Monomeric and dimeric states exhibited by the kinesin‐related motor protein KIF1A

Abstract: KIF1A, a kinesin‐related motor protein that transports pre‐synaptic vesicles in neurons, was originally presumed to translocate along microtubules (MT) as a monomer. Protein structure predictions from its amino acid sequence failed to identify the long coiled‐coil domains typical of kinesins, which led researchers to believe it does not oligomerize into the canonical kinesin dimer. However, mounting evidence using recombinant chimeric protein indicates that KIF1A, like conventional kinesin, requires dimerization for fast, unidirectional processive movement along MTs. Because these studies are somewhat indirect, we wished to test the oligomerization state of native KIF1A, and to compare that to full‐length recombinant protein. We have performed hydrodynamic analyses to determine the molecular weights of the respective complexes. Our results indicate that most native KIF1A is soluble and indeed monomeric, but recombinant KIF1A is a dimer. MT‐binding studies also showed that native KIF1A did not bind to MTs in either the presence of AMP‐PNP, apyrase, or adenosine triphosphate (ATP), but recombinant KIF1A bound to MTs most stably in the presence of ATP, indicating very different motor functional states. To further characterize KIF1A's dimerization potential, we prepared peptides corresponding to the neck domains of MmKIF1A and CeUnc104, and by circular dichroism spectroscopy compared these peptides for their ability to form coiled‐coils. Interestingly, both MmKIF1A and CeUnc104 neck peptides formed homodimeric coiled‐coils, with the MmKIF1A neck coiled‐coil exhibiting the greater stability. Collectively, from our data and from previous studies, we predict that native KIF1A can exist as both an inactive monomer and an active homodimer formed in part through its neck coiled‐coil domain.     

Osteohistology of Greererpeton provides insight into the life history of an early Carboniferous tetrapod

The vertebrate transition to land is one of the most consequential, yet poorly understood periods in tetrapod evolution. Despite the importance of the water–land transition in establishing modern ecosystems, we still know very little about the life histories of the earliest tetrapods. Bone histology provides an exceptional opportunity to study the biology of early tetrapods and has the potential to reveal new insights into their life histories. Here, we examine the femoral bone histology from an ontogenetic series of Greererpeton, an early tetrapod from the Middle-Late Mississippian (early Carboniferous) of North America. Thin-sections and micro-CT data show a moderately paced rate of bone deposition with significant cortical thickening through development. An interruption to regular bone deposition, as indicated by a zone of avascular tissue and growth marks, is notable at the same late juvenile stage of development throughout our sample. This suggests that an inherent aspect to the life history of juvenile Greererpeton resulted in a temporary reduction in bone deposition. We review several possible life history correlates for this bony signature including metamorphosis, an extended juvenile phase, environmental stress, and movement (migration/dispersal) between habitats. We argue that given the anatomy of Greererpeton, it is unlikely that events related to polymorphism (metamorphosis, extended juvenile phase) can explain the bony signature observed in our sample. Furthermore, the ubiquity of this signal in our sample indicates a taxon-level rather than a population-level trait, which is expected for an environmental stress. We conclude that movement via dispersal represents a likely correlate, as such events are a common life history strategy of aquatically bound vertebrates.     

Human papillomavirus vaccination: Where are we now?

The development of efficacious prophylactic human papillomavirus vaccines provided an opportunity for the primary prevention of related infections and diseases. Certain oncogenic human papillomaviruses that preferentially infect the genital epithelium cause cervical cancer and a substantial proportion of anal, penile, vaginal, vulvar and oropharyngeal cancers. Following extensive clinical trials demonstrating their efficacy and safety, two vaccines have been in global use for over 6 years. This review summarises the accumulated evidence regarding their high level of efficacy, safety in population usage, reductions in genital warts, infections and cervical disease following their adoption, and facilitators and barriers to achieving high vaccination coverage. The review also discusses practical issues and frequently asked questions regarding duration of effect, vaccination of women treated for cervical disease and alternate vaccination schedules, as well as the need to review cervical screening strategies in the post‐ vaccination environment.