			Home About us Contact

Many Stages (many + stage)

Distribution by Scientific Domains

Medical Sciences	40%
Life Sciences	40%

Selected Abstracts

Phenotypic analysis of deflated/Ints7 function in Drosophila development

DEVELOPMENTAL DYNAMICS, Issue 5 2009
Rachael J. Rutkowski
Abstract The Drosophila gene deflated (CG18176; renamed after the pupal lethal abdominal phenotype of mutant individuals) is a member of a conserved gene family found in all multicellular organisms. The human orthologue of deflated (Ints7) encodes a subunit of the Integrator complex that associates with RNA polymerase II and has been implicated in snRNA processing. Since loss-of-function analyses of deflated have not yet been reported, we undertook to investigate deflated expression patterns and mutant phenotypes. deflated mRNA was detected at low levels in proliferating cells in postblastoderm embryos and GFP tagged protein is predominately nuclear. Generation and analysis of four mutant alleles revealed deflated is essential for normal development, as mutant individuals displayed pleiotropic defects affecting many stages of development, consistent with perturbation of cell signalling or cell proliferation. Our data demonstrate multiple roles in development for an Ints7 homologue and to demonstrate its requirement for normal cell signalling and proliferation. Developmental Dynamics 238:1131,1139, 2009. © 2009 Wiley-Liss, Inc. [source]

Generation, persistence and plasticity of CD4 T-cell memories

IMMUNOLOGY, Issue 4 2010
Jason R. Lees
Summary The development of immune memory mediated by T lymphocytes is central to durable, long-lasting protective immunity. A key issue in the field is how to direct the generation and persistence of memory T cells to elicit the appropriate secondary response to provide protection to a specific pathogen. Two prevailing views have emerged; that cellular and molecular regulators control the lineage fate and functional capacities of memory T cells early after priming, or alternatively, that populations of memory T cells are inherently plastic and subject to alterations in function and/or survival at many stages during their long-term maintenance. Here, we will review current findings in CD4 T-cell memory that suggest inherent plasticity in populations of memory CD4 T cells at all stages of their development , originating with their generation from multiple types of primed CD4 T cells, during their persistence and homeostatic turnover in response to T-cell receptor signals, and also following secondary challenge. These multiple aspects of memory CD4 T-cell flexibility contrast the more defined lineages and functions ascribed to memory CD8 T cells, suggesting a dynamic nature to memory CD4 T-cell populations and responses. The flexible attributes of CD4 T-cell memory suggest opportunities and mechanisms for therapeutic manipulation at all phases of immune memory development, maintenance and recall. [source]

Could interchangeable use of dry powder inhalers affect patients?

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2005
D. Price
Summary The aim of asthma treatment is optimal disease control. Poor asthma control results in considerable patient morbidity, as well as contributing to the considerable burden placed by the disease on healthcare budgets. There is a need for costs to be carefully scrutinised, with the switching of patients to inhaler devices with lower acquisition costs likely to be increasingly considered. However, before such practice becomes widespread, it is important to establish whether or not this could adversely impact on patients and the level of disease control. For approval to have been given, all marketed inhalers must have satisfied current regulatory requirements for devices. Full preclinical and clinical development programmes are not required when application is made for authorisation to market a new inhaler containing an existing chemical entity, although clinical equivalence testing must be used. Both beneficial and adverse effects should be tested, and the limits of equivalence must be clearly defined, based on therapeutic relevance. It should be noted that equivalence studies are invalid when the end point is not responding (i.e. at the top of the dose,response curve) and when equivalence limits approach or are equal to the magnitude of the drug effect. Approval on the basis of regulations designed to safeguard quality of dry powder inhalers does not mean that devices are interchangeable. When using an inhaler, there are many stages between the patient and the therapeutic effect, involving device design, pharmaceutical performance and patient behaviour. Regulations governing new devices cover only a few of the many factors affecting disease control. Furthermore, clinical trials to assess equivalence may not take into account factors in patient behaviour or variations in patient inhaler technique that may affect use of devices in real-life situations. When assessing the consequences of interchangeable use of dry powder inhalers on healthcare costs, it is important to ensure that the acquisition cost of the devices is not the only cost considered. Other costs that should be considered include the cost of time spent demonstrating to the patient how to use the new device, the cost of additional physician visits to address patient concerns and the management costs if disease control is adversely affected. [source]

Impact of apoE genotype on oxidative stress, inflammation and disease risk

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 1 2008
Laia Jofre-Monseny
Abstract Although in developing countries an apolipoprotein E4 (apoE4) genotype may offer an evolutionary advantage, as it has been shown to offer protection against certain infectious disease, in Westernised societies it is associated with increased morbidity and mortality, and represents a significant risk factor for cardiovascular disease, late-onset Alzheimer's disease and other chronic disorders. ApoE is an important modulator of many stages of lipoprotein metabolism and traditionally the increased risk was attributed to higher lipid levels in E4 carriers. However, more recent evidence demonstrates the multifunctional nature of the apoE protein and the fact that the impact of genotype on disease risk may be in large part due to an impact on oxidative status or the immunomodulatory/anti-inflammatory properties of apoE. An increasing number of studies in cell lines, targeted replacement rodents and human volunteers indicate higher oxidative stress and a more pro-inflammatory state associated with the ,4 allele. The impact of genotype on the antioxidant and immunomodulatory/anti-inflammatory properties of apoE is the focus of the current review. Furthermore, current information on the impact of environment (diet, exercise, smoking status, alcohol) on apoE genotype-phenotype associations are discussed with a view to identifying particular lifestyle strategies that could be adapted to counteract the ,at-risk' E4 genotype. [source]

Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX AutoSol wizard

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2009
Thomas C. Terwilliger
Estimates of the quality of experimental maps are important in many stages of structure determination of macromolecules. Map quality is defined here as the correlation between a map and the corresponding map obtained using phases from the final refined model. Here, ten different measures of experimental map quality were examined using a set of 1359 maps calculated by re-analysis of 246 solved MAD, SAD and MIR data sets. A simple Bayesian approach to estimation of map quality from one or more measures is presented. It was found that a Bayesian estimator based on the skewness of the density values in an electron-density map is the most accurate of the ten individual Bayesian estimators of map quality examined, with a correlation between estimated and actual map quality of 0.90. A combination of the skewness of electron density with the local correlation of r.m.s. density gives a further improvement in estimating map quality, with an overall correlation coefficient of 0.92. The PHENIX AutoSol wizard carries out automated structure solution based on any combination of SAD, MAD, SIR or MIR data sets. The wizard is based on tools from the PHENIX package and uses the Bayesian estimates of map quality described here to choose the highest quality solutions after experimental phasing. [source]