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Potential Significance (potential + significance)
Selected AbstractsClinical dental examinations of 357 donkeys in the UK.EQUINE VETERINARY JOURNAL, Issue 4 2009Part 1: Prevalence of dental disorders Summary Reasons for performing study: Dental disorders have a high prevalence in older donkeys and horses, but the nature and pathogenesis of many of these disorders have yet to be established. Objectives: The identification and determination of the prevalence of important dental disorders in different age groups in a large single population of donkeys, to establish a better understanding of the nature and pathogenesis of these disorders. Methods: A prospective cross-sectional study was performed on the donkey population at The Donkey Sanctuary with detailed oral examinations of 357 donkeys within 7 different age groups (age range 2,53 years) recorded. Results: The prevalence of dental disease in all donkeys was 73%, increasing in prevalence from 28% in the youngest to 98% in the oldest age group. There was an increase in prevalence of commonly recognised dental disorders with increasing age, such as: diastemata (3.8% in youngest to 86% in oldest group); missing teeth (0,56%); overgrown teeth (15,86%); worn teeth (8,84%); displaced teeth (0,38%); and periodontal disease (0,28%). Conclusions: There was a significant increase in the prevalence of dental disorders with increasing age with the largest significant increase for most dental disorders occurring in the 15,20 year age group. Potential significance: Most dental disorders significantly increase in prevalence in the 15,20 year age group and, therefore, prophylactic geriatric dental treatment in donkeys should be commenced from age 15 years. [source] Clinical dental examinations of 357 donkeys in the UK.EQUINE VETERINARY JOURNAL, Issue 4 2009Part 2: Epidemiological studies on the potential relationships between different dental disorders, between dental disease, systemic disorders Summary Reasons for performing study: Dental disease has been shown to be a risk factor for weight loss and colic in horses. No extensive clinical studies in donkeys have investigated the potential relationship between different dental disorders, or between dental disease and systemic disorders. Objectives: To determine possible associations between dental disease and body condition score, weight loss, the need for supplemental feeding and prevalence of colic in donkeys of all ages, and to gain a better understanding of the pathogenesis of dental disease by the determination of associations between different dental disorders. Methods: A prospective cross-sectional analysis of clinical dental examinations of 357 donkeys in The Donkey Sanctuary, Sidmouth was performed. Other epidemiological factors such as estimated age group, body condition score, weight loss, medical history and supplemental feeding were also recorded, and multiple regression analyses were performed to determine possible associations. Results: Donkeys from older age groups were more likely to have dental disease, poor body condition score and suffered previous colic episodes. The presence of dental disease was also significantly associated with weight loss, colic, low body condition score and the need for supplemental feeding. The presence of diastemata, periodontal disease, wave mouth, smooth mouth and step mouth are frequently associated with the presence of other dental disorders. Conclusions: In addition to oral-related pain, dental disease can cause significant systemic disorders and so has increased welfare implications in donkeys. Some dental disorders promote the development of other types of dental abnormalities and thus increase the severity of dental disease in individual animals. Potential significance: Effective treatment of dental disorders slows down the progression of dental disease and decreases the risk of developing some medical disorders such as colic and weight loss that are associated with dental disease. [source] National sustainable development strategies: features, challenges and reflexivityENVIRONMENTAL POLICY AND GOVERNANCE, Issue 3 2007James Meadowcroft Abstract More than a decade has passed since the first countries issued national sustainable development strategies. This essay will consider recent developments in this area, and explore the extent to which such strategies can be considered an emergent mode of reflexive governance of the type required to promote sustainable development. The argument involves three steps: first, a review of the current state of play with respect to sustainable development strategies; second, an assessment of existing strategy processes, and third, a more theoretically focused discussion of their potential significance. Copyright © 2007 John Wiley & Sons, Ltd and ERP Environment. [source] Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiaeGENES TO CELLS, Issue 6 2006Daniel G. Gibson Chromosomal replication initiates through the assembly of a prereplicative complex (pre-RC) at individual replication origins in the G1-phase, followed by activation of these complexes in the S-phase. In Saccharomyces cerevisiae, the origin recognition complex (ORC) binds replication origins throughout the cell cycle and participates in pre-RC assembly. Whether the ORC plays an additional role subsequent to pre-RC assembly in replication initiation or any other essential cell cycle process is not clear. To study the function of the ORC during defined cell cycle periods, we performed cell cycle execution point analyses with strains containing a conditional mutation in the ORC1, ORC2 or ORC5 subunit of ORC. We found that the ORC is essential for replication initiation, but is dispensable for replication elongation or later cell cycle events. Defective initiation in ORC mutant cells results in incomplete replication and mitotic arrest enforced by the DNA damage and spindle assembly checkpoint pathways. The involvement of the spindle assembly checkpoint implies a defect in kinetochore-spindle attachment or sister chromatid cohesion due to incomplete replication and/or DNA damage. Remarkably, under semipermissive conditions for ORC1 function, the spindle checkpoint alone suffices to block proliferation, suggesting this checkpoint is highly sensitive to replication initiation defects. We discuss the potential significance of these overlapping checkpoints and the impact of our findings on previously postulated role(s) of ORCs in other cell cycle functions. [source] Genomic imbalances in rhabdomyosarcoma cell lines affect expression of genes frequently altered in primary tumors: An approach to identify candidate genes involved in tumor developmentGENES, CHROMOSOMES AND CANCER, Issue 6 2009Edoardo Missiaglia Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. They resemble developing skeletal muscle and are histologically divided into two main subtypes; alveolar and embryonal RMS. Characteristic genomic aberrations, including the PAX3 - and PAX7-FOXO1 fusion genes in alveolar cases, have led to increased understanding of their molecular biology. Here, we determined the effect of genomic copy number on gene expression levels through array comparative genomic hybridization (CGH) analysis of 13 RMS cell lines, confirmed by multiplex ligation-dependent probe amplification copy number analyses, combined with their corresponding expression profiles. Genes altered at the transcriptional level by genomic imbalances were identified and the effect on expression was proportional to the level of genomic imbalance. Extrapolating to a public expression profiling dataset for 132 primary RMS identified features common to the cell lines and primary samples and associations with subtypes and fusion gene status. Genes identified such as CDK4 and MYCN are known to be amplified, overexpressed, and involved in RMS tumorigenesis. Of the many genes identified, those with likely functional relevance included CENPF, DTL, MYC, EYA2, and FGFR1. Copy number and expression of FGFR1 was validated in additional primary material and found amplified in 6 out of 196 cases and overexpressed relative to skeletal muscle and myoblasts, with significantly higher expression levels in the embryonal compared with alveolar subtypes. This illustrates the ability to identify genes of potential significance in tumor development through combining genomic and transcriptomic profiles from representative cell lines with publicly available expression profiling data from primary tumors. © 2009 Wiley-Liss, Inc. [source] A Strategic Framework for Monitoring Coastal Change in Australia's Wet-dry Tropics , Concepts and ProgressGEOGRAPHICAL RESEARCH, Issue 2 2009C. MAX FINLAYSON Abstract A strategic framework for monitoring natural and human-induced change in the coastal plains of the Alligator Rivers Region in the wet-dry tropics of northern Australia is presented. The framework also supports refinement of methods used to monitor the vulnerability of coastal areas to change, including human-induced climate change and sea-level rise. The information derived through the framework can be used to assess scenarios, highlight the potential significance and implications of changes, and assist land managers formulate management responses. The framework incorporates several large-scale studies for monitoring atmospheric and hydrodynamic processes as well as mapping and monitoring projects specific to environmental change in the freshwater wetlands and the floodplains of the Region. Monitoring is proposed to address processes influencing the stability and rate of change of the floodplain environments. These include large-scale processes, such as inter-annual variability in weather conditions affecting the morphology of the coastal plains, shoreline and riverbank stabilisation, headward expansion of tidal creeks, and salinisation of freshwater basins. Information management is also addressed, and a Geographic Information System structure proposed for effective data collation, analysis and management. The information management system will facilitate data sharing and participation of multiple agencies and organisations interested in coastal change, especially where a landscape perspective or whole ecosystem approach is advocated. [source] Analysis and interpretation of flint toolmarks found on bones from West Tump long barrow, GloucestershireINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 1 2004M. J. Smith Abstract West Tump is a Neolithic chambered tomb originally excavated in 1880. The mound was found to contain a mixed skeletal assemblage, the majority of which was disarticulated. Between 2000 and 2001 material from the site including human bone was re-examined with a portion of this project focused on taphonomic evidence observed on the human skeletal material. Amongst the factors selected for investigation were deliberate toolmarks. Three specimens were identified as exhibiting toolmarks. Analysis demonstrated that the observed features were cutmarks, consistent with the use of flint tools. However those on two of the specimens were found to be both post-mortem and recent. The cutmarks observed on the remaining specimen, a right clavicle, were identified as having been inflicted during the peri-mortem period and consistent with decapitation. British Neolithic mortuary practice has been the subject of ongoing debate since the earliest excavations of relevant sites, but until very recently few assemblages from such contexts have been re-examined and much of the data in use has derived from sources of considerable age and questionable reliability. The selective removal of specific skeletal elements (particularly skulls) has repeatedly been described in the literature regarding the collective funerary monuments of this period. It has often been assumed that such practices took place after the soft tissues had decayed. One of the examples discussed, suggests this may not always have been the case and the potential significance of this finding is discussed in addition to a possible interpretation of the cutmarks seen on the remaining specimens. Copyright © 2004 John Wiley & Sons, Ltd. [source] Interaction strengths in food webs: issues and opportunitiesJOURNAL OF ANIMAL ECOLOGY, Issue 3 2004Eric L. Berlow Summary 1Recent efforts to understand how the patterning of interaction strength affects both structure and dynamics in food webs have highlighted several obstacles to productive synthesis. Issues arise with respect to goals and driving questions, methods and approaches, and placing results in the context of broader ecological theory. 2Much confusion stems from lack of clarity about whether the questions posed relate to community-level patterns or to species dynamics, and to what authors actually mean by the term ,interaction strength'. Here, we describe the various ways in which this term has been applied and discuss the implications of loose terminology and definition for the development of this field. 3Of particular concern is the clear gap between theoretical and empirical investigations of interaction strengths and food web dynamics. The ecological community urgently needs to explore new ways to estimate biologically reasonable model coefficients from empirical data, such as foraging rates, body size, metabolic rate, biomass distribution and other species traits. 4Combining numerical and analytical modelling approaches should allow exploration of the conditions under which different interaction strengths metrics are interchangeable with regard to relative magnitude, system responses, and species identity. 5Finally, the prime focus on predator,prey links in much of the research to date on interaction strengths in food webs has meant that the potential significance of non-trophic interactions, such as competition, facilitation and biotic disturbance, has been largely ignored by the food web community. Such interactions may be important dynamically and should be routinely included in future food web research programmes. [source] Evidence for indigenous selection and distribution of the shea tree, Vitellaria paradoxa, and its potential significance to prevailing parkland savanna tree patterns in sub-Saharan Africa north of the equatorJOURNAL OF BIOGEOGRAPHY, Issue 10 2003S. Maranz Abstract Aim, Woody vegetation patterns in African savannas north of the equator are closely connected to human presence, but the distinctions between natural and anthropogenic landscapes have not been clear to many observers. Criteria for identifying savanna landscapes on a continuum of intensity of anthropic impact are explored. Methods, A key savanna tree species, Vitellaria paradoxa (Sapotaceae), was used as model for evaluating anthropic impact. Fruits harvested from tree populations across the species range were analysed for variation in traits valued by indigenous peoples. A simple selection index was used to scale tree populations from a hypothetical wild state to a hypothetical domesticated state. Index values were compared with trait values along climate zone gradients and evaluated in the context of indigenous savanna management practices and historical species distribution reports. Results, Trait values such as fruit size and shape, pulp sweetness, and kernel fat content show a significant influence of temperature and rainfall. At the same time, the mean values of groups of traits vary perpendicular to the general climatic zone gradient. Selection index values between Vitellaria populations vary up to sixfold, with highest values in central Burkina Faso. Comparison of present day Vitellaria distribution with historical range limits show range expansion by human migration. Main conclusions, The prevalence of major economic tree species in the savannas of Africa north of the equator is a strong indicator of human involvement in tree dispersal. This conclusion is supported by paleobotanical evidence and by recent Vitellaria range expansion as a result of human migration. The presence of high mean values of several Vitellaria fruit traits in central Burkina Faso suggests that selection for desired characteristics has occurred. The impact of indigenous savanna peoples on woody species composition and spatial distribution is probably much greater than usually thought and is the result of a deliberate strategy of altering the landscape to provide needed human resources. [source] Peer evaluation in nurses' professional development: a pilot study to investigate the issuesJOURNAL OF CLINICAL NURSING, Issue 2 2000Riitta Vuorinen MNSc ,,Peer evaluation in nursing is a method by which the nurse evaluates the work of a peer, according to set evaluation criteria. ,,The aim of the study was to clarify the potential significance of peer evaluation with regard to nurses' career development and relates to the introduction of a career development programme for nurses in a Finnish University Hospital. ,,The research concepts were created on the basis of literature analysis. The concepts served as a basis for data collection, and five open-ended questions were devised from them. Informants (n = 24) gave free-form essay-type answers to these questions. The material was analysed using qualitative content analysis. ,,The results indicate that self-evaluation constitutes the basis for peer evaluation. Peer evaluation allows nurses to give and receive professional and personal support promoting professional development. Professional support offers possibilities for change and alternative action. Personal support requires respect for the peer's equality and individuality. Personal peer support can decrease feelings of uncertainty and insecurity caused by work. ,,The conclusion is drawn that peer evaluation is a means of promoting nurses' professional development to further on-the-job learning in collaboration with peers. [source] Closed loop folding units from structural alignments: Experimental foldons revisitedJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2010Sree V. Chintapalli Abstract Nonoverlapping closed loops of around 25,35 amino acids formed via nonlocal interactions at the loop ends have been proposed as an important unit of protein structure. This hypothesis is significant as such short loops can fold quickly and so would not be bound by the Leventhal paradox, giving insight into the possible nature of the funnel in protein folding. Previously, these closed loops have been identified either by sequence analysis (conservation and autocorrelation) or studies of the geometry of individual proteins. Given the potential significance of the closed loop hypothesis, we have explored a new strategy for determining closed loops from the insertions identified by the structural alignment of proteins sharing the same overall fold. We determined the locations of the closed loops in 37 pairs of proteins and obtained excellent agreement with previously published closed loops. The relevance of NMR structures to closed loop determination is briefly discussed. For cytochrome c, cytochrome b562 and triosephophate isomerase, independent folding units have been determined on the basis of hydrogen exchange experiments and misincorporation proton-alkyl exchange experiments. The correspondence between these experimentally derived foldons and the theoretically derived closed loops indicates that the closed loop hypothesis may provide a useful framework for analyzing such experimental data. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source] Expression patterns of MITF during human cutaneous embryogenesis: evidence for bulge epithelial expression and persistence of dermal melanoblastsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2008Briana C. Gleason Background:, The mechanisms whereby melanocytes populate the epidermis and developing hair follicles during embryogenesis are incompletely understood. Recent evidence implicates an intermediate mesenchymal stage in this evolutionary process in which HMB-45-positive melanocyte precursors (,melanoblasts') exist both in intradermal as well as intraepithelial and intrafollicular compartments. The melanocyte master transcriptional regulator, microphthalmia transcription factor (MITF), identifies mature melanocytes as well as melanocyte precursor stem cells that reside in the bulge region of the hair follicle. Methods:, To better define the use of MITF expression in the evaluation of melanocyte ontogeny, human embryonic and fetal skin samples (n = 28) at 6,24 weeks gestation were studied immunohistochemically for expression of MITF and Mart-1. Adjacent step sections were evaluated to correlate staining patterns with cell localization in the intraepidermal, intrafollicular and intradermal compartments. Results:, At 6,8 weeks, MITF and Mart-1-positive cells were primarily intradermal with only rare positive cells in the epidermis. By 12,13 weeks, most of these cells had migrated into the epidermis, predominantly the suprabasal layers. Between 15,17 weeks, these cells localized to the basal layer and colonized developing hair follicles. Rare intradermal MITF and Mart-1 positive cells were found as late as week 20. At 18,24 weeks, MITF and Mart-1 positive cells were identified in the outer root sheath, bulge, and follicular bulge epithelium, in addition to the epidermis. Unexpectedly, weak but diffuse nuclear MITF expression was also present in the keratinocytes of the bulge area. Conclusions:, The in situ migratory fate of MITF/Mart-1-expressing cells in fetal skin involves a well-defined progression from intradermal to intraepidermal to intrafollicular localization. Occasional intradermal melanocytes may persist after the intraepithelial stages are completed, a finding of potential significance to melanocytic proliferations that may arise de novo within the dermis. Because MITF may play a role in stem cell maintenance, the presence of MITF in bulge epithelial cells suggests that it may be a novel marker for follicular stem cells of both epithelial and melanocytic lineage. [source] Virus infection and grazing exert counteracting influences on survivorship of native bunchgrass seedlings competing with invasive exoticsJOURNAL OF ECOLOGY, Issue 2 2006C. M. MALMSTROM Summary 1,Invasive annual grasses introduced by European settlers have largely displaced native grassland vegetation in California and now form dense stands that constrain the establishment of native perennial bunchgrass seedlings. Bunchgrass seedlings face additional pressures from both livestock grazing and barley and cereal yellow dwarf viruses (B/CYDVs), which infect both young and established grasses throughout the state. 2,Previous work suggested that B/CYDVs could mediate apparent competition between invasive exotic grasses and native bunchgrasses in California. 3,To investigate the potential significance of virus-mediated mortality for early survivorship of bunchgrass seedlings, we compared the separate and combined effects of virus infection, competition and simulated grazing in a field experiment. We infected two species of young bunchgrasses that show different sensitivity to B/CYDV infection, subjected them to competition with three different densities of exotic annuals crossed with two clipping treatments, and monitored their growth and first-year survivorship. 4,Although virus infection alone did not reduce first-year survivorship, it halved the survivorship of bunchgrasses competing with exotics. Within an environment in which competition strongly reduces seedling survivorship (as in natural grasslands), virus infection therefore has the power to cause additional seedling mortality and alter patterns of establishment. 5,Surprisingly, clipping did not reduce bunchgrass survivorship further, but rather doubled it and disproportionately increased survivorship of infected bunchgrasses. 6,Together with previous work, these findings show that B/CYDVs can be potentially powerful elements influencing species interactions in natural grasslands. 7,More generally, our findings demonstrate the potential significance of multitrophic interactions in virus ecology. Although sometimes treated collectively as plant ,predators', viruses and herbivores may exert influences that are distinctly different, even counteracting. [source] Proliferative drive and liver carcinogenesis: Too much of a good thing?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2009Narci C Teoh Abstract There have been innumerable studies published in the attempt to identify gene expression signatures in hepatocellular carcinoma (HCC). When all the regulators and targets of the differentially expressed genes are analyzed from larger studies, the most striking theme is upregulation of mitosis-promoting and cell proliferation genes in HCC compared with ,liver-specific gene clusters' in non-tumorous tissue. A major limitation of expression profiling is that it only provides a ,snapshot' of what is an evolving process and thus cannot distinguish the differences in gene expression that are primary effectors of dysregulated growth from those that represent downstream consequences. The development of HCC in a chronically diseased liver, often referred to as hepatocarcinogenesis, is a multistep process characterized by the progressive accumulation and interplay of genetic alterations causing aberrant growth, malignant transformation of liver parenchymal cells, followed by vascular invasion and metastasis. This review will discuss HCC precursor lesions, draw on the ,proliferation cluster' genes highlighted from HCC expression profiling studies, relate them to a selection of regulatory networks important in liver regeneration, cell cycle control and their potential significance in the pathogenesis of HCC or primary liver cancer. [source] Repair of porcine articular cartilage defect with a biphasic osteochondral composite,JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2007Ching-Chuan Jiang Abstract Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with ,-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress,relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1277,1290, 2007 [source] Simultaneous inactivation of the wprA and dltB genes of Bacillus subtilis reduces the yield of ,-amylaseLETTERS IN APPLIED MICROBIOLOGY, Issue 6 2002K. Stephenson Aims:,In Gram-positive bacteria, signal peptide-bearing secretory proteins are translocated through the cytoplasmic membrane and fold into their native conformation on the outside of the cell. The products of the Bacillus subtilis wprA and dltB genes separately influence post-translocational stages of the secretion process by mediating proteolytic degradation and folding of secretory proteins. Inactivation of either wprA or dltB in B. subtilis increases the yield of secretory proteins released into the culture medium in an intact and biologically active conformation. The aim of this work was to study the combined influence of these genes. Methods and Results:,A wprA/dltB double mutant was constructed, but did not have an additive effect on secretion and caused a significant reduction in the yield of ,-amylase. Conclusions and Significance:,The activities of the wprA gene and the dlt operon interact in a negative way to influence the growth cycle and protein secretion. The mechanism by which this may occur, and its potential significance for the secretion of native and non-native proteins from B. subtilis and related bacteria, is discussed. [source] Structural alterations in a type IV pilus subunit protein result in concurrent defects in multicellular behaviour and adherence to host tissueMOLECULAR MICROBIOLOGY, Issue 2 2001Hae-Sun Moon Park The ability of bacteria to establish complex communities on surfaces is believed to require both bacterial,substratum and bacterial,bacterial interactions, and type IV pili appear to play a critical but incompletely defined role in both these processes. Using the human pathogen Neisseria gonorrhoeae, spontaneous mutants defective in bacterial self-aggregative behaviour but quantitatively unaltered in pilus fibre expression were isolated by a unique selective scheme. The mutants, carrying single amino acid substitutions within the conserved amino-terminal domain of the pilus fibre subunit, were reduced in the ability to adhere to a human epithelial cell line. Co-expression of the altered alleles in the context of a wild-type pilE gene confirmed that they were dominant negative with respect to aggregation and human cell adherence. Strains expressing two copies of the altered alleles produced twice as much purifiable pili but retained the aggregative and adherence defects. Finally, the defects in aggregative behaviour and adherence of each of the mutants were suppressed by a loss-of-function mutation in the twitching motility gene pilT. The correlations between self-aggregation and the net capacity of the microbial population to adhere efficiently demonstrates the potential significance of bacterial cell,cell interactions to colonization. [source] Shotgun proteomic analysis of Chlamydia trachomatisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2005Paul Skipp Abstract Chlamydiae are widespread bacterial pathogens responsible for a broad range of diseases, including sexually transmitted infections, pneumonia and trachoma. To validate the existence of hitherto hypothetical proteins predicted from recent chlamydial genome sequencing projects and to examine the patterns of expression of key components at the protein level, we have surveyed the expressed proteome of Chlamydia trachomatis strain,L2. A combination of two-dimensional gel analysis, multi-dimensional protein identification (MudPIT) and nanocapillary liquid chromatography-tandem mass spectrometry allowed a total of 328,chlamydial proteins to be unambiguously assigned. Proteins identified as being expressed in the metabolically inert form, elementary body, of Chlamydia include the entire set of predicted glycolytic enzymes, indicating that metabolite flux rather than de novo synthesis of this pathway is triggered upon infection of host cells. An enzyme central to cell wall biosynthesis was also detected in the intracellular form, reticulate body, of Chlamydia, suggesting that the peptidoglycan is produced during growth within host cells. Other sets of proteins identified include 17 outer membrane-associated proteins of potential significance in vaccine studies and 67,proteins previously annotated as hypothetical or conserved hypothetical. Taken together, ,35% of the predicted proteome for C.,trachomatis has been experimentally verified, representing the most extensive survey of any chlamydial proteome to date. [source] Viral Control of Phytoplankton Populations,a Review,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2004CORINA P. D. BRUSSAARD ABSTRACT. Phytoplankton population dynamics are the result of imbalances between reproduction and losses. Losses include grazing, sinking, and natural mortality. As the importance of microbes in aquatic ecology has been recognized, so has the potential significance of viruses as mortality agents for phytoplankton. The field of algal virus ecology is steadily changing and advancing as new viruses are isolated and new methods are developed for quantifying the impact of viruses on phytoplankton dynamics and diversity. With this development, evidence is accumulating that viruses can control phytoplankton dynamics through reduction of host populations, or by preventing algal host populations from reaching high levels. The identification of highly specific host ranges of viruses is changing our understanding of population dynamics. Viral-mediated mortality may not only affect algal species succession, but may also affect intraspecies succession. Through cellular lysis, viruses indirectly affect the fluxes of energy, nutrients, and organic matter, especially during algal bloom events when biomass is high. Although the importance of viruses is presently recognized, it is apparent that many aspects of viral-mediated mortality of phytoplankton are still poorly understood. It is imperative that future research addresses the mechanisms that regulate virus infectivity, host resistance, genotype richness, abundance, and the fate of viruses over time and space. [source] Junctin and the histidine-rich Ca2+ binding protein: potential roles in heart failure and arrhythmogenesisTHE JOURNAL OF PHYSIOLOGY, Issue 13 2009Tracy J. Pritchard Contractile dysfunction and ventricular arrhythmias associated with heart failure have been attributed to aberrant sarcoplasmic reticulum (SR) Ca2+ cycling. The study of junctin (JCN) and histidine-rich Ca2+ binding protein (HRC) becomes of particular importance since these proteins have been shown to be critical regulators of Ca2+ cycling. Specifically, JCN is a SR membrane protein, which is part of the SR Ca2+ release quaternary structure that also includes the ryanodine receptor, triadin and calsequestrin. Functionally, JCN serves as a bridge between calsequestrin and the Ca2+ release channel, ryanodine receptor. HRC is a SR luminal Ca2+ binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca2+ -ATPase, and may thus mediate the crosstalk between SR Ca2+ uptake and release. Indeed, evidence from genetic models of JCN and HRC indicate that they are important in cardiophysiology as alterations in these proteins affect SR Ca2+ handling and cardiac function. In addition, downregulation of JCN and HRC may contribute to Ca2+ cycling perturbations manifest in the failing heart, where their protein levels are significantly reduced. This review examines the roles of JCN and HRC in SR Ca2+ cycling and their potential significance in heart failure. [source] Determinants of Placental VascularityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2004Donald S. Torry Problem:, Vascular growth during implantation and placentation is critical for successful gestation and it is thought that vascular insufficiencies during placentation contribute to a number of obstetrical complications. However, relatively little is known regarding the regulation of angiogenesis in the placenta. Method of study:, We review literature concerning the potential significance of inadequate placental vascularity as a contributor to the obstetrical complications of spontaneous abortion, fetal growth restriction and preeclampsia. Gene expression assays were used to compare fluctuations of placenta growth factor (PlGF) and PlGF receptor expression in normal and preeclamptic trophoblast in vitro. Results:, Studies have shown that common obstetrical complications manifest altered placental vascularity. Both intrinsic defects (gene knockouts) and extrinsic factors (O2 tension, cytokines, etc) may be responsible for the defects. Some of these factors have been shown to influence trophoblast vascular endothelial growth factor (VEGF)/PlGF expression suggesting this particular family of angiogenic proteins play an important role in placental angiogenesis. Conclusion:, Placental vascularization reflects a complex interaction of regulatory factors. Understanding the regulation of vascular growth in the placenta will provide much needed insight into placenta-related vascular insufficiencies. [source] NEW ESTIMATES OF AUSTRALIAN PUBLIC BORROWING AND CAPITAL RAISED IN LONDON, 1849,1914AUSTRALIAN ECONOMIC HISTORY REVIEW, Issue 2 2007Article first published online: 7 JUN 200, Bernard Attard Australia; capital market; debt; foreign exchange; statistics Current statistics of Australian public borrowing to 1914 suffer from several limits. On the basis of a comprehensive revision, an upward bias is shown in all the alternative time series of London borrowing, while statistics of local bond issues are derived for the first time. The new time series show the importance of the initial borrowing cycle during the 1850s and 1860s; the scale of debt repatriation from the mid-1890s; the interaction between domestic and overseas borrowing before the 1880s; and the potential significance of remittance as an ,invisible stabiliser' of the exchanges and alternative indirect source of capital imports. [source] Cluster Formation as a Measure of Interpretability in Multiple TestingBIOMETRICAL JOURNAL, Issue 5 2008Juliet Popper Shaffer Abstract Multiple test procedures are usually compared on various aspects of error control and power. Power is measured as some function of the number of false hypotheses correctly identified as false. However, given equal numbers of rejected false hypotheses, the pattern of rejections, i.e. the particular set of false hypotheses identified, may be crucial in interpreting the results for potential application. In an important area of application, comparisons among a set of treatments based on random samples from populations, two different approaches, cluster analysis and model selection, deal implicitly with such patterns, while traditional multiple testing procedures generally focus on the outcomes of subset and pairwise equality hypothesis tests, without considering the overall pattern of results in comparing methods. An important feature involving the pattern of rejections is their relevance for dividing the treatments into distinct subsets based on some parameter of interest, for example their means. This paper introduces some new measures relating to the potential of methods for achieving such divisions. Following Hartley (1955), sets of treatments with equal parameter values will be called clusters. Because it is necessary to distinguish between clusters in the populations and clustering in sample outcomes, the population clusters will be referred to as P -clusters; any related concepts defined in terms of the sample outcome will be referred to with the prefix outcome. Outcomes of multiple comparison procedures will be studied in terms of their probabilities of leading to separation of treatments into outcome clusters, with various measures relating to the number of such outcome clusters and the proportion of true vs. false outcome clusters. The definitions of true and false outcome clusters and related concepts, and the approach taken here, is in the tradition of hypothesis testing with attention to overall error control and power, but with added consideration of cluster separation potential. The pattern approach will be illustrated by comparing two methods with apparent FDR control but with different ways of ordering outcomes for potential significance: The original Benjamini,Hochberg (1995) procedure (BH), and the Newman,Keuls (Newman, 1939; Keuls, 1952) procedure (NK). (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] High serum levels of B-lymphocyte stimulator are associated with clinical,pathological features and outcome in classical Hodgkin lymphomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2007C. Tecchio Summary B-lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As Hodgkin and Reed-Sternberg (HRS) cells express receptors through which BLyS promotes their growth and chemotherapy resistance, we investgated whether this molecule was increased in sera from patients with classical Hodgkin lymphoma (cHL) and whether it correlates with clinical-pathological features and outcomes. Enzyme-linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in sera from 87 patients and 33 donors; higher levels were detected in patients (mean ± standard error 4493·9 ± 264·9 pg/ml vs. 2687·0 ± 200·9 pg/ml; P < 0·0001). Levels above the median value (4242·0 pg/ml) were associated with age ,45 years (P = 0·042), advanced stages of disease (P = 0·005), systemic symptoms (P = 0·014) and extranodal involvement (P = 0·009). Five-year failure-free survival (FFS) of patients with sBLyS below or equal to median levels was 88·6% as compared to 65·1% of those with levels above the median (P = 0·009). Statistical analyses confirmed the prognostic significance of sBLyS (P = 0·046). When patients were analysed according to variables associated with high levels, sBLyS showed an independent predictive power in terms of FFS. Our findings support the involvement of BLyS in cHL pathogenesis. The association between high serum levels and an inferior FFS indicates that sBLyS is a possible prognostic predictor with a potential significance as a therapeutic target. [source] From tumor lymphangiogenesis to lymphvascular nicheCANCER SCIENCE, Issue 6 2009Satoshi Hirakawa Metastasis in sentinel lymph nodes indicates the initial spread of tumors from a primary site. The recent discovery of tumor-associated growth of lymphatic vessels clarified that tumor lymphangiogenesis actively promotes enhanced draining/sentinel lymph node metastasis. Studies of experimental carcinogenesis have further established that tumors continue to induce lymphangiogenesis in metastatic foci such as draining lymph nodes. Lymphangiogenesis within draining lymph nodes probably contributes to enhanced distant lymph node and distant organ metastases. Lymph node lymphangiogenesis has recently been identified in several human malignancies, such as cutaneous malignant melanoma. Tumor-associated lymphangiogenesis thus has potential significance not only at the primary site, but also in lymph nodes. Primary tumors induce new lymphatic vessel growth in draining lymph nodes before metastasis. The remarkable enlargement of sinusoidal lymphatic endothelium might facilitate tumor cell transport to the lymph nodes, and potentially contribute to the migration, residence, and/or survival of metastatic tumor cancer stem cells by inducing a specific tumor microenvironment. Therefore, the novel concept of ,lymphvascular niche' is proposed herein to explain lymphatic network expansion. This concept might help to improve understanding of the molecular mechanism of lymph node metastasis, and change therapeutic approaches to treating cancer metastasis. (Cancer Sci 2009; 100: 983,989) [source] The Significance of Insecure Attachment and Disorganization in the Development of Children's Externalizing Behavior: A Meta-Analytic StudyCHILD DEVELOPMENT, Issue 2 2010R. Pasco Fearon This study addresses the extent to which insecure and disorganized attachments increase risk for externalizing problems using meta-analysis. From 69 samples (N = 5,947), the association between insecurity and externalizing problems was significant, d = 0.31 (95% CI: 0.23, 0.40). Larger effects were found for boys (d = 0.35), clinical samples (d = 0.49), and from observation-based outcome assessments (d = 0.58). Larger effects were found for attachment assessments other than the Strange Situation. Overall, disorganized children appeared at elevated risk (d = 0.34, 95% CI: 0.18, 0.50), with weaker effects for avoidance (d = 0.12, 95% CI: 0.03, 0.21) and resistance (d = 0.11, 95% CI: ,0.04, 0.26). The results are discussed in terms of the potential significance of attachment for mental health. [source] |