Axoneme-specific β-tubulin specialization a conserved C-terminal motif specifies the central pair

AbstractAxonemes are ancient organelles that mediate motility of cilia and flagella in animals, plants, and protists. The long evolutionary conservation of axoneme architecture, a cylinder of nine doublet microtubules surrounding a central pair of singlet microtubules, suggests all motile axonemes may share common assembly mechanisms. Consistent with this, α- and β-tubulins utilized in motile axonemes fall among the most conserved tubulin sequences [1, 2], and the β-tubulins contain a sequence motif at the same position in the carboxyl terminus [3]. Axoneme doublet microtubules are initiated from the corresponding triplet microtubules of the basal body [4], but the large macromolecular “central apparatus” that includes the central pair microtubules and associated structures [5] is a specialization unique to motile axonemes. In Drosophila spermatogenesis, basal bodies and axonemes utilize the same α-tubulin but different β-tubulins [6–13]. β1 is utilized for the centriole/basal body, and β2 is utilized for the motile sperm tail axoneme. β2 contains the motile axoneme-specific sequence motif, but β1 does not [3]. Here, we show that the “axoneme motif” specifies the central pair. β1 can provide partial function for axoneme assembly but cannot make the central microtubules [14]. Introducing the axoneme motif into the β1 carboxyl terminus, a two amino acid change, conferred upon β1 the ability to assemble 9 + 2 axonemes. This finding explains the conservation of the axoneme-specific sequence motif through 1.5 billion years of evolution

Sediment Delivery to Sustain the Ganges-Brahmaputra Delta Under Climate Change and Anthropogenic Impacts

The principal nature-based solution for offsetting relative sea-level rise in the Ganges-Brahmaputra delta is the unabated delivery, dispersal, and deposition of the rivers’ ~1 billion-tonne annual sediment load. Recent hydrological transport modeling suggests that strengthening monsoon precipitation in the 21st century could increase this sediment delivery 34-60%; yet other studies demonstrate that sediment could decline 15-80% if planned dams and river diversions are fully implemented. We validate these modeled ranges by developing a comprehensive field-based sediment budget that quantifies the supply of Ganges-Brahmaputra river sediment under varying Holocene climate conditions. Our data reveal natural responses in sediment supply comparable to previously modeled results and suggest that increased sediment delivery may be capable of offsetting accelerated sea-level rise. This prospect for a naturally sustained Ganges-Brahmaputra delta presents possibilities beyond the dystopian future often posed for this system, but the implementation of currently proposed dams and diversions would preclude such opportunities

Smoke, curtains and mirrors: the production of race through time and title registration

This article analyses the temporal effects of title registration and their relationship to race. It traces the move away from the retrospection of pre-registry common law conveyancing and toward the dynamic, future-oriented Torrens title registration system. The Torrens system, developed in early colonial Australia, enabled the production of ‘clean’, fresh titles that were independent of their predecessors. Through a process praised by legal commentators for ‘curing’ titles of their pasts, this system produces indefeasible titles behind its distinctive ‘curtain’ and ‘mirror’, which function similarly to magicians’ smoke and mirrors by blocking particular realities from view. In the case of title registries, those realities are particular histories of and relationships with land, which will not be protected by property law and are thus made precarious. Building on interdisciplinary work which theorises time as a social tool, I argue that Torrens title registration produces a temporal order which enables land market coordination by rendering some relationships with land temporary and making others indefeasible. This ordering of relationships with land in turn has consequences for the human subjects who have those relationships, cutting futures short for some and guaranteeing permanence to others. Engaging with Renisa Mawani and other critical race theorists, I argue that the categories produced by Torrens title registration systems materialise as race

The Drosophila TRPP Cation Channel, PKD2 and Dmel/Ced-12 Act in Genetically Distinct Pathways during Apoptotic Cell Clearance

Apoptosis, a genetically programmed cell death, allows for homeostasis and tissue remodelling during development of all multi-cellular organisms. Phagocytes swiftly recognize, engulf and digest apoptotic cells. Yet, to date the molecular mechanisms underlying this phagocytic process are still poorly understood. To delineate the molecular mechanisms of apoptotic cell clearance in Drosophila, we have carried out a deficiency screen and have identified three overlapping phagocytosis-defective mutants, which all delete the fly homologue of the ced-12 gene, known as Dmel\ced12. As anticipated, we have found that Dmel\ced-12 is required for apoptotic cell clearance, as for its C. elegans and mammalian homologues, ced-12 and elmo, respectively. However, the loss of Dmel\ced-12 did not solely account for the phenotypes of all three deficiencies, as zygotic mutations and germ line clones of Dmel\ced-12 exhibited weaker phenotypes. Using a nearby genetically interacting deficiency, we have found that the polycystic kidney disease 2 gene, pkd2, which encodes a member of the TRPP channel family, is also required for phagocytosis of apoptotic cells, thereby demonstrating a novel role for PKD2 in this process. We have also observed genetic interactions between pkd2, simu, drpr, rya-r44F, and retinophilin (rtp), also known as undertaker (uta), a gene encoding a MORN-repeat containing molecule, which we have recently found to be implicated in calcium homeostasis during phagocytosis. However, we have not found any genetic interaction between Dmel\ced-12 and simu. Based on these genetic interactions and recent reports demonstrating a role for the mammalian pkd-2 gene product in ER calcium release during store-operated calcium entry, we propose that PKD2 functions in the DRPR/RTP pathway to regulate calcium homeostasis during this process. Similarly to its C. elegans homologue, Dmel\Ced-12 appears to function in a genetically distinct pathway

Analysis of the putative role of CR1 in Alzheimer’s disease: Genetic association, expression and function

Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer's disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved