Effects of estrogen on endothelial prostanoid production and cyclooxygenase-2 and heme oxygenase-1 expression

We studied the effects of 17β-estradiol (E?) (10, 40 nM) on 2 vasoprotective pathways, i.e. cyclooxygenase-2 (COX-2)-dependent prostanoids and the antioxidant heme oxygenase-1 (HO-1), in human umbilical vein endothelial cells (HUVEC) exposed for 6h to steady laminar shear stress (LSS, 10 dyn/cm2), characteristic of atherosclerotic lesion-protected areas. COX-2 was induced by LSS versus static condition (SC). E? did not significantly affect COX-2 expression in HUVEC cultured in SC or exposed to LSS. Prostacyclin (PGI?) and prostaglandin (PG)E? were induced while PGF(2α) was reduced by LSS. E? caused no effect or a small reduction of prostanoid biosynthesis. In HUVEC cultured in SC or exposed to LSS, E? 10 nM caused a comparable HO-1 induction (35-45%) while E? 40 nM was 5-fold more potent in LSS-exposed HUVEC than in SC (290% and 58%, respectively). PGI? receptor antagonist RO3244794 did not affect HO-1 induction by E?. In conclusion, E? may restrain oxidant stress in the endothelium through HO-1 induction by a mechanism independent on PGI? signaling.     

Effects of diet on reproductive performance of the Bank vole (Clethrionomys glareolus)

Laboratory experiments were carried out to test the effect of dietary supplements of fresh sprouted wheat on reproduction of the Bank vole, Clethrionomys glareolus. One hundred and twenty females were divided into three groups at weaning: (a) group NSS (no sprout supplement), (b) group LSS (low sprout supplement) and (c) group HSS (high sprout supplement). Six- to seven-week-old females were paired with fertile males. Both groups on sprout supplement showed a significantly higher incidence of pregnancy in primiparous females (76%) compared with controls (NSS) (46%). Diet had no significant effect on the incidence of pregnancy in multiparous females. Control females had consistently higher mean litter sizes up to and including the fifth litter, compared with experimental females. Primiparous NSS females had the highest mean litter size and the experimental group HSS had the lowest. Differences in mean litter interval between groups were related to litter size (number of sucklings) rather than diet. The number of foetuses in utero had no effect on litter interval. The incidence of post-partum conception was higher in group LSS as compared with groups HSS and NSS. Diet did not affect the mean number of young produced per female in a given time, or the percentage of young surviving to weaning. The results are discussed with reference to their implications regarding habitat suitability of C. glareolus.     

Malignant melanoma in Chile: different site distribution between private and state patients

Background

The body site location of primary Malignant Melanoma (MM) has been correlated with prognosis and survival. Ethnic, genetics, sun exposure factors are related to the anatomical distribution of MM. Low and high socioeconomic strata in Chile differ in ethnic, genetic and cultural conditions. The purpose of this study was to analyze the anatomical MM distribution in the Chilean population in both strata searching for differences due to their ethno-genetic-cultural differences. Records of 1148 MM, 575cases from state hospitals (Low Socioeconomic Strata, LSS) and 573 cases from private clinics (High Socioeconomic Strata, HSS) were analyzed by body site.

Results

Females from LSS showed a higher number of MM in soles, cheeks, and around the eye area. Females from the HSS showed a higher number of MM in dorsal feet and dorsal hands. Males from LSS showed a higher number of MM in soles, around the eye area, and cheeks. However, males from HSS showed a higher number of MM in the trunk, and in the arms. Acral MM was significantly higher in LSS than in the HSS in both sexes. The Chilean population from the HSS and LSS showed differences in the distribution of MM by site. Furthermore, gender differences in the proportion of MM analyzed by anatomical site are observed in both strata.

Conclusions

Results show evidence that differential genetics factors, sun exposure, or other environmental or cultural factors of both strata may account for these differences.     

Biofeedback training in frontalis muscle relaxation and enhancement of belief in personal control

The hypothesis that biofeedback training in frontalis muscle relaxation increases beliefs in internal (personal) locus of control was tested. Subjects were divided into two groups (internals and externals) based on Mirels' (1970) factor analyzedpersonal control subscale of Rotter's (1966) I-E Scale. Internal and external subjects were assigned randomly to one of three conditions: biofeedback (BF), false feedback (FF), or no feedback (NF). All subjects were measured on frontalis electromyographic (EMG) activity. Training consisted of three sessions spaced 1 week apart. Each session was comprised of a 5-minute baseline (nonfeedback) trial followed by a 20-minute experimental session. After each experimental session, subjects completed a questionnaire which assessed the extent to which they attributed their EMG performance to personal and environmental sources. After three sessions, subjects were posttested on the I-E Scale. Results indicated that subjects receiving BF reduced their EMG activity more than did subjects in either the FF or NF conditions, and this effect was maintained across all three sessions. Subjects who received BF shifted toward internal personal locus of control from pre- to posttesting, whereas no such change was found for either FF or NF subjects. Also, the relationship between BF training and change in personal locus of control was mediated by subjects attributing their EMG reduction more to personal effort than to properties of the task. Results are discussed in terms of the importance of contingent feedback as a determinant of cognitions of control.     

Ultrastructural characterization of RPA-containing domains in nuclei assembled in Xenopus egg extracts

We describe novel structural domains in in vitro reconstituted Xenopus sperm nuclei, which we term RPA bodies; RPA is the only known marker of these structures. These bodies contain DNA and represent special chromatin domains as seen by transmission electron microscopy. We show that RPA bodies exhibit a similar ultrastructure in nuclei assembled in high-speed supernatant (HSS) of Xenopus egg extract and in nuclei assembled in HSS supplemented with low-speed supernatant (HSS + LSS nuclei). Moreover, RPA bodies are also formed when sperm chromatin containing double-stranded DNA breaks is incubated with HSS of egg extracts. RPA bodies appear to be compartmentalized. By immunoelectron microscopy we show that RPA is preferentially localized at the periphery of the bodies where DNA synthesis also occurs in HSS + LSS nuclei.     

Genotypic variation in source and sink traits affects the response of photosynthesis and growth to elevated atmospheric CO2

This study aimed to understand the response of photosynthesis and growth to e-CO₂ conditions (800 vs. 400 μmol mol⁻¹) of rice genotypes differing in source–sink relationships. A proxy trait called local C source–sink ratio was defined as the ratio of flag leaf area to the number of spikelets on the corresponding panicle, and five genotypes differing in this ratio were grown in a controlled greenhouse. Differential CO₂ resources were applied either during the 2 weeks following heading (EXP1) or during the whole growth cycle (EXP2). Under e-CO₂, low source–sink ratio cultivars (LSS) had greater gains in photosynthesis, and they accumulated less nonstructural carbohydrate in the flag leaf than high source–sink ratio cultivars (HSS). In EXP2, grain yield and biomass gain was also greater in LSS probably caused by their strong sink. Photosynthetic capacity response to e-CO₂ was negatively correlated across genotypes with local C source–sink ratio, a trait highly conserved across environments. HSS were sink-limited under e-CO₂, probably associated with low triose phosphate utilization (TPU) capacity. We suggest that the local C source–sink ratio is a potential target for selecting more CO₂-responsive cultivars, pending validation for a broader genotypic spectrum and for field conditions.     

A leishmaniasis study: Structure-based screening and molecular dynamics mechanistic analysis for discovering potent inhibitors of spermidine synthase

Protozoa Leishmania donovani (Ld) is the main cause of the endemic disease leishmaniasis. Spermidine synthase (SS), an important enzyme in the synthetic pathway of polyamines in Ld, is an essential element for the survival of this protozoan. Targeting SS may provide an important aid for the development of drugs against Ld. However, absence of tertiary structure of spermidine synthase of Leishmania donovani (LSS) limits the possibilities of structure based drug designing. Presence of the same enzyme in the host itself further challenges the drug development process. We modeled the tertiary structure of LSS using homology modeling approach making use of homologous X-ray crystallographic structure of spermidine synthase of Trypanosoma cruzi (TSS) (2.5? resolution). The modeled structure was stabilized using Molecular Dynamics simulations. Based on active site structural differences between LSS and human spermidine synthase (HSS), we screened a large dataset of compounds against modeled protein using Glide virtual screen docking and selected two best inhibitors based on their docking scores (-10.04 and -13.11 respectively) with LSS and having least/no binding with the human enzyme. Finally Molecular Dynamics simulations were used to assess the dynamic stability of the ligand bound structures and to elaborate on the binding modes. This article is part of a Special Issue entitled: Computational Methods for Protein Interaction and Structural Prediction.     

Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism

Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL cholesteryl ester to triglyceride-rich lipoproteins (TRL). This study aimed to determine the effects of CETP inhibition with torcetrapib on TRL composition and apoB-48 metabolism. Study subjects with low HDL cholesterol (<40 mg/dl), either untreated (n = 9) or receiving atorvastatin 20 mg daily (n = 9), received placebo for 4 weeks, followed by torcetrapib 120 mg once daily for the next 4 weeks. A subset of the subjects not treated with atorvastatin participated in a third phase (n = 6), in which they received torcetrapib 120 mg twice daily for an additional 4 weeks. At the end of each phase, all subjects received a primed-constant infusion of [5,5,5-(2)H(3)]L-leucine, while in the constantly fed state, to determine the kinetics of TRL apoB-48 and TRL composition. Relative to placebo, torcetrapib markedly reduced TRL CE levels in all groups (≥-69%; P < 0.005). ApoB-48 pool size (PS) and production rate (PR) decreased in the nonatorvastatin once daily (PS: -49%, P = 0.007; PR: -49%, P = 0.005) and twice daily (PS: -30%, P = 0.01; PR: -27%, P = 0.13) cohorts. In the atorvastatin cohort, apoB-48 PS and PR, which were already lowered by atorvastatin, did not change with torcetrapib. Our findings indicate that CETP inhibition reduced plasma apoB-48 concentrations by reducing apoB-48 production but did not have this effect in subjects already treated with atorvastatin.     

The introduced clam Ensis americanus in the Wadden Sea: field experiment on impact of bird predation and tidal level on survival and growth

In the Danish Wadden Sea the intertidal distribution of the introduced bivalve Ensis americanus (syn. E. directus) is restricted to a narrow zone around the mean low water level. To test the possible impact of birds and submersion time on dynamics and distribution of the clams, adult specimens of E. americanus collected near the low water line were transplanted to two intertidal sites and established in open and net-covered experimental plots for 9 weeks (autumn 2001). The lowest survival of clams was registered at the low-shore-site (LSS) in plots open to bird predators, suggesting that birds such as Common Eider (Somateria mollissima) or Oystercatcher (Haematopus ostralegus) may control the abundance of E. americanus at the lower tidal levels. For clams showing increment in shell length during the study period, the shell growth rates were highest at the LSS and lowest in the open plots at the high-shore-site (HSS). Differences in immersion time and thus food supply may explain this pattern. Body mass index (BMI) of the clams showed basically the same pattern as the survivorship: lowest BMI in open plots at the LSS and highest in the covered plots at this site. Clams from the HSS were intermediate in their BMI. Disturbance by birds in the open plots at the LSS may explain the low BMI. In conclusion birds may be an important factor controlling abundance of E. americanus in the lower intertidal zone.     

Perceived control

The present study tested the hypothesis that perceived control results in reduced depressive cognitions. Subjects were divided into two groups, high and low in depressive cognitions (HDC and LDC) based on their scores on a Depression Scale. Subjects (HDC and LDC) were assigned randomly to one of the following treatment conditions: contingent feedback (CF), noncontingent (yoked) feedback (YF), or no feedback (NF) in pulse-rate (PR) regulation. Half the subjects were instructed to decrease (D) and half were instructed to increase (I) PR. The study consisted of three sessions spaced one week apart. Each session was comprised of a three-minute baseline (nonfeedback) trial followed by a 15-minute experimental session. After each experimental session, subjects completed a questionnaire which assessed how well they felt they regulated PR, and the extent to which they attributed such regulation to their ability, effort, the difficulty or ease of the task, and luck. After three sessions, subjects were posttested on the Depression Scale. Results indicated that a significant, though small, reduction in depressive cognitions occurred for CF and YF subjects who were instructed to decrease PR, and this effect was mediated by subjects attributing PR regulation to ability and effort. Results are discussed in terms of the effect that perceived control may have on attributions and reported depression. Also, limitations regarding the generalizability of the findings to a clinical population are discussed.     

Individual differences in the ability to discriminate the direction of spontaneous changes in peripheral finger temperature

Spontaneous fluctuations of .1° C in peripheral finger temperature were recorded for a 30-minute baseline period in 10 subjects. Those meeting specified criteria of temperature fluctuations were then asked to judge the direction of change in computer-detected temperature fluctuations of .1° C, first without feedback, then with feedback (knowledge of results). Only 1 subject produced convincing evidence of ability to make directional judgments at better than chance level, though more training with feedback might have benefited other subjects. The theoretical significance of these results for the relationship between discrimination and voluntary control is discussed.This research was supported by a grant from the Australian Research Grants Scheme.     

Evidence for a molecular polymorphis of cholinesterase in Sepia officinalis (cephalopoda: decapoda)

• 1.1. Three forms of cholinesterase were sequentially extracted from head and tentacles of Sepia officinalis and noted as low-salt (LSS), detergent (DS) and high-salt (HSS) soluble. They represent about 24, 30 and 46% of total activity.
• 2.2. All enzyme forms seem to be amphiphilic proteins with hydrophobic domains interacting with non-ionic detergent (Triton X-100) and giving self-aggregation (LSS form).
• 3.3. The DS form is membrane-anchored by a phosphatidylinositol, while the HSS form is likely linked to some proteoglycan molecule of the extracellular matrix by ionic interactions.
• 4.4. According to V_max/K_m values, all the enzymes are acetylcholinesterases, even if hydrolyze propionylthiocoline at the highest rate.
• 5.5. Some kinetic and molecular properties of the studied enzymes are compared with those of other cholinesterases from vertebrates and invertebrates. Possible phylogenic and adaptive features are discussed.

     

Neurofeedback—The Significance of Reinforcement and the Search for an Appropriate Strategy for the Success of Self-regulation

Nine healthy children took part in five sessions of feedback and instrumental conditioning of slow cortical potentials (SCPs). The feedback conditions (the relation between the feedback signal and amplitude of SCP) were inverted after two sessions. Neither the children nor the therapists were aware of this change. The adjustment of the children to the new feedback setting and the self-regulation strategies employed were investigated. The results were as follows: (a) Healthy children achieved control over cortical negativity within two sessions. (b) The change of feedback conditions worsened the regulation abilities, which then improved again within the following three sessions. (c) After the first two sessions, the participants were able to describe strategies that were successful during different phases of self-regulation. (d) Following the change in the feedback conditions, the children re-evaluated the way they influenced their SCPs. However, they did not alter the cognitive or behavioral strategies. The study demonstrated that positive and negative reinforcement and the knowledge of results are more important for successful self-regulation than the search for effective strategies. The relevance of these findings is discussed.     

Distribution of estrogen and progesteron receptors in the uterus: an immunohistochemical study in the immature and adult pseudopregnant rabbit.

In order to clarify the distribution and content of estrogen (ER) and progesteron receptors (PR) under changing hormonal influences within the various cell populations of the uterus (glandular and luminal endometrial epithelium, stroma, myometrium), immunohistochemical determinations using specific monoclonal antibodies were made. To correlate the immunohistochemical findings with peripheral hormone levels and specific tasks of the endometrium, 17 beta-estradiol and progesterone serum levels were measured and cell proliferation determined by use of BrdU-labelling-immunohistochemistry. At the subcellular level ER and PR were located exclusively in the cell nuclei of female rabbits, which were either immature and lacking any peripheral hormone levels or were pseudopregnant (d0-d8 p.hCG). In the immature rabbits a general faint ER and PR immunostaining was found. In addition to a general increase in ER and PR in all cell populations estrous rabbits (d0 p.hCG) showed a significant rise of ER in the epithelial cells and of PR in the myometrium. Within the epithelial cells and the myometrium the ER dropped heavily within a few days of pseudopregnancy. The PR, however, increased sharply during the first two days of pseudopregnancy and decreased gradually following d4 p.hCG. A close relationship was observed between the high PR content and the proliferation rate of the epithelial cells on d2 p.hCG. In spite of the more rapid decrease of ER compared with PR, the glandular epithelium retained positive immunostaining. In the stroma the ER and especially PR content did not change significantly during the course of pseudopregnancy suggesting that some of the well-known differentiation events in the luminal epithelium may be mediated by the stroma.     

Relationship between serum gonadotropins and pituitary immunoreactive gonadotropins and steroid receptors during the first FSH increase of the estrous cycle and following steroid treatment in heifers

The objectives were to determine the effects of (i) time during the first FSH increase of the estrous cycle (time-course study) and (ii) exogenous steroid treatment (steroid feedback study) on the relationship between circulating serum gonadotropins, and the proportions of pituitary cells immunoreactive for gonadotropins and steroid receptors during the estrous cycle in heifers. Pituitaries were collected from heifers (n=40) slaughtered at 13h (n=8), 30h (n=24) and 66h (n=8) after estrous onset, corresponding to before, during and after the first FSH increase of the estrous cycle. Heifers slaughtered during the FSH increase (at 30h) either received no treatment (n=8), or were treated (n=16) with estradiol benzoate and/or progesterone before slaughter. During the time-course study, the proportion of pituitary cells immunoreactive for FSH increased (P<0.05) during the first transient FSH increase reflecting serum concentrations. The proportion of pituitary cells immunoreactive for LH was unaltered, a reflection of serum LH concentrations. The proportion of estrogen receptors (ER)-alpha, but not ER-beta, was decreased (P<0.05) at 30h compared with at either 13 or 66h. During the steroid feedback study, exogenous progesterone with or without estradiol suppressed (P<0.05) the proportions of pituitary cells immunoreactive for gonadotropins, serum FSH concentrations and LH pulse frequency. Steroid treatment did not alter the proportion of pituitary cells positive for estrogen receptors (alpha and beta). While progesterone receptors (PR) were not detected in the anterior pituitary by immunohistochemistry during the early estrous cycle or in response to steroid treatment, quantitative real-time PCR revealed that mRNA for progesterone receptors was expressed at very low levels. The expression of pituitary PR mRNA was decreased (P<0.05) at 30 and 66h compared with 13h, and was suppressed (P<0.05) following steroid treatments. Alterations in pituitary steroid receptors are implicated in the differential regulation of gonadotropin secretion during the first transient FSH rise, but not in response to exogenous steroids. The time-course study and steroid feedback responses support the hypothesis that LH pulse frequency is tightly linked to regulation of GnRH pulse frequency. Serum FSH is regulated by its own synthesis, as reflected by pituitary FSH content and perhaps by alterations in pituitary sensitivity to circulating steroids by changes in steroid receptor content.     

Maintenance and generalization of 40-Hz EEG biofeedback effects

Maintenance of conditioning of 40-Hz EEG activity was investigated in six adults 1 to 3 years after they had experienced biofeedback training to increase 40-Hz EEG. Subjects were first retrained to alternately increase and suppress 40-Hz EEG. All six subjects achieved a preset performance criterion in 16–20 minutes. Five of these subjects also subsequently demonstrated significant control of 40-Hz EEG without feedback. The sixth subject did not demonstrate control after 76 minutes and four sessions of attempted retraining with feedback. Transfer of 40-Hz EEG control to a problem-solving task was tested in all subjects in a final session. Cognitive test items were presented and subjects were instructed to alternately increase and suppress 40-Hz EEG while solving the problems. Rates of 40-Hz EEG in suppression periods during problem solving were significantly greater than during suppression periods without problems. No significant differences in problem-solving performance were found comparing 40-Hz increase and suppression periods. This study supports previous research suggesting an association between 40-Hz EEG and mental activity, and suggests methods for further study of transfer of EEG biofeedback effects.     

Finger pulse amplitude and frontalis EMG biofeedback effects of single- and two-system training.

The relationship between finger pulse amplitude (PA) and frontalis EMG was studied first by looking at general physiological changes accompanying successful bidirectional PA control. Seven successful subjects were then asked to produce two patterns of PA and EMG (PAincEMGdec and PAdecEMGdec) while receiving both PA and frontalis EMG biofeedback. Results indicate subjects can easily produce the differentiation pattern of PAdecEMGdec but cannot produce the integration pattern of PAincEMGdec. These rather paradoxical results may indicate subjects were using an "attentional" rather than "arousal" strategy for controlling PA and have implications for the use of peripheral vasomotor training as a general relaxation technique.     

The influence of parachute-resisted sprinting on running mechanics in collegiate track athletes

The influence of parachute-resisted sprinting on running mechanics in collegiate track athletes. The aim of this investigation was to compare the acute effects of parachute-resisted (PR) sprinting on selected kinematic variables. Twelve collegiate sprinters (mean age 19.58 ± 1.44 years, mass 69.32 ± 14.38 kg, height 1.71 ± 9.86 m) ran a 40-yd dash under 2 conditions: PR sprint and sprint without a parachute (NC) that were recorded on a video computer system (60 Hz). Sagittal plane kinematics of the right side of the body was digitized to calculate joint angles at initial ground contact (IGC) and end ground contact (EGC), ground contact (GC) time, stride rate (SR), stride length (SL), and the times of the 40-yd dashes. The NC 40-yd dash time was significantly faster than the PR trial (p < 0.05). The shoulder angle at EGC significantly increased from 34.10 to 42.10° during the PR trial (p < 0.05). There were no significant differences in GC time, SR, SL, or the other joint angles between the 2 trials (p > 0.05). This study suggests that PR sprinting does not acutely affect GC time, SR, SL and upper extremity or lower extremity joint angles during weight acceptance (IGC) in collegiate sprinters. However, PR sprinting increased shoulder flexion by 23.5% at push-off and decreased speed by 4.4%. While sprinting with the parachute, the athlete's movement patterns resembled their mechanics during the unloaded condition. This indicates the external load caused by PR did not substantially overload the runner, and only caused a minor change in the shoulder during push-off. This sports-specific training apparatus may provide coaches with another method for training athletes in a sports-specific manner without causing acute changes to running mechanics.