Month: January 2020

It should be noted that according to a recently published study, there are at least 1849 human transcripts that can be translated by alternate ATG initiation codons. Its 62 amino-terminal portion bears no similarity with the previously characterized RNase k-01 isoform or other human proteins, whereas the 63–134 region is absolutely identical to the major part of RNase k-01. Based on this amino-acid sequence, we managed to produce and purify an RNase k-02 specific polyclonal antibody. By the means of our newly developed antibody we were able to demonstrate the biogenesis of the RNase k-02 protein resulting from the RNase k02 mRNA translation in human cells. This alternative protein isoform bears a cytoplasmic topology. To our knowledge, this is the first instance of a human protein isoform encoded by a D4 subtly alternatively spliced transcript. The finding that RNase k-02 protein isoform is detected only in the detergent-insoluble fraction of cell extracts after Triton X-114 phase separation is in agreement with the predicted highly hydrophobic nature of this protein. This fact, in combination with its cytoplasmic localization, supports the hypothesis that RNase k-02 could participate in the formation of macromolecular complexes in vivo or localize in membranic structures such as the endoplasmic reticulum. It is well established that prostate cancer is dependent on androgens. Therefore, androgen deprivation has been the main treatment for advanced prostate cancer. With this therapy, however, the disease rapidly progresses to androgen-independent prostate cancer in most patients. Currently, there are no effective long-term therapies for AIPC. Developing new treatment strategies for AIPC remains attractive but is a challenging problem in clinical oncology. Previous studies have shown that the growth of AIPC is dependent on the androgen receptor. Thus, blocking AR expression has great potential for the treatment of AIPC. Studies have demonstrated that suppressing AR expression with RNA interference technology is an effective way to inhibit the growth of prostate cancer cells, indicating that this method may have the potential to overcome hurdles associated with AIPC treatment. In our previous studies, AR double-stranded RNA with a high specificity for AR genes was designed to block the expression of AR in AIPC cells and to inhibit cell growth. However, this type of gene therapy approach is difficult to apply in a clinical setting due to low gene transfection efficiency. One of the key reasons for low transfection efficiency is the lack of an effective, noninvasive in vivo targeted gene delivery system. In recent years, ultrasound-destructible microbubbles have been shown to be a promising method for gene therapy. Indeed, ultrasound-mediated microbubble destruction can not only improve gene transfection efficiency but can also be used for the tissue-specific delivery of therapeutic agents.

Our results illustrated that spermatogenesis and steroidogenesis were affected by CYP treatment and that the vacuolation of germ cells may be a result of the decreased expression of these key proteins and the reduced T levels. The male-to-female ratio at birth is a marker of parental endocrine disruption. In this study, we found that the sex ratio of the offspring was decreased in a dose-dependent manner. In utero exposure is widely considered t the most sensitive exposure time in terms of reproductive effects. Studies have shown that the mammalian hormone levels around the time of conception are associated with the sex of the resulting offspring. Parental exposure to both dioxin and vinclozolin has been shown to cause excess female offspring due to altered hormone concentrations. In the present study, we found that the serum E2/T ratio was higher in the CYP groups, which may account for the decreased male-to-female sex ratio. In addition, the observed fetal death sites in utero after CYP treatment indicated that CYP affects male fetal development. Even we could not figure out the precise mechanism in this study, this decreased sex ratio resulting from CYP exposure should arouse the attention of researchers and policy makers. Does CYP affect the proteins that regulate fetal formation and maternal-fetus interface, or could it directly affect the genes controlling sex? The mechanism should be elucidated further. Although the gene expression profiles were mostly similar between the in vivo and in vitro CYP treatment conditions, the gene expression of ERa differed between the two conditions. It is known that the localization of ERa is different during different testicular development stages. In the fetal testis, ERa is present in Leydig cells only, whereas in the neonatal testis, ERa is present in Leydig cells, rete testis, and efferent ductules. In the adult testis, ERa expression is also found in round spermatids. CYP may not influence ERa expression in regions other than Leydig cells, which may explain the difference in the results between the in vitro and the in vivo conditions. In summary, our study determined that maternal low-dose CYP exposure during the perinatal stage impairs steroidogenesis and spermatogenesis in male offspring, which may have long-term effects on male fertility. These results have been found in mice, and our findings suggest that CYP may also impair testicular development in humans. Human dental stem cells are generally applied in tissue and organ regeneration; however, the regenerative application of these stem cells in dental therapy remains problematic. To date, five types of human dental stem cells have been isolated and characterized: dental pulp stem cells,, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, dental follicle stem cells and periodontal ligament stem cells.

Our data suggest that 170,377 SNPs is unique to G3116 and 37,380 SNPs is unique to DV92 ; this provides an opportunity to study the wild winter and cultivated spring habits of the two accessions in greater detail. The SNP and SSR genetic sites identified in our dataset, along with those identified in other genetic populations and wheat projects, will provide useful marker resources for fine mapping experiments and marker-assisted wheat breeding programs. Along with the T. monococcum transcriptomes from two accessions, we have provided additional genomic and genetic resources including their functional annotations, differential gene expression analyses and potential SNPs and SSRs, which can be used to explore Triticeae genome diversity, co-expression networks involved in photomorphogenesis and to develop stochastic and metabolic networks. In addition, these resources can be used to identify novel genes, transcript models and eQTLs, and to study plant’s adaptation to diverse climatic conditions, impacts of domestication on crop plants and evolution of novel genes. Th1 and Th2 cells play important roles in the immune response to many infectious diseases and in autoimmune disorders. Th1 and Th2 cells mutually impede their generation, and Th1and Th2-related cytokines are not thought to be simultaneously secreted from single helper T cells. However, it was recently reported that IFN-c-producing Th1 cells inherently possess the capacity to convert their cytokine productivity. Th1 cells stimulated by IL-18 and antigen acquire the potential to produce several Th2-related cytokines, including IL-13, but not IL-4, as well as IFN-c. Th1 cells which gain productivity of Th2 cytokines are termed “super Th1 cells”. Indeed, within the IL-18induced super Th1 cells, Gata3 and T-bet, which are the crucial transcription factors for the induction of Th2 and Th1 cells, respectively, coexist. Whilst some recent studies demonstrate that one transcription factor, promyelocytic leukemia zinc finger, which was originally identified as a partner fused with retinoic acid receptors in acute promyelocytic leukemia, is indispensable for the dual secretion of IFN-c and IL-4 from cd T cells or NKT cells. It has been also reported that exogenous PLZF leads to the concomitant production of IFN-c and IL-4 from single T cells upon TCR stimulation. Since PLZF-transgenic T cells seem to convert their nature from differentiated mature types into ‘innate’ types, PLZF might be involved in the plasticity of committed T cells, such as Th1 and Th2 cells. Very recently, we reported that some conventional CD4 + T cells acquire atypical cytokine production capacities, producing combinations of “IFN-c+IL-13” and “IFN-c+IL-4”, during Schistosoma mansoni infection. Furthermore, some of these unique populations displayed the potential for secreting three cytokines concomitantly.

DNA methylation, along with covalent histone posttranslational modifications, chromatin remodelling and non-coding RNAmediated gene interference, represents an important mechanism in the integrated apparatus of epigenetic regulation. In addition to playing a role in several physiological processes, epigenetic mechanisms have been described as key factors in modifying the accessibility of DNA to transcription factors and, therefore, in altering the gene expression patterns of several cancer types. Given the existence of relatively simple approaches that require even minute amounts of tumour DNA, the best factor described involved in melanoma epigenetics is DNA methylation, a covalent modification of mainly cytosines. The DNA hypermethylation is usually strictly localised to the transcriptionally active gene regions and promoters and directly inhibits gene expression. In the field of malignant melanoma epigenetics, there are substantial amounts of data available regarding gene silencing associated with the localised CpG hypermethylation of specific gene promoters. However, most of the provided data are derived from cell lines or were generated using single-gene approaches. Despite the fact that some groups have attempted to conduct array-based experiments, to date, there are no methylation markers of the diverse melanoma subgroups based on a stratified analysis with sufficient statistical power. Therefore, having chosen a powerful and high-throughput bead array technology, we performed array-based experiments to define the methylation pattern of 1,505 gene promoters. Previous studies have provided irrefutable proof of the reproducibility of this approach. The simultaneous detection of transposonal demethylation and promoter methylation changes should provide valuable information regarding the molecular mechanisms potentially responsible for the aggressive phenotype of malignant melanoma. Recently, it has become widely accepted that Knudson’s two-hit hypothesis is often confirmed through a combination of differing types of genomic alterations, which prompted us to investigate whether methylation patterns are associated with other types of somatic alterations, such as the most frequent mutations and DNA copy number alterations. Notable previous investigations demonstrated the prognostic relevance of CN aberrations. Therefore, we also highlighted the cis-and trans-acting CN alterations of gene expression in malignant melanoma. Moreover, we and others have demonstrated the association of BRAF and NRAS mutations with CN alterations using BAC arrays, suggesting a central role of BRAF mutations in gene copy number changes. Additionally, a single group reported that the impact of BRAF signalling on gene methylation is widespread. Despite the promising initial results, to our knowledge, no direct, array-based experiments have been performed in an integrative approach in a wide variety of primary melanomas.

Two other bilingual researchers performed back-translation of that version. Based on the minor differences between the back-translation and the original English instrument, we adjusted the forward translation into the final Dutch version of our BFI-11. Attending physicians’ gender was considered as a confounding variable, as research showed gender differences in personality as well as in teaching performance. We created a dummy for gender, with male as the reference category. Furthermore, we used age as a confounding variable as well, because research demonstrated differences in both personality traits and teaching performance across age. For attending physicians’ specialty, we created two categories, namely surgical and non-surgical specialties. Surgical specialties included: plastic and reconstructive surgery, neurosurgery, general surgery, orthopedics, urology, ophthalmology, otorhinolaryngology, obstetrics and gynecology. Non-surgical specialties included: internal medicine, gastroenterology, neurology, cardiology, pulmonology, pediatrics, dermatology, psychiatry, emergency medicine, radiology, radiotherapy, anesthesiology, rehabilitation medicine, pathology, nuclear medicine and clinical genetics. We hypothesized that conscientiousness, extraversion, emotional stability, agreeableness and openness would positively affect teaching performance of attending physicians. In general, the results suggest that different personality traits have different – both positive and negative – effects on different aspects of teaching performance. Of all findings, both on general and specific teaching performance. As for differences between specialties, surgeons who display higher levels of openness received lower scores on their quality of giving feedback and evaluation of residents. Non-surgical attending physicians who are more conscientious appeared to perform better on evaluation of residents. This study builds on existing body of knowledge on personality traits in relation to job performance and academic performance in medicine, as well as on qualitative research findings on traits of competent teachers in medical education. This is the first study that actually empirically quantified the relations using validated personality and teaching performance measures. In addition, this was the first study to explore this topic across surgical and nonsurgical specialties. This resulted in a more nuanced and realistic view on the role of personality traits in teaching practice, as the clinical specialty yields a specific context in which personality traits might have varying costs and benefits. Personality traits were self-reported, which means that the possibility of socially desirable responses should be considered when interpreting the results. Socially desirable reporting is generally higher in situations in which favorable self-presentation is required.