NMDA receptors, glial cells, and clinical medicine

Recent reports have overturned a series of dogmas that have been well entrenched in the neuroscience literature concerning NMDA-type glutamate receptors (NMDARs). The new data show that NMDARs exist on the myelin sheath formed by oligodendrocytes, that an uncompetitive NMDAR antagonist has successfully passed human clinical trials, and that NMDARs trigger multiple deleterious cascades to inflict cellular damage on both neurons and glia during cerebral ischemia (stroke). These recent findings bode well for clinical intervention with NMDAR antagonists in more neurological disorders than previously thought, including multiple sclerosis, cerebral palsy (periventricular leukomalacia), and spinal cord injury.     

Query Chem: a Google-powered web search combining text and chemical structures

Query Chem (www.QueryChem.com) is a Web program that integrates chemical structure and text-based searching using publicly available chemical databases and Google's Web Application Program Interface (API). Query Chem makes it possible to search the Web for information about chemical structures without knowing their common names or identifiers. Furthermore, a structure can be combined with textual query terms to further restrict searches. Query Chem's search results can retrieve many interesting structure-property relationships of biomolecules on the Web.     

Differential activation of Escherichia coli chemoreceptors by blue-light stimuli

Enteric bacteria tumble, swim slowly, and are then paralyzed upon exposure to 390- to 530-nm light. Here, we analyze this complex response in Escherichia coli using standard fluorescence microscope optics for excitation at 440 +/- 5 nm. The slow swimming and paralysis occurred only in dye-containing growth media or buffers. Excitation elicited complete paralysis within a second in 1 muM proflavine dye, implying specific motor damage, but prolonged tumbling in buffer alone. The tumbling half-response times were subsecond for onset but more than a minute for recovery. The response required the chemotaxis signal protein CheY and receptor-dependent activation of its kinase CheA. The study of deletion mutants revealed a specific requirement for either the aerotaxis receptor Aer or the chemoreceptor Tar but not the Tar homolog Tsr. The action spectrum of the wild-type response was consistent with a flavin, but the chromophores remain to be identified. The motile response processed via Aer was sustained, with recovery to either step-up or -down taking more than a minute. The response processed via Tar was transient, recovering on second time scales comparable to chemotactic responses. The response duration and amplitude were dependent on relative expression of Aer, Tar, and Tsr. The main response features were reproduced when each receptor was expressed singly from a plasmid in a receptorless host strain. However, time-resolved motion analysis revealed subtle kinetic differences that reflect the role of receptor cluster interactions in kinase activation-deactivation dynamics.     

Effects of successive seasons of genetically modified herbicide-tolerant maize cropping on weeds and invertebrates

The use of genetically modified herbicide‐tolerant (GMHT) crops influences the abundance of weeds and some invertebrate groups because the associated herbicide regime contrasts with that of conventional systems. However, it is not clear to what extent these effects might be cumulative; should GMHT crops be grown continuously. In northern Europe, in the near future, this situation is most likely to apply to maize crops. Here, we consider the effects of continuous GMHT maize cropping on plant and invertebrate taxa using a split‐field experiment. Half of each field was managed using GMHT and the other half with a conventional variety, with the treatments retained for two seasons. The treatment effects were broadly consistent with those found in the larger sample of non‐continuous maize sites within the Farm Scale Evaluations. There was little evidence of effects being significantly more pronounced in the second year; any cumulative differences in above‐ground biodiversity between GMHT and conventional cropping were too variable to be readily detected.     

Genome stability: a new member of the RFC family

Three distinct forms of replication factor C are known to play vital roles in genome replication and integrity in eukaryotic cells. A fourth such complex has recently been identified; initial results suggest that this new family member plays an important role during S phase.     

A Chronological History of the International Conference on Cryptococcus and Cryptococcosis (ICCC), an Invaluable Forum for Growth of the Cryptococcal Research Field and Clinical Practice

Cryptococcologists meet every 3 years to present their new research data and discuss the current state of cryptococcosis therapy at the International Conference on Cryptococcus and Cryptococcosis (ICCC). The ICCC has served as a unique forum where mycologists could interact and share their research data in a setting exclusively devoted to the study of Cryptococcus and cryptococcosis. This article presents an historical perspective on the ICCC meetings, beginning with the first ICCC that was held in Jerusalem, Israel in 1989. Subsequent ICCC meetings have grown, in terms of attendance and submitted abstracts. The history of the ICCC serves as a testimony to the remarkable progress that has been made in our basic understanding of the molecular biology, biochemistry, ecology, and taxonomy of Cryptococcus as well as the epidemiology, immunology, clinical manifestations, and treatment for cryptococcosis.     

Identification of essential and non-essential single-stranded DNA-binding proteins in a model archaeal organism

Single-stranded DNA-binding proteins (SSBs) play vital roles in all aspects of DNA metabolism in all three domains of life and are characterized by the presence of one or more OB fold ssDNA-binding domains. Here, using the genetically tractable euryarchaeon Haloferax volcanii as a model, we present the first genetic analysis of SSB function in the archaea. We show that genes encoding the OB fold and zinc finger-containing RpaA1 and RpaB1 proteins are individually non-essential for cell viability but share an essential function, whereas the gene encoding the triple OB fold RpaC protein is essential. Loss of RpaC function can however be rescued by elevated expression of RpaB, indicative of functional overlap between the two classes of haloarchaeal SSB. Deletion analysis is used to demonstrate important roles for individual OB folds in RpaC and to show that conserved N- and C-terminal domains are required for efficient repair of DNA damage. Consistent with a role for RpaC in DNA repair, elevated expression of this protein leads to enhanced resistance to DNA damage. Taken together, our results offer important insights into archaeal SSB function and establish the haloarchaea as a valuable model for further studies.     

Balancing the kinetochore ledger

Reduction of polo-like kinase-1 (Plk1) at kinetochores as cells progress from prometaphase to metaphase is surprising given that the kinase is thought to stabilize kinetochore-microtubule (kt-MT) attachments. In this issue, Liu et al. (2012. J. Cell Biol. doi:10.1083/jcb.201205090) demonstrate that kinetochore-associated Plk1 is a potent suppressor of microtubule plus-end dynamics. The authors propose that Plk1 activity facilitates the establishment of kt-MT attachments in prometaphase by stabilizing microtubules and that reduction of the kinase in metaphase promotes force generation by dynamic microtubules.