Dynamical modeling of the network controlling meiotic divisions

Mitosis and meiosis are both controlled by oscillations in the activities of cyclin- dependent kinase 1 (Cdk1) and the anaphase-promoting complex/cyclosome (APC/C). Nevertheless, these types of cell division differ in fundamental aspects. In mitosis, Cdk1 and APC/C-Cdc20 form a cyclical system whereby each cycle recreates the starting conditions for the next one. As a result, chromosomes duplication during S-phase alternates with chromosome segregation during M-phase. By contrast, meiosis is a linear pathway of precisely two waves of Cdk1 and APC/C-Cdc20 activity that govern the progression through one S-phase followed by two M-phases and a differentiation program dedicated to the formation of gametes or spores. Despite recent advances in our understanding of meiosis, it is unclear how the mitotic cell cycle engine is modified to regulate the two meiotic divisions. Therefore, we combined mathematical modeling with experimental studies on budding yeast to describe the general mechanism of progression through meiotic divisions with special emphasis on the regulation of the exit from meiosis II. We showed that progression through meiotic divisions is driven by a well conserved Cdk1-APC/C-Cdc20 oscillator complemented by a set of meiotic regulators in order to perform two, and only two, meiotic divisions. The machinery that terminates the oscillations after completion of meiosis II consists of a meiosis I-specific mechanism that unleashes the irreversible inactivation of M-phase regulators after the second wave of APC/C-Cdc20 activity, thereby preventing cells from undergoing an additional third division. Here, we describe the roles of the two main APC/C co- activators, Ama1 and Cdc20, in triggering the exit from meiosis and in terminating the oscillations. We show that Ama1 acts as a terminator of the meiotic oscillations, while Cdc20 is important for the proper timing of the exit from meiosis II. We propose that in the absence of Ama1, the properties of the system change, allowing Cdc20 to adopt the function of the terminator precisely after meiosis II. In addition, we evaluate an APC/C-independent mechanisms, which might be important for preventing a third meiotic division

Analysis of Trace Elements in Human Brain: Its Aim, Methods, and Concentration Levels

Trace elements play a crucial role in many biochemical processes, mainly as components of vitamins and enzymes. Although small amounts of metal ions have protective properties, excess metal levels result in oxidative injury, which is why metal ion homeostasis is crucial for the proper functioning of the brain. The changes of their level in the brain have been proven to be a risk factor for Alzheimer's, Parkinson's, and Huntington's diseases, as well as amyotrophic lateral sclerosis. Therefore, it is currently an important application of various analytical methods. This review covers the most important of them: inductively coupled ground mass spectrometry (ICP-MS), flame-induced atomic absorption spectrometry (FAAS), electrothermal atomic absorption spectrometry (GFAAS), optical emission spectrometry with excitation in inductively coupled plasma (ICP-OES), X-ray fluorescence spectrometry (XRF), and neutron activation analysis (NAA). Additionally, we present a summary of concentration values found by different research groups

The Evaluation of Optic Nerves Using 7 Tesla 'Silent' Zero Echo Time Imaging in Patients with Leber's Hereditary Optic Neuropathy with or without Idebenone Treatment

Magnetic Resonance Imaging (MRI) of the Optic Nerve is difficult due to the fine extended nature of the structure, strong local magnetic field distortions induced by anatomy, and large motion artefacts associated with eye movement. To address these problems we used a Zero Echo Time (ZTE) MRI sequence with an Adiabatic SPectral Inversion Recovery (ASPIR) fat suppression pulse which also imbues the images with Magnetisation Transfer contrast. We investigated an application of the sequence for imaging the optic nerve in subjects with Leber's hereditary optic neuropathy (LHON). Of particular note is the sequence's near-silent operation, which can enhance image quality of the optic nerve by reducing the occurrence of involuntary saccades induced during Magnetic Resonance (MR) scanning

Single stranded-DNA detection: the role of Wip1 in ATR-dependent pathway

Obszary pojedynczonciowego DNA (ssDNA) powstaja w komórkachw wyniku ekspozycji na stres na przykład- promieniowanie UVC-lub podczas naprawy podwójnoniciowych pekniec DNA. ATR (ataxia telangiectasia mutated and Rad3-related) jest odpowiedzialne za wykrywanie ssDNA. Niedawno wykazano kluczowa role fosfatazy Wip1, która inaktywuje główne elementy szlaków odpowiedzi na uszkodzenia DNA. Opracowalismy matematyczny model sciezki ATR i połaczylismygo z modelem szlaku supresora nowotworowego p53, odpowiadajacego za aktywacje genów zaangazowanych w reakcje komórki na uszkodzenie materiału genetycznego (naprawe DNA/apoptoze). Co wiecej, dodalismy fosfataze Wip1, jako główny czynnik odpowiedzialny za wyłaczenie sciezek sygnałowych uruchamianych w ramach reakcji na uszkodzenie. Uzyskane wyniki pokazuja, ze dzieki prawidłowo dobranej dawce UVC i wyciszeniu lub zablokowaniu aktywnosci Wip1, mozliwe jest skierowanie komórek nowotworowych na szlak apoptotycznySingle-stranded DNA (ssDNA) areas arise in cells as a result of exposure to stress agents - like UVC - or during repair of DNA double-strand breaks. ATR(ataxia telangiectasia mutated and Rad3-related) is responsible for detecting ssDNA. Recently, it has been shown that one of the most important components of cellular response to the damage is Wip1 phosphatase, which inactivates main elements of DNA damage response (DDR) pathways. We developed a mathematical model of ATR detector system, connected to p53 tumor suppressor responsible for activation of genes involved in cellular response to the damage (DNA repair/apoptosis). Moreover, we added Wip1 phosphatase, as a main agent responsible for turning o DDR. Our results show that the apoptotic threshold, where more than half of cells die, is equal to 20 J/m2. The threshold shifts when activity of the specied proteins involved in the pathway is blocked or reduced. Moreover with accurate dose of UVC and silenced or blocked Wip1, it may be possible to drive cancer cells to apoptotic pathway

Meeting report--Getting Into and Out of Mitosis

The Company of Biologists Workshop 'Getting Into and Out of Mitosis' was held 10-13 May 2015 at Wiston House in West Sussex, UK. The workshop brought together researchers from wide-ranging disciplines and provided a forum to discuss their latest work on the control of cell division from mitotic entry to exit. This report highlights the main topics and summarises the discussion around the key themes and questions that emerged from the meeting

Does experiencing poverty and lower economic status make us less pro-ecological?

The main aim of this study was to examine whether the economic status (current and in childhood) determined pro-ecological attitudes and behaviour. The survey involved 207 adults with different economic status. Both economic status in childhood and the present were taken into consideration. Analysis of the results indicated that people raised in families with low and medium material status have not only more eco-friendly attitudes but also have a greater tendency towards various ‘green’ behaviours. The differences among people with different current material status concerning their eco-friendly attitudes and behaviours are not so obvious. The most wealthy seem to have a less pro-ecological attitude, but on the other hand they are ready to put more money towards ecologically-friendly household expenses

Metformin as Potential Therapy for High-Grade Glioma

Metformin (MET), 1,1-dimethylbiguanide hydrochloride, is a biguanide drug used as the first-line medication in the treatment of type 2 diabetes. The recent years have brought many observations showing metformin in its new role. The drug, commonly used in the therapy of diabetes, may also find application in the therapy of a vast variety of tumors. Its effectiveness has been demonstrated in colon, breast, prostate, pancreatic cancer, leukemia, melanoma, lung and endometrial carcinoma, as well as in gliomas. This is especially important in light of the poor options offered to patients in the case of high-grade gliomas, which include glioblastoma (GBM). A thorough understanding of the mechanism of action of metformin can make it possible to discover new drugs that could be used in neoplasm therapy

Prefoldin 2 contributes to mitochondrial morphology and function

Prefoldin is an evolutionarily conserved co-chaperone of the tailless complex polypeptide 1 ring complex (TRiC)/chaperonin containing tailless complex 1 (CCT). The prefoldin complex consists of six subunits that are known to transfer newly produced cytoskeletal proteins to TRiC/CCT for folding polypeptides. Prefoldin function was recently linked to the maintenance of protein homeostasis, suggesting a more general function of the co-chaperone during cellular stress conditions. Prefoldin acts in an adenosine triphosphate (ATP)-independent manner, making it a suitable candidate to operate during stress conditions, such as mitochondrial dysfunction. Mitochondrial function depends on the production of mitochondrial proteins in the cytosol. Mechanisms that sustain cytosolic protein homeostasis are vital for the quality control of proteins destined for the organelle and such mechanisms among others include chaperones. We analyzed consequences of the loss of prefoldin subunits on the cell proliferation and survival of Saccharomyces cerevisiae upon exposure to various cellular stress conditions. We found that prefoldin subunits support cell growth under heat stress. Moreover, prefoldin facilitates the growth of cells under respiratory growth conditions. We showed that mitochondrial morphology and abundance of some respiratory chain complexes was supported by the prefoldin 2 (Pfd2/Gim4) subunit. We also found that Pfd2 interacts with Tom70, a receptor of mitochondrial precursor proteins that are targeted into mitochondria. Our fndings link the cytosolic prefoldin complex to mitochondrial function. Loss of the prefoldin complex subunit Pfd2 results in adaptive cellular responses on the proteome level under physiological conditions suggesting a continuous need of Pfd2 for maintenance of cellular homeostasis. Within this framework, Pfd2 might support mitochondrial function directly as part of the cytosolic quality control system of mitochondrial proteins or indirectly as a component of the protein homeostasis networ