Global transcriptional profiles of beating clusters derived from human induced pluripotent stem cells and embryonic stem cells are highly similar

Background

The C-terminal Eps15 homology domain-containing protein 1 (EHD1) is ubiquitously expressed and regulates the endocytic trafficking and recycling of membrane components and several transmembrane receptors. To elucidate the function of EHD1 in mammalian development, we generated Ehd1 ^-/- mice using a Cre/loxP system.

Results

Both male and female Ehd1 ^-/- mice survived at sub-Mendelian ratios. A proportion of Ehd1 ^-/- mice were viable and showed smaller size at birth, which continued into adulthood. Ehd1 ^-/- adult males were infertile and displayed decreased testis size, whereas Ehd1 ^-/- females were fertile. In situ hybridization and immunohistochemistry of developing wildtype mouse testes revealed EHD1 expression in most cells of the seminiferous epithelia. Histopathology revealed abnormal spermatogenesis in the seminiferous tubules and the absence of mature spermatozoa in the epididymides of Ehd1 ^-/- males. Seminiferous tubules showed disruption of the normal spermatogenic cycle with abnormal acrosomal development on round spermatids, clumping of acrosomes, misaligned spermatids and the absence of normal elongated spermatids in Ehd1 ^-/- males. Light and electron microscopy analyses indicated that elongated spermatids were abnormally phagocytosed by Sertoli cells in Ehd1 ^-/- mice.

Conclusions

Contrary to a previous report, these results demonstrate an important role for EHD1 in pre- and post-natal development with a specific role in spermatogenesis.     

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.     

Using RNA sample titrations to assess microarray platform performance and normalization techniques

We have assessed the utility of RNA titration samples for evaluating microarray platform performance and the impact of different normalization methods on the results obtained. As part of the MicroArray Quality Control project, we investigated the performance of five commercial microarray platforms using two independent RNA samples and two titration mixtures of these samples. Focusing on 12,091 genes common across all platforms, we determined the ability of each platform to detect the correct titration response across the samples. Global deviations from the response predicted by the titration ratios were observed. These differences could be explained by variations in relative amounts of messenger RNA as a fraction of total RNA between the two independent samples. Overall, both the qualitative and quantitative correspondence across platforms was high. In summary, titration samples may be regarded as a valuable tool, not only for assessing microarray platform performance and different analysis methods, but also for determining some underlying biological features of the samples.     

Anthropological and clinical characteristics in adolescent women with dysmenorrhea

The aim of this study was to examine the prevalence of dysmenorrhea in female adolescents and the influence of anthropological characteristics and lifestyle factors on menstrual pain. Two hundred and ninety seven girls from several elementary and secondary schools were interviewed about the presence of the menstrual pain, their age, height and weight, menarcheal age, menstrual cycles quality, smoking and sexual activity. There were 164 (55%) subjects with and one hundred and thirty three (45%) without dysmenorrhea. The adolescents with dysmenorrhea answered the questions about missing activities and taking pills for pain. No difference was observed between the girls with and the girls without dysmenorrhea in their chronological age, height, weight, menarcheal age, menstrual cycles quality, cigarette smoking and sexual activity. In the group of dysmenorrheic adolescents there was infrequent missing activities and bedrest, but missing school was observed in 22 percent and taking pills for pain was observed in 96 percent of the subjects. Young girls who experienced menstrual pain are good candidates for a prophylactic therapy, such as hormonal contraception. A replication of this study is needed for public health services in the future to improve the quality of life of the dysmenorrheic young women.     

Effects of war aggression in Croatia on histopathological manifestations of breast cancer in defined population of one county

The aim of the present study was to determine the differences in epidemiological and clinical manifestations of breast cancer during the war in Croatia and in peacetime. 660 consecutive patients were recorded (656 female and 4 male patients) from Pozesko-Slavonska County. The changes in histopathological features were recorded in war period (1991-1995, 156 patients) and through two control periods, before the war (1981-1990, 282 patients) and after the war (1995-2000, first five months, 223 patients). The relative predictive value was calculated using chi 2-test. The survival was calculated according to Kaplan-Meier analysis of survival. The histopathological analysis showed an equal distribution of noninvasive cancer (in situ cancer) across periods. In the war period, the level of the most common invasive cancer, ductal breast cancer, was lower (57.7%), compared to control periods (71.2%:63.7%:68.2%). Opposite to that, invasive lobular cancer was more common in the war period (3.2%), compared to control periods (0.7%-1.3%). Furthermore, mixed cancer was also increased in the war period (7.1%) compared to control periods (0.7%-2.2%), as was medullar cancer (10.9% vs. 5.5%-5.9%). The study showed statistically significant differences in the survival of patients with different histopathological diagnoses (Log Rank = 47.49, df = 7, p < 0.0001), while the histological grade of tumor, as a predictive factor was not proved to be statistically significant (p > 0.05). This study confirmed the influence of war of war on histopathological incidence of some forms of breast cancer.     

Effects of war aggression in Croatia on some forms and manifestations of breast cancer

The aim of this study was to determine the differences in epidemiological and clinical manifestations of breast cancer in time of war in Croatia and in peacetime before and after the war, in the defined population of Pozesko-Slavonska County. The methods used in this study were the evaluation of relative predictive value of variables by means of chi 2-test and the analysis of variance, while the survival studies were tested by Long Rank test according to Kaplan-Meier analysis of survival. This work encompasses 660 patients who had breast cancer. The differences between three time periods were evaluated: the war period (1991-1995), and two control periods: before the war (1981-1990) and after the war (1996-2000). The patients were grouped by age, localization of tumor and survival. During the war period the patients were, on the average, 4.2 years younger than those who acquired the disease in control periods, and the mean age of patients was between 50 and 59 years (36.5% of patients). Although the difference in tumor distribution by sides (left or right breast) and quadrants was statistically significant (war period vs. control periods; p < 0.001), there was no statistically significant difference in the survival of patients according to the results of Kaplan-Meier analysis of localization of tumor (p > 0.05). The length of survival in terms of age of patients in time of surgical procedure was significantly different (p < 0.001). This study confirms the effects of war on some epidemiological and clinical manifestation of breast cancer in the defined population of Pozesko-Slavonska County.     

Uterine artery embolization for the treatment of uterine fibroids

Uterine artery embolization can be regarded as a less invasive procedure for the treatment of fibroids compared with myomectomy, hysterectomy, and laparoscopic myolysis. The aim of this study was the evaluation of safety and efficacy of uterine artery embolization and of womens' opinion about this treatment. After gynecological examination sixty-nine premenopausal women underwent uterine artery embolization. All procedures but four were technically successful; three women underwent unilateral embolization because of vascular malformation and one of them had an allergic reaction to contrast medium. Of the 69 patients: 58 went home the day after embolization, and 11 within first week. The follow-up examinations after 3, 6 and 12 month showed a significant reduction of uterine and fibroid volume with significant improvement of bleeding. Therefore, according to this report, uterine artery embolization is a successful, minimal invasive treatment of myoma that preserves the uterus and requires shorter hospitalization and recovery times than surgery.     

Augmentation of NKT and NK cell-mediated cytotoxicity by peptidoglycan monomer linked with zinc

BACKGROUND: Peptidoglycan monomer (PGM), which was originally prepared by biosynthesis from culture fluids of penicillin-treated Brevibacterium divaricatum, is an immunostimulator, the activities of which might be improved by addition of zinc (Zn) to the basic molecule. METHODS: To test the possible cytotoxic effects of this new analogue, we analyzed the ability of PGM-Zn and PGM to change the phenotypic profile of hepatic and splenic mononuclear lymphatic cells and to affect the growth of malignant T-cell line YAC-1 and syngeneic thymocytes. RESULTS: Pretreatment of C57BL/6 mice primarily with PGM-Zn over 6 days (10/mg/kg intraperitoneally) significantly enhanced the proportions of NK1.1high+, CD4-CD8-, CD69+, and CD3intermediate/NK1.1+/IL2R-beta+ (NKT) cells in the liver, and major histocompatibility complex class II+, CD69+, and CD8+ cells in the spleen. Both types of cells were highly cytotoxic against YAC-1 and syngeneic thymocytes, increasing the destruction of YAC-1 by 70% on addition of hepatic cells and by 30% on addition of splenic cells. Destruction of thymocytes increased by 10 and 50%, respectively. CONCLUSION: The results point to PGM-Zn as a potent cytotoxicity-inducing agent, which also generates autoreactive NKT cells.     

The role of insulin-like growth factor 2 and its receptors in human tumors

Insulin-like growth factor 2 (IGF-2) is important for normal development and growth of an organism. In humans it is encoded by 11p15.5 paternally expressed imprinted gene. It binds at least two different types of receptors: IGF type 1 (IGF-1R) and IGF-2/mannose 6-phosphate receptors (IGF-2R/M6P). Ligand binding to IGF-1R provokes mitogenic and anti-apoptotic effects. IGF-2R/M6P has tumor suppressor function; it mediates IGF-2 degradation. When the IGF-2 gene/protein is overexpressed, mostly as a consequence of loss of heterozygosity resulting in paternal allele duplication (LOH) or by loss of imprinting (LOI), it is involved in the development and progression of many tumors and overgrowth syndromes by autocrine or paracrine mechanisms.     

Mental health and coping in a war situation: the case of Bosnia and Herzegovina

The latter part of the twentieth century has seen an increased concern for the implications of war for civilian populations, and more attention has been given to psychosocial impacts of uprooting and displacement. 'Loss of place', acute and chronic trauma, family disruption and problems of family reunification have become issues of concern. The war in Bosnia was characterized by massive displacement, disruption and loss of life, relatives and property. Health and psychosocial well-being were affected in a number of ways. There was an overwhelming loss of perceived power and self-esteem. Over 25%, of displaced people, for example, said they no longer felt they were able to play a useful role; even in non-displaced populations approximately 11% of those interviewed said that they had lost a sense of worth. Widespread depression and feelings of fatigue and listlessness were common and may have prevented people from taking steps to improve their situation. Almost a quarter of internally displaced people had a high startle capacity and said they were constantly nervous. Most adverse psychosocial responses increased with age and in a population that includes many elderly people this poses serious problems. The findings point to major challenges with respect to repatriation and reconstruction. They highlight the importance of family reunification and the facilitating of decision-making by affected people themselves. The findings also shed light on potential problems associated with over-dependence on external assistance and hence the need for people to be given the means of using their skills and knowledge to control their day-to-day lives.