Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation

About a quarter of pre-menopausal women will suffer from heavy menstrual bleeding in their lives. Here, Maybin and colleagues show hypoxia and subsequent activation of HIF-1α during menses are required for normal endometrial repair, and identify pharmacological stabilisation of HIF-1α as a potential therapeutic strategy for this debilitating condition

Hypoxyprobe™ reveals dynamic spatial and temporal changes in hypoxia in a mouse model of endometrial breakdown and repair

BACKGROUND: Menstruation is the culmination of a cascade of events, triggered by the withdrawal of progesterone at the end of the menstrual cycle. Initiation of tissue destruction and endometrial shedding causes spiral arteriole constriction in the functional layer of the endometrium. Upregulation of genes involved in angiogenesis and immune cell recruitment, two processes that are essential to successful repair and remodelling of the endometrium, both thought to be induced by reduced oxygen has been reported. Evidence for stabilisation/increased expression of the transcriptional regulator hypoxia inducible factor in the human endometrium at menses has been published. The current literature debates whether hypoxia plays an essential role during menstrual repair, therefore this study aims to delineate a role for hypoxia using a sensitive detection method (the Hypoxyprobe™) in combination with an established mouse model of endometrial breakdown and repair. RESULTS: Using our mouse model of menses, during which documented breakdown and synchronous repair occurs in a 24 h timeframe, in combination with the Hypoxyprobe™ detection system, oxygen tensions within the uterus were measured. Immunostaining revealed striking spatial and temporal fluctuations in hypoxia during breakdown and showed that the epithelium is also exposed to hypoxic conditions during the repair phase. Furthermore, time-dependent changes in tissue hypoxia correlated with the regulation of mRNAs encoding for the angiogenic genes vascular endothelial growth factor and stromal derived factor (Cxcl12). CONCLUSIONS: Our findings are consistent with a role for focal hypoxia during endometrial breakdown in regulating gene expression during menses. These data have implications for treatment of endometrial pathologies such as heavy menstrual bleeding

A global phylogeny of butterflies reveals their evolutionary history, ancestral hosts and biogeographic origins

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin similar to 100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants

Teachers' Answers to Students' Questions: Problematizing the Issue of Making Meaning

This paper analyzes how three university ESL teachers answered students' requests for help in understanding unknown vocabulary items during lessons that were mediated via a task-based, small group methodology. While considerable individual variation was observed, it was found that teachers rarely answered students' questions directly. Instead, they tended to answer learners' referential questions with display questions of their own, a strategy that is called here a counter-question strategy. It is argued that the use of this strategy for making meaning problematizes issues in the second language acquisition literature on the social construction of comprehensible input and output. Alternative interpretations of the implications of this meaning making strategy for second language acquisition theory are offered as a basis for further research

Transport of Toxic substances into Lake Superior by Suspended Solids

A primary threat to Great Lakes sport and commercial fisheries arises from contamination problems due to the introduction of certain xenobiotic chemicals in aquatic environments. Of particular concern are hydrophobic organic chemicals and heavy metals which bioaccumulate in aquatic animals. Fish bioaccumulation of toxic and/or carcinogenic substances can occur from water, suspended particles, sediments and through food chains (Byran, 1979). The threat of toxic substance contamination is likely to continue in the foreseeable future because of serious hazardous wastes disposal problems in the Great Lakes Basin (IJC, 1979) and the widespread dispersion of pollutants via the atmosphere (Eisenreich, 1981). Pollutants enter water systems from a variety of point and nonpoint sources, including surface runoff, atmospheric input, municipal and industrial discharges and vessel operations. The hydrophobic character of many organic pollutants and the affinity of heavy metals for colloidal material cause association with sediments and suspended solids such as clays, detritus material and various biomass forms (Baker, 1980). Suspended particles can represent a major river-lake transport host for chemical compounds such as chlorinated hydrocarbons (Shear and Watson, 1977). Finely divided colloidal-type particles such as clays can be transported to deep regions of lake basin areas (Leland et tl-, 1973; Baker, 1980). Some contaminants associated with sediments are resistant to biodegradation

BIOAVAILABILITY AND TOXICITY OF SILVER TO BENTHIC ORGANISMS IN FRESHWATER SYSTEMS CONTAINING SEDIMENTS OF DIFFERENT CHARACTERISTICS - PROGRESS REPORT (Quarter III)

This progress report covers the period of time between April 1, 1997, and June 30, 1997. Our efforts were focused on obtaining a better understanding of (l) the chemical behavior of silver in our specific test water as related to its passage through semipermeable ,;peeper" membranes, (2) the total binding capacity of our test sediment for silver, (3) the amount of AgN03 that will be required to be spiked into our test sediment to obtain dissolved silver in the pore water, and (4) the toxicity of AgN03 to larvae of Chironomus tentans in water-only toxicity tests. These efforts are in preparation for a toxicity test with AgN03-spiked sediments, using Chironomus tentans as the test species. Methods and results are summarized by task.National Association of Photographic Manufacturer

BIOAVAILABILITY AND TOXICITY OF SILVER TO BENTHIC ORGANISMS IN FRESHWATER SYSTEMS CONTAINING SEDIMENTS OF DIFFERENT CHARACTERISTICS - PROGRESS REPORT (Quarters I AND II)

Since the proposal for this project was submitted in early August, 1996, and approved by the National Association of Photographic Manufacturers (NAPM) for study starting on October 1, 1997, several changes have been discussed with members of the scientific panel within NAPM and with other national experts on silver and other heavy metals. Daniel Call had an opportunity to present the planned research at a meeting of renowned environmental chemists and toxicologists in early September, 1996, who had convened for a meeting on the development of national criteria for chemicals in sediment at the EPA Laboratory in Duluth, MN. This meeting was attended by several EPA-Duluth staff, including Gary Ankley, David Mount, and Russell Erickson; Mary Reilly of EPA-Washington, D.C.; Richard Swartz of EPA­ Newport, OR; David Hansen and Walter Berry of EPA-Narragansett, RI; Dominic DiToro and Paul Paquin of HydroQual; and Herbert Allen of the University of Delaware. Based upon discussion following this presentation and a subsequent teleconference call that included Joe Gorsuch of Eastman Kodak Co., Dominic DiToro of HydroQual, Tom Purcell of NAPM, Dave Mount of EPA-Duluth, and David Hansen and Walter Berry of EPA-Narragansett, it was concluded that the most useful information to both the silver industry and the regulatory community would be achieved by modifying the Year I plan from that of the approved proposal. The major suggested changes were to focus on a single sediment, and to perform a definitive toxicity test with a single freshwater sediment, rather than to use the four-sediment matrix as originally proposed; and to increase the chemical analyses and resultant documentation of silver chemistry in this definitive test