638 research outputs found
Internal representations, external representations and ergonomics: towards a theoretical integration
Identification of Mechanosensitive Genes during Embryonic Bone Formation
Although it is known that mechanical forces are needed for normal bone
development, the current understanding of how biophysical stimuli are
interpreted by and integrated with genetic regulatory mechanisms is limited.
Mechanical forces are thought to be mediated in cells by
“mechanosensitive” genes, but it is a challenge to
demonstrate that the genetic regulation of the biological system is dependant on
particular mechanical forces in vivo. We propose a new means of selecting
candidate mechanosensitive genes by comparing in vivo gene expression patterns
with patterns of biophysical stimuli, computed using finite element analysis. In
this study, finite element analyses of the avian embryonic limb were performed
using anatomically realistic rudiment and muscle morphologies, and patterns of
biophysical stimuli were compared with the expression patterns of four candidate
mechanosensitive genes integral to bone development. The expression patterns of
two genes, Collagen X (ColX) and Indian hedgehog (Ihh), were shown to colocalise
with biophysical stimuli induced by embryonic muscle contractions, identifying
them as potentially being involved in the mechanoregulation of bone formation.
An altered mechanical environment was induced in the embryonic chick, where a
neuromuscular blocking agent was administered in ovo to modify skeletal muscle
contractions. Finite element analyses predicted dramatic changes in levels and
patterns of biophysical stimuli, and a number of immobilised specimens exhibited
differences in ColX and Ihh expression. The results obtained indicate that
computationally derived patterns of biophysical stimuli can be used to inform a
directed search for genes that may play a mechanoregulatory role in particular
in vivo events or processes. Furthermore, the experimental data demonstrate that
ColX and Ihh are involved in mechanoregulatory pathways and may be key mediators
in translating information from the mechanical environment to the molecular
regulation of bone formation in the embryo
Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone
We report on the comparative genomics and characterization of the virulence phenotypes of four <i>S. pneumoniae</i> strains that belong to the multidrug resistant clone PMEN1 (Spain<sup>23F</sup> ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant
Cross-Clade Recognition of HIV-1 CAp24 by CD4+ T Cells in HIV-1-Infected Individuals in Burkina Faso and Germany
The presence of antigen-specific cellular immune responses may be an indicator of long-term asymptomatic HIV-1-disease. The detection of cellular immune responses to infection with different subtypes of HIV-1 may be hampered by genetic differences of immunodominant antigens such as the capsid protein CAp24. In Nouna, Burkina Faso, HIV-1 circulating recombinant forms CRF02_AG and CRF06_cpx are the 2 major strains detectable in HIV-1-infected individuals, while subtype B strains prevail in Europe and North America. Amino acid sequences of CAp24 were assessed in blood samples from 10 HIV-1-infected patients in Nouna, Burkina Faso. Production of interferon-gamma (IFN-γ) in peripheral blood CD4+ lymphocytes in response to recombinant HIV-1 proteins derived from clade B (including CAp24NL4-3) was measured using a modified flow-cytometry-based whole blood short term activation assay (FASTimmune, BDBiosciences). IFN-γ production following stimulation with a whole length CAp24 protein derived from clade B (CAp24NL4-3) was additionally quantified in comparison to a CAp24 protein derived from CRF02_AG (CAp24BD6-15) in 16 HIV-1-infected patients in Heidelberg, Germany. Amino acid sequence identity of CAp24 obtained from patients in Nouna ranged between 86 and 89% when compared to the clade B CAp24NL4-3 consensus sequence, between 90 and 95% when compared to the circulating recombinant form CRF06_CPX consensus sequence, and between 92 and 96% when compared to the CAp24BD6-15 consensus sequence. Significant numbers of HIV-1-specific CD4+ lymphocytes producing IFN-γ were detected in 4 of 10 HIV-1-infected patients. In 7 of 16 patients in Heidelberg, recombinant CAp24BD6-15 stimulated IFN-γ-production in CD4+ lymphocytes to a similar extent as the clade B-derived CAp24NL4-3. Thus, antigen-specific CD4+ lymphocytes from both West African and European patients infected with different strains of HIV-1 show relevant cross-clade recognition of HIV-1 CAp24 in a flow-cytometry-based whole blood short term activation assay
Signature of multilayer growth of 2D layered Bi2Se3 through heteroatom-assisted step-edge barrier reduction
During growth of two-dimensional (2D) materials, abrupt growth of multilayers is practically unavoidable even in the case of well-controlled growth. In epitaxial growth of a quintuple-layered Bi2Se3 film, we observe that the multilayer growth pattern deduced from in situ x-ray diffraction implies nontrivial interlayer diffusion process. Here we find that an intriguing diffusion process occurs at step edges where a slowly downward-diffusing Se adatom having a high step-edge barrier interacts with a Bi adatom pre-existing at step edges. The Se???Bi interaction lowers the high step-edge barrier of Se adatoms. This drastic reduction of the overall step-edge barrier and hence increased interlayer diffusion modifies the overall growth significantly. Thus, a step-edge barrier reduction mechanism assisted by hetero adatom???adatom interaction could be fairly general in multilayer growth of 2D heteroatomic materials
Parks and Tourism
To protect biodiversity, parks agencies need political and financial support. Recreational visitors can bring both, but commercial tourism carries risks
Neutrophils in cancer: neutral no more
Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets
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