An investigation of the effects of endometriosis on the proteome of human eutopic endometrium: a heterogeneous tissue with a complex disease

The pathogenesis of endometriosis includes the proliferation of heterogeneous endometrial cells and their invasion into ectopic sites within the peritoneal cavity. This may be due to abnormalities of the eutopic endometrium itself, predisposing the cells to survive and implant ectopically. We investigated the applicability of 2-DE gels and peptide mass mapping to identify candidate endometrial proteins with a role in endometriosis. Despite the heterogeneous nature of endometrium, our results show that combining the analysis of 2-DE gels and peptide mass mapping yields consistent data. We identified dysregulated proteins in women with endometriosis which included: (i) molecular chaperones including heat shock protein 90 and annexin A2, (ii) proteins involved in cellular redox state, such as peroxiredoxin 2, (iii) proteins involved in protein and DNA formation/breakdown, including ribonucleoside-diphosphate reductase, prohibitin and prolyl 4-hydroxylase, and (iv) secreted proteins, such as apolipoprotein A1. These proteins have functions which suggest that they could play a role in the pathogenesis of endometriosis. This study demonstrated that 2-DE gel analysis and mass spectroscopic protein identification are suitable for the identification of proteins with candidate associations with endometriosis. These techniques should be used on a larger scale to identify endometriosis-related proteins, thus improving the understanding of this complex disease.     

Commitment to relationships and preferences for femininity and apparent health in faces are strongest on days of the menstrual cycle when progesterone level is high

Previous studies of changes in women's behavior during the menstrual cycle have offered insight into the motivations underpinning women's preferences for social cues associated with possible direct benefits (e.g., investment, low risk of infection) and indirect benefits (e.g., offspring viability). Here we sought to extend this work by testing for systematic variation in women's preferences for male and female faces and in their attitudes to their romantic relationship during the menstrual cycle. In Study 1, we found partnered women's reported commitment to their romantic relationship and preferences for femininity in male and female faces were strongest on days of the menstrual cycle when progesterone levels are increased (and fertility is low). Happiness in relationships did not change across the cycle. In Study 2, we found that the effect of cycle phase on women's preference for feminine faces was independent of increased attraction to apparent health in faces during the luteal phase. Collectively, these findings are further evidence that women's preferences for social cues associated with possible direct benefits and commitment to relationships are strongest during conditions characterized by raised progesterone level, while attraction to men displaying cues associated with possible indirect benefits is strongest when women are most fertile.     

Effects of the menstrual cycle on auditory event-related potentials

Gonadal steroids (estradiol and progesterone) can alter neuronal functioning, but electrophysiological evidence in women is still sparse. Therefore, the present study investigated event-related potentials (ERPs) to neutral stimuli over the course of the menstrual cycle. In addition, associations between ERPs and salivary estradiol and progesterone concentrations were investigated. Eighteen young healthy women were tested at three different phases of their menstrual cycle (menses, and follicular and luteal phases). ERPs (i.e., the N1 and P2 components, reflecting cortical arousal and the orienting response, the N2, P3, and the Slow Wave (SW), reflecting controlled processing) were measured using two different paradigms. In the luteal phase, early ERPs reflecting the cortical arousal response were diminished in the first stimulus block indicating an attenuated orienting response. These changes were significantly correlated with estradiol as well as progesterone levels. As to the later ERP components, the N2 latency was shorter during menses compared to the other two phases. No menstrual cycle-associated changes were apparent in other late ERP components. In sum, this study documents changes in auditory ERPs across the menstrual cycle with the most prominent changes occurring during the luteal phase. Future ERP studies therefore need to be more attentive to the issue of menstrual phase when studying female subjects or female patients.     

Rescue behavior in white-faced capuchin monkeys during an intergroup attack: support for the infanticide avoidance hypothesis

In this work we report the first published observational evidence of rescue behavior during an intergroup interaction in white-faced capuchin monkeys (Cebus capucinus). The study groups (groups AA and RR) inhabit the forest of Lomas Barbudal Biological Reserve in Guanacaste, Costa Rica, and have been under investigation since 1990 and 1997, respectively. Here we report a single interaction in which a victim mother-infant pair was rescued from potential injury or death by the intervention of an adult male from their social group during an intergroup encounter. We discuss several hypotheses that may be relevant in explaining this unique observation.     

The effects of paradoxical sleep deprivation on estrous cycles of the female rats

The present purpose was to examine how sleep deprivation affects the estrous cycle of the female rat. Paradoxical sleep-deprived (PSD) adult female Wistar rats were compared to home-cage control (CTRL) on their estrous cyclicity. Forty-four PSD and forty-four CTRL female rats were distributed into 4 subgroups of 11 animals each according to the phase of estrous cycle and were subjected to sleep deprivation for 96 h by the multiple platform technique. After PSD period, vaginal estrous cycles were taken for an additional 9 days. Animals that were submitted to PSD in diestrus phase (PSD-diestrus) had their estrous cycles disrupted during the recovery period by showing a constant diestrus during the first week. As for hormone alterations, progesterone concentrations were statistically higher in PSD-diestrus compared to respective phase control and to PSD-proestrus and PSD-estrus rats while CTRL-metestrus had higher levels than CTRL-proestrus and estrus groups. Testosterone was significantly decreased in PSD-estrus in relation to PSD-proestrus and PSD-diestrus groups and was lower in CTRL-diestrus rats than in home-cage rats in proestrus. In addition, PSD-diestrus phase exhibited higher concentrations of corticosterone and lower estrogen than the respective control rats. These data indicate that PSD may modulate the ovarian hormone release through alterations in hormonal-neurochemical mechanisms.     

Paternity in mallards: effects of sperm quality and female sperm selection for inbreeding avoidance

Postcopulatory processes might play an important role in sexualselection. In theory, fertilization success could be controlledby females via selection of particular sperm within their reproductivetract, or it could be determined by sperm competition per se.In practice, these two mechanisms are difficult to disentangle.To assess the relative importance of both mechanisms we usedartificial insemination in combination with measurements ofsperm quality (swimming speed and motility) in mallards. Inthis species, females often lack behavioral control over copulationsand hence may use postcopulatory mechanisms to optimize theirreproductive output. One important factor affecting female fitnessmay be selection of genetically compatible males. To investigatethe influence of sperm quality and parental relatedness on paternitywe inseminated 12 groups of related females with a sperm mixturecontaining equal numbers of sperm from a brother and from anunrelated male. Paternity was independent of the relatednessof the siring male to the female but was significantly affectedby long-term sperm swimming speed and motility. No interactionbetween relatedness and sperm quality on paternity was observed.These results suggest that female mallards are not able to selectsperm on a purely genetic basis and emphasize the importanceof sperm quality in gaining paternity.     

Endocrinology of pregnancy: consequences for the diagnosis and treatment of pregnancy disorders

Placental human chorionic gonadotropin and corpus luteum secretion of progesterone and oestradiol are the main endocrine events at the beginning of pregnancy, whilst the luteo-placental shift is an important step during the later stages. Progesterone not only affects decidualisation, but is the major immunological determinant and controls uterine contractibility and cervical competence. These properties all contribute considerably towards the correct development of pregnancy and delivery at term.     

Paternal care in rodents: weakening support for hormonal regulation of the transition to behavioral fatherhood in rodent animal models of biparental care

Male rodents that are naturally paternal, like all females, must inhibit infanticide and activate direct parental behavior as they become parents. Males, however, alter their behavior in the absence of parturition, postpartum ovulation and lactation, and therefore do not experience the hormone dynamics associated with such conditions. Paternal males might nevertheless use the same hormones to activate pre-existing maternal behavior pathways in the brain. Positive and inverse associations between prolactin, sex steroids (estradiol, testosterone, progesterone), glucocorticoids, oxytocin and vasopressin and paternal behavior are reviewed. Across biparental rodents (Phodopus campbelli, Peromyscus californicus, Microtus ochrogaster, and Meriones unguiculatus), as well as non-human primates and men, hormone-behavior associations are broadly supported. However, experimental manipulations (largely restricted to P. campbelli) suggest that the co-variation of hormones and paternal behavior is not causal in paternal behavior. Perhaps the hormone-behavior associations shared by P. campbelli and other paternal males are important for other challenges at the same time as fatherhood (e.g., mating during the postpartum estrus). On the other hand, each paternal species might, instead, have unique neuroendocrine pathways to parental behavior. In the latter case, future comparisons might reveal extraordinary plasticity in how the brain forms social bonds and alters behavior in family groups.     

Genetic origins of the Japanese: A partial support for the dual structure hypothesis

Based on the morphological characteristics of the skull and teeth, Hanihara ([1991] Japan Review 2:1–33) proposed the “dual structure model” for the formation of modern Japanese populations. We examine this model by dividing it into two independent hypotheses: 1) the Upper Paleolithic population of Japan that gave rise to the Neolithic Jomon people was of southeast Asian origin, and 2) modern Ainu and Ryukyuan (Okinawa) populations are direct descendants of the Jomon people, while Hondo (Main Island)-Japanese are mainly derived from the migrants from the northeast Asian continent after the Aeneolithic Yayoi period. Our aim is to examine the extent to which the model is supported by genetic evidence from modern populations, particularly from Japan and other Asian areas. Based on genetic distance analyses using data from up to 25 “classic” genetic markers, we find first that the three Japanese populations including Ainu and Ryukyuan clearly belong to a northeast Asian cluster group. This negates the first hypothesis of the model. Then, we find that Ainu and Ryukyuans share a group contrasting with Hondo-Japanese and Korean, supporting the second hypothesis of the model. Based on these results, we propose a modified version of the dual structure model which may explain the genetic, morphological, and archaeological evidence concerning the formation of modern Japanese populations. Am J Phys Anthropol 102:437–446, 1997. © 1997 Wiley-Liss, Inc.     

定坤丹联合益母草冲剂治疗孕妇流产后月经失调的临床效果分析

目的:探讨定坤丹联合益母草冲剂治疗孕妇流产后月经失调的临床效果。方法:选取2016年1月-2016年12月我院接受药物流产终止妊娠的妇女120例为研究对象,根据数字随机表法将其随机分为研究组和对照组,每组60例。研究组在妊娠囊排出宫腔后开始服益母草冲剂,1包/次,3次/日,服用2周后加服定坤丹,1丸/次,2次/日,持续服用到月经恢复正常。对照组在同一时间段期间服用益母草冲剂。对比两组患者腹痛消失时间和月经恢复正常时间、恢复正常月经后月经周期、月经量以及治疗有效率。结果:对照组和研究组腹痛消失时间分别为7.62±1.33 d、3.17±0.76 d,月经恢复正常时间分别为69.62±8.45 d、43.21±6.65 d,研究组均显著短于对照组(P0.05)。患者月经恢复后,对照组中有42例正常,研究组有54例正常,研究组月经周期时间正常率显著高于对照组(P0.05)。对照组中月经量有45例正常,研究组中月经量有54例正常,两组月经量比较,研究组月经量正常率显著高于对照组(P0.05)。对照组中痊愈39例,研究组中痊愈51例,研究组治疗有效率显著高于对照组(P0.05)。结论:定坤丹联合益母草冲剂治疗孕妇流产后月经失调临床疗效明显优于单用益母草冲剂治疗。     

A test of alternative hypotheses for the evolution of reproductive isolation between spadefoot toads: support for the reinforcement hypothesis

Abstract How do species that interbreed become reproductively isolated? If hybrids are less fit than parental types, natural selection should promote reproductive isolation by favoring the evolution of premating mechanisms that prevent hybridization (a process termed reinforcement). Although reinforcement should generate a decline in hybridization over time, countervailing forces of gene flow and recombination are thought to preclude natural selection from enhancing and finalizing reproductive isolation. Here, I present recent estimates of hybridization frequency between two species of spadefoot toad, Spea multiplicata and S. bombifrons. I compare these recent measures of hybrid frequency with previously published estimates and show that hybridization between these species has declined precipitously over the past 27 years. Although previous studies suggest that reinforcement possibly accounts for this decline in hybrids over time, three alternative hypotheses also can explain the observed decrease in hybridization. First, if one of the two interacting species becomes rare, opportunities for and incidence of hybridization may decrease. Second, if one of the two interacting species is initially rare, hybridization may be initially common if the rare species has difficulty locating conspecific mates. Third, if hybrids are produced only in particular environments, hybrid frequency may decline if habitat changes result in loss of those environments that promote hybrid formation. I found no support for these three alternative explanations of the decline in hybrids. Instead, reinforcement appears to best account for the evolution of enhanced reproductive isolation between these species. Moreover, the finding that hybridization declined precipitously in only 27 years suggests that many systems that have undergone reinforcement may be overlooked because reproductive isolation between the interacting populations or species may already be complete.     

The impact of reproductive investment and early‐life environmental conditions on senescence: support for the disposable soma hypothesis

Several hypotheses have been put forward to explain the evolution of senescence. One of the leading hypotheses, the disposable soma hypothesis, predicts a trade‐off, whereby early‐life investment in reproduction leads to late‐life declines in survival (survival senescence). Testing this hypothesis in natural populations is challenging, but important for understanding the evolution of senescence. We used the long‐term data set from a contained, predator‐free population of individually marked Seychelles warblers (Acrocephalus sechellensis) to investigate how age‐related declines in survival are affected by early‐life investment in reproduction and early‐life environmental conditions. The disposable soma hypothesis predicts that higher investment in reproduction, or experiencing harsh conditions during early life, will lead to an earlier onset, and an increased rate, of senescence. We found that both sexes showed similar age‐related declines in late‐life survival consistent with senescence. Individuals that started breeding at a later age showed a delay in survival senescence, but this later onset of breeding did not result in a less rapid decline in late‐life survival. Although survival senescence was not directly related to early‐life environmental conditions, age of first breeding increased with natal food availability. Therefore, early‐life food availability may affect senescence by influencing age of first breeding. The disposable soma hypothesis of senescence is supported by delayed senescence in individuals that started breeding at a later age and therefore invested less in reproduction.     

Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies

Systematic behavioral phenotyping of genetically modified mice is a powerful method with which to identify the molecular factors implicated in control of animal behavior, with potential relevance for research into neuropsychiatric disorders. A number of such disorders display sex differences, yet the use of female mice in phenotyping strategies has been a rare practice because of the potential variability related to the estrous cycle. We have now investigated the behavioral effects of the estrous cycle in a battery of behavioral tests in C57BL/6J and BALB/cByJ inbred strains of mice. Whereas the performance of BALB/cByJ female mice varied significantly depending on the phase of the estrous cycle in the open field, tail flick and tail suspension tests, the behavior of C57BL/6J females, with the exception of the tail suspension performance, remained stable across all four phases of the estrous cycle in all of the tests including open field, rotarod, startle reflex and pre-pulse inhibition, tail flick and hot plate. We also found that irrespective of the estrous cycle, the behavior of C57BL/6J females was different from that of BALB/cByJ groups in all of the behavioral paradigms. Such strain differences were previously reported in male comparisons, suggesting that the same inter-group differences can be revealed by studying female or male mice. In addition, strain differences were evident even for behaviors that were susceptible to estrous cycle modulations, although their detection might necessitate the constitution of large experimental groups.     

The effect of tautomeric constant on the specificity of nucleotide incorporation during DNA replication: support for the rare tautomer hypothesis of substitution mutagenesis

The nucleoside analogue dP (6-(2-deoxy-beta-D-ribofuranosyl)-3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-2-one) displays ambivalent hydrogen bonding characteristics whereby the imino tautomer of P can base-pair with adenine and its amino tautomer can base-pair with guanine. Fixed imino and amino tautomers of 6-methyl-3,4-dihydro-6H,8H-pyrimido[4,5-c][1,2]oxazin-2-one (N-methyl P) have been synthesised and their structures obtained by X-ray crystallography. The tautomeric constant of N-methyl P has been calculated from pK(a) values of the fixed tautomers and the kinetic parameters for the incorporation of its 5'-triphosphate (dPTP) by exonuclease-free Klenow fragment of DNA polymerase I have been determined. A strong correlation between the tautomeric constant and the incorporation specificity of dPTP is found. These results lend support to the proposal that the minor tautomeric forms of the natural bases may play an important role in substitution mutagenesis during DNA replication. Furthermore, they imply that DNA polymerases impose specific steric requirements on the base-pair during nucleotide incorporation.     

Monitoring ovulation and implantation in the cynomolgus macaque (Macaca fascicularis) through evaluations of urinary estrone conjugates and progesterone metabolites: a technique for the routine evaluation of reproductive parameters

Investigations were undertaken to determine the applicability of recently reported specific radioimmunoassays for urinary estrone conjugates and progesterone metabolites for monitoring ovarian function in the cynomolgus macaque (Macaca fasciularis) and other macaque species. Mean estrone conjugate measurements appear to accurately reflect the preovulatory estrogen peak in both conceptive (n = 5) and nonconceptive (n = 6) cycles, as well as to indicate early pregnancy through increases which are significantly elevated by Day + 15 (p less than 0.049) post estrone conjugates peak. The mean luteal phase levels of these progesterone metabolites are significantly elevated by Day + 14 (p less than 0.012) in conceptive cycles when compared to the mean values for nonconceptive cycles.     

Large brood sizes of pied flycatcher, sparrowhawk and goshawk in peak microtine years: support for the mast depression hypothesis

The mast depression hypothesis (MDH) proposes that cyclic population fluctuations of microtines and other herbivores are an effect of cyclic seed cropping of plants. This is because high seed crops, termed masts, are produced at the expense of chemical defence against herbivores. It has generally been assumed that bird-hunting raptors produce high numbers of offspring when microtine prey are abundant because of reduced competition from generalist predators. However, this may also be caused by higher production of herbivorous insects, and thus insectivorous bird prey, because of lower contents of chemical defence compounds in some plant species, such as bilberry Vaccinium myrtillus and cowberry V. vitis-idaea. In Aust-Agder county, southern Norway, the mean brood size of pied flycatcher Ficedula hypoleuca, sparrowhawk Accipiter nisus and goshawk A. gentilis was higher in peak vole years than in other years. The effect was not due to variation in nest predation, as only successful nesting attempts were included in the analyses. For the pied flycatcher, the annual proportion of large broods (>6 fledglings) was positively correlated with the vole trapping index. No correlation was found between the offspring production of goshawks and the proportion of voles in their diet. During a 3-year light-trapping study of nocturnal moths prior to our study, four moth species whose larvae ate Vaccinium were commonest in the vole peak year. All these results are consistent with the MDH. Received: 16 March 1998 / Accepted: 20 April 1998     

Entangled lives: Implications of the developmental origins of health and disease hypothesis for bioarchaeology and the life course

Epidemiological research since the 1980s has highlighted the consequences of early life adversity, particularly during gestation and early infancy, for adult health (the “Barker hypothesis”). The fast‐evolving field of molecular epigenetics is providing explanatory mechanisms concerning phenotypic plasticity in response to developmental stressors and the accumulation of disease risk throughout life. In addition, there is now evidence for the heritability of poor health across generations via epigenetic modifications. This research has the potential to invoke a paradigmatic shift in how we interpret factors such as growth insults and immune response in past skeletal remains. It demonstrates that health cannot be understood in terms of immediate environmental circumstances alone. Furthermore, it requires both a theoretical and practical re‐evaluation of disease biographies and the life course more generally. Individual life courses can no longer be regarded as discrete, bounded, life histories, with clearly defined beginning and end points. If socioeconomic circumstances can have intergenerational effects, including disease susceptibility and growth stunting, then individual biographies should be viewed as nested or “embedded” within the lives of others. This commingling of life courses may prove problematic to unravel; nevertheless, this review aims to consider the potential consequences for bioarchaeological interpretations. These include a greater consideration of: the temporal power of human skeletons and a life course approach to past health; infant health and the implications for maternal well‐being; and the impact of non‐proximate stressors (e.g., early life and ancestral environments) on the presence of health indicators. Am J Phys Anthropol 158:530–540, 2015. © 2015 Wiley Periodicals, Inc.     

Studies on the functional significance of a C-terminal S-shaped motif in human arginase type I: essentiality for cooperative effects

The functional significance of a C-terminal S-shaped motif (residues 304-322) in human arginase I was explored by examining the kinetic properties of the R308A mutant and truncated species terminating in either Arg-308 or Ala-308. Replacement of Arg-308 with alanine, with or without truncation, yielded monomeric species. All mutants were kinetically indistinguishable from the wild-type enzyme at the optimum pH of 9.5. At the more physiological, pH 7.5, hyperbolic kinetics was observed for all the mutants, in contrast with the cooperative behavior exhibited by the wild-type species. In the presence of 2 mM guanidinium chloride (Gdn⁺), the single mutant R308A changed to a trimeric and kinetically cooperative form, whereas the other enzyme variants were not altered. The S-shaped motif is suggested as essential for the cooperative response of the enzyme to l-arginine at pH 7.5. Gdn⁺ is suggested to mimic the guanidine group of Arg-308 at the monomer-monomer interface.