Possible Skull Base Erosion After Prolonged Frontal Sinus Stenting

Frontal sinus stenting is widely used with the goal of maintaining nasofrontal duct patency after sinus surgery. The general recommendation is to leave stents in place for 6 months; however, prolonged stenting up to 6 years has been reported with no complication. We present the first reported case of frontal sinus posterior table and skull base erosion following prolonged frontal sinus stenting. A 57-year-old female presented with chronic sinusitis and nasal obstruction. Imaging revealed pansinusitis with retained stents in each frontal sinus that were placed 8 years prior. On the right, there was an area of skull base erosion at the tip of the stent. The patient underwent functional endoscopic sinus surgery with polypectomy. The stents were removed, revealing posterior table erosion on the right side but intact mucosa. Two months after surgery, there were no signs or symptoms of cerebrospinal fluid leak or other complications. Recent literature has suggested that prolonged stenting is safe; however, this case highlights a complication with potentially serious outcomes that can result from prolonged stenting. We recommend stent removal once stable nasofrontal duct patency has been achieved. If prolonged stenting is utilized, patients should be closely monitored and consideration should be given to periodic imaging to evaluate stent position

Myosin VI Lever Arm Rotation: Fixed or Variable?

Two recent articles addressed the power-stroke of myosin VI molecules during stepping. Although both groups measured the angles of fluorescent probes attached on the myosin VI molecule lever arm using polarized fluorescence techniques, they differ about whether the myosin VI lever arm rotation is fixed1 or variable2. Here we discuss the causes of the discrepancy between the two studies and the implications for myosin VI processive motility

Twirling of Actin by Myosins II and V Observed via Polarized TIRF in a Modified Gliding Assay

The force generated between actin and myosin acts predominantly along the direction of the actin filament, resulting in relative sliding of the thick and thin filaments in muscle or transport of myosin cargos along actin tracks. Previous studies have also detected lateral forces or torques that are generated between actin and myosin, but the origin and biological role of these sideways forces is not known. Here we adapt an actin gliding filament assay in order to measure the rotation of an actin filament about its axis (“twirling”) as it is translocated by myosin. We quantify the rotation by determining the orientation of sparsely incorporated rhodamine-labeledactin monomers, using polarized total internal reflection (polTIRF) microscopy. In order to determine the handedness of the filament rotation, linear incident polarizations in between the standard s- and p-polarizations were generated, decreasing the ambiguity of our probe orientation measurement four-fold. We found that whole myosin II and myosin V both twirl actin with a relatively long (~ µm), left-handed pitch that is insensitive to myosin concentration, filament length and filament velocity

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Clonal Progression during the T Cell-Dependent B Cell Antibody Response Depends on the Immunoglobulin DH Gene Segment Repertoire

The diversity of the third complementarity determining region of the IgH chain is constrained by natural selection of immunoglobulin diversity (D(H)) sequence. To test the functional significance of this constraint in the context of thymus-dependent (TD) immune responses, we immunized BALB/c mice with WT or altered D(H) sequence with 2-phenyloxazolone-coupled chicken serum albumin (phOx-CSA). We chose this antigen because studies of the humoral immune response to the hapten phOx were instrumental in the development of the current theoretical framework on which our understanding of the forces driving TD responses is based. To allow direct comparison, we used the classic approach of generating monoclonal Ab (mAb) from various stages of the immune response to phOx to assess the effect of changing the sequence of the D(H) on clonal expansion, class switching, and affinity maturation, which are hallmarks of TD responses. Compared to WT, TD-induced humoral IgM as well as IgG antibody production in the D-altered ΔD-DμFS and ΔD-iD strains were significantly reduced. An increased prevalence of IgM-producing hybridomas from late primary, secondary, and tertiary memory responses suggested either impaired class switch recombination (CSR) or impaired clonal expansion of class switched B cells with phOx reactivity. Neither of the D-altered strains demonstrated the restriction in the V(H)/V(L) repertoire, the elimination of V(H)1 family-encoded antibodies, the focusing of the distribution of CDR-H3 lengths, or the selection for the normally dominant Ox1 clonotype, which all are hallmarks of the anti-phOx response in WT mice. These changes in clonal selection and expansion, as well as CSR indicate that the genetic constitution of the D(H) locus, which has been selected by evolution, can strongly influence the functional outcome of a TD humoral response

VpreB serves as an invariant surrogate antigen for selecting immunoglobulin antigen-binding sites

Developmental checkpoints eliminate B cells that synthesize defective immunoglobulin (Ig) heavy (HC) and light (LC) chains. The first checkpoint tests mHCs paired with VpreB/l5 in a pre-B cell receptor (pre-BCR) to determine whether the mHC will be able to bind conventional LCs to form membrane IgM. VpreB and l5 also create a sensing site that interacts with the mHC antigen-binding region complementarity-determining region (CDR)\u2013H3; however, whether this site contributes to Ig repertoire selection and function is unknown. We analyzed the amino acid content of CDR-H3s from HCs cloned from living and apoptotic pre-B cells and from IgG-antigen structures. Using a panel of DH gene\u2013targeted mice, we showed that progressively reducing CDR-H3 tyrosine content increasingly impaired pre-BCR checkpoint passage. Counting from cysteine at framework 3 position 96, we found that VpreB particularly selected for tyrosine at CDR-H3 position 101 and that Y101 also bound antigen in IgG-antigen structures. Therefore, in addition to its stabilization role in the pre-BCR, VpreB also acts as an early invariant antigen by selecting for particular CDR-H3 amino acids. These interactions shape the specificity of the IgG humoral response and may thus impose limitations on development of certain neutralizing antibodies