Differentiation and visualization of diverse cellular phenotypic responses in primary high-content screening

High-throughput screening, based on subcellular imaging, has become a powerful tool in lead discovery. Through the generation of high-quality images, not only the specific target signal can be analyzed but also phenotypic changes of the whole cell are recorded. Yet analysis strategies for the exploration of high-content screening results, in a manner that is independent from predefined control phenotypes, are largely missing. The approach presented here is based on a well-established modeling technique, self-organizing maps (SOMs), which uses multiparametric results to group treatments that create similar morphological effects. This report describes a novel visualization of the SOM clustering by using an image of the cells from each node, with the most representative cell highlighted to deploy the phenotype described by each node. The approach has the potential to identify both expected hits and novel cellular phenotypes. Moreover, different chemotypes, which cause the same phenotypic effects, are identified, thus facilitating "scaffold hopping."     

PULMONARY HEART DISEASE—A Panel Discussion

Abruptio placentae, in its severe form, causes the most hazardous type of third trimester bleeding. The severe grade may be accompanied by systemic effects, some of which are potentially lethal. A knowledge of these, as well as a system of grading the severity in terms of maternal risk, is essential to an understanding of therapy. Cases should be graded in severity from I to III on the basis of clinical factors. A delay in delivery, in Grade III, may result in an increased incidence of serious maternal complications. In Grade II, immediate cesarean section has reduced the fetal mortality rate.In managing Grade III premature separation of the placenta, the following steps should be carried out: (1) Laboratory study, including blood cross-matching and determination of plasma fibrinogen; (2) vaginal examination to confirm the diagnosis and to rupture of the membranes; (3) indicated therapy of systemic effects with fresh whole blood and fibrinogen, before considering any operative delivery; (4) election of a mode of delivery which will terminate the pregnancy in less than about six hours after onset of separation; this will frequently be cesarean section; (5) careful attention to postpartum care to avoid shock and renal failure.In Grade II, the same principles of therapy obtain. If the fetal heart tones are present, however, and vaginal delivery is not imminent, immediate cesarean section is justified. Complete conservatism, with vaginal delivery, is recommended in Grade I.     

Pyruvate Fermentation by Oenococcus oeni and Leuconostoc mesenteroides and Role of Pyruvate Dehydrogenase in Anaerobic Fermentation

The heterofermentative lactic acid bacteria Oenococcus oeni and Leuconostoc mesenteroides are able to grow by fermentation of pyruvate as the carbon source (2 pyruvate → 1 lactate + 1 acetate + 1 CO₂). The growth yields amount to 4.0 and 5.3 g (dry weight)/mol of pyruvate, respectively, suggesting formation of 0.5 mol ATP/mol pyruvate. Pyruvate is oxidatively decarboxylated by pyruvate dehydrogenase to acetyl coenzyme A, which is then converted to acetate, yielding 1 mol of ATP. For NADH reoxidation, one further pyruvate molecule is reduced to lactate. The enzymes of the pathway were present after growth on pyruvate, and genome analysis showed the presence of the corresponding structural genes. The bacteria contain, in addition, pyruvate oxidase activity which is induced under microoxic conditions. Other homo- or heterofermentative lactic acid bacteria showed only low pyruvate fermentation activity.