113 research outputs found
Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.
The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition
Assessment of clonal relationships in ipsilateral and bilateral multiple breast carcinomas by comparative genomic hybridisation and hierarchical clustering analysis
Acquired Type III Secretion System Determines Environmental Fitness of Epidemic Vibrio parahaemolyticus in the Interaction with Bacterivorous Protists
Genome analyses of marine microbial communities have revealed the widespread occurrence of genomic islands (GIs), many of which encode for protein secretion machineries described in the context of bacteria-eukaryote interactions. Yet experimental support for the specific roles of such GIs in aquatic community interactions remains scarce. Here, we test for the contribution of type III secretion systems (T3SS) to the environmental fitness of epidemic Vibrio parahaemolyticus. Comparisons of V. parahaemolyticus wild types and T3SS-defective mutants demonstrate that the T3SS encoded on genome island VPaI-7 (T3SS-2) promotes survival of V. parahaemolyticus in the interaction with diverse protist taxa. Enhanced persistence was found to be due to T3SS-2 mediated cytotoxicity and facultative parasitism of V. parahaemolyticus on coexisting protists. Growth in the presence of bacterivorous protists and the T3SS-2 genotype showed a strong correlation across environmental and clinical isolates of V. parahaemolyticus. Short-term microcosm experiments provide evidence that protistan hosts facilitate the invasion of T3SS-2 positive V. parahaemolyticus into a coastal plankton community, and that water temperature and productivity further promote enhanced survival of T3SS-2 positive V. parahaemolyticus. This study is the first to describe the fitness advantage of GI-encoded functions in a microbial food web, which may provide a mechanistic explanation for the global spread and the seasonal dynamics of V. parahaemolyticus pathotypes, including the pandemic serotype cluster O3:K6, in aquatic environments
Does the routine use of global coronary heart disease risk scores translate into clinical benefits or harms? A systematic review of the literature
<p>Abstract</p> <p>Background</p> <p>Guidelines now recommend routine assessment of global coronary heart disease (CHD) risk scores. We performed a systematic review to assess whether global CHD risk scores result in clinical benefits or harms.</p> <p>Methods</p> <p>We searched MEDLINE (1966 through June 13, 2007) for articles relevant to our review. Using predefined inclusion and exclusion criteria, we included studies of any design that provided physicians with global risk scores or allowed them to calculate scores themselves, and then measured clinical benefits and/or harms. Two reviewers reviewed potentially relevant studies for inclusion and resolved disagreement by consensus. Data from each article was then abstracted into an evidence table by one reviewer and the quality of evidence was assessed independently by two reviewers.</p> <p>Results</p> <p>11 studies met criteria for inclusion in our review. Six studies addressed clinical benefits and 5 addressed clinical harms. Six studies were rated as "fair" quality and the others were deemed "methodologically limited". Two fair quality studies showed that physician knowledge of global CHD risk is associated with increased prescription of cardiovascular drugs in high risk (but not all) patients. Two additional fair quality studies showed no effect on their primary outcomes, but one was underpowered and the other focused on prescribing of lifestyle changes, rather than drugs whose prescribing might be expected to be targeted by risk level. One of these aforementioned studies showed improved blood pressure in high-risk patients, but no improvement in the proportion of patients at high risk, perhaps due to the high proportion of participants with baseline risks significantly exceeding the risk threshold. Two fair quality studies found no evidence of harm from patient knowledge of global risk scores when they were accompanied by counseling, and optional or scheduled follow-up. Other studies were too methodologically limited to draw conclusions.</p> <p>Conclusion</p> <p>Our review provides preliminary evidence that physicians' knowledge of global CHD risk scores may translate into modestly increased prescribing of cardiovascular drugs and modest short-term reductions in CHD risk factors without clinical harm. Whether these results are replicable, and translate across other practice settings or into improved long-term CHD outcomes remains to be seen.</p
A Novel Protein Kinase-Like Domain in a Selenoprotein, Widespread in the Tree of Life
Selenoproteins serve important functions in many organisms, usually providing essential oxidoreductase enzymatic activity, often for defense against toxic xenobiotic substances. Most eukaryotic genomes possess a small number of these proteins, usually not more than 20. Selenoproteins belong to various structural classes, often related to oxidoreductase function, yet a few of them are completely uncharacterised
Fungal extracellular polymeric substance matrices – Highly specialized microenvironments that allow fungi to control soil organic matter decomposition reactions
Fungal extracellular polymeric substance matrices – Highly specialized microenvironments that allow fungi to control soil organic matter decomposition reactions
Filamentous fungi play a key role in the terrestrial carbon cycle as they are the primary decomposers of lignocellulose in soil organic matter (SOM). Fungi secrete a wide range of oxidative and hydrolytic enzymes, and generate radicals through extracellular secondary metabolites to decompose SOM. To study fungal decomposition of SOM, the activities of isolated enzymes are typically studied as proxies for the decomposition activity of fungi. However, extracellular enzymes involved in lignocellulose decomposition are often bound to fungal extracellular polymeric substance (EPS) matrices. This association between extracellular enzymes and EPS matrices affects the activities of the enzymes. Moreover, extracellular enzymes and fungal cells are prone to attack by radicals and proteolytic enzymes themselves. Hence, these seemingly incompatible decomposition mechanisms must be regulated in some way in the fungal extracellular space to allow efficient decomposition of SOM, while preventing damage to secreted extracellular enzymes or the fungal cells themselves. We here review studies investigating the associations between fungal extracellular enzymes and EPS matrices and how these associations affect hydrolytic and oxidative reactions involved in SOM decomposition. Based on the knowledge compiled in the current review, we propose that fungal EPS matrices should be viewed as highly dynamic and functional parts of the fungal extracellular decomposition machinery. We also build a conceptual illustration that describes how the molecular composition and structure of fungal EPS matrices ensure that extracellular decomposition reactions only proceed at the right time and in the right place
Decomposition of soil organic matter by ectomycorrhizal fungi : Mechanisms and consequences for organic nitrogen uptake and soil carbon stabilization
A major fraction of nitrogen (N) in boreal forest soils is found in organic forms associated with soil organic matter (SOM) and mineral particles. The capacity of ectomycorrhizal (ECM) fungal symbionts to access this N is debated, considering that these fungi have lost many of the genes for decomposing organic matter that were present in their saprotrophic ancestors. To gain a molecular-level understanding of the N-mining processes in ECM fungi, we developed an experimental approach where the processes of decomposition were studied in parallel with the changes in the structure and properties of the organic matter. We showed that ECM fungi have significant capacities to assimilate organic N associated with SOM and mineral surfaces. The decomposition mechanisms differ between species, reflecting the lignocellulose decomposition mechanisms found in their saprotrophic ancestors. During N-mining, the ECM fungi processed the SOM to a material with increased adsorptive properties to iron oxide mineral particles. Two pathways contributed to these changes: Extracellular modifications of the SOM and secretion of mineral surface reactive metabolites. Some of these metabolites have iron(III)-reducing activities and can participate in extracellular Fenton reactions and redox reactions at iron oxide mineral surfaces. We conclude that the traditional framework for understanding organic N acquisition by ECM fungi from recalcitrant SOM must be extended to a framework that includes how those decomposition activities affect the stabilization and reactivity of mineral-associated SOM. The activity through these complex networks of reactions is decisive for the overall effect of ECM fungal decomposition on nutrients and C-cycling in forest ecosystems
Elucidating fungal decomposition of organic matter at sub-micrometer spatial scales using optical photothermal infrared (O-PTIR) microspectroscopy
In microbiological studies, a common goal is to link environmental factors to microbial activities. Both environmental factors and microbial activities are typically derived from bulk samples. It is becoming increasingly clear that such bulk environmental parameters poorly represent the microscale environments microorganisms experience. Using infrared (IR) microspectroscopy, the spatial distribution of chemical compound classes can be visualized, making it a useful tool for studying the interactions between microbial cells and their microenvironments. The spatial resolution of conventional IR microspectroscopy has been limited by the diffractionlimit of IR light. The recent development of optical photothermal infrared (O-PTIR) microspectroscopy has pushed the spatial resolution of IR microspectroscopy beyond this diffractionlimit, allowing the distribution of chemical compound classes to be visualized at sub-micrometer spatial scales. To examine the potential and limitations of O-PTIR microspectroscopy to probe the interactions between fungal cells and their immediate environments, we imaged the decomposition of cellulose filmsby cells of the ectomycorrhizal fungus Paxillus involutus and compared O-PTIR results using conventional IR microspectroscopy. Whereas the data collected with conventional IR microspectroscopy indicated that P. involutus has only a very limited ability to decompose cellulose films,O-PTIR data suggested that the ability of P. involutus to decompose cellulose was substantial. Moreover, the O-PTIR method enabled the identificationof a zone located outside the fungal hyphae where the cellulose was decomposed by oxidation. We conclude that O-PTIR can provide valuable new insights into the abilities and mechanisms by which microorganisms interact with their surrounding environments
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