X.Zhang and S.Moréra contributed equally to this workThe BRCT domain (BRCA1 C-terminus), first identified in the breast cancer suppressor protein BRCA1, is an evolutionarily conserved protein-protein interaction region of~95 amino acids found in a large number of proteins involved in DNA repair, recombination and cell cycle control. Here we describe the first threedimensional structure and fold of a BRCT domain determined by X-ray crystallography at 3.2 Å resolution. The structure has been obtained from the C-terminal region of the human DNA repair protein XRCC1, and comprises a four-stranded parallel β-sheet surrounded by three α-helices, which form an autonomously folded domain. The compact XRCC1 structure explains the observed sequence homology between different BRCT motifs and provides a framework for modelling other BRCT domains. Furthermore, the established structure of an XRCC1 BRCT homodimer suggests potential protein-protein interaction sites for the complementary BRCT domain in DNA ligase III, since these two domains form a stable heterodimeric complex. Based on the XRCC1 BRCT structure, we have constructed a model for the C-terminal BRCT domain of BRCA1, which frequently is mutated in familial breast and ovarian cancer. The model allows insights into the effects of such mutations on the fold of the BRCT domain.

Disease-associated autoantibodies to basement membrane proteins have been used to characterize structural components of the epidermal basement membrane such as bullous pemphigoid (BP) antigen and epidermolysis bullosa acquisita (EBA) antigen (type VII collagen). The autoimmune bullous diseases characterized by IgA autoantibodies to the basement membrane zone (BMZ), i.e. linear IgA disease of adults (LAD) and chronic bullous disease of childhood (CBDC) may have circulating antibodies. Previous studies of tissue distribution and ultrastructural binding have suggested that the LAD and CBDC antigens are similar, if not identical, and differ from the target antigens of the other bullous diseases. We present the molecular characterization of the LAD/CBDC antigens by Western blotting of a large series of antisera. Seven of 33 sera (21%) were positive on immunoblotting and bound to the same antigen which has a molecular weight (MW) of 285 kDa. Using both defined polyclonal antisera to BP and LH 7.2 monoclonal antibody to type VII collagen (carboxy terminal) we have shown that the LAD and CBDC antisera both bind to an identical molecular weight protein which clearly differs from both the BP and EBA (type VII collagen) antigens. Although detectable in dermal tissue extracts like EBA, the MW of 285 kDa is heavier than type VII collagen (250 kDa, in our system, using non-collagenous standards). This study confirms the identity of LAD and CBDC antigens to be the same and to differ from previously described basement membrane proteins.

Objectives:To identify interventions that aim to reduce dependency in activities of daily living (ADL) in homecare service users. To determine: content; effectiveness in improving ability to perform ADL; and whether delivery by qualified occupational therapists influences effectiveness.Data sources:The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, OTseeker, PEDro, Web of Science, CIRRIE, and ASSIA.Review methods:We included: randomised controlled trials, non-randomised controlled trials and controlled before and after studies. Two reviewers independently screened studies for inclusion, assessed risk of bias and extracted data. A narrative synthesis of the findings was conducted.Results:Thirteen studies were included, totalling 4975 participants. Ten (77%) were judged to have risk of bias. Interventions were categorised as those termed ‘re-ablement’ or ‘restorative homecare’ (n=5/13); and those involving separate components which were not described using this terminology (n=8/13). Content of the intervention and level of health professional input varied within and between studies. Effectiveness on ADL: eight studies included an ADL outcome, five favoured the intervention group, only two with statistical significance, both these were controlled before and after studies judged at high risk of bias. ADL outcome was reported using seven different measures. Occupational therapy: there was insufficient evidence to determine whether involvement of qualified occupational therapists influenced effectiveness.Conclusion:There is limited evidence that interventions targeted at personal ADL can reduce homecare service users’ dependency with activities, the content of evaluated interventions varies greatly.

Objective: To assess the feasibility of conducting a randomized controlled trial of occupational therapy predischarge home visits for people after stroke. Design: Randomized controlled trial and cohort study. We randomized eligible patients for whom there was clinical uncertainty about the need to conduct a home visit to a randomized controlled trial; patients for whom a visit was judged 'essential' were enrolled into a cohort study. Setting: Stroke rehabilitation unit of teaching hospital. Participants: One hundred and twenty-six participants hospitalized following recent stroke. Interventions: Predischarge home visit or structured, hospital-based interview. Main outcome measures:The primary objective was to collect information on the feasibility of a randomized controlled trial, including eligibility, control intervention and outcome assessments. The primary outcome measure was the Nottingham Extended Activities of Daily Living Scale at one month after discharge from hospital. Secondary outcomes included mood, quality of life and costs at one week and one month following discharge. Results: Ninety-three people were allocated to the randomized controlled trial; 47 were randomized to intervention and 46 to control. Thirty-three were enrolled into the cohort study. More people were allocated to the randomized controlled trial as the study progressed. One hundred and thirteen people (90%) received the proposed intervention, although there was a need for stricter protocol adherence. Follow-up was good: at one month 114 (90%) were assessed. There were no significant differences Clinical Rehabilitation 27(5) between the groups in the randomized controlled trial for the primary outcome measure at one month. The average cost of a home visit was £208. Conclusion: A trial is feasible and warranted given the resource implications of predischarge occupational therapy home visits.

Monospecific antibodies to individual keratin polypeptides can be used to examine the tissue and cellular coexpression of members of keratin pairs. Monospecific monoclonal and polyclonal antibodies have been raised to keratins 1 and 10 using both crude cytoskeletal extracts and synthetic peptides. The tissue distribution of these keratins has been determined against a panel of freshly frozen normal tissues from humans, rodents and pigs. Epidermal expression has been examined in psoriatic plaques, and healing wounds, as examples of epidermal hyperproliferation. Cultured keratinocytes in monolayer (low calcium), stratified (high calcium), and complex cultures, transformed keratinocytes, and tumour cell lines, have been examined for the in vitro expression of these keratins. The sensitivity and precise localization of reactivity with these monospecific antibodies gives a highly accurate picture of individual cell expression. There is confirmation of coexpression of keratins 1 and 10 in epidermal and mucosal sites, and with keratin 16 in hyperproliferative states. These monospecific antibodies provide an important means of examining keratin expression in epidermal tumours and keratinizing disorders, and of seeking keratin mutations in cell lines and in skin diseases.