Project description:Collagens are the most abundant glycoproteins in the body. One characteristic of this protein family is that the amino acid sequence consists of repeats of three amino acids -(X-Y-Gly)n. Within this motif, the Y residue is often 4-hydroxyproline (HyP) or 5-hydroxylysine (HyK). Glycosylation in collagen occurs at the 5-OH group in HyK in the form of two glycosides, galactosylhydroxylysine (Gal-HyK) and glucosyl galactosylhydroxylysine (GlcGal-HyK). In collision induced dissociation (CID), collagen tryptic glycopeptides exhibit unexpected gas-phase dissociation behavior compared to typical N- and O-linked glycopeptides (i.e., in addition to glycosidic bond cleavages, extensive cleavages of the amide bonds are observed). The Gal- or GlcGal- glycan modifications are largely retained on the fragment ions. These features enable unambiguous determination of the amino acid sequence of collagen glycopeptides and the location of the glycosylation site. This dissociation pattern was consistent for all analyzed collagen glycopeptides, regardless of their length or amino acid composition, collagen type or tissue. The two fragmentation pathways-amide bond and glycosidic bond cleavage-are highly competitive in collagen tryptic glycopeptides. The number of ionizing protons relative to the number of basic sites (i.e., Arg, Lys, HyK, and N-terminus) is a major driving force of the fragmentation. We present here our experimental results and employ quantum mechanics calculations to understand the factors enhancing the labile character of the amide bonds and the stability of hydroxylysine glycosides in gas phase dissociation of collagen glycopeptides.
Project description:RationaleModification of cysteines by aminoethylation results in side chains similar to those of lysine. Trypsin cleaves at this modified residue and this labeling method can facilitate the analysis of proteins, specifically antibodies. In this work, the ability to identify peptides containing aminoethylated cysteines is investigated through digestion, covalent labeling, and low-energy ion fragmentation.MethodsA prototype antibody was reduced, aminoethylated, and digested with either Lys-N or Glu-C. The resulting peptides were amidinated with SMTA and analyzed by PSD in a MALDI-TOF/TOF mass spectrometer or by CID in an ESI ion trap/orbitrap mass spectrometer.ResultsPSD and CID fragmentation of peptides with an amidinated aminoethylated cysteine can produce an intense characteristic loss from this modified residue. A neutral loss of 118 Da or charged loss of 119 Da is observed when peptides have low charges. This fragment can form when the cysteine is located in any position in the peptide. The rationalization for this ion is that the amidino group can be initially neutral or protonated and initiates fragmentation.ConclusionsThe combination of a dual-labeling technique and low-energy fragmentation produces an abundant diagnostic ion for the analysis of cysteine-containing peptides. These 118 and 119 Da losses are observed when protons are sequestered.
Project description:Flexible radiofrequency coils for magnetic resonance imaging (MRI) have garnered attention in research and industrial communities because they provide improved accessibility and performance and can accommodate a range of anatomic postures. Most recent flexible coil developments involve customized conductors or substrate materials and/or target applications at 3 T or above. In contrast, we set out to design a flexible coil based on an off-the-shelf conductor that is suitable for operation at 0.55 T (23.55 MHz). Signal-to-noise ratio (SNR) degradation can occur in such an environment because the resistance of the coil conductor can be significant with respect to the sample. We found that resonating a commercially available RG-223 coaxial cable shield with a lumped capacitor while the inner conductor remained electrically floating gave rise to a highly effective "cable coil." A 10-cm diameter cable coil was flexible enough to wrap around the knee, an application that can benefit from flexible coils, and had similar conductor loss and SNR as a standard-of-reference rigid copper coil. A two-channel cable coil array also provided good SNR robustness against geometric variability, outperforming a two-channel coaxial coil array by 26 and 16% when the elements were overlapped by 20-40% or gapped by 30-50%, respectively. A 6-channel cable coil array was constructed for 0.55 T knee imaging. Incidental cartilage and bone pathologies were clearly delineated in T1- and T2-weighted turbo spin echo images acquired in 3-4 min with the proposed coil, suggesting that clinical quality knee imaging is feasible in an acceptable examination timeframe. Correcting for T1, the SNR measured with the cable coil was approximately threefold lower than that measured with a 1.5 T state-of-the-art 18-channel coil, which is expected given the threefold difference in main magnetic field strength. This result suggests that the 0.55 T cable coil conductor loss does not deleteriously impact SNR, which might be anticipated at low field.
Project description:A 54-year-old man presented in profound obstructive shock. Investigations revealed a right atrial mass causing severe right ventricular inflow obstruction and compromised cardiac output. The patient was treated with emergency balloon catheter intervention to relieve the obstruction, with resulting hemodynamic stability. The pathology report later returned a positive result for diffuse large B-cell lymphoma. (Level of Difficulty: Intermediate.).
Project description:Ion-electron reaction based fragmentation methods (ExD) in tandem mass spectrometry (MS), such as electron capture dissociation (ECD) and electron transfer dissociation (ETD) represent a powerful tool for biological analysis. ExD methods have been used to differentiate the presence of the isoaspartate (isoAsp) from the aspartate (Asp) in peptides and proteins. IsoAsp is a ?(3)-type amino acid that has an additional methylene group in the backbone, forming a C(?)-C(?) bond within the polypeptide chain. Cleavage of this bond provides specific fragments that allow differentiation of the isomers. The presence of a C(?)-C(?) bond within the backbone is unique to ?-amino acids, suggesting a similar application of ExD toward the analysis of peptides containing other ?-type amino acids. In the current study, ECD and ETD analysis of several ?-amino acid containing peptides was performed. It was found that N-C(?) and C(?)-C(?) bond cleavages were rare, providing few c and z• type fragments, which was attributed to the instability of the C(?) radical. Instead, the electron capture resulted primarily in the formation of a• and y fragments, representing an alternative fragmentation pathway, likely initiated by the electron capture at a backbone amide nitrogen protonation site within the ? amino acid residues.
Project description:The deformation and fracture mechanism of two-dimensional (2D) materials are still unclear and not thoroughly investigated. Given this, mechanical properties and mechanisms are explored on example of gallium telluride (GaTe), a promising 2D semiconductor with an ultrahigh photoresponsivity and a high flexibility. Hereby, the mechanical properties of both substrate-supported and suspended GaTe multilayers were investigated through Berkovich-tip nanoindentation instead of the commonly used AFM-based nanoindentation method. An unusual concurrence of multiple pop-in and load-drop events in loading curve was observed. Theoretical calculations unveiled this concurrence originating from the interlayer-sliding mediated layers-by-layers fracture mechanism in GaTe multilayers. The van der Waals force dominated interlayer interactions between GaTe and substrates was revealed much stronger than that between GaTe interlayers, resulting in the easy sliding and fracture of multilayers within GaTe. This work introduces new insights into the deformation and fracture of GaTe and other 2D materials in flexible electronics applications.
Project description:The precise mechanisms underlying cranial bone development, evolution and patterning remain incompletely characterised. This poses a challenge to understanding the etiologies of craniofacial malformations evolving in nature. Capitalising on natural variation, "evolutionary model systems" provide unique opportunities to identify underlying causes of aberrant phenotypes as a complement to studies in traditional systems. Mexican blind cavefish are a prime evolutionary model for cranial disorders since they frequently exhibit extreme alterations to the skull and lateral asymmetries. These aberrations occur in stark contrast to the normal cranial architectures of closely related surface-dwelling fish, providing a powerful comparative paradigm for understanding cranial bone formation. Using a longitudinal and in vivo analytical approach, we discovered two unusual ossification processes in cavefish that underlie the development of 'fragmented' and asymmetric cranial bones. The first mechanism involves the sporadic appearance of independent bony elements that fail to fuse together later in development. The second mechanism involves the "carving" of channels in the mature bone, a novel form of post-ossification remodeling. In the extreme cave environment, these novel mechanisms may have evolved to augment sensory input, and may indirectly result in a trade-off between sensory expansion and cranial bone development.
Project description:Wooden foreign bodies penetrating through the orbit into paranasal sinuses are rare. We report a case of a young male who complained of double vision, pain and redness after a fall from a tree. There was no external wound over periocular skin. The clinical and radiological examination was suggestive of an inferior orbito-sinal wooden foreign body with floor fracture, which was managed by surgical removal of the foreign body and orbital floor fracture repair using a silicon sheet in a single sitting.
Project description:The deposition of amyloid within human tissue can be detrimental to the proper functioning of multiple organ systems. While the infiltration of the amyloid protein within the musculoskeletal soft tissues can lead to compressive neuropathies, tendon irritation or rupture, and joint stiffness, pathologic fracture as a result of amyloid deposition in bone is a rare manifestation of amyloidosis. We present a case of pathologic fracture of the femoral neck from amyloid deposition in a 59-year-old male on chronic hemodialysis who was found to have lytic lesions in his proximal femur. At the time of hemiarthroplasty, histopathologic analysis of a femoral head sample revealed apple-green birefringence of the deposits under polarized light, consistent with amyloid deposition. Clinicians should have a high index of suspicion for the atypical presentation of amyloidosis in a patient on chronic hemodialysis with lytic bone lesions.
Project description:Expanded polytetrafluoroethylene (ePTFE) coated and medical adhesive back-filled (MABF) implantable cardioverter-defibrillator (ICD) coils have been promoted to reduce the fibrous ingrowth into coils that can complicate lead extraction.The purpose of this study was to test the hypothesis that ePTFE or MABF coatings are associated with greater ease of extraction.Consecutive isolated ICD lead extraction cases were identified from a prospectively collected clinical database. Primary endpoints included total procedure and fluoroscopy times, radiation dose, and fibrosis sites. Data were analyzed using univariate and multivariate analyses in total and propensity-matched groups, adjusting for lead age and other factors.Among 329 patients (80% male; age 63.7 +/- 5.4 years), 284 (86.3%) had standard coil ICD and 45 (13.7%) had treated coil ICD leads extracted, of which 17 (5.2%) were ePTFE coated and 28 (8.5%) were MABF ICD leads. The ePTFE and MABF leads were associated with lower procedure and fluoroscopy times, radiation dose, and fibrosis sites, even after adjustment for lead age, which was significantly shorter in the treated coil leads. To further adjust for the difference in lead age, a propensity-matched group was analyzed. Procedure time, fluoroscopy time, radiation dose, and brachiocephalic fibrosis remained significantly lower in the treated coil lead group.The ePTFE- and MABF-treated coils appear to provide some incremental benefit in ease of extraction over conventional, nontreated coil ICD leads. Although many current ICD leads do not have fibrosis ingrowth-limiting strategies, our study may rationalize the consideration of adding such technologies to future leads.