Brain composition in Heliconius butterflies, posteclosion growth and experience-dependent neuropil plasticity

Behavioral and sensory adaptations are often reflected in the differential expansion of brain components. These volumetric differences represent changes in cell number, size, and/or connectivity, which may denote changes in the functional and evolutionary relationships between different brain regions, and between brain composition and behavioral ecology. Here we describe the brain composition of two species of Heliconius butterflies, a long-standing study system for investigating ecological adaptation and speciation. We confirm a previous report of a striking volumetric expansion of the mushroom body, and explore patterns of differential posteclosion and experience-dependent plasticity between different brain regions. This analysis uncovers age- and experience-dependent posteclosion mushroom body growth comparable to that in foraging Hymenoptera, but also identifies plasticity in several other neuropils. An interspecific analysis indicates that Heliconius display a remarkably large investment in mushroom bodies for a lepidopteran, and indeed rank highly compared to other insects. Our analyses lay the foundation for future comparative and experimental analyses that will establish Heliconius as a valuable case study in evolutionary neurobiology.Grant sponsor: Research Fellowships from the Royal Commission for the Exhibition of 1851 and Leverhulme Trust; Grant sponsor: Royal Society; Grant number: RG110466; Grant sponsor: British Ecological Society Early Career Project Grant (all to S.H.M.); Junior Research Fellowship from King’s College, Cambridge, and an Ernst Mayr Fellowship from Smithsonian Tropical Research Institute (STRI) (both to R.M.M.); Grant sponsor: University Research Fellowship from the Royal Society,London (UK); Grant sponsor: BBSRC (UK); Grant number: BB/L02389X/1 (both to S.R.O.)

Selective progesterone receptor modulators (SPRMs): Progesterone receptor action, mode of action on the endometrium and treatment options in gynaecological therapies.

Introduction: The progesterone receptor plays an essential role in uterine physiology and reproduction. Selective progesterone receptor modulators (SPRMs) have emerged as a valuable treatment option for hormone dependent conditions like uterine fibroids, which have a major impact on women’s quality of life. SPRMs offer potential for longer term medical treatment and thereby patients may avoid surgical intervention. Areas covered: The authors have reviewed the functional role of the progesterone receptor and its isoforms and their molecular mechanisms of action via genomic and non-genomic pathways. The current knowledge of the interaction of the PR and different SPRMs tested in clinical trials has been reviewed. The authors focused on pharmacological effects of selected SPRMs on the endometrium, their anti-proliferative action, and their suppression of bleeding. Potential underlying molecular mechanisms and the specific histological changes in the endometrium induced by SPRMs (PAEC; Progesterone receptor modulator Associated Endometrial Changes) have been discussed. The clinical potential of this compound class including its impact on quality of life has been covered. Expert Opinion: Clinical studies indicate SPRMs hold promise for treatment of benign gynecological complaints (fibroids, heavy menstrual bleeding; HMB). There however remains a knowledge gap concerning mechanism of action

Comparison of two methods based on cross-sectional data for correcting corpus uterine cancer incidence and probabilities

BACKGROUND: Two methods are presented for obtaining hysterectomy prevalence corrected estimates of invasive cancer incidence rates and probabilities of the corpus uterine. METHODS: The first method involves cross-sectional hysterectomy data from the Utah Hospital Discharge Data Base and mortality data applied to life-table methods. The second involves hysterectomy prevalence estimates obtained directly from the Utah Behavior Risk Factor Surveillance System (BRFSS) survey. RESULTS: Hysterectomy prevalence estimates based on the first method are lower than those obtained from the second method through age 74, but higher in the remaining ages. Correction for hysterectomy prevalence is greatest among women ages 75–79. In this age group, the uncorrected rate is 125 (per 100,000) and the corrected rate based on the life-table method is 223 using 1995–97 data, 243 using 1992–94 data, and 228 from the survey method. The uncorrected lifetime probability of developing corpus uterine cancer is 2.6%; the corrected probability from the life-table method using 1995–97 data is 4.2%, using 1992–94 data is 4.5%; and based on prevalence data from the survey method is 4.6%. CONCLUSIONS: Both methods provide reasonable hysterectomy prevalence estimates for correcting corpus uterine cancer rates and probabilities. Because of declining trends in hysterectomy in recent decades, corrected estimates from the life-table method are less pronounced than those based on the survey method. These methods may be useful for obtaining corrected uterine cancer rates and probabilities in areas of the world that do not have sufficient years of hysterectomy data to directly compute prevalence

What shapes the continuum of reproductive isolation? Lessons from Heliconius butterflies

The process by which species evolve can be illuminated by investigating barriers that limit gene flow between taxa. Recent radiations, such as Heliconius butterflies, offer the opportunity to compare isolation between pairs of taxa at different stages of ecological, geographical, and phylogenetic divergence. Here, we report a comparative analysis of existing and novel data in order to quantify the strength and direction of isolating barriers within a well-studied clade of Heliconius Our results highlight that increased divergence is associated with the accumulation of stronger and more numerous barriers to gene flow. Wing pattern is both under natural selection for Müllerian mimicry and involved in mate choice, and therefore underlies several isolating barriers. However, pairs which share a similar wing pattern also display strong reproductive isolation mediated by traits other than wing pattern. This suggests that, while wing pattern is a key factor for early stages of divergence, it may become facultative at later stages of divergence. Additional factors including habitat partitioning, hybrid sterility, and chemically mediated mate choice are associated with complete speciation. Therefore, although most previous work has emphasized the role of wing pattern, our comparative results highlight that speciation is a multi-dimensional process, whose completion is stabilized by many factors.This work was supported by ERC Starting Grant Stg-243179 (MimEvol) and French Research Agency grant ANR-12-JSV7-0005 (HybEvol) to M.J. C.S. was funded by the Universidad del Rosario FIUR grant QDN-DG001 and COLCIENCIAS (Grant FP44842-5-2017). R.M.M. was funded by a Research Fellowship at King's College, Cambridge, UK. R.M.M. and C.D.J. were funded by an ERC grant (Speciation Genetics 339873)

Chronic Opioid Use in Women Following Hysterectomy: Patterns and Predictors

Background: Most women are prescribed an opioid after hysterectomy. The goal of this study was to determine the association between initial opioid prescribing characteristics and chronic opioid use after hysterectomy. Methods: This study included women enrolled in a commercial health plan who had a hysterectomy between 1 July 2010 and 31 March 2015. We used trajectory models to define chronic opioid use as patients with the highest probability of having an opioid prescription filled during the 6 months post‐surgery. A multivariable logistic regression was applied to examine the association between initial opioid dispensing (amount prescribed and duration of treatment) and chronic opioid use after adjusting for potential confounders. Results: A total of 693 of 50 127 (1.38%) opioid‐naïve women met the criteria for chronic opioid use following hysterectomy. The baseline variables and initial opioid prescription characteristics predicted the pattern of long‐term opioid use with moderate discrimination (c statistic = 0.70). Significant predictors of chronic opioid use included initial opioid daily dose (≥60 MME vs \u3c40 MME, aOR: 1.43, 95% CI: 1.14‐1.79) and days\u27 supply (4‐7 days vs 1‐3 days, aOR: 1.28, 95% CI: 1.06‐1.54; ≥8 days vs 1‐3 days, aOR: 1.41, 95% CI: 1.05‐1.89). Other significant baseline predictors included older age, abdominal or laparoscopic/robotic hysterectomy, tobacco use, psychiatric medication use, back pain, and headache. Conclusion: Initial opioid prescribing characteristics are associated with the risk of chronic opioid use after hysterectomy. Prescribing lower daily doses and shorter days\u27 supply of opioids to women after hysterectomy may result in lower risk of chronic opioid use

The diversification of Heliconius butterflies: what have we learned in 150 years?

Research into Heliconius butterflies has made a significant contribution to evolutionary biology. Here, we review our understanding of the diversification of these butterflies, covering recent advances and a vast foundation of earlier work. Whereas no single group of organisms can be sufficient for understanding life's diversity, after years of intensive study, research into Heliconius has addressed a wide variety of evolutionary questions. We first discuss evidence for widespread gene flow between Heliconius species and what this reveals about the nature of species. We then address the evolution and diversity of warning patterns, both as the target of selection and with respect to their underlying genetic basis. The identification of major genes involved in mimetic shifts, and homology at these loci between distantly related taxa, has revealed a surprising predictability in the genetic basis of evolution. In the final sections, we consider the evolution of warning patterns, and Heliconius diversity more generally, within a broader context of ecological and sexual selection. We consider how different traits and modes of selection can interact and influence the evolution of reproductive isolation.RMM is funded by a Junior Research Fellowship at King’s College, Cambridge. KMK is supported by the Balfour Studentship, University of Cambridge, SHMa by a Research Fellowship at St John's College, Cambridge, and SHMo by a Research Fellowship from the Royal Commission for the Exhibition of 1851. Our work on Heliconius has been additionally supported by the Agence Nationale de la Recherche (France), the Biology and Biotechnology Research Council (UK), the British Ecological Society, the European Research Council, the Natural Environment Research Council (UK), and the Smithsonian Tropical Research Institute.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/jeb.1267

Unstaged cancer in the United States: a population-based study

<p>Abstract</p> <p>Background</p> <p>The current study examines unstaged disease for 18 cancer sites in the United States according to the influence of age, sex, race, marital status, incidence, and lethality.</p> <p>Methods</p> <p>Analyses are based on 1,040,381 male and 1,011,355 female incident cancer cases diagnosed during 2000 through 2007. Data were collected by population-based cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program.</p> <p>Results</p> <p>The level of unstaged disease was greater in more lethal cancers (e.g., liver, esophagus, and pancreas) compared with less deadly cancers (i.e., colon, urinary bladder, and female breast). Unstaged disease increased with age and is greater among non-married patients. Blacks compared with whites experienced significantly higher levels of unstaged cancers of the stomach, rectum, colon, skin (melanoma), urinary bladder, thyroid, breast, corpus, cervix, and ovaries, but lower levels of unstaged liver, lung and bronchial cancers. Males compared with females experienced significantly lower levels of unstaged cancers of the liver, pancreas, esophagus, and stomach, but significantly higher levels of unstaged lung and bronchial cancer and thyroid cancer. The percent of unstaged cancer significantly decreased over the study period for 15 of the 18 cancer sites.</p> <p>Conclusion</p> <p>Tumor staging directly affects treatment options and survival, so it is recommended that further research focus on why a decrease in unstaged disease did not occur for all of the cancer sites considered from 2000 to 2007, and why there are differential levels of staging between whites and blacks, males and females for several of the cancer sites.</p

Stochastic Theory of Early Viral Infection: Continuous versus Burst Production of Virions

Viral production from infected cells can occur continuously or in a burst that generally kills the cell. For HIV infection, both modes of production have been suggested. Standard viral dynamic models formulated as sets of ordinary differential equations can not distinguish between these two modes of viral production, as the predicted dynamics is identical as long as infected cells produce the same total number of virions over their lifespan. Here we show that in stochastic models of viral infection the two modes of viral production yield different early term dynamics. Further, we analytically determine the probability that infections initiated with any number of virions and infected cells reach extinction, the state when both the population of virions and infected cells vanish, and show this too has different solutions for continuous and burst production. We also compute the distributions of times to establish infection as well as the distribution of times to extinction starting from both a single virion as well as from a single infected cell for both modes of virion production