167 research outputs found
MR imaging of overuse injuries in the skeletally immature gymnast: spectrum of soft-tissue and osseous lesions in the hand and wrist
In the pediatric gymnast, stress-related physeal injuries have been well described with characteristic imaging findings. However, a spectrum of overuse injuries, some rarely reported in the literature, can be encountered in the gymnast’s hand and wrist.
To demonstrate the MR appearance of a spectrum of overuse injuries in the skeletally immature wrist and hand of pediatric gymnasts.
A total of 125 MR exams of the hand and wrist in skeletally immature children were performed at our institution during a 2-year period. Clinical histories were reviewed for gymnastics participation. MR studies of that subpopulation were reviewed and abnormalities tabulated.
Of the MR studies reviewed, ten gymnasts were identified, all girls age 12–16 years (mean age 14.2 years) who presented with wrist or hand pain. Three of these children had bilateral MR exams. Abnormalities included chronic physeal injuries in three children. Two girls exhibited focal lunate osteochondral defects. Triangular fibrocartilage tears were present in three girls, one of whom had a scapholunate ligament tear. Two girls manifested metacarpal head flattening and necrosis.
A variety of soft-tissue and osseous lesions can be encountered in the skeletally immature gymnast. Familiarity with these stress-related injuries is important for accurate diagnosis
OrgConv: detection of gene conversion using consensus sequences and its application in plant mitochondrial and chloroplast homologs
<p>Abstract</p> <p>Background</p> <p>The ancestry of mitochondria and chloroplasts traces back to separate endosymbioses of once free-living bacteria. The highly reduced genomes of these two organelles therefore contain very distant homologs that only recently have been shown to recombine inside the mitochondrial genome. Detection of gene conversion between mitochondrial and chloroplast homologs was previously impossible due to the lack of suitable computer programs. Recently, I developed a novel method and have, for the first time, discovered recurrent gene conversion between chloroplast mitochondrial genes. The method will further our understanding of plant organellar genome evolution and help identify and remove gene regions with incongruent phylogenetic signals for several genes widely used in plant systematics. Here, I implement such a method that is available in a user friendly web interface.</p> <p>Results</p> <p><monospace>OrgConv</monospace> (<b>Org</b>anellar <b>Conv</b>ersion) is a computer package developed for detection of gene conversion between mitochondrial and chloroplast homologous genes. <monospace>OrgConv</monospace> is available in two forms; source code can be installed and run on a Linux platform and a web interface is available on multiple operating systems. The input files of the feature program are two multiple sequence alignments from different organellar compartments in FASTA format. The program compares every examined sequence against the consensus sequence of each sequence alignment rather than exhaustively examining every possible combination. Making use of consensus sequences significantly reduces the number of comparisons and therefore reduces overall computational time, which allows for analysis of very large datasets. Most importantly, with the significantly reduced number of comparisons, the statistical power remains high in the face of correction for multiple tests.</p> <p>Conclusions</p> <p>Both the source code and the web interface of <monospace>OrgConv</monospace> are available for free from the <monospace>OrgConv</monospace> website <url>http://www.indiana.edu/~orgconv</url>. Although <monospace>OrgConv</monospace> has been developed with main focus on detection of gene conversion between mitochondrial and chloroplast genes, it may also be used for detection of gene conversion between any two distinct groups of homologous sequences.</p
Intracellular directed evolution of proteins from combinatorial libraries based on conditional phage replication
Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene—or gene circuit function—that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ~7 weeks
Motion in classical field theories and the foundations of the self-force problem
This article serves as a pedagogical introduction to the problem of motion in
classical field theories. The primary focus is on self-interaction: How does an
object's own field affect its motion? General laws governing the self-force and
self-torque are derived using simple, non-perturbative arguments. The relevant
concepts are developed gradually by considering motion in a series of
increasingly complicated theories. Newtonian gravity is discussed first, then
Klein-Gordon theory, electromagnetism, and finally general relativity. Linear
and angular momenta as well as centers of mass are defined in each of these
cases. Multipole expansions for the force and torque are then derived to all
orders for arbitrarily self-interacting extended objects. These expansions are
found to be structurally identical to the laws of motion satisfied by extended
test bodies, except that all relevant fields are replaced by effective versions
which exclude the self-fields in a particular sense. Regularization methods
traditionally associated with self-interacting point particles arise as
straightforward perturbative limits of these (more fundamental) results.
Additionally, generic mechanisms are discussed which dynamically shift ---
i.e., renormalize --- the apparent multipole moments associated with
self-interacting extended bodies. Although this is primarily a synthesis of
earlier work, several new results and interpretations are included as well.Comment: 68 pages, 1 figur
Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration
Oxidative stress is a common etiological feature of neurological disorders, although the pathways that govern defence against reactive oxygen species (ROS) in neurodegeneration remain unclear. We have identified the role of oxidation resistance 1 (Oxr1) as a vital protein that controls the sensitivity of neuronal cells to oxidative stress; mice lacking Oxr1 display cerebellar neurodegeneration, and neurons are less susceptible to exogenous stress when the gene is over-expressed. A conserved short isoform of Oxr1 is also sufficient to confer this neuroprotective property both in vitro and in vivo. In addition, biochemical assays indicate that Oxr1 itself is susceptible to cysteine-mediated oxidation. Finally we show up-regulation of Oxr1 in both human and pre-symptomatic mouse models of amyotrophic lateral sclerosis, indicating that Oxr1 is potentially a novel neuroprotective factor in neurodegenerative disease
AKR1C enzymes sustain therapy resistance in paediatric T-ALL
BACKGROUND: Despite chemotherapy intensification, a subgroup of high-risk paediatric T-cell acute lymphoblastic leukemia (TALL) patients still experience treatment failure. In this context, we hypothesised that therapy resistance in T-ALL might involve aldo-keto reductase 1C (AKR1C) enzymes as previously reported for solid tumors.METHODS: Expression of NRF2-AKR1C signaling components has been analysed in paediatric T-ALL samples endowed with different treatment outcomes as well as in patient-derived xenografts of T-ALL. The effects of AKR1C enzyme modulation has been investigated in T-ALL cell lines and primary cultures by combining AKR1C inhibition, overexpression, and gene silencing approaches.RESULTS: We show that T-ALL cells overexpress AKR1C1-3 enzymes in therapy-resistant patients. We report that AKR1C1-3 enzymes play a role in the response to vincristine (VCR) treatment, also ex vivo in patient-derived xenografts. Moreover, we demonstrate that the modulation of AKR1C1-3 levels is sufficient to sensitise T-ALL cells to VCR. Finally, we show that T-ALL chemotherapeutics induce overactivation of AKR1C enzymes independent of therapy resistance, thus establishing a potential resistance loop during T-ALL combination treatment.CONCLUSIONS: Here, we demonstrate that expression and activity of AKR1C enzymes correlate with response to chemotherapeutics in T-ALL, posing AKR1C1-3 as potential targets for combination treatments during T-ALL therapy
Synergy in Efficacy of Fungal Entomopathogens and Permethrin against West African Insecticide-Resistant Anopheles gambiae Mosquitoes
Background Increasing incidences of insecticide resistance in malaria vectors are threatening the sustainable use of contemporary chemical vector control measures. Fungal entomopathogens provide a possible additional tool for the control of insecticide-resistant malaria mosquitoes. This study investigated the compatibility of the pyrethroid insecticide permethrin and two mosquito-pathogenic fungi, Beauveria bassiana and Metarhizium anisopliae, against a laboratory colony and field population of West African insecticide-resistant Anopheles gambiae s.s. mosquitoes. Methodology/Findings A range of fungus-insecticide combinations was used to test effects of timing and sequence of exposure. Both the laboratory-reared and field-collected mosquitoes were highly resistant to permethrin but susceptible to B. bassiana and M. anisopliae infection, inducing 100% mortality within nine days. Combinations of insecticide and fungus showed synergistic effects on mosquito survival. Fungal infection increased permethrin-induced mortality rates in wild An. gambiae s.s. mosquitoes and reciprocally, exposure to permethrin increased subsequent fungal-induced mortality rates in both colonies. Simultaneous co-exposure induced the highest mortality; up to 70.3±2% for a combined Beauveria and permethrin exposure within a time range of one gonotrophic cycle (4 days). Conclusions/Significance Combining fungi and permethrin induced a higher impact on mosquito survival than the use of these control agents alone. The observed synergism in efficacy shows the potential for integrated fungus-insecticide control measures to dramatically reduce malaria transmission and enable control at more moderate levels of coverage even in areas where insecticide resistance has rendered pyrethroids essentially ineffective
Polyamide-Scorpion Cyclam Lexitropsins Selectively Bind AT-Rich DNA Independently of the Nature of the Coordinated Metal
Cyclam was attached to 1-, 2- and 3-pyrrole lexitropsins for the first time
through a synthetically facile copper-catalyzed “click” reaction.
The corresponding copper and zinc complexes were synthesized and characterized.
The ligand and its complexes bound AT-rich DNA selectively over GC-rich DNA, and
the thermodynamic profile of the binding was evaluated by isothermal titration
calorimetry. The metal, encapsulated in a scorpion azamacrocyclic complex, did
not affect the binding, which was dominated by the organic tail
Self-force: Computational Strategies
Building on substantial foundational progress in understanding the effect of
a small body's self-field on its own motion, the past 15 years has seen the
emergence of several strategies for explicitly computing self-field corrections
to the equations of motion of a small, point-like charge. These approaches
broadly fall into three categories: (i) mode-sum regularization, (ii) effective
source approaches and (iii) worldline convolution methods. This paper reviews
the various approaches and gives details of how each one is implemented in
practice, highlighting some of the key features in each case.Comment: Synchronized with final published version. Review to appear in
"Equations of Motion in Relativistic Gravity", published as part of the
Springer "Fundamental Theories of Physics" series. D. Puetzfeld et al.
(eds.), Equations of Motion in Relativistic Gravity, Fundamental Theories of
Physics 179, Springer, 201
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