An Assessment of Song Admixture as an Indicator of Hybridization in Black-capped Chickadees (Poecile atricapillus) and Carolina Chickadees (Poecile carolinensis)

Vocal admixture often occurs where differentiated populations or species of birds meet. This may entail song sympatry, bilingually singing birds, and songs with intermediate or atypical characteristics. Different levels of vocal admixture at the range interface between Black-capped Chickadees (Poecile atricapillus) and Carolina Chickadees (P. carolinensis) have been interpreted as indicating that hybridization is frequent at some locations but not others. However, song ontogeny in these birds has a strong nongenetic component, so that inferences regarding hybridization based on vocal admixture require confirmation. We used diagnostic genetic markers and quantitative analyses of song to characterize population samples along two transects of the chickadee contact zone in the Appalachian Mountains. More than 50% of individuals at the range interface were of hybrid ancestry, yet only 20% were observed to be bilingual or to sing atypical songs. Principal component analysis revealed minimal song intermediacy. This result contrasts with an earlier analysis of the hybrid zone in Missouri that found considerable song intermediacy. Re-analysis of the Missouri data confirmed this difference. Correlation between an individual\u27s genetic composition and its song type was weak in Appalachian hybrid populations, and genetic introgression in both forms extended far beyond the limits of vocal admixture. Therefore, song is not a reliable indicator of levels of hybridization or genetic introgression at this contact zone. Varying ecological factors may play a role in producing variable levels of song admixture in different regions of the range interface

Structures of fibrils formed by α-synuclein hereditary disease mutant H50Q reveal new polymorphs.

Deposits of amyloid fibrils of α-synuclein are the histological hallmarks of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, with hereditary mutations in α-synuclein linked to the first two of these conditions. Seeing the changes to the structures of amyloid fibrils bearing these mutations may help to understand these diseases. To this end, we determined the cryo-EM structures of α-synuclein fibrils containing the H50Q hereditary mutation. We find that the H50Q mutation results in two previously unobserved polymorphs of α-synuclein: narrow and wide fibrils, formed from either one or two protofilaments, respectively. These structures recapitulate conserved features of the wild-type fold but reveal new structural elements, including a previously unobserved hydrogen-bond network and surprising new protofilament arrangements. The structures of the H50Q polymorphs help to rationalize the faster aggregation kinetics, higher seeding capacity in biosensor cells and greater cytotoxicity that we observe for H50Q compared to wild-type α-synuclein

Catastrophic disassembly of actin filaments via Mical-mediated oxidation.

Actin filament assembly and disassembly are vital for cell functions. MICAL Redox enzymes are important post-translational effectors of actin that stereo-specifically oxidize actin's M44 and M47 residues to induce cellular F-actin disassembly. Here we show that Mical-oxidized (Mox) actin can undergo extremely fast (84 subunits/s) disassembly, which depends on F-actin's nucleotide-bound state. Using near-atomic resolution cryoEM reconstruction and single filament TIRF microscopy we identify two dynamic and structural states of Mox-actin. Modeling actin's D-loop region based on our 3.9 Å cryoEM reconstruction suggests that oxidation by Mical reorients the side chain of M44 and induces a new intermolecular interaction of actin residue M47 (M47-O-T351). Site-directed mutagenesis reveals that this interaction promotes Mox-actin instability. Moreover, we find that Mical oxidation of actin allows for cofilin-mediated severing even in the presence of inorganic phosphate. Thus, in conjunction with cofilin, Mical oxidation of actin promotes F-actin disassembly independent of the nucleotide-bound state

Gastric plexiform fibromyxoma tumor in a child – Case report and review of the literature

AbstractPlexiform fibromyxoma tumor (PFT) is an exceedingly rare tumor, particularly in children where only four cases have been reported to date. The patient reported herein presented with abdominal pain and vomiting related to gastric outlet obstruction caused by a large, polypoid PFT. We describe the clinical features, diagnostic evaluation, and surgical treatment of this rare tumor in our patient. Further, we review the literature of FPT to bring attention to this rare gastric tumor to the Pediatric Surgeon

Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain.

Overproduction of immunoglobulin light chains leads to systemic amyloidosis, a lethal disease characterized by the formation of amyloid fibrils in patients' tissues. Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. Here we identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer

Crystal Structure of T7 Gene 4 Ring Helicase Indicates a Mechanism for Sequential Hydrolysis of Nucleotides

AbstractWe have determined the crystal structure of an active, hexameric fragment of the gene 4 helicase from bacteriophage T7. The structure reveals how subunit contacts stabilize the hexamer. Deviation from expected six-fold symmetry of the hexamer indicates that the structure is of an intermediate on the catalytic pathway. The structural consequences of the asymmetry suggest a “binding change” mechanism to explain how cooperative binding and hydrolysis of nucleotides are coupled to conformational changes in the ring that most likely accompany duplex unwinding. The structure of a complex with a nonhydrolyzable ATP analog provides additional evidence for this hypothesis, with only four of the six possible nucleotide binding sites being occupied in this conformation of the hexamer. This model suggests a mechanism for DNA translocation