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Genetic Level (genetic + level)
Selected AbstractsEffect of 5-lipoxygenase inhibitor MK591 on early molecular and signaling events induced by staphylococcal enterotoxin B in human peripheral blood mononuclear cellsFEBS JOURNAL, Issue 12 2008Chanaka Mendis Staphylococcal enterotoxin B (SEB) has been the focus of a number of studies due to its ability to promote septic shock and a massive impact on the human immune system. Even though symptoms and pathology associated with SEB is well known, early molecular events that lead to lethality are still poorly understood. Our approach was to utilize SEB induced human peripheral blood mononuclear cells (PBMCs) as a prototype module to further investigate the complexity of signaling cascades that may ultimately lead to lethal shock. Our study revealed the activation of multiple divergent intracellular pathways within minutes of SEB induction including components that interconnect investigated pathways. A series of performed inhibitor studies identified a specific inhibitor of 5-LO (MK591), which has the ability to block JNK, MAPK, p38kinase and 5-LO signaling-cascades and drastically reducing the activity of pro-inflammatory cytokine TNF-,. Further evaluation of MK591 utilizing cell proliferation assays in PBMCs, human proximal tubule cells and in vivo studies (monkey) showed a decrease in cell proliferation. The inhibitory effect of MK591 was reconfirmed at a genetic level through the utilization of a set of SEB specific genes. Signaling activities, inhibitor studies, cellular analysis and gene expression analysis in unison illustrated the significance of pathway interconnectors such as 5-LO as well as inhibiting such inter-connectors (using MK591) in SEB induced human PBMCs. [source] Genotype differences in cognitive functioning in Noonan syndromeGENES, BRAIN AND BEHAVIOR, Issue 3 2009E. I. Pierpont Noonan syndrome (NS) is an autosomal-dominant genetic disorder associated with highly variable features, including heart disease, short stature, minor facial anomalies and learning disabilities. Recent gene discoveries have laid the groundwork for exploring whether variability in the NS phenotype is related to differences at the genetic level. In this study, we examine the influence of both genotype and nongenotypic factors on cognitive functioning. Data are presented from 65 individuals with NS (ages 4,18) who were evaluated using standardized measures of intellectual functioning. The cohort included 33 individuals with PTPN11 mutations, 6 individuals with SOS1 mutations, 1 individual with a BRAF mutation and 25 participants with negative, incomplete or no genetic testing. Results indicate that genotype differences may account for some of the variation in cognitive ability in NS. Whereas cognitive impairments were common among individuals with PTPN11 mutations and those with unknown mutations, all of the individuals with SOS1 mutations exhibited verbal and nonverbal cognitive skills in the average range or higher. Participants with N308D and N308S mutations in PTPN11 also showed no (or mild) cognitive delays. Additional influences such as hearing loss, motor dexterity and parental education levels accounted for significant variability in cognitive outcomes. Severity of cardiac disease was not related to cognitive functioning. Our results suggest that some NS-causing mutations have a more marked impact on cognitive skills than others. [source] Genomic analysis of Barrett's esophagus after ablative therapy: Persistence of genetic alterations at tumor suppressor lociINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Mariska Hage Abstract Barrett's esophagus (BE) is a major predisposing factor for the development of esophageal adenocarcinoma. Current strategies for treatment of BE, both dysplastic and nondysplastic, include photodynamic therapy (PDT) and argon plasma coagulation (APC). However, the effect of ablative therapy at the genetic level is unclear. We performed loss of heterozygosity (LOH) analysis of BE in baseline and follow-up biopsy specimens from 21 patients with BE (17 male, 4 female) treated with PDT and/or APC. At baseline, 14 patients had intestinal metaplasia without dysplasia (MET), 4 low-grade dysplasia (LGD) and 3 high-grade dysplasia (HGD). LOH was assessed using a panel of 9 polymorphic markers for evaluation of the P53 gene on 17p, P16 on 9p, DCC and SMAD4 on 18q and the APC gene on 5q. The tissue specimens obtained at baseline (t = 0) were analysed, as well as the first (t = 1; mean interval: 4 months) and last (t = 2; mean interval: 8 months) available biopsy with residual or recurrent BE after ablation. At t = 0, allelic loss was detected of 5q in 27%, 9p in 56%, 17p in 31% and 18q in 6% of informative cases. At t = 1 (18 patients with persistent MET and 3 with LGD) and at t = 2 (8 MET, 2 LGD), the LOH patterns were not statistically different from t = 0. Further, multiple genetic lineages before and after therapy were detected in 15 cases illustrating the multiclonal nature of BE. We conclude that recurrent and/or persistent BE after ablative therapy still contains genetic alterations associated with malignant progression to cancer. Therefore, the goal of treatment should be the complete elimination of Barrett's mucosa. © 2005 Wiley-Liss, Inc. [source] Blood group antigens and immune responses,detailed knowledge is necessary to prevent immunization and to follow up immunized individualsISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n1 2010A. Husebekk Background The immune system is educated to detect and react with foreign antigens and to tolerate self-antigen. Transfusion of blood cells and plasma and pregnancies challenge the immune system by the introduction of foreign antigens. The antigens may cause an immune response, but in many instances this is not the case and the individual is not immunised after exposure of blood group antigens. Aims The aim of the presentation is to dissect some immune responses to blood group antigens in order to understand the mechanism of immunisation. Methods The results of immune responses to blood group antigens can be detected by the presence of antibodies to the antigens. If the antibodies are of IgG class, the activated B cells have received help from antigen specific T cells. Both antibodies, B cells and T cells can be isolated from immunised individuals and studied in the laboratory. Also B-cell receptors and T-cell receptors as well as MHC molecules on antigen presenting cells can be studied and models of the immune synapses can be created in vitro. Results The most classic immune responses in transfusion medicine and in incompatible pregnancies are immune responses to the RhD antigen on red cells, HLA class I molecules on white cells and platelets and human platelet antigens. The nature of these antigens are different; RhD antigens are part of a large complex, present on red cells from RhD positive individuals and completely lacking on red cells from RhD negative individuals. It is likely that many peptides derived from this antigen complex may stimulate T cells and B cells. HLA antigens are highly polymorphic and the antigens are known to induce strong alloimmune responses. The HPA antigens are created by one amino acid difference in allotypes based on a single nucleotide polymorphism at the genetic level. HPA 1a induce immune responses in 10% of HPA 1b homozygote pregnant women. The result of these immune responses is destruction of blood cells with clinical consequences connected to the effect of transfusions or the outcome of pregnancies. Summary/Conclusions Even though there is emerging knowledge about the immune responses to some of the blood group antigens, more information must be gained in order to understand the complete picture. The action of the innate immune response initiating the adaptive immune response to blood group antigens is not well understood. A detailed understanding of both the innate ad the adaptive part of the immune response is necessary to identify individuals at risk for immunisation and to prevent immunisation to blood group antigens. [source] Heritability of human cranial dimensions: comparing the evolvability of different cranial regionsJOURNAL OF ANATOMY, Issue 1 2009Neus Martínez-Abadías Abstract Quantitative craniometrical traits have been successfully incorporated into population genetic methods to provide insight into human population structure. However, little is known about the degree of genetic and non-genetic influences on the phenotypic expression of functionally based traits. Many studies have assessed the heritability of craniofacial traits, but complex patterns of correlation among traits have been disregarded. This is a pitfall as the human skull is strongly integrated. Here we reconsider the evolutionary potential of craniometric traits by assessing their heritability values as well as their patterns of genetic and phenotypic correlation using a large pedigree-structured skull series from Hallstatt (Austria). The sample includes 355 complete adult skulls that have been analysed using 3D geometric morphometric techniques. Heritability estimates for 58 cranial linear distances were computed using maximum likelihood methods. These distances were assigned to the main functional and developmental regions of the skull. Results showed that the human skull has substantial amounts of genetic variation, and a t -test showed that there are no statistically significant differences among the heritabilities of facial, neurocranial and basal dimensions. However, skull evolvability is limited by complex patterns of genetic correlation. Phenotypic and genetic patterns of correlation are consistent but do not support traditional hypotheses of integration of the human shape, showing that the classification between brachy- and dolicephalic skulls is not grounded on the genetic level. Here we support previous findings in the mouse cranium and provide empirical evidence that covariation between the maximum widths of the main developmental regions of the skull is the dominant factor of integration in the human skull. [source] Discrimination of Staphylococcus aureus biotypes by pulsed-field gel electrophoresis of DNA macro-restriction fragmentsJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2003J.A. Hennekinne Abstract Aims: To examine whether pulsed-field gel electrophoresis (PFGE) of DNA macro-restriction fragments could provide better discrimination among the different biotypes previously described within the species Staphylococcus aureus than the traditional biochemical approach. Methods and Results: Seventy three Staph. aureus strains from various sources (human, animal or food origin) and belonging to eight biotypes, including the poultry-like biotype, tentatively designated as an ,abattoir' biotype, were genotyped by PFGE after SmaI digestion of DNA. The PFGE patterns were compared using the average linkage matching method (UPGMA) with the Dice coefficient. A total of 61 PFGE patterns were observed, showing between 31 and 100% similarity. In most cases, strains with the same biotype were grouped specifically into one, two or three separate sub-clusters. Strains from the ,abattoir' biotype were clustered in one separate sub-cluster. Conclusions: The PFGE typing is useful to distinguish the traditional biotypes of Staph. aureus and has a more discriminatory power than the biochemical typing. Significance and Impact of the Study: The PFGE typing confirms the ,abattoir' biotype as a separate group on a genetic level and is well suited to investigate modes of staphylococcal contamination of food. [source] Archaeal diversity in acid mine drainage from Dabaoshan Mine, ChinaJOURNAL OF BASIC MICROBIOLOGY, Issue 5 2008Guan-zhou Qiu Abstract Three acid mine drainage (AMD) samples collected from Dabaoshan Mine (Guangdong Province, China) were studied. In addition to physicochemical analyses, the diversity and community structures of the archaeal communities in these samples were described at the genetic level by amplified ribosomal DNA restriction analysis (ARDRA). Nine different ARDRA patterns were obtained from 146 clones and were studied as operational taxonomic units (OTUs), which were re-amplified and sequenced. Sequence data and phylogenetic analysis showed that most of the clones belonged to the Thermoplasmatales, and that archaea belonging to the Sulfolobales were absent. Only 1 OTU attributed to Ferroplasma was found and was observed to be abundant in all 3 samples. Eight OTUs were related to 2 new undefined groups in the Thermoplasmatales. Of the 8 OTUs, the clones in 2 similar units were isolated from samples collected from an abandoned sulfide mine (Huelva, Spain) and those in 5 similar units were isolated from samples collected from a closed copper mine (Tonglushan, China). These diversities were characterized by the reciprocal of Simpson's index (1/D) and correlated with the concentrations of ferrous ions and toxic ions in the AMD samples. The high temperature of the sampling sites was one of the factors that could explain why archaea belonging to the Thermoplasmatales were abundant in the analyzed AMD samples while those belonging to the Sulfolobales were absent. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] A New Farnesyl Diphosphate Synthase Gene from Taxus media Rehder: Cloning, Characterization and Functional ComplementationJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 6 2006Zhi-Hua Liao Abstract Farnesyl diphosphate synthase (FPS; EC 2.5.1.10) catalyzes the production of 15-carbon farnesyl diphosphate which is a branch-point intermediate for many terpenoids. This reaction is considered to be a rate-limiting step in terpenoid biosynthesis. Here we report for the first time the cloning of a new full-length cDNA encoding farnesyl diphosphate synthase from a gymnosperm plant species, Taxus media Rehder, designated as TmFPS1. The full-length cDNA of TmFPS1 (GenBank accession number: AY461811) was 1 464 bp with a 1 056-bp open reading frame encoding a 351-amino acid polypeptide with a calculated molecular weight of 40.3 kDa and a theoretical pI of 5.07. Bioinformatic analysis revealed that TmFPS1 contained all five conserved domains of prenyltransferases, and showed homology to other FPSs of plant origin. Phylogenetic analysis showed that farnesyl diphosphate synthases can be divided into two groups: one of prokaryotic origin and the other of eukaryotic origin. TmFPS1 was grouped with FPSs of plant origin. Homology-based structural modeling showed that TmFPS1 had the typical spatial structure of FPS, whose most prominent structural feature is the arrangement of 13 core helices around a large central cavity in which the catalytic reaction takes place. Our bioinformatic analysis strongly suggests that TmFPS1 is a functional gene. Southern blot analysis revealed that TmFPS1 belongs to a small FPS gene family in T. media. Northern blot analysis indicated that TmFPS1 is expressed in all tested tissues, including the needles, stems and roots of T. media. Subsequently, functional complementation with TmFPS1 in a FPS-deficient mutant yeast demonstrated that TmFPS1 did encode farnesyl diphosphate synthase, which rescued the yeast mutant. This study will be helpful in future investigations aiming at understanding the detailed role of FPS in terpenoid biosynthesis flux control at the molecular genetic level. (Managing editor: Wei Wang) [source] Transplantation of mesenchymal stem cells in a canine disc degeneration modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2008Akihiko Hiyama Abstract Transplantation of mesenchymal stem cells (MSCs) is effective in decelerating disc degeneration in small animals; much remains unknown about this new therapy in larger animals or humans. Fas-ligand (FasL), which is only found in tissues with isolated immune privilege, is expressed in IVDs, particularly in the nucleus pulposus (NP). Maintaining the FasL level is important for IVD function. This study evaluated whether MSC transplantation has an effect on the suppression of disc degeneration and preservation of immune privilege in a canine model of disc degeneration. Mature beagles were separated into a normal control group (NC), a MSC group, and the disc degeneration (nucleotomy-only) group. In the MSC group, 4 weeks after nucleotomy, MSCs were transplanted into the degeneration-induced discs. The animals were followed for 12 weeks after the initial operation. Subsequently, radiological, histological, biochemical, immunohistochemical, and RT-PCR analyses were performed. MSC transplantation effectively led to the regeneration of degenerated discs. FACS and RT-PCR analyses of MSCs before transplantation demonstrated that the MSCs expressed FasL at the genetic level, not at the protein level. GFP-positive MSCs detected in the NP region 8 weeks after transplantation expressed FasL protein. The results of this study suggest that MSC transplantation may contribute to the maintenance of IVD immune privilege by the differentiation of transplanted MSCs into cells expressing FasL. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:589,600, 2008 [source] Cancer, chitosan nanoparticles and catalytic nucleic acidsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2009Mei Lin Tan Abstract Objectives The aim of this review was to examine gene therapy involving DNAzyme and siRNA encapsulation into chitosan nanoparticles, discussing the current and future status of this drug delivery system in enhancing drug delivery and cancer therapy. Key findings Cancer is a disease state in which the cells in our body undergo mutations at the genetic level and are transformed, acquiring the ability to replicate limitlessly. Conventional cancer treatment involves the use of surgery and cytotoxic chemotherapy and/or radiotherapy, which have the potential of harming normal, otherwise healthy, non-neoplastic cells. Newer forms of therapy such as immunotherapy and gene therapy have shown initial promise, but still require better ways to limit exposure to cancerous lesions in the body. As a result drug delivery systems have been developed in attempts to deliver therapeutics specifically to the target lesion site. One recent drug delivery system has revolved around the use of chitosan nanoparticle technology, where therapeutics are encapsulated into nanoparticles and targeted to tumours. Summary Though few, attempts at encapsulating therapeutics such as deoxyribozymes and small or short interfering RNA have been optimistic and encouraging. [source] New established melanoma cell lines: genetic and biochemical characterization of cell division cycleJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2003A Vozza ABSTRACT Background Cancer might be envisaged as the result of a genetic process causing the unregulated proliferation of a given cell as well as its inability to undergo differentiation and/or apoptosis. Alterations of genes regulating cell division cycle appear to play a key role in the development of human cancer. Objective On the bases of the above considerations, we decided to establish new cell lines from human melanoma specimens, in order to analyse the molecular alterations in primary preparations of malignant cells. Results The present paper describes two new established cell lines and their genetic and biochemical features. Both the melanoma cell lines show inactivation of the cyclin-dependent kinase inhibitor gene, CDKN2A/p16INK4A, thus demostrating that this alteration occurs in primary human melanomas. No other alterations were observable when we investigated several different cell cycle genes including those encoding cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Analyses at protein level by means of immunoblotting confirmed the results obtained at the genetic level. Moreover, the inducibility of a pivotal cyclin-dependent kinase inhibitor gene, namely p21CIP1 gene, was obtained by treating the cells with histone deacetylase inhibitors, namely butyrate and phenylbutyrate. Conclusions Our results suggest a primary role of cyclin-dependent kinase inhibitor genes inactivation in the origin of human melanoma and allow the proposal of new therapeutic strategies based on the transcriptional activation of p21CIP1 gene. [source] Breeding of Pleurotus florida (oyster mushroom) for phenotypic pigmentation and high yield potentialJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 15 2008Jatinder Kaur Abstract BACKGROUND: Cross-hybridisation is a technique for exchange of genetic material between two compatible nuclei to develop a recombinant genome with a probable expression for a desirable trait. This technique as an example of classical genetics has been applied in a heterothallic bifactorial/tetrapolar fungus Pleurotus florida. It has worked successfully during this study in a small number of experiments. RESULTS: Fruit bodies from the Pleurotus florida PAU-5 were allowed to shed their basidiospores on filter paper under aseptic conditions. Forty-nine monokaryons were isolated from three spore prints, namely Ja, Jb and K. Three hundred and fifty-six crosses were laid to result in five compatible reactions (PFJ4, PFJ9, PFJ11, PFJ13 and PFJ14). The fruit bodies of the hybrid dikaryon PFJ4 were found to show grey pigmentation. The hybrid dikaryons PFJ11 and PFJ14 grew faster in wheat straw substrate to take 39 and 41 days, respectively, for complete mycelial impregnation as compared to the parent, PAU-5 (48 days). The dikaryon PFJ11 out-yielded the parent by giving 34.2% biological efficiency compared to 29.8% for the parent. CONCLUSION: Through cross-hybridisation various changes at the genetic level are possible, showing altered phenotypic expression of the characters, such as change in fruiting efficiency and variability in fruit body characteristics (e.g., pileus shape and pigmentation). This technique can also be applied to other crops to improve their yield potential and bring about desirable phenotypic changes. Copyright © 2008 Society of Chemical Industry [source] Review article: should we kill or should we save Helicobacter pylori?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2001R.H. Hunt Results from epidemiological studies and therapeutic clinical trials have shown that Helicobacter pylori infection causes acute and chronic active gastritis and is the initiating factor for the majority of peptic ulcer disease. Eradication of the infection with antibiotics resolves gastritis and restores normal gastric physiology, accelerates healing of peptic ulcer disease, and virtually eliminates recurrence of duodenal ulcer disease. The infection also plays an important role in the initiation and/or progression of gastric atrophy and intestinal metaplasia, which may eventually lead to the development of distal gastric cancer. Furthermore, almost all patients with gastric MALT lymphoma are infected with H. pylori and cure of the infection leads to histological regression of the tumor and maintains the regression in over 80% of patients during long-term follow-up. Preliminary uncontrolled data from Japan show that eradication of the infection significantly reduced metachronous intestinal-type gastric cancer following initial endoscopic resection of early gastric cancer and might also prevent the progression of gastric adenoma to gastric dysplasia or gastric cancer. Although this overwhelming evidence has demonstrated that H. pylori infection is bad for humans, some have questioned the wisdom of eradicating the infection in all those infected. Their arguments are largely based on hypothesis and circumstantial evidence: 1) Less than 20% of all H. pylori infected persons will develop significant clinical consequences in their lifetime. 2) H. pylori strains are highly diverse at a genetic level and are of different virulence. 3) The antiquity of H. pylori infection in humans and their co-evolution suggests that H. pylori may be a commensal to humans. Eradication of H. pylori may remove some beneficial bacterial strains and may provoke esophageal disease or gastric cancer at the cardia. However, careful review of the literature confirms that H. pylori infection is a serious pathogen albeit in a minority of those infected. It remains for carefully designed prospective studies, rather than hypothesis to make changes in the current consensus position. [source] Absence of FGFR3 mutations in urinary bladder tumours of rats and mice treated with N -butyl- N -(-4-hydroxybutyl)nitrosamineMOLECULAR CARCINOGENESIS, Issue 3 2005Claire Dunois-Lardé Abstract Frequent activating mutations of FGFR3 (fibroblast growth factor receptor 3) are found in human urothelial cell carcinomas, particularly in superficial papillary tumours (in 74%,84% of pTaG1-G2), but not in carcinomas in situ (CIS) and at a low rate in invasive tumours (in 16%,21% of pT1-4). In mice and rats, BBN (N -butyl- N -(4-hydroxybutyl)nitrosamine) specifically induces bladder tumours. In rats, superficial papillary tumours are mostly observed. In mice, tumour progression follows the CIS pathway: CIS are first observed, followed by tumours that invade surrounding muscle. Therefore, we looked for FGFR3 mutations in these two animal models of bladder cancer. Only the FGFR3b isoform is expressed in human urothelium and derived tumours. We identified the FGFR3b isoform in rats for the first time and showed that this is the main isoform expressed in the bladder urothelium and derived carcinomas in mice and rats, as in humans. SSCP and sequence analysis of FGFR3b showed sequence changes (polymorphisms or silent mutations) in four BBN-induced rat and mouse bladder tumours. The absence of activating mutations of FGFR3 in the mouse model was in agreement with the fact that mouse BBN-induced bladder tumour progression mimics the CIS pathway. The absence of FGFR3 mutations in the rat bladder tumours suggests that, at least at the genetic level, rat superficial papillary tumours differ from their human counterparts. © 2005 Wiley-Liss, Inc. [source] Molecular ecology of global changeMOLECULAR ECOLOGY, Issue 19 2007THORSTEN B. H. REUSCH Abstract Global environmental change is altering the selection regime for all biota. The key selective factors are altered mean, variance and seasonality of climatic variables and increase in CO2 concentration itself. We review recent studies that document rapid evolution to global climate change at the phenotypic and genetic level, as a response to shifts in these factors. Among the traits that have changed are photoperiod responses, stress tolerance and traits associated with enhanced dispersal. The genetic basis of two traits with a critical role under climate change, stress tolerance and photoperiod behaviour, is beginning to be understood for model organisms, providing a starting point for candidate gene approaches in targeted nonmodel species. Most studies that have documented evolutionary change are correlative, while selection experiments that manipulate relevant variables are rare. The latter are particularly valuable for prediction because they provide insight into heritable change to simulated future conditions. An important gap is that experimental selection regimes have mostly been testing one variable at a time, while synergistic interactions are likely under global change. The expanding toolbox available to molecular ecologists holds great promise for identifying the genetic basis of many more traits relevant to fitness under global change. Such knowledge, in turn, will significantly advance predictions on global change effects because presence and polymorphism of critical genes can be directly assessed. Moreover, knowledge of the genetic architecture of trait correlations will provide the necessary framework for understanding limits to phenotypic evolution; in particular as lack of critical gene polymorphism or entire pathways, metabolic costs of tolerance and linkage or pleiotropy causing negative trait correlations. Synergism among stressor impacts on organismal function may be causally related to conflict among transcriptomic syndromes specific to stressor types. Because adaptation to changing environment is always contingent upon the spatial distribution of genetic variation, high-resolution estimates of gene flow and hybridization should be used to inform predictions of evolutionary rates. [source] Bipolar gene flow in deep-sea benthic foraminiferaMOLECULAR ECOLOGY, Issue 19 2007J. PAWLOWSKI Abstract Despite its often featureless appearance, the deep-ocean floor includes some of the most diverse habitats on Earth. However, the accurate assessment of global deep-sea diversity is impeded by a paucity of data on the geographical ranges of bottom-dwelling species, particularly at the genetic level. Here, we present molecular evidence for exceptionally wide distribution of benthic foraminifera, which constitute the major part of deep-sea meiofauna. Our analyses of nuclear ribosomal RNA genes revealed high genetic similarity between Arctic and Antarctic populations of three common deep-sea foraminiferal species (Epistominella exigua, Cibicides wuellerstorfi and Oridorsalis umbonatus), separated by distances of up to 17 000 km. Our results contrast with the substantial level of cryptic diversity usually revealed by molecular studies, of shallow-water benthic and planktonic marine organisms. The very broad ranges of the deep-sea foraminifera that we examined support the hypothesis of global distribution of small eukaryotes and suggest that deep-sea biodiversity may be more modest at global scales than present estimates suggest. [source] Isolation and characterization of microsatellites in Chinese soft-shelled turtle, Pelodiscus sinensisMOLECULAR ECOLOGY RESOURCES, Issue 6 2007YANFU QUE Abstract Fifteen polymorphic microsatellite loci were developed for the Chinese soft-shelled turtle (Pelodiscus sinensis) from the (GT)n microsatellite-enriched genomic library, using the fast isolation by amplified fragment length polymorphism of sequences containing repeats protocol. The polymorphism of all 15 loci ranged from two to seven alleles with observed heterozygosities ranging from 0.03 to 0.98 (mean 0.43) in one population of 40 individuals. These novel loci will be helpful for understanding the population structure at genetic level and marker-assisted breeding of this vulnerable species. [source] Analysis of Saccharomyces cerevisiae null allele strains identifies a larger role for DNA damage versus oxidative stress pathways in growth inhibition by seleniumMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 11 2008Eden Seitomer Abstract Selenium toxicity is a growing environmental concern due to widespread availability of high-dose selenium supplements and the development of high-selenium agricultural drainage basins. To begin to analyze the effects of selenium toxicity at the genetic level, we have systematically determined which genes are involved in responding to high environmental selenium using a collection of viable haploid null allele strains of Saccharomyces cerevisiae representing three major stress pathways: the RAD9 -dependent DNA repair pathway, the RAD6/RAD18 DNA damage tolerance pathway, and the oxidative stress pathway. A total of 53 null allele strains were tested for growth defects in the presence of a range of sodium selenite and selenomethionine (SeMet) concentrations. Our results show that ,64,72% of the strains lacking RAD9 -dependent DNA repair or RAD6/RAD18 DNA damage tolerance pathway genes show reduced growth in sodium selenite versus ,28,36% in SeMet. Interestingly both compounds reduced growth in ,21,25% of the strains lacking oxidative stress genes. These data suggest that both selenite and SeMet are likely inducing DNA damage by generating reactive species. The anticipated effects of loss of components of the oxidative stress pathway were not observed, likely due to apparent redundancies in these gene products that may keep the damaging effects in check. [source] Towards an integrated environmental assessment for wetland and catchment managementTHE GEOGRAPHICAL JOURNAL, Issue 2 2003R Kerry Turner This paper develops a decision support system for evaluation of wetland ecosystem management strategy and examines its, so far partial, application in a case study of an important complex coastal wetland known as the Norfolk and Suffolk Broads, in the east of England, UK. Most managed ecosystems are complex and often poorly understood hierarchically organized systems. Capturing the range of relevant impacts on natural and human systems under different management options will be a formidable challenge. Biodiversity has a hierarchical structure which ranges from the ecosystem and landscape level, through the community level and down to the population and genetic level. There is a need to develop methodologies for the practicable detection of ecosystem change, as well as the evaluation of different ecological functions. What is also required is a set of indicators (environmental, social and economic) which facilitate the detection of change in ecosystems suffering stress and shock and highlight possible drivers of the change process. A hierarchical classification of ecological indicators of sustainability would need to take into account existing interactions between different organization levels, from species to ecosystems. Effects of environmental stress are expressed in different ways at different levels of biological organization and effects at one level can be expected to impact other levels, often in unpredictable ways. The management strategy, evaluation methodologies and indicators adopted should also assess on sustainability grounds whether any given management option is supporting, or reducing, the diversity of functions which are providing stakeholders with the welfare benefits they require. [source] Genetic, Morphological, and Ecological Diversity of Spatially Separated Clones of Meseres corlissi Petz & Foissner, 1992 (Ciliophora, Spirotrichea)THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 4 2008THOMAS WEISSE ABSTRACT. We investigated the intraspecific variation of the spirotrich freshwater ciliate Meseres corlissi at the level of genes (SSrDNA, ITS), morphology (14 characters), and ecophysiology (response to temperature and pH). Five of the eight clonal M. corlissi cultures isolated from five localities on four continents were studied at all levels. The null hypothesis was that geographic distance plays no role: M. corlissi lacks biogeography. The intraspecific variation was low at the genetic level (0%,4%), moderate at the morphological level (5%,15%), and high at the ecophysiological level (10%,100%). One clone, isolated from subtropical China, differed significantly at all levels from all other clones, suggesting limited dispersal and local adaptation among M. corlissi. However, other clones from distant areas, such as Australia and Austria, were genetically identical and differed only slightly in morphology and temperature response. We speculate that our findings may be typical for rare species; the chances may be equally high for both global dispersal of most and local adaptation of some populations in areas where dispersal has been permanently or temporarily reduced. [source] A de Novo PABPN1 Germline Mutation in a Patient with Oculopharyngeal Muscular Dystrophy,THE LARYNGOSCOPE, Issue 1 2006Nicolas Gürtler Abstract Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominantly inherited disorder characterized by dysphagia, ptosis, and proximal limb weakness and is caused by germline mutations (triplet repeat expansions) in the polyadenylate binding protein nuclear 1 (PABPN1) gene. Objective: To describe a 70-year-old female patient with OPMD on the clinical and molecular genetic level and to develop a rapid and efficient molecular genetic screening method to study large patient groups. Methods: Detailed family history and clinical assessment of the OPMD patient were followed by mutation analysis of the PABPN1 gene by direct DNA sequencing and by our newly developed method, fluorescent PABPN1 polymerase chain reaction (PCR) product (flPPP) method. A cohort of 50 healthy Swiss probands was screened using the flPPP to assess the frequency of the (GCG)7 allele in the Swiss population. Cricopharyngeal myotomy was performed as treatment for dysphagia. Results: A heterozygous (GCG)9 triplet repeat expansion in PABPN1 was identified. Since the family history proved to be negative, the mutation is likely to have occurred de novo. The frequency of the (GCG)7 allele among healthy Swiss controls amounted to 1%. The flPPP method showed a sensitivity and specificity of 100%. Two years after cricopharyngeal myotomy, the patient is still relieved of dysphagia. Conclusions: An otolaryngologist should include OPMD in the differential diagnosis of a patient presenting with dysphagia, as this symptom can be the first sign of the disease and family history can be negative. Molecular genetic testing represents a highly accurate and rapid way to confirm the clinical diagnosis of OPMD. Cricopharyngeal myotomy relieves the patient of dysphagia in the majority of cases. [source] First Evidence of Genetic Imbalances in AngiofibromasTHE LARYNGOSCOPE, Issue 2 2002Bernhard Schick MD Abstract Objective/Hypothesis Angiofibromas are clinically well characterized by their origin at the posterior lateral nasal wall close to the sphenopalatine foramen, their occurrence in male adolescent patients, and the histological findings of a benign fibrovascular neoplasm with irregular, endothelium-lined vascular spaces in a fibrous stroma. However, their etiology and genetic causes remain unknown. The present study addresses genetic imbalances in angiofibromas. Study Design The present pilot study compared genomic hybridization in three angiofibromas to search for chromosomal abnormalities in this rare tumor. Methods Fluorescence-marked normal DNA and angiofibroma DNA were compared using genomic hybridization screening to detect chromosomal abnormalities. Their binding ratio to metaphase chromosomes were analyzed by special digital image analysis. Results Chromosomal gains and losses showing a high level of agreement were detected in all three angiofibromas. Specifically, DNA gains were observed on chromosomes 3q, 4q, 5q, 6q, 7q, 8q, 12p, 12q, 13q, 14q, 18q, 21q, and X, and DNA losses were screened on chromosomes 17, 19p, 22q, and Y. Finding chromosomal abnormalities at the sex chromosomes X and Y of this rare tumor is remarkable. Concurrent chromosomal gain on 8q12q22 was noted in all three tumor specimens. Conclusions Comparative genomic hybridization is suitable for screening angiofibromas on a genetic level. The results on these screens indicate that further genetic investigations of this rare benign tumor may provide more details about the tumor's genetic abnormalities and perhaps clarify the etiology of angiofibromas. [source] Management of systemic lupus erythematosus in the coming decade: potentials and challengesINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2006Hiok Hee CHNG Abstract The management of systemic lupus erythematosus (SLE) has improved in the past 50 years, but there is still a 3,5-fold increased mortality compared to the general population, with major organ failure due to active disease, infection and cardiovascular disease as the major challenges for the coming decade. Research advances at cellular, molecular and genetic levels enhance our understanding of the immunopathogenic mechanisms of SLE, leading to the development of drugs targeting specific sites of immune dysregulation , with therapies directed at cytokines, B- and T-cells, and their interactions showing promise. Advances are expected in the field of haematopoietic stem cell transplant (HSCT) as a therapeutic option for a subset of patients. Furthermore, some non-traditional immunomodulating therapies like statins, leflunomide and tacrolimus may prove useful as alternative or adjunct treatment in some patients. A better understanding of how current immunosuppressants act at the cellular and molecular level should guide the re-evaluation of the indications, doses and duration of therapy in clinical trials using these agents, many of which have not been subjected to proper double-blinded placebo-controlled studies. Research on triggers of SLE onset and flare of activity continues to yield information helpful in prevention. The evidence on the impact of psychosocial and economic factors on the outcome of SLE is overwhelming and the rheumatology community should enlist the assistance of other healthcare professionals, patient advocates and local health authorities to address these issues pertinent to good patient care and outcome. [source] Chromosome organization and gene control: It is difficult to see the picture when you are inside the frameJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Pernette J. Verschure Abstract The organization of the genome in the nucleus is related to its function. The functional compartmentalization of the genome is described at the nuclear, chromosomal, subchromosomal, nucleosomal, and DNA sequence level. These descriptions originate from the techniques that were used for analysis. The different levels of compartmentalization are not easily reconciled, because the techniques applied to identify genome compartmentalization generally cannot be performed in combination. We have obtained a large body of information on individual "actors" and "scenes" in the nucleus regarding genome compartmentalization, but we still do not understand how and by what pieces of equipment the "actors" play their game. The next challenge is to understand the combined operation of the various levels of functional genome organization in the nucleus, that is, how do the epigenetic and genetic levels act together. In this paper, I will highlight some of the general features and observations of functional organization of the eukaryotic genome in interphase nuclei and discuss the concepts and views based on observed correlations between genome organization and function. I will reflect on what is to be expected from this field of research when the functional levels of genome compartmentalization are integrated. In this context I will draw attention to what might be needed to improve our understanding. J. Cell. Biochem. © 2006 Wiley-Liss, Inc. [source] The evolutionary ecology of individual phenotypic plasticity in wild populationsJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2007D. H. NUSSEY Abstract The ability of individual organisms to alter morphological and life-history traits in response to the conditions they experience is an example of phenotypic plasticity which is fundamental to any population's ability to deal with short-term environmental change. We currently know little about the prevalence, and evolutionary and ecological causes and consequences of variation in life history plasticity in the wild. Here we outline an analytical framework, utilizing the reaction norm concept and random regression statistical models, to assess the between-individual variation in life history plasticity that may underlie population level responses to the environment at both phenotypic and genetic levels. We discuss applications of this framework to date in wild vertebrate populations, and illustrate how natural selection and ecological constraint may alter a population's response to the environment through their effects at the individual level. Finally, we present future directions and challenges for research into individual plasticity. [source] Gibberellin controls the nodulation signaling pathway in Lotus japonicusTHE PLANT JOURNAL, Issue 2 2009Takaki Maekawa Summary Root nodule formation is regulated by several plant hormones, but the details of the regulation of the nodulation signaling pathway are largely unknown. In this study, the role of gibberellin (GA) in the control of root nodule symbiosis was investigated at the physiological and genetic levels in Lotus japonicus. Exogenous application of biologically active GA, GA3, inhibited the formation of infection threads and nodules, which was counteracted by the application of a biosynthesis inhibitor of GA, Uniconazole P. Nod factor-induced root hair deformation was severely blocked in the presence of GA, which was phenocopied by nsp2 mutants. The number of spontaneous nodules triggered by the gain-of-function mutation of calcium/calmodulin-dependent kinase (CCaMK) or the lotus histidine kinase 1 (LHK1) was decreased upon the addition of GA; moreover, the overexpression of the gain-of-function mutation of L. japonicus, SLEEPY1, a positive regulator of GA signaling, resulted in a reduced nodule number, without other aspects of root development being affected. These results indicate that higher GA signaling levels specifically inhibit the nodulation signaling pathway. Nod factor-dependent induction of NSP2 and NIN was inhibited by exogenous GA. Furthermore, the cytokinin-dependent induction of NIN was suppressed by GA. From these results, we conclude that GA inhibits the nodulation signaling pathway downstream of cytokinin, possibly at NSP2, which is required for Nod factor-dependent NIN expression. These results clarify the roles of GA in the nodulation signaling pathway, and in relation to the cytokinin signaling pathway for nodulation in L. japonicus. [source] | ||||||||||||||||||||||||||||