The Conserved PFT1 Tandem Repeat Is Crucial for Proper Flowering in Arabidopsis thaliana

It is widely appreciated that short tandem repeat (STR) variation underlies substantial phenotypic variation in organisms. Some propose that the high mutation rates of STRs in functional genomic regions facilitate evolutionary adaptation. Despite their high mutation rate, some STRs show little to no variation in populations. One such STR occurs in the Arabidopsis thaliana gene PFT1 (MED25), where it encodes an interrupted polyglutamine tract. Although the PFT1 STR is large (∼270 bp), and thus expected to be extremely variable, it shows only minuscule variation across A. thaliana strains. We hypothesized that the PFT1 STR is under selective constraint, due to previously undescribed roles in PFT1 function. We investigated this hypothesis using plants expressing transgenic PFT1 constructs with either an endogenous STR or synthetic STRs of varying length. Transgenic plants carrying the endogenous PFT1 STR generally performed best in complementing a pft1 null mutant across adult PFT1-dependent traits. In stark contrast, transgenic plants carrying a PFT1 transgene lacking the STR phenocopied a pft1 loss-of-function mutant for flowering time phenotypes and were generally hypomorphic for other traits, establishing the functional importance of this domain. Transgenic plants carrying various synthetic constructs occupied the phenotypic space between wild-type and pft1 loss-of-function mutants. By varying PFT1 STR length, we discovered that PFT1 can act as either an activator or repressor of flowering in a photoperiod-dependent manner. We conclude that the PFT1 STR is constrained to its approximate wild-type length by its various functional requirements. Our study implies that there is strong selection on STRs not only to generate allelic diversity, but also to maintain certain lengths pursuant to optimal molecular function.     

Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer

Ovarian cancer, the most aggressive gynecologic cancer, is the foremost cause of death from gynecologic malignancies in the developed world. Two primary reasons explain its aggressive behavior: most patients present with advanced disease at diagnosis, and die of recurrences from disease that has become resistant to conventional chemotherapies. In this paper on epithelial ovarian cancer (EOC), we will review molecular alterations associated with the few precursor lesions identified to date, followed by the more commonly recognized processes of de novo carcinogenesis, metastasis, and the development of chemoresistance. We will propose a unifying model of ovarian epithelial tumorigenesis that takes into account various hypotheses. We will also review novel approaches to overcome the major problem of chemoresistance in ovarian cancer. Finally, we will discuss advances and new challenges in the development of mouse model systems to investigate EOC precursor lesions, progression, metastasis, and chemoresistance.     

Loss of pregnancy-associated plasma protein A extends lifespan in mice

Genetic deletion in mice of pregnancy-associated plasma protein A (PAPP-A), a recently identified metalloproteinase in the insulin-like growth factor system, extends by 30-40% both mean and maximum lifespan with no reduction in food intake or secondary endocrine abnormalities. Furthermore, these mice have markedly reduced incidence of spontaneous tumors. The findings implicate PAPP-A as a critical regulator of lifespan and age-related diseases, and suggest PAPP-A as a possible target to promote longevity.     

Harmonization of regulations for invertebrate biocontrol agents in Europe: progress,problems and solutions

The use of non‐native invertebrate biological control agents (IBCAs) in Europe is not covered by a Directive equivalent to that which regulates biocontrol with microorganisms or the genetic modification of crop plants. Regulation is at the discretion of individual member states and largely derived from national legislation on pesticides, plant health or environmental protection. There is no EU country with regulation of IBCAs that requires information on the microbial symbiont content of candidate species, and in the absence of horizontal transfer under natural conditions, this policy is unlikely to change. Although there have been few reported negative effects linked to the import and release of IBCAs, a number of countries have introduced or revised their regulatory frameworks in recent years. This article reviews major developments in the regulation and environmental risk assessment (ERA) of IBCAs in Europe over the last 10 years including: the fragmented pattern of regulation between countries, variation in information requirements for release licences, format and methods of ERA for different taxonomic groups of IBCAs, use and updating of the European Plant Protection Organisation Positive List, sources of expert advice on ERA data, communication between IBCA regulators, and options for the provision of international leadership to coordinate regulatory and ERA‐related issues with IBCA‐based biocontrol in Europe.     

Inhibition of eukaryotic translation elongation by the antitumor natural product Mycalamide B

Mycalamide B (MycB) is a marine sponge-derived natural product with potent antitumor activity. Although it has been shown to inhibit protein synthesis, the molecular mechanism of action by MycB remains incompletely understood. We verified the inhibition of translation elongation by in vitro HCV IRES dual luciferase assays, ribosome assembly, and in vivo [(35)S]methinione labeling experiments. Similar to cycloheximide (CHX), MycB inhibits translation elongation through blockade of eEF2-mediated translocation without affecting the eEF1A-mediated loading of tRNA onto the ribosome, AUG recognition, or dipeptide synthesis. Using chemical footprinting, we identified the MycB binding site proximal to the C3993 28S rRNA residue on the large ribosomal subunit. However, there are also subtle, but significant differences in the detailed mechanisms of action of MycB and CHX. First, MycB arrests the ribosome on the mRNA one codon ahead of CHX. Second, MycB specifically blocked tRNA binding to the E-site of the large ribosomal subunit. Moreover, they display different polysome profiles in vivo. Together, these observations shed new light on the mechanism of inhibition of translation elongation by MycB.     

Use of Thermal Data as a Screen for the Establishment Potential of Non-native Biological Control Agents in the UK

A series of recent studies have investigated the development, cold tolerance and winter field survival of glasshouse biological control agents that are non-native to the UK: Neoseiulus californicus, Macrolophus caliginosus, Delphastus catalinae, Eretmocerus eremicus and Typhlodromips montdorensis. The combined data sets for these species have been analysed to identify laboratory indices of cold tolerance that correlate with the duration of survival under winter field conditions. A strong correlation was found between the laboratory LTime₅₀ at 5 °C and maximum field survival time. Both N. californicus and M. caliginosus survived substantially longer in the laboratory and in the field than the other species. It is suggested that the LTime₅₀ at 5 °C may provide a reliable ‘first stage’ screen of establishment potential for candidate non-native biological control agents in the UK.     

Cold shock injury and ecological costs of rapid cold hardening in the grain aphid Sitobion avenae (Hemiptera: Aphididae)

The ability of first instar nymphs and newly moulted pre-reproductive adults of the grain aphid S. avenae to rapidly cold harden was investigated. When nymphs reared at 20 degrees C were transferred directly to -8 degrees C for 3 h, there was 18% survival. This exposure was selected as the discriminating temperature. Maximum increases in survival were achieved by acclimating nymphs for 2 h at 0 degrees C and adults for 3 h at 0 degrees C, resulting in survival of 83% and 68%, respectively. Cooling nymphs from 10 to 0 degrees C at different rates (1, 0.1 and 0.05 degrees C min(-1)) also increased cold hardiness, with the slowest rate of 0.05 degrees C min(-1) conferring the highest survival following exposure to the discriminating temperature. Adult aphids also expressed a rapid cold hardening response but to a lesser extent, with survival increasing from 16% to 68% following 3 h at 0 degrees C. There were no 'ecological costs' associated with rapid cold hardening in terms of development, longevity or fecundity. The data support the hypothesis that rapid cold hardening can be induced during the cooling phase of natural diurnal temperature cycles, allowing insects to track daily changes in environmental temperatures.