Steven Lam-Yuk-Tseung Summary Historically, the laboratory mouse (Mus musculus) has been the experimental model of choice to study pathophysiology of infection with bacterial pathogens, including natural and acquired host defence mechanisms. Inbred mouse strains differ significantly in their degree of susceptibility to infection with various human pathogens such as Mycobacterium, Salmonella, Legionella and many others. Segregation analyses and linkage studies have indicated that some of these differences are under simple genetic control whereas others behave as complex traits. Major advances in genome technologies have greatly facilitated positional cloning of single gene effects. Thus, a number of genes playing a key role in initial susceptibility, progression and outcome of infection have been uncovered and the functional characterization of the encoded proteins has provided new insight into the molecular basis of antimicrobial defences of polymorphonuclear leukocytes, macrophages, as well as T and B lymphocytes. The multigenic control of susceptibility to infection with certain human pathogens is beginning to be characterized by quantitative trait locus mapping in genome wide scans. This review summarizes recent progress on the mapping, cloning and characterization of genes and proteins that affect susceptibility to infection with major intracellular bacterial pathogens. [source] An overview of insulin glargineDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S3 2002Philip D. Home Abstract Insulin glargine is an innovative, long-acting human insulin analogue, whose prolonged mean activity profile has no pronounced peak. Accordingly, it mimics more closely the natural physiological profile of basal endogenous insulin secretion than do traditional extended-acting insulins such as NPH insulin. As would be expected for a more satisfactory basal insulin, clinical trials comparing insulin glargine with NPH insulin show less nocturnal hypoglycaemia, improved pre-breakfast blood glucose levels, or both. Furthermore, no substantive safety concerns have emerged for insulin glargine. Thus, insulin glargine represents the first major advance in the provision of basal insulin injection therapy for people with type 1 and type 2 diabetes for over 50 years. Copyright © 2002 John Wiley & Sons, Ltd. [source] Trends and opportunities in the metabolic syndromeDRUG DEVELOPMENT RESEARCH, Issue 7 2006John H. "Wick" JohnsonArticle first published online: 16 NOV 200 Abstract Metabolic Syndrome consists of a multifactoral set of indications and, unfortunately, definitions. There is, at present, no consensus definition for Metabolic Syndrome and physicians who recognize the syndrome use different definitions. Some of the major stakeholder associations do not believe that Metabolic Syndrome is an approvable indication and no regulatory agency has weighed in on the matter. This has been the cause of confusion among many physicians resulting in different emphasis on intervention. However, there is close agreement between physicians surveyed in major markets as to the top three indications. The largest unmet medical need among these indications is obesity and obesity represents the largest opportunity. However, any single NCE or combination of existing drugs that can treat 3 indications will be a major advance. Any therapy will be an intervention and will have to have a very clean safety profile. Morbidity and mortality studies with existing therapies and combinations will be needed to establish outcomes. Drug Dev. Res. 67:539,544, 2006. © 2006 Wiley-Liss, Inc. [source] Towards second-generation proteome analysis of murine enamel-forming cellsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2006Jonathan E. Mangum Proteome analysis of rat enamel-forming cells, initiated over a decade ago, has provided valuable insights to enamel biology. In preparation for a more comprehensive, second-generation proteomic exploration, we evaluated an updated microsample-profiling strategy that comprises sequential extraction of enamel epithelium, parallel one- and two-dimensional gel electrophoresis, and mass spectrometric sequence analysis. The results indicated that several hundred proteins, representing various cellular compartments (including membranes), are amenable to identification with a starting tissue volume of <,10 µl. With its increased proteomic depth and breadth, this straightforward approach constitutes a major advance from the first-generation work (10-fold increased proteome coverage), although care was needed to ensure a comparably high stringency of protein identification. Expression proteomics has an exciting potential to elucidate the inner workings of murine enamel epithelial cells, leading to an improved understanding of enamel in health and disease. [source] Remission induction, consolidation and novel agents in development for adults with acute myeloid leukaemiaHEMATOLOGICAL ONCOLOGY, Issue 1 2010Mehdi Hamadani Abstract Chemotherapy regimens used for remission induction in AML have not changed significantly over the last several decades. However the recognition of the prognostic value of cytogenetics and genomics has been a major advance which is helping clarify the most optimal post-remission consolidation strategy among various risk groups. We are not only beginning to realize the pitfalls of a ,one-fits-all' approach with intensive, cytarabine-based chemotherapy as the mainstay, but we are finally beginning to reap the rewards of decades of basic, translational, and clinical research. Developing individualized, ,targeted' therapy for each AML patient based on unique molecular features of disease remains a daunting goal yet one that we can now begin to envision. Hypothesis-based study designs,from pre-clinical/laboratory experiments to phase-I and subsequent efficacy trials,provide the foundation for advances in the diagnosis, risk stratification, and treatment for patients with AML. Here we critically review the literature for the management of AML, try to give recommendations regarding the appropriate induction and remission strategy, clarify the role of stem cell transplantation and discuss novel agents on the horizon. Copyright © 2009 John Wiley & Sons, Ltd. [source] Interstitial lung disease,the new synergy between radiology and pathologyHISTOPATHOLOGY, Issue 4 2006M Quigley In the last 30 years, high-resolution computed tomography (HRCT) has been the major advance in diagnosis of diffuse parenchymal lung disease (DPLD). We review the diagnostic accuracy of HRCT and discuss how the gold standard in diagnosis of DPLD has shifted from histopathological diagnosis in isolation to a multidisciplinary approach. This latter process is now accepted as providing the highest levels of diagnostic accuracy in patients with DPLD and lung biopsy is primarily reserved for cases with atypical clinical or radiological presentations. [source] Transcutaneous delivery and thermostability of a dry trivalent inactivated influenza vaccine patchINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 2 2008Vladimir G. Frolov A patch containing a trivalent inactivated influenza vaccine (TIV) was prepared in a dried, stabilized formulation for transcutaneous delivery. When used in a guinea pig immunogenicity model, the dry patch was as effective as a wet TIV patch in inducing serum anti-influenza IgG antibodies. When the dry TIV patch was administered with LT as an adjuvant, a robust immune response was obtained that was comparable with or better than an injected TIV vaccine. When stored sealed in a nitrogen-purged foil, the dry TIV patch was stable for 12 months, as measured by HA content, under both refrigerated and room temperature conditions. Moreover, the immunological potency of the vaccine product was not affected by long-term storage. The dry TIV patch was also thermostable against three cycles of alternating low-to-high temperatures of ,20/25 and ,20/40°C, and under short-term temperature stress conditions. These studies indicate that the dry TIV patch product can tolerate unexpected environmental stresses that may be encountered during shipping and distribution. Because of its effectiveness in vaccine delivery and its superior thermostable characteristics, the dry TIV patch represents a major advance for needle-free influenza vaccination. [source] Migraine: diagnosis and managementINTERNAL MEDICINE JOURNAL, Issue 9-10 2003P. J. Goadsby Abstract Migraine is the most common form of disabling primary headache and affects approximately 12% of studied Caucasian populations. Non-pharmacological management of migraine largely consists of lifestyle advice to help sufferers avoid situations in which attacks will be triggered. Preventive treatments for migraine should usually be considered on the basis of attack frequency, particularly its trend to change with time, and tractability to acute care. Acute care treatments for migraine can be divided into non-specific treatments (general analgesics, such as aspirin or non-steroidal anti-inflammatory drugs) and treatments relatively specific to migraine (ergotamine and the triptans). The triptans , sumatriptan, naratriptan, rizatriptan, zolmitriptan, almotriptan, eletriptan and frovatriptan , are potent serotonin, 5-HT1B/1D, receptor agonists which represent a major advance in the treatment of acute migraine. Chronic daily headache in association with analgesic overuse is probably the major avoidable cause of headache disability in the developed world. (Intern Med J 2003; 33: 436,442) [source] Applying aggregation operators for information access systems: An application in digital librariesINTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 12 2008Enrique Herrera-Viedma Nowadays, the information access on the Web is a main problem in the computer science community. Any major advance in the field of information access on the Web requires the collaboration of different methodologies and research areas. In this paper, the concept of aggregation operator playing a role for information access on the Web is analyzed. We present some Web methodologies, as search engines, recommender systems, and Web quality evaluation models and analyze the way aggregation operators help toward the success of their activities. We also show an application of the aggregation operators in digital libraries. In particular, we introduce a Web information system to analyze the quality of digital libraries that implements an important panel of aggregation operators to obtain the quality assessments. © 2008 Wiley Periodicals, Inc. [source] Can grazing response of herbaceous plants be predicted from simple vegetative traits?JOURNAL OF APPLIED ECOLOGY, Issue 3 2001Sandra Díaz Summary 1,Range management is based on the response of plant species and communities to grazing intensity. The identification of easily measured plant functional traits that consistently predict grazing response in a wide spectrum of rangelands would be a major advance. 2,Sets of species from temperate subhumid upland grasslands of Argentina and Israel, grazed by cattle, were analysed to find out whether: (i) plants with contrasting grazing responses differed in terms of easily measured vegetative and life-history traits; (ii) their grazing response could be predicted from those traits; (iii) these patterns differed between the two countries. Leaf mass, area, specific area (SLA) and toughness were measured on 83 Argentine and 19 Israeli species. Species were classified by grazing response (grazing-susceptible or grazing-resistant) and plant height (< or > 40 cm) as well as by life history (annual or perennial) and taxonomy (monocotyledon or dicotyledon). 3,Similar plant traits were associated with a specific response to grazing in both Argentina and Israel. Grazing-resistant species were shorter in height, and had smaller, more tender, leaves, with higher SLA than grazing-susceptible species. Grazing resistance was associated with both avoidance traits (small height and leaf size) and tolerance traits (high SLA). Leaf toughness did not contribute to grazing resistance and may be related to selection for canopy dominance. 4,Plant height was the best single predictor of grazing response, followed by leaf mass. The best prediction of species grazing response was achieved by combining plant height, life history and leaf mass. SLA was a comparatively poor predictor of grazing response. 5,The ranges of plant traits, and some correlation patterns between them, differed markedly between species sets from Argentina and Israel. However, the significant relationships between plant traits and grazing response were maintained. 6,The results of this exploratory study suggest that prediction of grazing responses on the basis of easily measured plant traits is feasible and consistent between similar grazing systems in different regions. The results challenge the precept that intense cattle grazing necessarily favours species with tough, unpalatable, leaves. [source] Where is the wisdom?JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 6 2009A conceptual history of evidence-based medicine Abstract Rationale, Evidence-based medicine (EBM) has been acclaimed as a major advance in medical science, but criticized as a proposed alternative model for the practice and teaching of medicine. Ambiguity regarding the proper role of the contributions of EBM within the fabric of medicine and health care has contributed to this discrepancy. Aims and objectives, We undertook a critical review of the history of the EBM movement, beginning with its origins in the 1970s and continuing through this century. We drew upon the results of an independent project that rationalized the EBM domain from the perspective of educational evaluation and assessment. We considered the content of EBM in relationship to the propositions and promises embodied in advocacy publications. Results, EBM emerged in the context of the explosion of biomedical information in the decade preceding public access to the Internet in the mid-1990s and drew upon the independently derived ,information literacy' formula developed by information scientists during the 1980s. The critically important content and achievements of EBM are fully explained within the confines of the information literacy model. The thesis that EBM offers an alternative paradigm for individualized health care, asserted in the advocacy literature, is not supported by published models of evidence-based clinical practice. Conclusion, A critical historical review of the origins, content and development of the EBM movement proposes that full integration of the fruits of the movement into routine clinical care remains a conceptual and practical challenge. [source] The World Development Report: concepts, content and a Chapter 12,JOURNAL OF INTERNATIONAL DEVELOPMENT, Issue 3 2001Robert Chambers The World Development Report (WDR) process set new standards for openness and consultation. Its concepts and content are a major advance on its 1990 predecessor. The intention that its concepts and content should be influenced by voices of the poor was partly fulfilled. Conceptually, the VOP findings support the multidimensional view of poverty as ,pronounced deprivation of wellbeing', and the use of income-poverty to describe what is only one dimension of poverty (though this welcome usage is not consistent throughout in the WDR). Two concepts or analytical orientations were not adopted: powerlessness and disadvantage seen as a multidimensional interlinked web; and livelihoods. On content, three areas where the influence fell short were: how the police persecute and impoverish poor people; the diversity of the poorest people; and the significance of the body as the main but vulnerable and indivisible asset of many poor people. A weakness of the WDR is its lack of critical self-awareness. Chapter 11 is self-serving for the International Financial Institutions: it lumps loans with grants as concessional finance; it makes liberal use of the term donor, but never lender; and it does not consider debt avoidance as a strategy. The Report ends abruptly, a body without a head. Its multidimensional view of poverty is not matched by a multidimensional view of power and responsibility. A Chapter 12 is crying out to be written. This would confront issues of professional, institutional and personal commitment and change. It would stress critical reflection as a professional norm, disempowerment for democratic diversity as institutional practice, and personal values, attitudes and courageous behaviour as primary and crucial if development is to be change that is good for poor people. A new conclusion is suggested for the WDR, and a title for the World Development Report 2010. Copyright © 2001 John Wiley & Sons, Ltd. [source] From large analogical instruments to small digital black boxes: 40 years of progress in mass spectrometry and its role in proteomics.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2009Part II 198 Abstract This is the continuation of a personal retrospective on the developments that since 1965 have given shape to Mass Spectrometry (MS) and taken it from a position of simply playing a role in Protein Chemistry to becoming an indispensable tool in Proteomics, all within a 40-year span. Part I covered the period from 1965 to 1984. This second part reviews the Mass Spectrometry timeline of events from 1985 to 2000, stopping at various time points where MS made significant contributions to protein chemistry or where the development of new instrumentation for MS represented a major advance for peptide and protein work. Major highlights in the field and their significance for peptide and protein characterization such as the advent and practical consequences of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) are covered, including work done with triple quads, the development of time-of-flight (TOF) instruments and new ion traps and going on to the more recent work on the full characterization of the Proteome with ion traps, TOF instruments and new ionization and tagging techniques for protein sequencing. Copyright © 2009 John Wiley & Sons, Ltd. [source] Future Prospects for Biomarkers of Alcohol Consumption and Alcohol-Induced DisordersALCOHOLISM, Issue 6 2010Willard M. Freeman The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis, treatment, and research of alcohol abuse and alcoholism. Successful development of a biomarker that allows for accurate assessment of alcohol intake and drinking patterns would not only be a major advance in clinical care but also a valuable research tool. A number of advances have been made in testing the validity of proposed biomarkers as well as in identifying potential new biomarkers through systems biology approaches. This commentary will examine the definition of a biomarker of heavy drinking, the types of potential biomarkers, the steps in biomarker development, the current state of biomarker development, and critical obstacles for the field. The challenges in developing biomarkers for alcohol treatment and research are similar to those found in other fields. However, the alcohol research field must reach a competitive level of rigor and organization. We recommend that NIAAA consider taking a leadership role in organizing investigators in the field and providing a common set of clinical specimens for biomarker validation studies. [source] The nonmotor symptoms of Parkinson's disease,An overview,MOVEMENT DISORDERS, Issue S1 2010FRACP, Shen-Yang Lim MBBS Abstract Nonmotor symptoms (NMS) are very common in Parkinson's disease (PD) and may result in significant disability. The increased focus on these important clinical features represents a major advance in the care of PD patients. In this article, we provide an overview of recent developments in the field. © 2010 Movement Disorder Society [source] A gene repertoire for nitrogen transporters in Laccaria bicolorNEW PHYTOLOGIST, Issue 2 2008Eva Lucic Summary ,,Ectomycorrhizal interactions established between the root systems of terrestrial plants and hyphae from soil-borne fungi are the most ecologically widespread plant symbioses. The efficient uptake of a broad range of nitrogen (N) compounds by the fungal symbiont and their further transfer to the host plant is a major feature of this symbiosis. Nevertheless, we far from understand which N form is preferentially transferred and what are the key molecular determinants required for this transfer. ,,Exhaustive in silico analysis of N-compound transporter families were performed within the genome of the ectomycorrhizal model fungus Laccaria bicolor. A broad phylogenetic approach was undertaken for all families and gene regulation was investigated using whole-genome expression arrays. ,,A repertoire of proteins involved in the transport of N compounds in L. bicolor was established that revealed the presence of at least 128 gene models in the genome of L. bicolor. Phylogenetic comparisons with other basidiomycete genomes highlighted the remarkable expansion of some families. Whole-genome expression arrays indicate that 92% of these gene models showed detectable transcript levels. ,,This work represents a major advance in the establishment of a transportome blueprint at a symbiotic interface, which will guide future experiments. [source] Prenatal diagnosis of Niemann,Pick diseases types A, B and CPRENATAL DIAGNOSIS, Issue 7 2002Marie T. Vanier Abstract Prenatal diagnosis of Niemann,Pick disease types A and B is routinely accomplished by sphingomyelinase assay. For Niemann,Pick type C disease, demonstration of an abnormal intracellular cholesterol trafficking is a complex procedure, and mutational analysis (NPC1 or NPC2/HE1 gene), whenever feasible, represents a major advance. Copyright © 2002 John Wiley & Sons, Ltd. [source] Lipid-based transfection as a method for gene delivery in zebrafish (Danio rerio) embryosAQUACULTURE RESEARCH, Issue 12 2007Vanesa Robles Abstract A major challenge to the widespread production of transgenic, knockout and knockdown zebrafish has been the absence of a simple and effective procedure for introducing macromolecules into the fertilized egg. None of the existing techniques for gene transfer in fish embryos has proven to be a major advance over cytoplasm microinjection, which is a technically demanding and time-consuming procedure. This report addresses this need, considering that the development of protocols for lipid-based transfection with fish embryos would considerably simplify gene transfer in this complex biological model. In this study, lipid-based transfection with two different reporter vectors was carried out in zebrafish embryos at different developmental stages. The parameters tested included different plasmid/transfection reagent ratios as well as the influence of an added transfection enhancer reagent. When embryos were transfected in the blastula stage with a pEGFP-N1 vector, more than 35% successfully incorporated the plasmid and expressed the fluorescent protein 24 h after transfection. The transfection enhancer did not show any significant effect in our experiments. This work presents an approach to implement this technique as a faster, cheaper and more practical alternative than microinjection. [source] Biotic affinities of rocky reef fishes, invertebrates and macroalgae in different zones of the Port Davey marine protected area, south-western TasmaniaAQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue 3 2010Graham J. Edgar Abstract 1.Assemblages of fishes, invertebrates, and macroalgae showed strong and predictable distributional patterns within the newly declared Port Davey marine protected area (MPA) in south-western Tasmania. Biotic assemblages in the eastern estuarine section of the MPA within Bathurst Channel were extremely anomalous, both in relation to biota elsewhere in the Port Davey region and also to those present along the wider Tasmanian and Australian coasts. Much of this variation was due to the phenomenon of deepwater emergence, with species in 5,m water depth in eastern Bathurst Channel possessing a mean maximum recorded depth of 200,m, compared with<80,m for the same metric when calculated for sites studied elsewhere around Australia. Deepwater emergence in Bathurst Channel was particularly notable for sessile organisms, although also evident among fishes and mobile macro-invertebrates. 2.Quantitative baseline surveys of reef-associated species were undertaken at sites interspersed among MPA management zone types and biotic community types, thereby providing an appropriate benchmark for assessing ecological changes in different management zones within the Port Davey region through the long term. Distinctive biota present in eastern and western Bathurst Channel, and eastern Port Davey, are well protected within ,no-take' sanctuary zones; however, a bias in location of sanctuary zones towards areas with little fishery resources resulted in less protection for the western Port Davey biota, which also extends along the open coast. Although the lack of high level protection for sites with fishery resources detracts from conservation goals, the Port Davey MPA nevertheless represents a major advance in environmental protection because the ecologically unique, fully protected locations are a necessary inclusion within any comprehensive Australian MPA network. Copyright © 2009 John Wiley & Sons, Ltd. [source] Treatment of vulval Crohn's disease with infliximabCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2006P. W. Preston Summary Anti-tumour necrosis factor-, therapy of Crohn's disease (CD) with infliximab has proved a major advance in the treatment of patients with difficult disease. We report our experience of the use of infliximab in a patient with recalcitrant vulval CD. The introduction of infliximab has improved disease control, although a search for an optimum remittive dosing schedule is ongoing. [source] The renin,angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerationsDIABETIC MEDICINE, Issue 8 2003R. E. Gilbert Abstract The relationship between the renin,angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro- and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long-term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue-based RAS and its role in end-organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS. [source] |