The influence of factors associated with lighting on the welfare of farm animals

Report supported by the Farm Animal Care TrustSIGLEAvailable from British Library Document Supply Centre- DSC:q95/19821 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The assessment of stress in laboratory animals

Available from British Library Document Supply Centre-DSC:98/11773 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Colorectal cancer registration: the central importance of pathology

Background—Changes in cancer care have increased the importance of cancer registries in monitoring trends and outcomes. Registries are increasingly using computerised systems, such as patient administration and histopathology, as data sources. Omissions by registries can cause interpretation errors, but use of multiple data sources can overcome this. Methods—Registrations of new colorectal cancers in Cornwall were compared with cases identified from primary sources over one year. Results—Two hundred and thirty cases were identified locally, 93% in documentary records, 89.6% via histopathology, and 81.3% in the clinical data capture module of the patient administration system. Two hundred and forty four cases were known to the regional registry, but after eliminating wrongly assigned and unconfirmed cases only 201 remained. Twenty nine cases identified locally, particularly cases of advanced disease, were unknown to the registry. Conclusions—District registers based on histopathology augmented from other sources would provide more accurate and less biased information than existing regionally based methods. Key Words: colorectal cancer • cancer registration • district register

Paxillin-dependent Paxillin Kinase Linker and p21-Activated Kinase Localization to Focal Adhesions Involves a Multistep Activation Pathway

The precise temporal-spatial regulation of the p21-activated serine-threonine kinase PAK at the plasma membrane is required for proper cytoskeletal reorganization and cell motility. However, the mechanism by which PAK localizes to focal adhesions has not yet been elucidated. Indirect binding of PAK to the focal adhesion protein paxillin via the Arf-GAP protein paxillin kinase linker (PKL) and PIX/Cool suggested a mechanism. In this report, we demonstrate an essential role for a paxillin–PKL interaction in the recruitment of activated PAK to focal adhesions. Similar to PAK, expression of activated Cdc42 and Rac1, but not RhoA, stimulated the translocation of PKL from a generally diffuse localization to focal adhesions. Expression of the PAK regulatory domain (PAK1–329) or the autoinhibitory domain (AID 83–149) induced PKL, PIX, and PAK localization to focal adhesions, indicating a role for PAK scaffold activation. We show PIX, but not NCK, binding to PAK is necessary for efficient focal adhesion localization of PAK and PKL, consistent with a PAK–PIX–PKL linkage. Although PAK activation is required, it is not sufficient for localization. The PKL amino terminus, containing the PIX-binding site, but lacking paxillin-binding subdomain 2 (PBS2), was unable to localize to focal adhesions and also abrogated PAK localization. An identical result was obtained after PKLΔPBS2 expression. Finally, neither PAK nor PKL was capable of localizing to focal adhesions in cells overexpressing paxillinΔLD4, confirming a requirement for this motif in recruitment of the PAK–PIX–PKL complex to focal adhesions. These results suggest a GTP-Cdc42/GTP-Rac triggered multistep activation cascade leading to the stimulation of the adaptor function of PAK, which through interaction with PIX provokes a functional PKL PBS2–paxillin LD4 association and consequent recruitment to focal adhesions. This mechanism is probably critical for the correct subcellular positioning of PAK, thereby influencing the ability of PAK to coordinate cytoskeletal reorganization associated with changes in cell shape and motility

ADP-Ribosylation Factor 6 and a Functional PIX/p95-APP1 Complex Are Required for Rac1B-mediated Neurite Outgrowth

The mechanisms coordinating adhesion, actin organization, and membrane traffic during growth cone migration are poorly understood. Neuritogenesis and branching from retinal neurons are regulated by the Rac1B/Rac3 GTPase. We have identified a functional connection between ADP-ribosylation factor (Arf) 6 and p95-APP1 during the regulation of Rac1B-mediated neuritogenesis. P95-APP1 is an ADP-ribosylation factor GTPase-activating protein (ArfGAP) of the GIT family expressed in the developing nervous system. We show that Arf6 has a predominant role in neurite extension compared with Arf1 and Arf5. Cotransfection experiments indicate a specific and cooperative potentiation of neurite extension by Arf6 and the carboxy-terminal portion of p95-APP1. Localization studies in neurons expressing different p95-derived constructs show a codistribution of p95-APP1 with Arf6, but not Arf1. Moreover, p95-APP1–derived proteins with a mutated or deleted ArfGAP domain prevent Rac1B-induced neuritogenesis, leading to PIX-mediated accumulation at large Rab11-positive endocytic vesicles. Our data support a role of p95-APP1 as a specific regulator of Arf6 in the control of membrane trafficking during neuritogenesis