Tervete rasedate naiste kehavedelikest eraldatud mikroRNA-de profiil

MikroRNA-de (miRNA-de) peamine eesmärk on reguleerida post-transkriptsiooniliselt geenide ekspressiooni kas translatsiooni inhibeerimise või mRNA degradeerimise kaudu. Erinevate kudede poolt produtseeritud ekstratsellulaarsed miRNA-d on leitavad kehavedelikes ning nende muutuva ekspressiooni tõttu saab neid kasutada mitteinvasiivsete biomarkeritena haiguste detekteerimisel. Platsenta kui rasedusaegne organ ekspresseerib samuti kindlas koguses miRNA-sid, mille ekspressioonitasemeid on võimalik jälgida ema vereringest. Hiljuti märkimisväärset panust mitteinvasiivsete biomarkerite väljatöötamisse on avaldanud uriinis ringlevad miRNA-d. Seetõttu antud bakalaureusetöö eesmärk on leida, kas tervete rasedate uriinis on olemas platsentaspetsiifilised miRNA-d, mille kaudu oleks võimalik tulevikus mitteinvasiivselt tuvastada rasedusega kaasnevaid komplikatsioon

Hybrids of Ixodes ricinus and Ixodes persulcatus ticks effectively acquire and transmit tick-borne encephalitis virus

Ixodes rici nus and Ixodes persulcatus ticks are the main vectors of tick-borne encephalitis virus (TBEV), which has three main subtypes connected with certain tick species: the European subtype, associated with I. ricinus, and the Siberian and Far-Eastern subtypes, associated with I. persulcatus. Distribution ranges of these species overlap and form large sympatric areas in the East European Plain and Baltic countries. It has previously been shown that crossing of I. ricinus and I. persulcatus is possible, with the appearance of sterile hybrids. Hybridization of ticks can affect not only the spread of ticks but also the properties of natural foci of arbovirus infections, in particular TBEV. In the present study, we analyzed the effectiveness of virus transmission from infected mice to larvae and nymphs and trans-stadial transmission (from larvae to nymph and adult) in I. ricinus, I. persulcatus, and hybrids. For this purpose, we bred a hybrid generation from the crossing of I. persulcatus females and I. ricinus males, and we used the Siberian and European subtypes of TBEV. We showed that after feeding on infected mice, virus prevalence in engorged ticks decreased over time, and after molting, the opposite was true. In hybrids we observed the highest acquisition effectiveness and RNA copy numbers during Siberian TBEV subtype transmission. The efficiency of trans-stadial transmission of both TBEV subtypes was similar in hybrids and parental species. After the second trans-stadial TBEV transmission, a significant increase in ticks’ infection rates was observed only in specific subtype-tick combination. Our data demonstrate the possible features of TBEV circulation in the I. ricinus and I. persulcatus sympatry area

Micro-Environment Causes Reversible Changes in DNA Methylation and mRNA Expression Profiles in Patient-Derived Glioma Stem Cells

In vitro and in vivo models are widely used in cancer research. Characterizing the similarities and differences between a patient\u27s tumor and corresponding in vitro and in vivo models is important for understanding the potential clinical relevance of experimental data generated with these models. Towards this aim, we analyzed the genomic aberrations, DNA methylation and transcriptome profiles of five parental tumors and their matched in vitro isolated glioma stem cell (GSC) lines and xenografts generated from these same GSCs using high-resolution platforms. We observed that the methylation and transcriptome profiles of in vitro GSCs were significantly different from their corresponding xenografts, which were actually more similar to their original parental tumors. This points to the potentially critical role of the brain microenvironment in influencing methylation and transcriptional patterns of GSCs. Consistent with this possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to return to their initial in vitro states even after a short time in culture, supporting a rapid dynamic adaptation to the in vitro microenvironment. These results show that methylation and transcriptome profiles are highly dependent on the microenvironment and growth in orthotopic sites partially reverse the changes caused by in vitro culturing

Tecnologias e dispositivos de microondas que separam a pele da pele de coelho

The purpose of this work is the development of microwave technology and de-vices separating fur from rabbit skins in a continuous mode at reduced operating costs. They developed the method for the action of the ultrahigh frequency electro-magnetic field (UFEF), which provides the reduction of fur fiber holding power in the meat fabric of rabbit skins with simultaneous combing and gathering. They calcu-lated the mathematical dependences describing the dynamics of multicomponent raw material heating with the change of dielectric and physicomechanical parameters in the process of UFEF. They calculated and visualized the electromagnetic field distri-butions in the developed resonators, on the basis of which they substantiated the ef-fective parameters of the electrodynamic system: the maximum property, the quality of resonators and the electric field strength. They substantiated the complex of struc-tural and technological parameters of devices with new structural design of working chambers by a multi-criteria evaluation of the technological process for the separation of fur from rabbit skin. They manufactured and tested the microwave device under production conditions for the separation of fur from rabbit skin, and adjusted the op-erating modes, which allow to reduce operating costs. They evaluated the technical and economic efficiency of microwave technology introduction for the processing of fur and the devices for rabbit farms; they developed practical recommendations for the operation of microwave units to separate fur from rabbit skins.El propósito de este trabajo es el desarrollo de la tecnología de microondas y los dispositivos que separan la piel de los cueros de conejo en un modo continuo a costos operativos reducidos. Desarrollaron el método para la acción del campo electromagnético de frecuencia ultraalta (UFEF), que proporciona la reducción del poder de retención de la fibra de la piel en el tejido de carne de la piel de conejo con el peinado y la recolección simultáneos. Calcularon las dependencias matemáticas que describen la dinámica del calentamiento de materias primas de componentes múltiples con el cambio de los parámetros dieléctricos y fisicomecánicos en el proceso de la UFEF. Calcularon y visualizaron las distribuciones del campo electromagnético en los resonadores desarrollados, sobre la base de los cuales fundamentaron los parámetros efectivos del sistema electrodinámico: la propiedad máxima, la calidad de los resonadores y la intensidad del campo eléctrico. Ellos sustentaron el complejo de parámetros estructurales y tecnológicos de los dispositivos con un nuevo diseño estructural de las cámaras de trabajo mediante una evaluación de múltiples criterios del proceso tecnológico para la separación de la piel del cuero del conejo.  Fabricaron y probaron el dispositivo de microondas en condiciones de producción para la separación de la piel de la piel de conejo, y ajustaron los modos de operación, lo que permite reducir los costos operativos. Evaluaron la eficiencia técnica y económica de la introducción de la tecnología de microondas para el procesamiento de pieles y los dispositivos para granjas de conejos; desarrollaron recomendaciones prácticas para el uncionamiento de las unidades de microondas para separar las pieles de los cueros de conejo.O objetivo deste trabalho é o desenvolvimento de tecnologia e dispositivos que separam a pele de peles de coelho em um modo contínuo a custos operacionais reduzidos microondas. Eles desenvolveram o método para a acção do campo electromagnético de alta frequência ultra-(UFEF), que fornece pele de coelho carne tecido de pele para retenção de fibras de energia reduzido com cabelo e recolha simultânea. Calcularam as dependências matemático para descrever a dinâmica do aquecimento materiais multicomponentes com a mudança de dieltricos e parâmetros fisicomecánicos no processo de UFEF. Eles calculado e visualizado as distribuições de campo eletromagnético em ressonadores desenvolvidos, com base na qual fundamentar os parâmetros reais do sistema electrodynamic: a propriedade máximo, a qualidade dos ressonadores e intensidade do campo elétrico. Eles sustentadas parâmetros estruturais e tecnológicas complexas dos dispositivos com um novo design estrutural das câmaras de trabalho através de uma avaliação multi-critérios do processo tecnológico para a separação de couro pele de coelho. Eles fabricado e testado o dispositivo de micro-ondas, sob condições de produção para a separação da pele da pele de coelho, e modos de operação ajustados, reduzindo assim os custos operacionais. Eles avaliaram a eficiência técnica e econômica da introdução de tecnologia de microondas para o processamento de dispositivos fazendas de peles e de coelho; desenvolveu recomendações práticas para a operação de unidades de microondas para separar peles de peles de coelho

Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.

Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation

Undiagnosed RASopathies in infertile men

RASopathies are syndromes caused by congenital defects in the Ras/mitogen-activated protein kinase (MAPK) pathway genes, with a population prevalence of 1 in 1,000. Patients are typically identified in childhood based on diverse characteristic features, including cryptorchidism (CR) in >50% of affected men. As CR predisposes to spermatogenic failure (SPGF; total sperm count per ejaculate 0–39 million), we hypothesized that men seeking infertility management include cases with undiagnosed RASopathies. Likely pathogenic or pathogenic (LP/P) variants in 22 RASopathy-linked genes were screened in 521 idiopathic SPGF patients (including 155 CR cases) and 323 normozoospermic controls using exome sequencing. All 844 men were recruited to the ESTonian ANDrology (ESTAND) cohort and underwent identical andrological phenotyping. RASopathy-specific variant interpretation guidelines were used for pathogenicity assessment. LP/P variants were identified in PTPN11 (two), SOS1 (three), SOS2 (one), LZTR1 (one), SPRED1 (one), NF1 (one), and MAP2K1 (one). The findings affected six of 155 cases with CR and SPGF, three of 366 men with SPGF only, and one (of 323) normozoospermic subfertile man. The subgroup “CR and SPGF” had over 13-fold enrichment of findings compared to controls (3.9% vs. 0.3%; Fisher’s exact test, p = 5.5 × 10−3). All ESTAND subjects with LP/P variants in the Ras/MAPK pathway genes presented congenital genitourinary anomalies, skeletal and joint conditions, and other RASopathy-linked health concerns. Rare forms of malignancies (schwannomatosis and pancreatic and testicular cancer) were reported on four occasions. The Genetics of Male Infertility Initiative (GEMINI) cohort (1,416 SPGF cases and 317 fertile men) was used to validate the outcome. LP/P variants in PTPN11 (three), LZTR1 (three), and MRAS (one) were identified in six SPGF cases (including 4/31 GEMINI cases with CR) and one normozoospermic man. Undiagnosed RASopathies were detected in total for 17 ESTAND and GEMINI subjects, 15 SPGF patients (10 with CR), and two fertile men. Affected RASopathy genes showed high expression in spermatogenic and testicular somatic cells. In conclusion, congenital defects in the Ras/MAPK pathway genes represent a new congenital etiology of syndromic male infertility. Undiagnosed RASopathies were especially enriched among patients with a history of cryptorchidism. Given the relationship between RASopathies and other conditions, infertile men found to have this molecular diagnosis should be evaluated for known RASopathy-linked health concerns, including specific rare malignancies