Genome-wide gene expression responses to experimental manipulation of Saccharomyces cerevisiae repressor activator protein 1 (Rap1) expression level.

Precise regulation of transcription in gene expression is critical for all aspects of normal organism form, fitness, and function and even minor alterations in the level, location, and timing of gene expression can result in phenotypic variation within and between species including evolutionary innovations and human disease states. Eukaryotic transcription is regulated by a complex interplay of multiple factors working both at a physical and molecular levels influencing this process. In Saccharomyces cerevisiae, the TF with the greatest number of putative regulatory targets is the essential gene Repressor Activator Protein 1 (RAP1). While much is known about the roles of Rap1 in gene regulation and numerous cellular processes, the response of Rap1 target genes to systematic titration of RAP1 expression level remains unknown. To fill this knowledge gap, we used a strain with a tetracycline-titratable promoter replacing wild-type regulatory sequences of RAP1 to systematically reduce the expression level of RAP1 and followed this with RNA sequencing (RNA-seq) to measure genome-wide gene expression responses. Previous research indicated that Rap1 plays a significant regulatory role in particular groups of genes including telomere-proximal genes, homothallic mating (HM) loci, glycolytic genes, DNA repair genes, and ribosomal protein genes; therefore, we focused our analyses on these groups and downstream targets to determine how they respond to reductions in RAP1 expression level. Overall, despite being known as both an activator and as a repressor of its target genes, we found that Rap1 acts as an activator for more target genes than as a repressor. Additionally, we found that Rap1 functions as an activator of ribosomal protein genes and a repressor for HM loci genes consistent with predictions from the literature. Unexpectedly, we found that Rap1 functions as a repressor of glycolytic enzyme genes contrary to prior reports of it having the opposite effect. We also compared the expression of RAP1 to five different genes related to DNA repair pathway and found that decreasing RAP1 downregulated four of those five genes. Finally, we found no effect of RAP1 depletion on telomere-proximal genes despite its functioning to silence telomeric repeat-containing RNAs. Together our results enrich our understanding of this important transcriptional regulator.

Analysis of cytochrome P450 contribution to evolved plant toxin resistance in Drosophila sechellia.

Drosophila sechellia is a dietary specialist species of fruit fly that has evolved resistance to the toxic secondary defence compounds produced by the fruit of its preferred host plant Morinda citrifolia. The genetic basis of adult toxin resistance is the result of evolution at five loci across the genome. Genetic mapping between D. sechellia and Drosophila simulans and subsequent functional studies in Drosophila melanogaster have identified candidate genes potentially underlying one locus involved in toxin resistance but the remainder of the genes involved are unknown. Genes in the mixed function oxidase or cytochrome P450 gene family are frequently utilized in evolved toxin resistance in insects, yet whether they play a role in D. sechellia's resistance to the toxins found in its host plant is unknown. Here we test the role of cytochrome P450 enzymatic activity in evolved resistance to the two primary toxins found in M. citrifolia fruit: octanoic acid and hexanoic acid. We found that although cytochrome P450 enzymatic activity is involved in basal resistance it is not involved in derived toxin resistance in D. sechellia.

Postpartum surveillance of urinary retention by ultrasonography: the effect of epidural analgesia.

Our objective was to investigate by ultrasonography whether the risk for postpartum urinary retention is increased following administration of epidural analgesia during labor and delivery. In a prospective study, 106 healthy women who had undergone vaginal delivery were evaluated. Sixty-eight of the women had received epidural analgesia during labor and delivery. All subjects had an ultrasound examination at a mean of 42 h after delivery, and residual urine volume was estimated immediately after voiding. Correlations among obstetric parameters, epidural analgesia and residual urine volumes were evaluated. The mean accuracy rate of ultrasonography for estimation of bladder volumes was +/- 10.2%. No cases of clinically evident urinary retention were diagnosed in the total puerperal population. There were no significant differences between the groups in the average amounts of residual urine as measured by ultrasonography. With modern obstetric practice, epidural analgesia for labor is not associated with an increased risk for postpartum urinary retention. The non-invasive nature of ultrasound renders it especially attractive and useful for measuring residual urine volume in postpartum patients. The safety, simplicity and relative comfort of this method over-ride the slightly imperfect calculations that it currently yields, and makes it preferable to catheterization or cystometry for evaluation of residual urine volume.

Are Israeli women in a low risk group for developing squamous cell carcinoma of the uterine cervix?

OBJECTIVE: Invasive cervical squamous cell carcinoma is not a common disease among Jewish women. In the present study an attempt was made to find what is the distribution of the known risk factors in this population. METHODS: Three hundred and ninety-one patients with various cervical cytological abnormalities comprised the study group. They were compared to 350 Israeli women with negative cytology. The risk factors were extracted from an anonymous questionnaire. The results were statistically analyzed and compared to the equivalent figures published in the literature pertaining to non-Jewish women. RESULTS: The prevalence of abnormal cytology among the Israeli women was almost the same as that of the non-Jewish group: 24/1000 and 26/1000, respectively. Significant statistical differences were found between the following risk factors: number of sexual partners, age at first intercourse, age at first pregnancy. Women in the study group were younger when they became sexually active and at first pregnancy, they had a larger number of sexual partners, fewer of them were married and fewer of them were observant of Jewish ritual practices. In addition, they had achieved higher academic levels than the women in the control group. CONCLUSIONS: It was found that the distribution of the known risk factors among the study group was practically the same as those in the non-Jewish population. Moreover, it was found that there was an increase of 29.2% (from 17/1000 to 24/1000) in the prevalence of cervical premalignant lesions among the Israeli women. We believe that this population can no longer be considered as being at low risk for this disease.

Prevalence of human papillomavirus infection and HPV DNA among male partners of Israeli women with genital premalignant and human papillomavirus lesions.

The role of the males who are sexual partners of females with genital human papillomavirus (HPV) infection and premalignant lesions is explored in the present study. Within a period of 3 years, 391 females with genital premalignant and HPV-associated lesions were examined and treated at the Cervical Pathology Unit of the Tel Aviv Medical Center. The male partners of all the women were asked to attend this unit, and 322 of them responded. All participants underwent colposcopic examination of the anogenital area followed by colposcopically guided biopsies from the most representative lesions, when present, part of which included in situ hybridization (ISH) of HPV DNA sequences 6/11 and 16/18. The histological prevalence of HPV among the male partners was 86.6% (185 of 213 biopsies). Of the 48 couples who had ISH evaluations, the ISH could not identify any copy of HPV DNA in 58.3% of the males (28 cases) and 41.6% of the females (20 cases). Among the males, HPV 6/11 and 16/18 were found in 17 (35.4%) and 3 cases (6.2%), respectively, and among the females there were 23 (48.0%) and 5 cases (10.4%), respectively. Correlation of HPV DNA sequences 6/11 and 16/18 between the couples was found in six (12.5%) and in one (2.0%), respectively. These data do not support a direct contamination by the current male partner. The question of treating the male partner of a woman with genital HPV and premalignant lesions remains to be evaluated.

Flow velocity waveforms of the uterine artery in pregnancy: transvaginal versus transabdominal approach.

Our objective was to compare recordings of flow velocity waveforms from the uterine artery via the transvaginal and transabdominal approach in normal human pregnancies. In a cross-sectional study from 16 to 40 weeks' gestation, 88 healthy pregnant women underwent a continuous-wave Doppler examination of their uterine arteries by both the transvaginal and the transabdominal approach. Measurements were recorded for both uterine arteries and averaged. Values recorded transabdominally were significantly lower than those obtained transvaginally in all patients < or = 27 weeks' gestation. From 28 weeks to term, transabdominal values remained lower, but the difference was smaller and insignificant, and noted only as a trend. Transvaginal velocimetry of the uterine artery produces significantly higher systolic:diastolic ratios than that of transabdominal recordings until 27 weeks' gestation. Thereafter, trophoblastic invasion of the uteroplacental circulation is maximal, and the difference between the values are minimal and insignificant. However, a pattern of lower resistance in the transabdominal approach remains consistent until term.

Vaginal ulcerations due to lithium carbonate therapy.

A twenty-nine-year-old woman who had been taking lithium carbonate for seven years experienced ulcerated lesions of the vaginal mucosa and acneiform eruption on both thighs. Histopathologic appearance of the skin biopsy specimens was consistent with lichenoid cutaneous changes. The cutaneous lesions cleared when use of the drug was discontinued.

The establishment of an ovum donation program using a simple fixed-dose estrogen-progesterone replacement regimen.

Most ovum donation (OD) programs involve cycle synchronization between recipient and donor for normally cycling recipients and a complex estrogen-progesterone replacement regimen for recipients with ovarian failure. In 1987, Serhal and Craft (1) suggested the use of a fixed-dose estrogen-progesterone regimen for recipients who were normally ovulatory and to those with ovarian failure. Following this protocol, and simplifying it still, the authors administered 6 mg estradiol valerate (E2) daily orally starting on day 2-6 of induced withdrawal bleeding, augmented with 100 mg progesterone in ethyl oleate (P) intramuscularly daily, starting any time between 4 days prior to and the day of oocyte pickup. All recipients underwent embryo transfer at a 2-pronuclei (2PN)-10-cell stage. A group of 21 patients underwent 26 treatment cycles, resulting in 16 pregnancies. Twelve of the patients gave birth, one to triplets, two to twins, and nine to singletons. Four patients miscarried in the first trimester of pregnancy.

Hypotensive effect of bromocriptine in normal eyes.

The effect of a single oral dose of 2.5 mg Bromocriptine on intraocular pressure over a 12 hour period in a group of 20 puerperal women with normal eyes, is reported. Intraocular pressure was significantly reduced, the maximal response being 3-4 hours after administration. Possible explanations for the reducing effect of Bromocriptine on intraocular pressure are discussed.

Diffuse unilateral subacute neuroretinitis.

In December 1980, a 26-year-old black man came to the Washington Hospital Center Eye Clinic with a unilateral decrease in visual acuity, vitreous inflammation, optic disk pallor, and a degenerated retinal pigment epithelium. A motile subretinal worm was subsequently found. Unlike an earlier series of 18 patients with diffuse unilateral subacute neuroretinitis reported by other authors, this patient exhibited eosinophilia and a highly positive ELISA for Toxocara.

Vaginal versus cesarean section oriented approaches in the management of breech delivery.

In a 5-year retrospective study, 543 singleton breech presented infants weighing more than 1000 g were reviewed in two obstetric departments. Department "A" actively conducted the labor with lower cesarean section rate (26%). Department "B" attempted a trial of labor with less invasive procedures and performed more cesarean sections (38% P less than 0.05 S). The management of labor, fetal and maternal outcome were compared between the two departments. Both vaginal and abdominal routes of delivery in fetuses weighing more than 1500 g resulted in the same fetal and maternal outcome. For fetuses weighing 1000-1500 g cesarean section is probably the recommended delivery route.

Light intensity and visual acuity following cataract surgery.

The authors analyzed 310 cataract operations that were randomly distributed between two operating rooms, each containing a microscope with different light intensities. The light intensity of one microscope was almost threefold greater than the other. One hundred seventy-seven patients were excluded from this study because of medical or ocular problems that might affect visual acuity. The remaining 133 patients are the subjects of this paper. Seventy-one were operated upon under high intensity light, and 62 were subjected to lower illumination in the operating room. Visual acuity after operation was correlated with type of microscope, age, sex, method of cataract extraction, and use of intraocular lenses. Reduced visual acuity (20/40 or worse) was consistently more common with high intensity light and with increasing age. Further investigation is recommended to establish the cause of this reduced acuity.