Two-way traffic on the road to plasma membrane repair

Ca(2+) influx through plasma membrane wounds triggers a rapid-repair response that is essential for cell survival. Earlier studies showed that repair requires the exocytosis of intracellular vesicles. Exocytosis was thought to promote resealing by 'patching' the plasma membrane lesion or by facilitating bilayer restoration through reduction in membrane tension. However, cells also rapidly repair lesions created by pore-forming proteins, a form of injury that cannot be resealed solely by exocytosis. Recent studies indicate that, in cells injured by pores or mechanical abrasions, exocytosis is followed by lesion removal through endocytosis. Describing the relationship between wound-induced exocytosis and endocytosis has implications for the understanding of muscular degenerative diseases that are associated with defects in plasma membrane repair.     

Imidazoles: SAR and development of a potent class of cyclin-dependent kinase inhibitors

An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been developed. Protein inhibitor structure determination has provided an understanding of the emerging structure activity trends for the imidazole series. The introduction of a methyl sulfone at the aniline terminus led to a more orally bioavailable CDK inhibitor that was progressed into clinical development.     

HIV and malaria co-infection: interactions and consequences of chemotherapy

The global epidemiology of HIV/AIDS and malaria overlap because a significant number of HIV-infected individuals live in regions with different levels of malaria transmission. Although the consequences of co-infection with HIV and malaria parasites are not fully understood, available evidence suggests that the infections act synergistically and together result in worse outcomes. The importance of understanding chemotherapeutic interactions during malaria and HIV co-infection is now being recognized. We know that some antimalarial drugs have weak antiretroviral effects; however, recent studies have also demonstrated that certain antiretroviral agents can inhibit malaria-parasite growth. Here, we discuss recent findings on the impact of HIV/AIDS and malaria co-infection and the possible roles of chemotherapy in improving the treatment of these diseases.     

Co-option and dissociation in larval origins and evolution: the sea urchin larval gut

SUMMARY The origin of marine invertebrate larvae has been an area of controversy in developmental evolution for over a century. Here, we address the question of whether a pelagic "larval" or benthic "adult" morphology originated first in metazoan lineages by testing the hypothesis that particular gene co-option patterns will be associated with the origin of feeding, indirect developing larval forms. Empirical evidence bearing on this hypothesis is derivable from gene expression studies of the sea urchin larval gut of two closely related but differently developing congenerics, Heliocidaris tuberculata (feeding indirect-developing larva) and H. erythrogramma (nonfeeding direct developer), given two subsidiary hypotheses. (1) If larval gut gene expression in H. tuberculata was co-opted from an ancestral adult expression pattern, then the gut expression pattern will remain in adult H. erythrogramma despite its direct development. (2) Genes expressed in the larval gut of H. tuberculata will not have a coordinated expression pattern in H. erythrogramma larvae due to loss of a functional gut. Five structural genes expressed in the invaginating archenteron of H. tuberculata during gastrulation exhibit substantially different expression patterns in H. erythrogramma with only one remaining endoderm specific. Expression of these genes in the adult of H. erythrogramma and larval gut of H. tuberculata , but not in H. erythrogramma larval endoderm, supports the hypothesis that they first played roles in the formation of adult structures and were subsequently recruited into larval ontogeny during the origin and evolution of feeding planktotrophic deuterostome larvae.     

Electron crystallography of aquaporins

Aquaporins are a family of ubiquitous membrane proteins that form a pore for the permeation of water. Both electron and X-ray crystallography played major roles in determining the atomic structures of a number of aquaporins. This review focuses on electron crystallography, and its contribution to the field of aquaporin biology. We briefly discuss electron crystallography and the two-dimensional crystallization process. We describe features of aquaporins common to both electron and X-ray crystallographic structures; as well as some structural insights unique to electron crystallography, including aquaporin junction formation and lipid-protein interactions.     

Effect of artificial surveillance cues on reported moral judgment: Experimental failures to replicate and two meta-analyses

Several papers have reported that artificial surveillance cues, such as images of watching eyes, cause anonymous participants to behave as if they are actually under surveillance, thus increasing moral behavior. In a series of four experiments, we found no evidence that artificial surveillance cues impact reported moral judgment, self-rated possession of positive traits, or religiosity. Two small meta-analyses, both comprising six experiments investigating the effect of artificial surveillance cues on moral judgment, provided mixed conclusions. One meta-analysis produced a mean effect size not significantly different from zero and the other produced a mean effect size on the edge of significance. On the whole, artificial surveillance cues have inconsistent effects, or possibly no effect, on moral outcomes.