Deprotection of centromeric cohesin at meiosis II requires APC/C activity but not kinetochore tension

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. However, deprotection has been proposed to rely on spindle forces separating the Rec8 protector from cohesin at metaphase II in mammalian oocytes and on APC/C-dependent destruction of the protector at anaphase II in yeast. Here, we have activated APC/C in the absence of sister kinetochore biorientation at meiosis II in yeast and mouse oocytes, and find that bipolar spindle forces are dispensable for sister centromere separation in both systems. Furthermore, we show that at least in yeast, protection of Rec8 by shugoshin and inhibition of separase by securin are both required for the stability of centromeric cohesin at metaphase II. Our data imply that related mechanisms preserve the integrity of dyad chromosomes during the short metaphase II of yeast and the prolonged metaphase II arrest of mammalian oocytes

Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in Ductal Carcinoma in Situ and Invasive Ductal Carcinoma of the Breast

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-β1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-β1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer

Design of a Barrier-free Stairway Platform for Handicapped Persons Living in Family Houses

Tato bakalářská práce se zabývá návrhem schodišťové plošiny pro hendikepované osoby. Teoretická část je věnována analýze trhu schodišťových plošin a dále návrhem nové konstrukční varianty plošiny včetně návrhu jejího pohonu s využitím pastorku a ozubeného hřebene. Návrh je zpracován formou 3D modelu a práce obsahuje rovněž ekonomické hodnocení nově navržené varianty.This bachelor thesis deals with the design of a stair lifts platform for handicap people. The theoretical part is devoted to analysis of stair lifts market and torsion torque calculation between pinion and toothed wheel. The practical part consists of designing a 3D model and evaluating approximate costs

Analysis of mechanical behavior of 3D printed elastomer

Tato diplomová práce se zabývá konstitutivním modelováním vybraných vzorků pryže, Tyto vzorky jsou vytvořeny z Tango+ materiálu, které mají odlišné materiálové parametry. V první části jsou vyloženy základy makromolekulární chemie s důrazem na elastomery. V další části je vysvětlen experiment jednoosé tahové zkoušky, ze které jsou následná data pro vyhodnocování. Pomocí těchto dat a Gentův model byly odhadnuty materiálové parametry obou materiálů.This diploma thesis deals with constitutive modeling of selected rubber samples. These samples are made of Tango + material, which have different material parameters. The first part explains the basics of macromolecular chemistry with emphasis on elastomers. The next part explains the experiment of a uniaxial tensile test, from which there are subsequent data for evaluation. Using these data and Gent's models, the material parameters of both materials were estimated

Effect of Gene SFU1 on Riboflavin Synthesis in Flavinogenic Yeast Candida famata

Riboflavin or vitamin B-2 is a necessary component for all living organisms since it is the precursor of flavin coenzymes FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide), which are involved in numerous enzymatic reactions. Flavinogenic yeastCandida famataoverproduces riboflavin under iron starvation; however, regulation of this process is poorly understood. Regulatory gene SEF1 encoding the transcription activator has been identified. Its deletion blocks yeast's ability to overproduce riboflavin under iron starvation. It is known that, in the pathogenic flavinogenic yeastC. albicans, Sfu1 (GATA-type transcription factor) represses SEF1. It is demonstrated in this study that deletion of the SEF1 gene in wild typeC. famataleads to overproduction of riboflavin

Co-Overexpression of RIB1 and RIB6 Increases Riboflavin Production in the Yeast Candida famata

Riboflavin or vitamin B2 is a water-soluble vitamin and a precursor of flavin coenzymes, flavin mononucleotide, and flavin adenine dinucleotide, which play a key role as enzyme cofactors in energy metabolism. Candida famata yeast is a promising producer of riboflavin, as it belongs to the group of so-called flavinogenic yeasts, capable of riboflavin oversynthesis under conditions of iron starvation. The role of the particular structural genes in the limitation of riboflavin oversynthesis is not known. To study the impact of overexpression of the structural genes of riboflavin synthesis on riboflavin production, a set of plasmids containing genes RIB1, RIB6, and RIB7 in different combinations was constructed. The transformants of the wild-type strain of C. famata, as well as riboflavin overproducer, were obtained, and the synthesis of riboflavin was studied. It was found that overexpression of RIB1 and RIB6 genes coding for enzymes GTP cyclohydrolase II and 3,4-dihydroxy-2-butanone-4-phosphate synthase, which catalase the initial steps of riboflavin synthesis, elevated riboflavin production by 13-28% relative to the parental riboflavin-overproducing strains

Modern Trends in Management: Transition to a Hybrid Work Model and Remote Management

Стаття присвячена дослідженню дистанційного управління та організації гібридної робочої моделі. Досліджено переваги та недоліки дистанційного управління, проте в умовах розвитку комп'ютерних технологій набуває все більшої актуальності віддалена робота. Дано визначення сутності понять «дистанційне управління» та «гібридна модель роботи». Розглянуто типи гібридних робочих моделей: Remote-First, Офісно-часова робота, OfficeFirst. Практичний досвід використання цієї моделі в Quora та Dropbox показали позитивні результати. Досліджено переваги та недоліки гібридної робочої моделі, визначено відмінність між роботою вдома та змішаною моделлю роботи. Виділено складові гібридної моделі роботи: варіанти віддаленої роботи; доступ до офісу або робочого місця; гнучкі графіки; технології та інфраструктуру; інструменти для спілкування та спільної роботи; політика та рекомендації. Розглянуто найкращі практики розробки ефективної гібридної моделі робочого місця. Виокремлено компоненти такої роботи: комунікація, співпраця, культура, зв'язок.In the context of today's changing labor landscape, the importance of remote work has increased significantly, which has sparked conversations between various businesses and their staff. This methodology provides an in-depth look at the multifaceted nature of remote work, examining its benefits, potential challenges, and solutions. The advantages and disadvantages of remote control have been studied, however, in the conditions of the development of computer technologies, it is gaining more and more relevance. The essence of understanding "remote control" and "hybrid work model" is defined. Notably, when used wisely, remote work offers significant benefits such as financial savings, increased flexibility, increased efficiency and innovation combined with improved work-life balance. The telecommuting paradigm is not without its challenges, including potential productivity declines, communication difficulties, data integrity concerns, the destruction of organizational morale, and barriers to newcomer assimilation. To meet these challenges, a range of interventions and technological tools are proposed, including definitive guidelines, capacity building, periodic evaluations and professional development pathways. A hybrid work model that combines the benefits of remote work with episodic office tasks is advertised as the optimal way to advance. Within this framework, the office turns into a center of collective cooperation and meetings, rather than a permanent professional residence. Emphasis is placed on the potential benefits of creating an aesthetically pleasing office environment and reallocating funds previously used to maintain it as a magnet for attracting and retaining talent. Types of hybrid working models are considered. Practical experience using this model at Quora and Dropbox showed positive results. The advantages and disadvantages of the hybrid working model are studied. The difference between working at home and the hybrid work model is defined. The components of the hybrid work model are highlighted. Best practices for developing an effective hybrid workplace model are considered. The components of hybrid work are highlighted

SEF1 and VMA1 Genes Regulate Riboflavin Biosynthesis in the Flavinogenic Yeast Candida Famata

Riboflavin (vitamin B-2) is an important component of the diet of living organisms since it is a precursor of flavin coenzymes FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide) involved in numerous enzymatic reactions. It is known that flavinogenic yeastC. famatais able to perform riboflavin overproduction under conditions of iron deficiency, but the regulation of this process remains unknown. It was shown that the deletion of the SEF1 gene (encoding transcription activator) blocked the ability for riboflavin overproduction under conditions of iron deficiency. It was determined that SEF1 promoters of other flavinogenic yeasts (Candida albicansandCandida tropicalis) fused with SEF1 ORF ofC. famatacan restore the overproduction of riboflavin in the sef1 Delta mutant. The disruption of the VMA1 gene (encoding the vacuolar ATPase subunit A) led to overproduction of riboflavin in C. famatain iron complete medium