Overview of the Alliance for Cellular Signaling

The Alliance for Cellular Signaling is a large-scale collaboration designed to answer global questions about signalling networks. Pathways will be studied intensively in two cells--B lymphocytes (the cells of the immune system) and cardiac myocytes--to facilitate quantitative modelling. One goal is to catalyse complementary research in individual laboratories; to facilitate this, all alliance data are freely available for use by the entire research community.     

Evolutionary genetics: CCR5 mutation and plague protection

A recent and prevalent mutation in the chemokine receptor CCR5 in humans of northern European ancestry has been proposed to provide protection against bubonic plague. Here we infect both normal and CCR5-deficient mice with the bacterium Yersinia pestis, the cause of the plague epidemics that wiped out one-third of Europeans in the Middle Ages, and find no difference in either bacterial growth or survival time between the two groups. Unless the pathogenesis of Yersinia infection differs markedly between mice and humans, our results indicate that CCR5 deficiency in people is unlikely to protect against plague.     

True paternal care in a multi-male primate society

Although male parental care is rare among mammals, adult males of many cercopithecine primate species provide care for infants and juveniles. This care is often in the form of grooming, carrying, support in agonistic interactions, and protection against infanticide. For these behaviours to be interpreted as true parental care, males must selectively direct care towards their own offspring and this care must result in fitness benefits. With the exception of males defending probable offspring from infanticide, male primates living in multi-male, multi-female social groups have not been shown to selectively direct care towards their own offspring. We determined paternity for 75 juveniles in a population of wild savannah baboons (Papio cynocephalus) and collected data on interventions in agonistic disputes by adult males on behalf of juveniles as a form of male care. Here we show that adult males differentiate their offspring from unrelated juveniles and selectively support their offspring in agonistic disputes. As support in agonistic disputes is likely to contribute to rank acquisition and protect juveniles from injury and stress, this can be considered true parental care.     

Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates

Containment of highly lethal Ebola virus outbreaks poses a serious public health challenge. Although an experimental vaccine has successfully protected non-human primates against disease, more than six months was required to complete the immunizations, making it impractical to limit an acute epidemic. Here, we report the development of accelerated vaccination against Ebola virus in non-human primates. The antibody response to immunization with an adenoviral (ADV) vector encoding the Ebola glycoprotein (GP) was induced more rapidly than with DNA priming and ADV boosting, but it was of lower magnitude. To determine whether this earlier immune response could nonetheless protect against disease, cynomolgus macaques were challenged with Ebola virus after vaccination with ADV-GP and nucleoprotein (NP) vectors. Protection was highly effective and correlated with the generation of Ebola-specific CD8(+) T-cell and antibody responses. Even when animals were immunized once with ADV-GP/NP and challenged 28 days later, they remained resistant to challenge with either low or high doses of virus. This accelerated vaccine provides an intervention that may help to limit the epidemic spread of Ebola, and is applicable to other viruses.     

Non-reciprocal contact inhibition

Résumé On a constaté jusqu'ici, in vitro, que deux cellules entrant en contact cessent ou continuent toutes deux de se mouvoir. Cette action n'est toujours pas réciproque. Ainsi lorsqu'une cellule cancéreuse de souris rencontre un fibroblaste de cur de poulet elle continue à se mouvoir tandis que ce dernier s'arrête.     

Activity of sulfa drugs and dihydrofolate reductase inhibitors againstCandida albicans

Summary Growth ofCandida albicans can be inhibited by sulfa drugs which prevent biosynthesis of folic acid. The dihydrofolate reductase (E.C. 1.5.1.3) inhibitors aminopterin and methotrexate also exhibit anticandidal activity, but trimethoprim does not. Kinetic evaluations withC. albicans dihydrofolate reductase indicate that methotrexate and aminopterin are tight-binding inhibitors whereas trimethoprim binds poorly.