Comparison of prospective and retrospective measurements of frequency of sexual intercourse.

Measurements of sexual intercourse frequency are informative for research on pregnancy, contraception, and the transmission of sexually transmitted infections; however, efficiently collecting data on this sensitive topic is complex. The purpose of this study was to determine whether retrospective recall of sexual intercourse frequency was consistent with information obtained through the use of prospective daily diary methods corresponding to the same time period in a diverse sample of women. A total of 185 women participated in a longitudinal, prospective cohort study of oral contraceptive users and 98 of these women provided complete information on sexual intercourse frequency on diaries (prospective) and postcards (retrospective). Linear mixed models were used to test for variation in response within categories of demographic and other variables. The mean number of days women had sexual intercourse per week was 1.5 days using prospective diary information versus 2.0 days when using 3-month retrospective recall (p < 0.001). Mean differences for the various sociodemographic subgroups were positive for all groups indicating that women consistently reported a higher frequency of sexual intercourse on the retrospective postcards than they recorded on their prospective diaries; however, these mean differences did not vary significantly. If confirmed in other samples, the use of retrospective methods may be adequate to accurately collect data on sexual intercourse frequency-and may be preferable. Using only retrospective measurements could decrease study costs, the burden to participants, and have a higher response rate.

A chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells.

BACKGROUND: Methuosis is a unique form of non-apoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. RESULTS: Here we describe a novel chalcone-like molecule, 3-(2-methyl-1H- indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MIPP) that induces cell death with the hallmarks of methuosis. MIPP causes rapid accumulation of vacuoles derived from macropinosomes, based on time-lapse microscopy and labeling with extracellular fluid phase tracers. Vacuolization can be blocked by the cholesterol-interacting compound, filipin, consistent with the origin of the vacuoles from non-clathrin endocytic compartments. Although the vacuoles rapidly acquire some characteristics of late endosomes (Rab7, LAMP1), they remain distinct from lysosomal and autophagosomal compartments, suggestive of a block at the late endosome/lysosome boundary. MIPP appears to target steps in the endosomal trafficking pathway involving Rab5 and Rab7, as evidenced by changes in the activation states of these GTPases. These effects are specific, as other GTPases (Rac1, Arf6) are unaffected by the compound. Cells treated with MIPP lose viability within 2-3 days, but their nuclei show no evidence of apoptotic changes. Inhibition of caspase activity does not protect the cells, consistent with a non-apoptotic death mechanism. U251 glioblastoma cells selected for temozolomide resistance showed sensitivity to MIPP-induced methuosis that was comparable to the parental cell line. CONCLUSIONS: MIPP might serve as a prototype for new drugs that could be used to induce non-apoptotic death in cancers that have become refractory to agents that work through DNA damage and apoptotic mechanisms.

Clarifying debates in invasion biology: a survey of invasion biologists.

Invasion biology is a relatively new field, so there are ongoing debates about foundational issues regarding terminology and assessment of the causes and consequences of invasive species. These debates largely reflect differing views about the extent to which invasion biologists should advocate on behalf of native species. We surveyed reviewers of the journal Biological Invasions to obtain a better sense of how invasion biologists evaluate several foundational issues. We received 422 replies, which represented a very good response rate for an online survey of 42.5% of those contacted. Responses to several debates in the field were distributed bimodally, but respondents consistently indicated that contemporary biological invasions are unprecedented. Even still, this was not seen as justification for exaggerated language (hyperbole). In contrast to prevalent claims in the literature, only 27.3% of respondents ranked invasive species as the first or second greatest threat to biodiversity. The responses also highlighted the interaction of invasive species with other threats and the role of human activity in their spread. Finally, the respondents agreed that they need to be both more objective and better at communicating their results so that those results can be effectively integrated into management.

Executive functions and health behaviors associated with the leading causes of death in the United States: A systematic review.

Research indicates that executive functioning may predict health behavior. This systematic review provides an overview of the relationship between domains of executive functioning and health behaviors associated with the leading causes of death in the United States. A total of 114 articles met the inclusion criteria (adult sample, published in English between 1990 and November 2016) and were reviewed and synthesized. Results indicated that although many studies had mixed findings, at least one executive function component was associated with every health behavior. Based on these results, health professionals should consider the role of executive functions in behavior change interventions.

Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell death.

Methuosis is a novel caspase-independent form of cell death in which massive accumulation of vacuoles derived from macropinosomes ultimately causes cells to detach from the substratum and rupture. We recently described a chalcone-like compound, 3-(2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e., MIPP), which can induce methuosis in glioblastoma and other types of cancer cells. Herein, we describe the synthesis and structure-activity relationships of a directed library of related compounds, providing insights into the contributions of the two aryl ring systems and highlighting a potent derivative, 3-(5-methoxy, 2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e., MOMIPP) that can induce methuosis at low micromolar concentrations. We have also generated biologically active azide derivatives that may be useful for future studies aimed at identifying the protein targets of MOMIPP by photoaffinity labeling techniques. The potential significance of these studies is underscored by the finding that MOMIPP effectively reduces the growth and viability of Temozolomide-resistant glioblastoma and doxorubicin-resistant breast cancer cells. Thus, it may serve as a prototype for drugs that could be used to trigger death by methuosis in cancers that are resistant to conventional forms of cell death (e.g., apoptosis).

Induction of nonapoptotic cell death by activated Ras requires inverse regulation of Rac1 and Arf6.

Methuosis is a unique form of nonapoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. Methuosis can be induced in glioblastoma cells by expression of constitutively active Ras. This study identifies the small GTPases, Rac1 and Arf6, and the Arf6 GTPase-activating protein, GIT1, as key downstream components of the signaling pathway underlying Ras-induced methuosis. The extent to which graded expression of active H-Ras(G12V) triggers cytoplasmic vacuolization correlates with the amount of endogenous Rac1 in the active GTP state. Blocking Rac1 activation with the specific Rac inhibitor, EHT 1864, or coexpression of dominant-negative Rac1(T17N), prevents the accumulation of vacuoles induced by H-Ras(G12V). Coincident with Rac1 activation, H-Ras(G12V) causes a decrease in the amount of active Arf6, a GTPase that functions in the recycling of clathrin-independent endosomes. The effect of H-Ras(G12V) on Arf6 is blocked by EHT 1864, indicating that the decrease in Arf6-GTP is directly linked to the activation of Rac1. Constitutively active Rac1(G12V) interacts with GIT1 in immunoprecipitation assays. Ablation of GIT1 by short hairpin RNA prevents the decrease in active Arf6, inhibits vacuolization, and prevents loss of cell viability in cells expressing Rac1(G12V). Together, the results suggest that perturbations of endosome morphology associated with Ras-induced methuosis are due to downstream activation of Rac1 combined with reciprocal inactivation of Arf6. The latter seems to be mediated through Rac1 stimulation of GIT1. Further insights into this pathway could suggest opportunities for the induction of methuosis in cancers that are resistant to apoptotic cell death.