Antagonism of the ATP-gated P2X7 receptor: a potential therapeutic strategy for cancer

Purinergic Signalling - The P2X receptor 7 (P2X7R) is a plasma membrane receptor sensing extracellular ATP associated with a wide variety of cellular functions. It is most commonly expressed on...     

Antifertility drugs. Introductory remarks

The introductory remarks on the subject of antifertility drugs made by V.A. Drill at the 1970 Pharmacology Society Symposium are presented. The development of oral contraceptives is described. It is noted that oral contraceptives were develoepd coincident with the increasing public awareness of the "population explosion". At a certain point in the population growth, the public interest will become manifest, and each nation will establish a population policy. Among the papers presented at the symposium will be 2 by Dr. Saunders and Dr. Goldzieher, which review certain of the basic and clinical studies performed with oral contraceptives. Dr. Rudel will discuss the low-dose progestins. Drs. Duncan and Pharris will describe new approaches which are currently being explored. Ultimately, in order to control world population effectively, an immunological treatment may be required whereby 1 injection will control fertility for 2.5, or even 10 years. Dr. Garcia will summarize papers on this area of study.     

Can Genetic Pleiotropy Replicate Common Clinical Constellations of Cardiovascular Disease and Risk?

The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD) is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS) catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.     

Protocols for listing threatened species can forecast extinction

Risk‐ranking protocols are used widely to classify the conservation status of the world's species. Here we report on the first empirical assessment of their reliability by using a retrospective study of 18 pairs of bird and mammal species (one species extinct and the other extant) with eight different assessors. The performance of individual assessors varied substantially, but performance was improved by incorporating uncertainty in parameter estimates and consensus among the assessors. When this was done, the ranks from the protocols were consistent with the extinction outcome in 70–80% of pairs and there were mismatches in only 10–20% of cases. This performance was similar to the subjective judgements of the assessors after they had estimated the range and population parameters required by the protocols, and better than any single parameter. When used to inform subjective judgement, the protocols therefore offer a means of reducing unpredictable biases that may be associated with expert input and have the advantage of making the logic behind assessments explicit. We conclude that the protocols are useful for forecasting extinctions, although they are prone to some errors that have implications for conservation. Some level of error is to be expected, however, given the influence of chance on extinction. The performance of risk assessment protocols may be improved by providing training in the application of the protocols, incorporating uncertainty in parameter estimates and using consensus among multiple assessors, including some who are experts in the application of the protocols. Continued testing and refinement of the protocols may help to provide better absolute estimates of risk, particularly by re‐evaluating how the protocols accommodate missing data.