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Fifteen hundred 12–15-month-old tropically adapted heifers inadvertently grazed a paddock which had a refuse dump in it containing burnt out vehicle batteries. The cattle grazed this paddock for approximately seven days. Subsequently these cattle were managed as two cohorts (cull and potential replacement breeding animals). Deaths commenced in the cull heifer group approximately 18 days after initial exposure to the refuse dump during relocation to a feedlot. Mortalities continued for 12 days, with other heifers showing clinical signs of marked central nervous system dysfunction requiring euthanasia. Necropsy of several clinically affected cattle plus blood sampling for lead analysis confirmed a diagnosis of lead intoxication. The crude mortality rate in the cull heifers was 6.6% (n = 685). Following confirmation of the diagnosis most of the potential replacement heifers (second cohort) were also relocated to the feedlot. The estimated crude mortality rate in this cohort was 5.8% (n = 815). All possible lead intoxication deaths occurred within 34 days of initial exposure, and apparently after day 16 at the feedlot no further heifers showed any clinical signs which could be attributed to lead intoxication. Longitudinal monitoring of blood lead concentrations was used to identify cattle suitable for slaughter. Overall, 70% of heifers initially blood sampled (n = 1408) had no detectable lead in their blood, however 16% had markedly elevated blood lead concentrations (> 0.7µmol/L) which persisted, and 2% had above the maximum normal threshold 1.5 years later. These latter cattle were subsequently euthanized, and necropsy revealed that visible pieces of lead were still present in the reticulum of several animals. At no time did any of these heifers with persistently high blood lead concentrations show clinical signs of lead intoxication.

The centrosome plays a pivotal role in a wide range of cellular processes and its dysfunction is causally linked to many human diseases including cancer and developmental and neurological disorders. This organelle contains more than one hundred components, and yet many of them remain uncharacterised. Here we identified a novel centrosome protein Wdr8, based upon the structural conservation of the fission yeast counterpart. We showed that Wdr8 constitutively localises to the centrosome and super resolution microscopy uncovered that this protein is enriched at the proximal end of the mother centriole. Furthermore, we identified hMsd1/SSX2IP, a conserved spindle anchoring protein, as one of Wdr8 interactors by mass spectrometry. Wdr8 formed a complex and partially colocalised with hMsd1/SSX2IP. Intriguingly, knockdown of Wdr8 or hMsd1/SSX2IP displayed very similar mitotic defects, in which spindle microtubules became shortened and misoriented. Indeed, Wdr8 depletion resulted in the reduced recruitment of hMsd1/SSX2IP to the mitotic centrosome, though the converse is not true. Together, we propose that the conserved Wdr8-hMsd1/SSX2IP complex plays a critical role in controlling proper spindle length and orientation., T.T. and A.P.S were supported by Cancer Research UK., Supplementary data related to this article can be found at http://dx.doi.org/10.1016/j.bbrc.2015.10.169.

Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.