A role for Tctex-1 (DYNLT1) in controlling primary cilium length

The microtubule motor complex cytoplasmic dynein is known to be involved in multiple processes including endomembrane organization and trafficking, mitosis, and microtubule organization. The majority of studies of cytoplasmic dynein have focussed on the form of the motor that is built around the dynein-1 heavy chain. A second isoform, dynein heavy chain-2, and its specifically associated light intermediate chain, LIC3 (D2LIC), are known to be involved in the formation and function of primary cilia. We have used RNAi in human epithelial cells to define the cytoplasmic dynein subunits that function with dynein heavy chain 2 in primary cilia. We identify the dynein light chain Tctex-1 as a key modulator of cilia length control; depletion of Tctex-1 results in longer cilia as defined by both acetylated tubulin labelling of the axoneme and Rab8a labelling of the cilia membrane. Suppression of dynein heavy chain-2 causes concomitant loss of Tctex-1 and this correlates with an increase in cilia length. Compared to individual depletions, double siRNA depletion of DHC2 and Tctex-1 causes an even greater increase in cilia length. Our data show that Tctex-1 is a key regulator of cilia length and most likely functions as part of dynein-2

Proposing a Tool for Supply Chain Configuration: An Application to Customised Production

The full implementation of collaborative production networks is crucial for companies willing to respond to consumer demand strongly focused on product customisation. This chapter proposes an approach to evaluate the performance of different Supply Chain (SC) configurations in a customised production context. The model is based on discrete-event simulation and is applied to the case of supply chain in the fashion sector to support the comparison between mass and customised production. A prototype web-based interface is also developed and proposed to facilitate the use of the model not only for experts in simulation but for any user in the SC management field

Case-control study of paternal occupation and childhood leukaemia in Great Britain, 1962-2006

Background: Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain. Methods: The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers’ occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father’s occupation at the time of the child’s birth. Results: A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05–1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes. Conclusion: Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class