176 research outputs found
Association of treatment satisfaction and psychopathological sub-syndromes among involuntary patients with psychotic disorders
Publisher's version: http://www.springerlink.com/content/rx24036274667t10
Star forming dwarf galaxies
Star forming dwarf galaxies (SFDGs) have a high gas content and low
metallicities, reminiscent of the basic entities in hierarchical galaxy
formation scenarios. In the young universe they probably also played a major
role in the cosmic reionization. Their abundant presence in the local volume
and their youthful character make them ideal objects for detailed studies of
the initial stellar mass function (IMF), fundamental star formation processes
and its feedback to the interstellar medium. Occasionally we witness SFDGs
involved in extreme starbursts, giving rise to strongly elevated production of
super star clusters and global superwinds, mechanisms yet to be explored in
more detail. SFDGs is the initial state of all dwarf galaxies and the relation
to the environment provides us with a key to how different types of dwarf
galaxies are emerging. In this review we will put the emphasis on the exotic
starburst phase, as it seems less important for present day galaxy evolution
but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy
Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon,
September 2010, Springer Verlag, in pres
Use of surface plasmon resonance for the measurement of low affinity binding interactions between HSP72 and measles virus nucleocapsid protein
The 72 kDa heat shock protein (HSP72) is a molecular chaperone that binds native protein with low affinity. These interactions can alter function of the substrate, a property known as HSP-mediated activity control. In the present work, BIAcore instrumentation was used to monitor binding reactions between HSP72 and naturally occurring sequence variants of the measles virus (MV) nucleocapsid protein (N), a structural protein regulating transcription/replication of the viral genome. Binding reactions employed synthetic peptides mimicking a putative HSP72 binding motif of N. Sequences were identified that bound HSP72 with affinities comparable to well-characterized activity control reactions. These sequences, but not those binding with lesser affinity, supported HSP72 activity control of MV transcription/replication. BIAcore instrumentation thus provides an effective way to measure biologically relevant low affinity interactions with structural variants of viral proteins
High-Precision, Whole-Genome Sequencing of Laboratory Strains Facilitates Genetic Studies
Whole-genome sequencing is a powerful technique for obtaining the reference sequence information of multiple organisms. Its use can be dramatically expanded to rapidly identify genomic variations, which can be linked with phenotypes to obtain biological insights. We explored these potential applications using the emerging next-generation sequencing platform Solexa Genome Analyzer, and the well-characterized model bacterium Bacillus subtilis. Combining sequencing with experimental verification, we first improved the accuracy of the published sequence of the B. subtilis reference strain 168, then obtained sequences of multiple related laboratory strains and different isolates of each strain. This provides a framework for comparing the divergence between different laboratory strains and between their individual isolates. We also demonstrated the power of Solexa sequencing by using its results to predict a defect in the citrate signal transduction pathway of a common laboratory strain, which we verified experimentally. Finally, we examined the molecular nature of spontaneously generated mutations that suppress the growth defect caused by deletion of the stringent response mediator relA. Using whole-genome sequencing, we rapidly mapped these suppressor mutations to two small homologs of relA. Interestingly, stable suppressor strains had mutations in both genes, with each mutation alone partially relieving the relA growth defect. This supports an intriguing three-locus interaction module that is not easily identifiable through traditional suppressor mapping. We conclude that whole-genome sequencing can drastically accelerate the identification of suppressor mutations and complex genetic interactions, and it can be applied as a standard tool to investigate the genetic traits of model organisms
Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes
BACKGROUND: Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. METHODS: Orthologous (whole, sub-) transcriptome profiles were compared among four mouse-human transcriptome datasets: (M) six muscle groups obtained from three mouse strains (wildtype, mdx, mdx(5cv)); (H1) biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2) four different control human muscle types obtained at autopsy; and (H3) 12 different control human tissues (ten non-muscle). RESULTS: Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy). Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3), indicating this finding to be muscle specific. CONCLUSION: This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled
Low genotypic diversity and long-term ecological decline in a spatially structured seagrass population
In isolated or declining populations, viability may be compromised further by loss of genetic diversity. Therefore, it is important to understand the relationship between long-term ecological trajectories and population genetic structure. However, opportunities to combine these types of data are rare, especially in natural systems. Using an existing panel of 15 microsatellites, we estimated allelic diversity in seagrass, Zostera marina, at five sites around the Isles of Scilly Special Area of Conservation, UK, in 2010 and compared this to 23 years of annual ecological monitoring (1996–2018). We found low diversity and long-term declines in abundance in this relatively pristine but isolated location. Inclusion of the snapshot of genotypic, but less-so genetic, diversity improved prediction of abundance trajectories; however, this was spatial scale-dependent. Selection of the appropriate level of genetic organization and spatial scale for monitoring is, therefore, important to identify drivers of eco-evolutionary dynamics. This has implications for the use of population genetic information in conservation, management, and spatial planning
Chagas Disease Risk in Texas
Chagas disease is endemic in Texas and spread through triatomine insect vectors known as kissing bugs, assassin bugs, or cone–nosed bugs, which transmit the protozoan parasite, Trypanosoma cruzi. We examined the threat of Chagas disease due to the three most prevalent vector species and from human case occurrences and human population data at the county level. We modeled the distribution of each vector species using occurrence data from México and the United States and environmental variables. We then computed the ecological risk from the distribution models and combined it with disease incidence data to produce a composite risk map which was subsequently used to calculate the populations expected to be at risk for the disease. South Texas had the highest relative risk. We recommend mandatory reporting of Chagas disease in Texas, testing of blood donations in high risk counties, human and canine testing for Chagas disease antibodies in high risk counties, and that a joint initiative be developed between the United States and México to combat Chagas disease
Optimization of Muscle Activity for Task-Level Goals Predicts Complex Changes in Limb Forces across Biomechanical Contexts
Optimality principles have been proposed as a general framework for understanding motor control in animals and humans largely based on their ability to predict general features movement in idealized motor tasks. However, generalizing these concepts past proof-of-principle to understand the neuromechanical transformation from task-level control to detailed execution-level muscle activity and forces during behaviorally-relevant motor tasks has proved difficult. In an unrestrained balance task in cats, we demonstrate that achieving task-level constraints center of mass forces and moments while minimizing control effort predicts detailed patterns of muscle activity and ground reaction forces in an anatomically-realistic musculoskeletal model. Whereas optimization is typically used to resolve redundancy at a single level of the motor hierarchy, we simultaneously resolved redundancy across both muscles and limbs and directly compared predictions to experimental measures across multiple perturbation directions that elicit different intra- and interlimb coordination patterns. Further, although some candidate task-level variables and cost functions generated indistinguishable predictions in a single biomechanical context, we identified a common optimization framework that could predict up to 48 experimental conditions per animal (n = 3) across both perturbation directions and different biomechanical contexts created by altering animals' postural configuration. Predictions were further improved by imposing experimentally-derived muscle synergy constraints, suggesting additional task variables or costs that may be relevant to the neural control of balance. These results suggested that reduced-dimension neural control mechanisms such as muscle synergies can achieve similar kinetics to the optimal solution, but with increased control effort (≈2×) compared to individual muscle control. Our results are consistent with the idea that hierarchical, task-level neural control mechanisms previously associated with voluntary tasks may also be used in automatic brainstem-mediated pathways for balance
Microgenomic Analysis in Skeletal Muscle: Expression Signatures of Individual Fast and Slow Myofibers
BACKGROUND: Skeletal muscle is a complex, versatile tissue composed of a variety of functionally diverse fiber types. Although the biochemical, structural and functional properties of myofibers have been the subject of intense investigation for the last decades, understanding molecular processes regulating fiber type diversity is still complicated by the heterogeneity of cell types present in the whole muscle organ.
METHODOLOGY/PRINCIPAL FINDINGS: We have produced a first catalogue of genes expressed in mouse slow-oxidative (type 1) and fast-glycolytic (type 2B) fibers through transcriptome analysis at the single fiber level (microgenomics). Individual fibers were obtained from murine soleus and EDL muscles and initially classified by myosin heavy chain isoform content. Gene expression profiling on high density DNA oligonucleotide microarrays showed that both qualitative and quantitative improvements were achieved, compared to results with standard muscle homogenate. First, myofiber profiles were virtually free from non-muscle transcriptional activity. Second, thousands of muscle-specific genes were identified, leading to a better definition of gene signatures in the two fiber types as well as the detection of metabolic and signaling pathways that are differentially activated in specific fiber types. Several regulatory proteins showed preferential expression in slow myofibers. Discriminant analysis revealed novel genes that could be useful for fiber type functional classification.
CONCLUSIONS/SIGNIFICANCE: As gene expression analyses at the single fiber level significantly increased the resolution power, this innovative approach would allow a better understanding of the adaptive transcriptomic transitions occurring in myofibers under physiological and pathological condition
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