Expansion of the Protein Repertoire in Newly Explored Environments: Human Gut Microbiome Specific Protein Families

The microbes that inhabit particular environments must be able to perform molecular functions that provide them with a competitive advantage to thrive in those environments. As most molecular functions are performed by proteins and are conserved between related proteins, we can expect that organisms successful in a given environmental niche would contain protein families that are specific for functions that are important in that environment. For instance, the human gut is rich in polysaccharides from the diet or secreted by the host, and is dominated by Bacteroides, whose genomes contain highly expanded repertoire of protein families involved in carbohydrate metabolism. To identify other protein families that are specific to this environment, we investigated the distribution of protein families in the currently available human gut genomic and metagenomic data. Using an automated procedure, we identified a group of protein families strongly overrepresented in the human gut. These not only include many families described previously but also, interestingly, a large group of previously unrecognized protein families, which suggests that we still have much to discover about this environment. The identification and analysis of these families could provide us with new information about an environment critical to our health and well being

Bisphosphonates induce apoptosis in human breast cancer cell lines

Breast cancer has a prodigious capacity to metastasize to bone. In women with advanced breast cancer and bone metastases, bisphosphonates reduce the incidence of hypercalcaemia and skeletal morbidity. Recent clinical findings suggest that some bisphosphonates reduce the tumour burden in bone with a consequent increase in survival, raising the possibility that bisphosphonates may have a direct effect on breast cancer cells. We have investigated the in vitro effects of bisphosphonates zoledronate, pamidronate, clodronate and EB 1053 on growth, viability and induction of apoptosis in three human breast cancer cell lines (MDA-MB-231, Hs 578T and MCF-7). Cell growth was monitored by crystal violet dye assay, and cell viability was quantitated by MTS dye reduction. Induction of apoptosis was determined by identification of morphological features of apoptosis using time-lapse videomicroscopy, identifying morphological changes in nucleis using Hoechst staining, quantitation of DNA fragmentation, level of expression of bcl-2 and bax proteins and identification of the proteolytic cleavage of Poly (ADP)-ribose polymerase (PARP). All four bisphosphonates significantly reduced cell viability in all three cell lines. Zoledronate was the most potent bisphosphonate with IC50values of 15, 20 and 3 μM respectively in MDA-MB-231, MCF-7 and Hs 578T cells. Corresponding values for pamidronate were 40, 35 and 25 μM, whereas clodronate and EB 1053 were more than two orders of magnitude less potent. An increase in the proportion of cells having morphological features characteristic of apoptosis, characteristic apoptotic changes in the nucleus, time-dependent increase in the percentage of fragmented chromosomal DNA, down-regulation in bcl-2 protein and proteolytic cleavage of PARP, all indicate that bisphosphonates have direct anti-tumour effects on human breast cancer cells. © 2000 Cancer Research Campaig

Structuring effect of tools conceptualized through initial goal fixedness for work activity

Analysis of work activities in nuclear industry has highlighted a new psycho-cognitive phenomenon: the structuring effect of tools (SET) sometimes leading to unexpected operating deviations; the subject is unable to perform a task concerning object A using or adapting a tool designed and presented to perform the same task concerning object B when object A is expected by the subject. Conditions to isolate and identify the SET were determined and reproduced in experiments for further analysis. Students and seven professional categories of adults (N = 77) were involved in three experimental conditions (control group, group with prior warning, group with final control) while individually performing a task with similar characteristics compared to real operating conditions and under moderate time-pressure. The results were: (1) highest performance with prior warning and (2) demonstration that academic and professional training favor the SET. After discussing different cognitive processes potentially related to the SET, we described (3) the psycho-cognitive process underlying the SET: Initial Goal Fixedness (IGF), a combination of the anchoring of the initial goal of the activity with a focus on the features of the initial goal favored by an Einstellung effect. This suggested coping with the negative effect of the SET by impeding the IGF rather than trying to increase the subjects’ awareness at the expense of their health. Extensions to other high-risk industries were discussed

Family Communication in Inherited Cardiovascular Conditions in Ireland

Over 100,000 individuals living in Ireland carry a mutated gene for an inherited cardiac condition (ICC), most of which demonstrate an autosomal dominant pattern of inheritance. First-degree relatives of individuals with these mutations are at a 50 % risk of being a carrier: disclosing genetic information to family members can be complex. This study explored how families living in Ireland communicate genetic information about ICCs and looked at the challenges of communicating information, factors that may affect communication and what influence this had on family relationships. Face to face interviews were conducted with nine participants using an approved topic guide and results analysed using thematic analysis. The participants disclosed that responsibility to future generations, gender, proximity and lack of contact all played a role in family communication. The media was cited as a source of information about genetic information and knowledge of genetic information tended to have a positive effect on families. Results from this study indicate that individuals are willing to inform family members, particularly when there are children and grandchildren at risk, and different strategies are utilised. Furthermore, understanding of genetics is partially regulated not only by their families, but by the way society handles information. Therefore, genetic health professionals should take into account the familial influence on individuals and their decision to attend genetic services, and also that of the media.postprin

Building bridges in palliative care: evaluating a GP facilitator programme

The objective of this study was to evaluate the impact of the Macmillan GP Facilitator Programme in Palliative Care on the knowledge, attitudes and confidence in symptom control of general practitioners (GPs), communication with patients and out-of-hours practice. GP Facilitators work on average for two sessions a week with practices in their locality. The design included a before and after study, with geographical controls matched on type of area (inner city, urban and rural) and broadly on Jarman scores using postal questionnaires sent to GPs. Scores measured change in GP awareness, attitudes and practice over two years of the intervention, derived from Likert scale responses to the postal questionnaires. Although overall few significant results were found, we did identify an increase in the use of palliative care guidelines in Facilitator districts, together with an increase in awareness of day care. The programme was associated with increased positive attitudes towards specialist palliative care services and results suggested increased satisfaction with out-of-hours services for patients. No change was found for confidence in symptom control and communication over diagnosis with cancer patients was less than in control districts. The design also incorporated a qualitative component, and from this we found the Facilitator programme to be popular with local GPs who valued the support of a colleague who knew the demands and constraints of general practice. In conclusion, we have demonstrated an impact of the GP Facilitator programme on GP awareness of, use and increased positive attitudes towards specialist palliative care services. By improving communication between primary and specialist palliative care, the programme should contribute substantially to improved care of the dying at home