The meaning of difference: A response to Michael Banton

The role of the state in Africa in terms of resource allocation is generally linked to class politics and demands. Policy processes are shaped by powerful class factors, usually urban, which lead to a biased allocation of economic goods. Ethnicity and regional factors are not totally ignored but are often treated as epiphenomenal to the overall dynamics that determine who gets what, when and how. This study adopts a different reasoning. It suggests that the state in the Ivory Coast has attempted to manage ethno‐regional demands and conflicts by linking them directly to the policy process. The large‐scale economic projects undertaken by African governments are a reflection of this effort. In the case of the Ivory Coast, the construction of several costly sugar complexes in the northern region of the country is analysed within the context of state and ethnic politics in contemporary Africa.     

A reply to Michael Coughlan

Ford's book on the question of when human personhood begins, When Did I Begin? Conception of the Human Individual in History, Philosophy and Science (Cambridge University Press; 1988), is reviewed by Michael J. Coughlan in this issue of Bioethics. Here Ford responds to Coughlan's review, focusing on three topics: the importance of rationality for personhood, how far back one can trace the ontological identity of what is indisputably a human individual and human person, and the difference between the awareness of the reality of human persons and the varying degrees of perception of their value in the family and society.     

A response to Purdy

The authors respond to Laura Purdy's article, "Surrogate mothering: exploitation or empowerment?," in the same issue of Bioethics. They contend that focusing on what is necessarily wrong with surrogate motherhood contracts allows Purdy to overlook the contingent features of classist, patriarchal society that make such contracts morally wrong and to marginalize feminist concerns. Theoretical fallacies within Purdy's consequentialist framework create too individualistic and narrow a discussion of the possible harms of surrogate contracts, ignoring influences upon women as a group and the psychological risks to the surrogate mother. If surrogacy contracts have the potential to empower women, then we must see some specific changes that would make this a reality, given that Purdy does not mean surrogacy as it is currently practised.     

Acid catalyzed Michael additions to artemisitene

A series of 14-substituted-artemisinin and 9-epiartemisinin derivatives was prepared by a titanium-tetrachloride catalyzed addition of trimethylsilyl enol ethers to artemisitene. Several compounds were four to seven times more active than artemisinin against Plasmodium falciparum.     

Clinical and Molecular Characterization of Brazilian Patients Suspected to Have Lynch Syndrome

Lynch syndrome (LS) accounts for 3–5% of all colorectal cancers (CRC) and is inherited in an autosomal dominant fashion. This syndrome is characterized by early CRC onset, high incidence of tumors in the ascending colon, excess of synchronous/metachronous tumors and extra-colonic tumors. Nowadays, LS is regarded of patients who carry deleterious germline mutations in one of the five mismatch repair genes (MMR), mostly in MLH1 and MSH2, but also in MSH6, PMS1 and PMS2. To comprehensively characterize 116 Brazilian patients suspected for LS, we assessed the frequency of germline mutations in the three minor genes MSH6, PMS1 and PMS2 in 82 patients negative for point mutations in MLH1 and MSH2. We also assessed large genomic rearrangements by MLPA for detecting copy number variations (CNVs) in MLH1, MSH2 and MSH6 generating a broad characterization of MMR genes. The complete analysis of the five MMR genes revealed 45 carriers of pathogenic mutations, including 25 in MSH2, 15 in MLH1, four in MSH6 and one in PMS2. Eleven novel pathogenic mutations (6 in MSH2, 4 in MSH6 and one in PMS2), and 11 variants of unknown significance (VUS) were found. Mutations in the MLH1 and MSH2 genes represented 89% of all mutations (40/45), whereas the three MMR genes (MSH6, PMS1 and PMS2) accounted for 11% (5/45). We also investigated the MLH1 p.Leu676Pro VUS located in the PMS2 interaction domain and our results revealed that this variant displayed no defective function in terms of cellular location and heterodimer interaction. Additionally, we assessed the tumor phenotype of a subset of patients and also the frequency of CRC and extra-colonic tumors in 2,365 individuals of the 116 families, generating the first comprehensive portrait of the genetic and clinical aspects of patients suspected of LS in a Brazilian cohort.     

DNA mismatch repair and Lynch syndrome

The evolutionary conserved mismatch repair proteins correct a wide range of DNA replication errors. Their importance as guardians of genetic integrity is reflected by the tremendous decrease of replication fidelity (two to three orders of magnitude) conferred by their loss. Germline mutations in mismatch repair genes, predominantly MSH2 and MLH1, have been found to underlie the Lynch syndrome (also called hereditary non-polyposis colorectal cancer, HNPCC), a hereditary predisposition for cancer. Lynch syndrome affects predominantly the colon and accounts for 2–5% of all colon cancer cases. During more than 30 years of biochemical, crystallographic and clinical research, deep insight has been achieved in the function of mismatch repair and the diseases that are associated with its loss. We review the biochemistry of mismatch repair and also introduce the clinical, diagnostic and genetic aspects of Lynch syndrome.     

A response to Dodds and Jones

In response to "Surrogacy and Autonomy," by Susan Dodds and Karen Jones in this issue of Bioethics, the author concedes that only a surrogacy practice stringently regulated by good counseling, escape clauses for pregnant women, and the prohibition of profit-making agencies will save women from exploitation, but she objects to singling out women for paternalistic "protection against themselves," and to defending women's autonomy to the extent of their right to behave in ways known to harm a fetus. Dodds and Jones' concerns about attitudes toward women, genetic bias, the concept of children as property, and the harm principle generated by surrogacy contracts are answered with arguments for why surrogacy should not be illegal.