Pathomechanisms of ulnar ligament lesions of the wrist in a cadaveric distal radius fracture model

Background and purpose: Mechanisms of injury to ulnar sided ligaments, stabilizing the distal radioulnar joint and the ulna to the carpus, associated with dorsally displaced distal radius fractures are poorly described. We investigated the injury patterns in a human cadaver fracture model. Methods: Fresh frozen human cadaver arms were used. A dorsal open wedge osteotomy was made in the distal radius. In 8 specimens pressure was applied to the palm with the wrist in dorsiflexion and ulnar sided stabilizing structures subsequently severed. Dorsal angulation was measured on digitized radiographs. In 8 more specimens the triangular fibrocartilage complex was forced into rupture by axially loading the forearm with the wrist in dorsiflexion. The ulnar side was dissected and injuries were recorded. Results: Intact ulnar soft tissues limited the dorsal angulation of the distal radius fragment to a median of 32o (16-34o). A combination of bending and shearing of the distal radius fragment was needed to create TFCC injuries. Both palmar and dorsal injuries were observed simultaneously in 6/8 specimens. Interpretation: A TFCC injury can be expected when dorsal angulation of a distal radius fracture exceeds 32o. The extensor carpi ulnaris subsheath may be a functionally integral part of the TFCC. Both dorsal and palmar structures can tear simultaneously. These findings may have implications for reconstruction of ulnar sided soft tissue injuries

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

The Functions of Myosin II and Myosin V Homologs in Tip Growth and Septation in Aspergillus nidulans

Because of the industrial and medical importance of members of the fungal genus Aspergillus, there is considerable interest in the functions of cytoskeletal components in growth and secretion in these organisms. We have analyzed the genome of Aspergillus nidulans and found that there are two previously unstudied myosin genes, a myosin II homolog, myoB (product = MyoB) and a myosin V homolog, myoE (product = MyoE). Deletions of either cause significant growth defects. MyoB localizes in strings that coalesce into contractile rings at forming septa. It is critical for septation and normal deposition of chitin but not for hyphal extension. MyoE localizes to the Spitzenkörper and to moving puncta in the cytoplasm. Time-lapse imaging of SynA, a v-SNARE, reveals that in myoE deletion strains vesicles no longer localize to the Spitzenkörper. Tip morphology is slightly abnormal and branching occurs more frequently than in controls. Tip extension is slower than in controls, but because hyphal diameter is greater, growth (increase in volume/time) is only slightly reduced. Concentration of vesicles into the Spitzenkörper before incorporation into the plasma membrane is, thus, not required for hyphal growth but facilitates faster tip extension and a more normal hyphal shape

Calibration of the charge and energy loss per unit length of the MicroBooNE liquid argon time projection chamber using muons and protons

We describe a method used to calibrate the position- and time-dependent response of the MicroBooNE liquid argon time projection chamber anode wires to ionization particle energy loss. The method makes use of crossing cosmic-ray muons to partially correct anode wire signals for multiple effects as a function of time and position, including cross-connected TPC wires, space charge effects, electron attachment to impurities, diffusion, and recombination. The overall energy scale is then determined using fully-contained beam-induced muons originating and stopping in the active region of the detector. Using this method, we obtain an absolute energy scale uncertainty of 2% in data. We use stopping protons to further refine the relation between the measured charge and the energy loss for highly-ionizing particles. This data-driven detector calibration improves both the measurement of total deposited energy and particle identification based on energy loss per unit length as a function of residual range. As an example, the proton selection efficiency is increased by 2% after detector calibration

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector.

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies

Comparative Proteomics of Inner Membrane Fraction from Carbapenem-Resistant Acinetobacter baumannii with a Reference Strain

Acinetobacter baumannii has been identified by the Infectious Diseases Society of America as one of the six pathogens that cause majority of hospital infections. Increased resistance of A. baumannii even to the latest generation of β-lactams like carbapenem is an immediate threat to mankind. As inner-membrane fraction plays a significant role in survival of A. baumannii, we investigated the inner-membrane fraction proteome of carbapenem-resistant strain of A. baumannii using Differential In-Gel Electrophoresis (DIGE) followed by DeCyder, Progenesis and LC-MS/MS analysis. We identified 19 over-expressed and 4 down-regulated proteins (fold change>2, p<0.05) in resistant strain as compared to reference strain. Some of the upregulated proteins in resistant strain and their association with carbapenem resistance in A. baumannii are: i) β-lactamases, AmpC and OXA-51: cleave and inactivate carbapenem ii) metabolic enzymes, ATP synthase, malate dehydrogenase and 2-oxoglutarate dehydrogenase: help in increased energy production for the survival and iii) elongation factor Tu and ribosomal proteins: help in the overall protein production. Further, entry of carbapenem perhaps is limited by controlled production of OmpW and low levels of surface antigen help to evade host defence mechanism in developing resistance in A. baumannii. Present results support a model for the importance of proteins of inner-membrane fraction and their synergistic effect in the mediation of resistance of A. baumannii to carbapenem

A degenerate primer MOB typing (DPMT) method to classify gamma-proteobacterial plasmids in clinical and environmental settings

Transmissible plasmids are responsible for the spread of genetic determinants, such as antibiotic resistance or virulence traits, causing a large ecological and epidemiological impact. Transmissible plasmids, either conjugative or mobilizable, have in common the presence of a relaxase gene. Relaxases were previously classified in six protein families according to their phylogeny. Degenerate primers hybridizing to coding sequences of conserved amino acid motifs were designed to amplify related relaxase genes from γ-Proteobacterial plasmids. Specificity and sensitivity of a selected set of 19 primer pairs were first tested using a collection of 33 reference relaxases, representing the diversity of γ-Proteobacterial plasmids. The validated set was then applied to the analysis of two plasmid collections obtained from clinical isolates. The relaxase screening method, which we call "Degenerate Primer MOB Typing" or DPMT, detected not only most known Inc/Rep groups, but also a plethora of plasmids not previously assigned to any Inc group or Rep-type